Do we need surgery in all rectal carcinoma patients? Mohamed Abdulla M.D. Prof. of Clinical Oncology Cairo University PACC 16 th – Cairo City Stars Intercontinental Thursday,
Do we need surgery in all rectal carcinoma patients
Mohamed Abdulla MDProf of Clinical Oncology
Cairo University
PACC 16th ndash CairoCity Stars IntercontinentalThursday 28042016
Member of Advisory Board Consultant and Speaker forbull Amgen Astellas AstraZeneca Hoffman la Roche Janssen Cilag
Merck Serono Novartis Pfizer Mundipharmabull The content of this presentation does not relate to any product of a
commercial interest
Speaker Disclosures
Basic Facts
bull 2nd amp 3rd most common cancer in females amp malesbull 14 million new case and 694000 deathsbull Males gt Femalesbull Lowest rates in Africa amp South Central Asiabull Low SES 30 increased riskbull Rising incidence lt 50 years Left sided colon amp
rectal symptomatic amp advanced Poor outcomebull Sporadic gt Hereditary
Siegel RL Miller KD Jemal A Cancer statistics 2016 CA Cancer J Clin 2016 667 Ahnen DJ Wade SW Jones WF et al The increasing incidence of young-onset colorectal cancer a call to action Mayo Clin Proc 2014 89216
Principles
Surgery is the cornerstone in management
However
Local Recurrence Following Surgery Alone
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Adjuvant Radiation Therapy
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Cuthbert Dukes 1932 Nodes as a prognostic factor
Local Recurrence Better Insight
Circumferential Margins
Number Local Recurrence Rate
P
gt 2 mm 987 33 lt 00001
1 ndash 2 mm 100 85 002
lt 1 mm 227 131 008
Int J Radiation Oncology Biol Phys Vol 55 No 5 pp 1311ndash1320 2003
CRM or LNs
MURCERY Trial
Fiona et al JCO 20141(32) 34-46
Limitations of the TNM ndash T3 category forms 80 of rectal cancers
(J Natl Compr Canc Netw 2015131111ndash1119)
Total Mesorectal Excision (TME)
bull Removal of peri-rectal tissues involving lateral amp circumferential margins of mesorectal envelop
Dis Colon Rectum 2013 May56(5)535-50
Total Mesorectal Excision (TME)
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004N Engl J Med 2001345638 ndash 646
Adjuvant Radiation Therapy
LR = 24
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Member of Advisory Board Consultant and Speaker forbull Amgen Astellas AstraZeneca Hoffman la Roche Janssen Cilag
Merck Serono Novartis Pfizer Mundipharmabull The content of this presentation does not relate to any product of a
commercial interest
Speaker Disclosures
Basic Facts
bull 2nd amp 3rd most common cancer in females amp malesbull 14 million new case and 694000 deathsbull Males gt Femalesbull Lowest rates in Africa amp South Central Asiabull Low SES 30 increased riskbull Rising incidence lt 50 years Left sided colon amp
rectal symptomatic amp advanced Poor outcomebull Sporadic gt Hereditary
Siegel RL Miller KD Jemal A Cancer statistics 2016 CA Cancer J Clin 2016 667 Ahnen DJ Wade SW Jones WF et al The increasing incidence of young-onset colorectal cancer a call to action Mayo Clin Proc 2014 89216
Principles
Surgery is the cornerstone in management
However
Local Recurrence Following Surgery Alone
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Adjuvant Radiation Therapy
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Cuthbert Dukes 1932 Nodes as a prognostic factor
Local Recurrence Better Insight
Circumferential Margins
Number Local Recurrence Rate
P
gt 2 mm 987 33 lt 00001
1 ndash 2 mm 100 85 002
lt 1 mm 227 131 008
Int J Radiation Oncology Biol Phys Vol 55 No 5 pp 1311ndash1320 2003
CRM or LNs
MURCERY Trial
Fiona et al JCO 20141(32) 34-46
Limitations of the TNM ndash T3 category forms 80 of rectal cancers
(J Natl Compr Canc Netw 2015131111ndash1119)
Total Mesorectal Excision (TME)
bull Removal of peri-rectal tissues involving lateral amp circumferential margins of mesorectal envelop
Dis Colon Rectum 2013 May56(5)535-50
Total Mesorectal Excision (TME)
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004N Engl J Med 2001345638 ndash 646
Adjuvant Radiation Therapy
LR = 24
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Basic Facts
bull 2nd amp 3rd most common cancer in females amp malesbull 14 million new case and 694000 deathsbull Males gt Femalesbull Lowest rates in Africa amp South Central Asiabull Low SES 30 increased riskbull Rising incidence lt 50 years Left sided colon amp
rectal symptomatic amp advanced Poor outcomebull Sporadic gt Hereditary
