Testis Cancer The Management of Residual Masses Post-chemotherapy Dr Manish I. Patel Urologic Oncologist Westmead Hospital / University of Sydney.

Testis CancerTestis CancerThe Management of Residual Masses The Management of Residual Masses

Post-chemotherapy Post-chemotherapy

Dr Manish I. PatelDr Manish I. Patel

Urologic OncologistUrologic Oncologist

Westmead Hospital / University of SydneyWestmead Hospital / University of Sydney

Questions to be Answered.Questions to be Answered.

• Do all masses have to be resected or can the histology be accurately predicted?

• Do normal (or minimal) residual masses in the RP need resection?

• Is a modified template safe?• Is nerve sparing safe?• Is there a place for surgery post salvage chemo?• When do you resect a post-chemo seminomatous

mass?• Is there any way to predict the histology?

NSGCT-Resection of tumor is important.NSGCT-Resection of tumor is important.

• Teratoma:– Chemo-resistant (Baniel et al. JCO 1995)

– Resection is curative.– Unpredictable malignant potential- TMT.– Late relapse.

• Median relapse time is 5-7 years.-flawed by short FU studies.

Resection of Viable Cancer is Important.Resection of Viable Cancer is Important.

• Complete resection for viable GCT– May be curative– Prognostic

Predicitive Factors of Outcome

In patients with viable cancer on

Multivariate analysis.

•Complete resection

•Proportion of viable cancer cells

•Good risk IGCCC criteria

Surgery for necrosis is not beneficial.Surgery for necrosis is not beneficial.

• Need to accurately predict those with necrosis.

• Minimise morbidity of surgery.

Accurately predicting the histology of PC Accurately predicting the histology of PC residual masses has been difficult.residual masses has been difficult.

Instit. Policy N Necrosis Teratoma Cancer

Resect None 716 45% 42% 13%

Indiana <10mm or >70%red+ 10 T. -ve 237 72% 23% 5%

Mass <10mm 204 70% 25% 5%

Steyerberg Prediction model >70% necrosisSteyerberg JCO 1998 16(1): 269-274

181 81% 13% 7%

Netherlands Mass < 10mm and 10 T. -ve 114 76% 17% 7%

MSKCC (old) <10mm + prechemo <=30mm 113 65% 30% 5%

NRH <20mm+ 10 T. –ve+ prechemo markers normal

52 88% 4% 8%

ReHit Study Group716 PC RPLND Histology from 6 centers.>90% residual masses >5mmHistology of mass not resected by various policies

PC-RPLND Good Risk (IGCCCG) PatientsPC-RPLND Good Risk (IGCCCG) Patients

Histology of Residual Retroperitoneal MassHistology of Residual Retroperitoneal Mass Size: MSKCC Size: MSKCC

Residual RP

Mass Size

Total Cancer Teratoma Malignant Transformation

Necrosis

No Mass 41 0 15 (37%) 0 26 (63%)

<2cm 101 7 (7%) 26 (26%) 2 (2%) 66 (65%)

> 2cm and <5cm 41 3 (7%) 21 (51%) 0 17 (42%)

>5cm and <10cm 17 3 (18%) 10 (59%) 0 4 (24%)

>10cm and <20cm 5 0 3 (60%) 1 (20%) 1(20%)

Total 205 13 (6%) 75 (37%) 3 (2%) 114 (56%)

Patel et.al. presented AUA 2003

PC-RPLND Good Risk (IGCCCG) Patients PC-RPLND Good Risk (IGCCCG) Patients Presence of Teratoma in the Residual RP MassPresence of Teratoma in the Residual RP Mass

Residual Mass <2cm and Histology of Primary TumorResidual Mass <2cm and Histology of Primary TumorResidual Retroperitoneal

Mass Size

Teratoma in Primary

TotalTeratoma in

Retroperitoneum

No Mass+

-

18

23

10 (56%)

5 (22%)

>0cm and <0.5cm+

-

6

6

1 (17%)

2 (33%)

>0.5cm and <1.0cm+

-

8

16

2 (25%)

4 (25%)

>1.0cm and <1.5cm+

-

8

7

3 (38%)

1 (14%)

>1.5cm and >2.0cm+

-

6

12

5 (83%)

0

Total+

-

46

64

21 (46%)

12 (19%)

Patel et.al. presented AUA 2003

• 87 patients with PC masses <=20mm.

• 23 patients mass<=5mm

• All had RPLND

• Increasing incidence of teratoma with size of mass.

• No significant pre or post PC factor predicted necrosis.

Decision analysis model predicts increased survival Decision analysis model predicts increased survival with resection of minimal residual masses.with resection of minimal residual masses.