Siegel RL Miller KD Jemal A Cancer statistics 2016 CA Cancer J Clin 2016 667 Ahnen DJ Wade SW Jones WF et al The increasing incidence of young-onset colorectal cancer a call to action Mayo Clin Proc 2014 89216
Principles
Surgery is the cornerstone in management
However
Local Recurrence Following Surgery Alone
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Adjuvant Radiation Therapy
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Cuthbert Dukes 1932 Nodes as a prognostic factor
Local Recurrence Better Insight
Circumferential Margins
Number Local Recurrence Rate
P
gt 2 mm 987 33 lt 00001
1 ndash 2 mm 100 85 002
lt 1 mm 227 131 008
Int J Radiation Oncology Biol Phys Vol 55 No 5 pp 1311ndash1320 2003
CRM or LNs
MURCERY Trial
Fiona et al JCO 20141(32) 34-46
Limitations of the TNM ndash T3 category forms 80 of rectal cancers
(J Natl Compr Canc Netw 2015131111ndash1119)
Total Mesorectal Excision (TME)
bull Removal of peri-rectal tissues involving lateral amp circumferential margins of mesorectal envelop
Dis Colon Rectum 2013 May56(5)535-50
Total Mesorectal Excision (TME)
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004N Engl J Med 2001345638 ndash 646
Adjuvant Radiation Therapy
LR = 24
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Principles
Surgery is the cornerstone in management
However
Local Recurrence Following Surgery Alone
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Adjuvant Radiation Therapy
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Cuthbert Dukes 1932 Nodes as a prognostic factor
Local Recurrence Better Insight
Circumferential Margins
Number Local Recurrence Rate
P
gt 2 mm 987 33 lt 00001
1 ndash 2 mm 100 85 002
lt 1 mm 227 131 008
Int J Radiation Oncology Biol Phys Vol 55 No 5 pp 1311ndash1320 2003
CRM or LNs
MURCERY Trial
Fiona et al JCO 20141(32) 34-46
Limitations of the TNM ndash T3 category forms 80 of rectal cancers
(J Natl Compr Canc Netw 2015131111ndash1119)
Total Mesorectal Excision (TME)
bull Removal of peri-rectal tissues involving lateral amp circumferential margins of mesorectal envelop
Dis Colon Rectum 2013 May56(5)535-50
Total Mesorectal Excision (TME)
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004N Engl J Med 2001345638 ndash 646
Adjuvant Radiation Therapy
LR = 24
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Local Recurrence Following Surgery Alone
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Adjuvant Radiation Therapy
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Cuthbert Dukes 1932 Nodes as a prognostic factor
Local Recurrence Better Insight
Circumferential Margins
Number Local Recurrence Rate
P
gt 2 mm 987 33 lt 00001
1 ndash 2 mm 100 85 002
lt 1 mm 227 131 008
Int J Radiation Oncology Biol Phys Vol 55 No 5 pp 1311ndash1320 2003
CRM or LNs
MURCERY Trial
Fiona et al JCO 20141(32) 34-46
Limitations of the TNM ndash T3 category forms 80 of rectal cancers
(J Natl Compr Canc Netw 2015131111ndash1119)
Total Mesorectal Excision (TME)
bull Removal of peri-rectal tissues involving lateral amp circumferential margins of mesorectal envelop
Dis Colon Rectum 2013 May56(5)535-50
Total Mesorectal Excision (TME)
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004N Engl J Med 2001345638 ndash 646
Adjuvant Radiation Therapy
LR = 24
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Adjuvant Radiation Therapy
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004
Cuthbert Dukes 1932 Nodes as a prognostic factor
Local Recurrence Better Insight
Circumferential Margins
Number Local Recurrence Rate
P
gt 2 mm 987 33 lt 00001
1 ndash 2 mm 100 85 002
lt 1 mm 227 131 008
Int J Radiation Oncology Biol Phys Vol 55 No 5 pp 1311ndash1320 2003
CRM or LNs
MURCERY Trial
Fiona et al JCO 20141(32) 34-46
Limitations of the TNM ndash T3 category forms 80 of rectal cancers
(J Natl Compr Canc Netw 2015131111ndash1119)
Total Mesorectal Excision (TME)
bull Removal of peri-rectal tissues involving lateral amp circumferential margins of mesorectal envelop
Dis Colon Rectum 2013 May56(5)535-50
Total Mesorectal Excision (TME)
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004N Engl J Med 2001345638 ndash 646
Adjuvant Radiation Therapy
LR = 24
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Cuthbert Dukes 1932 Nodes as a prognostic factor
Local Recurrence Better Insight
Circumferential Margins
Number Local Recurrence Rate
P
gt 2 mm 987 33 lt 00001
1 ndash 2 mm 100 85 002
lt 1 mm 227 131 008
Int J Radiation Oncology Biol Phys Vol 55 No 5 pp 1311ndash1320 2003
CRM or LNs
MURCERY Trial
Fiona et al JCO 20141(32) 34-46
Limitations of the TNM ndash T3 category forms 80 of rectal cancers
(J Natl Compr Canc Netw 2015131111ndash1119)
Total Mesorectal Excision (TME)
bull Removal of peri-rectal tissues involving lateral amp circumferential margins of mesorectal envelop
Dis Colon Rectum 2013 May56(5)535-50
Total Mesorectal Excision (TME)
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004N Engl J Med 2001345638 ndash 646
Adjuvant Radiation Therapy
LR = 24
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Local Recurrence Better Insight
Circumferential Margins
Number Local Recurrence Rate
P
gt 2 mm 987 33 lt 00001
1 ndash 2 mm 100 85 002
lt 1 mm 227 131 008
Int J Radiation Oncology Biol Phys Vol 55 No 5 pp 1311ndash1320 2003
CRM or LNs
MURCERY Trial
Fiona et al JCO 20141(32) 34-46
Limitations of the TNM ndash T3 category forms 80 of rectal cancers
(J Natl Compr Canc Netw 2015131111ndash1119)
Total Mesorectal Excision (TME)
bull Removal of peri-rectal tissues involving lateral amp circumferential margins of mesorectal envelop
Dis Colon Rectum 2013 May56(5)535-50
Total Mesorectal Excision (TME)
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004N Engl J Med 2001345638 ndash 646
Adjuvant Radiation Therapy
LR = 24
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
CRM or LNs
MURCERY Trial
Fiona et al JCO 20141(32) 34-46
Limitations of the TNM ndash T3 category forms 80 of rectal cancers
(J Natl Compr Canc Netw 2015131111ndash1119)
Total Mesorectal Excision (TME)
bull Removal of peri-rectal tissues involving lateral amp circumferential margins of mesorectal envelop
Dis Colon Rectum 2013 May56(5)535-50
Total Mesorectal Excision (TME)
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004N Engl J Med 2001345638 ndash 646
Adjuvant Radiation Therapy
LR = 24
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
MURCERY Trial
Fiona et al JCO 20141(32) 34-46
Limitations of the TNM ndash T3 category forms 80 of rectal cancers
(J Natl Compr Canc Netw 2015131111ndash1119)
Total Mesorectal Excision (TME)
bull Removal of peri-rectal tissues involving lateral amp circumferential margins of mesorectal envelop
Dis Colon Rectum 2013 May56(5)535-50
Total Mesorectal Excision (TME)
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004N Engl J Med 2001345638 ndash 646
Adjuvant Radiation Therapy
LR = 24
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Limitations of the TNM ndash T3 category forms 80 of rectal cancers
(J Natl Compr Canc Netw 2015131111ndash1119)
Total Mesorectal Excision (TME)
bull Removal of peri-rectal tissues involving lateral amp circumferential margins of mesorectal envelop
Dis Colon Rectum 2013 May56(5)535-50
Total Mesorectal Excision (TME)
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004N Engl J Med 2001345638 ndash 646
Adjuvant Radiation Therapy
LR = 24
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
(J Natl Compr Canc Netw 2015131111ndash1119)
Total Mesorectal Excision (TME)
bull Removal of peri-rectal tissues involving lateral amp circumferential margins of mesorectal envelop
Dis Colon Rectum 2013 May56(5)535-50
Total Mesorectal Excision (TME)
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004N Engl J Med 2001345638 ndash 646
Adjuvant Radiation Therapy
LR = 24
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Total Mesorectal Excision (TME)
bull Removal of peri-rectal tissues involving lateral amp circumferential margins of mesorectal envelop
Dis Colon Rectum 2013 May56(5)535-50
Total Mesorectal Excision (TME)
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004N Engl J Med 2001345638 ndash 646
Adjuvant Radiation Therapy
LR = 24
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Total Mesorectal Excision (TME)
Clinical Colorectal Cancer Vol 4 No 4 233-240 2004N Engl J Med 2001345638 ndash 646
Adjuvant Radiation Therapy
LR = 24
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Adjuvant Chemoradiation in Stages II amp III Rectal Cancer
bull GITSGbull NCCTGbull NSABP R-01
N Engl J Med 1986 3151294FJ Natl Cancer Inst 1988 8021 N Engl J Med 1991 324709
Adjuvant Fluoroupyremidine
X 2 monthsCRT ndash 6 Weeks
Adjuvant Fluoroupyremidine
X 2 months
Adjuvant Therapy = 6 months
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Neoadjuvant Therapy The German Study A Shifting Concept
N Engl J Med 20043511731-40
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Slide 4
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Slide 3
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Slide 2
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Slide 6
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Slide 7
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Slide 9
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Slide 11
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Slide 12
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Radiation + Chemotherapy are MANDATORY in Neoadjuvant Therapy
Gastrointest Cancer Res 149-56 copy2007 by International Society of Gastrointestinal Oncology
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Neoadjuvant TherapyThe Use of Capecitabine
The Cancer Journal bull Volume 13 Number 3 MayJune 2007
EQUIVALENT
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Neoadjuvant TherapyAdding Oxaliplatin
Curr Opin Oncol 2012 24441ndash447
bull ++ Toxicity amp -- Compliancebull Did not improve
1 R0 RR2 pCR3 Sphincter Preservation
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Neoadjuvant TherapyAdding EGFRVEGF Inhibition
Curr Opin Oncol 2012 24441ndash447
No Significant Added Benefit over Chemotherapy amp Higher G 3 amp 4
Adverse Events
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Neoadjuvant TherapyIndications
1 T3 ndash T4 Lesions The only definitive indication2 cT3N0 Should be treated (understaging)3 Depth of Extramural Invasion ndash T3 lesions (gt5 mm) ++ LNs involvement Higher Cancer
Specific Mortality (54 Versus 85)ndash Selection of high risk T3 for treatmentndash Approved outside US
4 T1 ndash 2 lesions with Positive Nodes5 Low situated lesions6 Invasion of mesorectal fasciaBr J Cancer 2000 821131wwwuptodatecom (September 2015)
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Neoadjuvant TherapyTreatment Outcome
Complete Response cCRpCR
bull 15 ndash 30bull Small amp Less
Advanced Lesionsbull 10 ndash 12 Weeks
bull Involution to flat scarbull DRE amp Endoscopybull Imaging
bull Endorectal USbull PET-CTbull MRI
bull ypT0N0
BIASED
NOT ACCEPTED
Martin R et al Surg Oncol Clin N Am 23 (2014) 113ndash125
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Neoadjuvant TherapyTreatment Outcome in Relation to pCR German Study
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Neoadjuvant TherapyImpact of Pathological CR
British Journal of Surgery 2012 99 918ndash928
Can we Avoid Surgery
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Can we Avoid Surgery
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Can we Avoid Surgery
JCO VOLUME 29 1113097 NUMBER 35 1113097 DECEMBER 10 2011
21 Patients pCR
Neoadjuvant CRTFor Stages II amp III Wait amp See
MRI Endoscopy amp Biopsy
Median Follow up =25 months
1 Patient LR Surgery
20 Pts Stages II amp III NAT pCR
Median Follow up =35 months
2 ndash Year DFS 91 2 ndash Year OAS 93
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Habr-Gama A Sao Juliao GP Perez RO Nonoperative manage ment of rectal cancer identifying the ideal patients Hematol Oncol Clin North Am 2015 29 135 151 [PMID 25475576 DOI 101016jhoc201409004]
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Predicting Pathologic CR Questions amp Debatesbull DRE Under estimationbull CT and ERUS Residual disease amp nodes (ypT0 LN +ve = 2
ndash 9)bull Timing of Assessment 6 or 12 or 6 amp 12 monthsbull CEA Cutoff Point = 27 ngml at 4 or 8 weeksbull Diffusion Weighted MRI Higher sensitivity and specificitybull Full Thickness Excision Biopsybull PET CT Scan 6 and 12 monthsbull Molecular Signature 33 amp 54 genes signatures
Chawla et al Am J Clin Oncol 201538534ndash540
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Neoadjuvant TherapyProblems with Current Practice
CRT 55 Weeks 6 wks TME
1 ndash 2 weeks 4-6 wks Adjuvant Cth
18 weeksbull Delayedbull Reducedbull Omitted
CRT TME Neodjuvant Chemoth
Neodjuvant Chemoth CRT TME
bull Total Neoadjuvant Therapy Paradigm
bull Better down-staging
bull Better pCR
bull Higher R 0 Resection Rates
Adopted from Deborah Schragrsquos Presentation at 2015 ASCO Annual Meeting
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
The Art of Today
bull Radical resection remains the cornerstone in management regardless the achieved response
bull The identification of patients with pCR is challenging however patients should be informed about watch and wait strategy
bull Data showed higher incidence of relapse during the 1st year then becoming comparable to those following radical surgery intensive follow up during the 1st year
bull Adoption of MDT should be encouragedbull The need for more clinical trials is highly appreciated
Thank You
Thank You