• Decision analysis model for estimating survival achieved by resection or observation of minimal residual masses.

According to the model:

Survival=+2 years with resection of masses 10-20mm.

Survival=+1 year with resection of masses 0-10mm.

Indiana University Outcomes of patients with RP disease Indiana University Outcomes of patients with RP disease who underwent induction chemotherapywho underwent induction chemotherapy

Median FU approx 4 years.

A: No residual mass (n=78). OBSERVE

5/78 NED patients: recurrent disease. 4/5 in RP

B: Unresectable (n=50). Mainly marker elevation.

C: Residual mass, 10 Teratoma +ve (n=90).RPLND

10 did not have RPLND.

8/86 NED patients relapsed. 6 distant, 2 in RP.

D: Residual mass, 10 Teratoma –ve, <90% radiographic PR (n=50).RPLND

5/48 NED patients relapsed. 1 in RP

E: Residual mass, 10 Teratoma –ve, >90% radiographic PR (n=27).OBSERVE

2/23 NED patients relapsed

Survival

Complete Resection after Complete Resection after Salvage Chemotherapy is Paramount!Salvage Chemotherapy is Paramount!

• 580 PC-RPLND at Indiana University.– 417 after induction chemo.(markers normal)

• 10% viable cancer rate.

– 163 after salvage chemotherapy (markers normal)• 55% (90) viable cancer rate.

– 53/90 were able to be completely resected.

» 25 had adjuvant chemotherapy: only 9 (36%) cNED

» 28 had no adj. Chemotherapy: 23 (43%) cNED

– All incompletely resected patients died.

• Imperative to resect all post-salvage chemo masses.• Must attempt complete resection as post-op Chemo does not

appear effective.

Fox et.al. JCO 1993; 11(7): 1294

Desperation Surgery Has A Place.Desperation Surgery Has A Place.

• When all chemotherapy options have been exhausted, surgical resection is an option.– Solitary RP masses have a much better outcome.

• 2 studies Murphy and Wood.– 63 patients underwent desperation surgery.– 50/63 had a complete resection.

• 17/50 (34%) are cNED with no further therapy.• 6/50 (12%) are NED with further chemotherapy.

Murphy et.al.J Clin Oncol, 11:324, 1993Wood et al. Cancer, 70: 2354, 1992

What type of surgery is required?What type of surgery is required?

• With extensive prechemo disease in the RP, a full bilateral dissection is required.– The incidence of tumor away from the primary landing

zone or main mass is common. (Donohue 1982 JUrol 127)

• The dissection may be limited when the prechemo disease is minimal and limited to the primary landing zone.– Advantage: limited morbidity– Disadvantage: RP recurrence

Only a small number of non-palapable tumors will be Only a small number of non-palapable tumors will be located outside the modified dissection template.located outside the modified dissection template.

Herr et.al. J Urol. 1992;148(6):1812-5 • Studied 113 patients.PC RPLND for initial bulky disease.

– Tumor was located outside the boundaries of a modified retroperitoneal lymph node dissection in 14/ 60 with residual disease.

– But tumor was present within a palpable mass in 6/14 patients. – If the residual mass was removed and a modified retroperitoneal lymph

node dissection was performed only 8% would have tumor left in the retroperitoneum.

Rabbani et.al. BJU. 1998; 81(2): 295-300• 50 patients undergoing PC-RPLND

– 39=BRPLND. 1 patient had tumor outside modified template.– 9= modified RPLND. No recurrence with 55month FU.– 2= lumpectomy. 1 pt had recurrence.

Frozen section maybe useful during PC-RPLND.Frozen section maybe useful during PC-RPLND.• Does necrosis on frozen-section analysis of a mass after

chemotherapy justify a limited retroperitoneal resection in patients with advanced testis cancer?

• HERR, H. W. BJU. 1997; 80(4): 653-657.

• 62 PC-RPLND patients. Underwent modified RPLND if residual mass showed necrosis only.

• 89% concordance between FS and final parraffin section.

• 4 false negatives, all specimen confined.

• 6 years media FU: 14 relapses, 1 in the RP.

Nerve-sparing PC-RPLND is safe.Nerve-sparing PC-RPLND is safe.

• Ejaculatory status of 81 patients after nerve sparing PC-RPLND.

• 35 months FU– 6 recurrences– 0 in RP.

• This data confirmed by SD Fossa’s data

BJC 1999 80(1/2): 249-255

Lumber nerve roots spared

Antegrade Ejaculation

Total Patients

All Right 80% 30

3 right 92% 12

2 right 67% 6

1 right 0% 1

All Left 70% 20

3 Left 67% 3

2 Left 75% 4

Bilateral All 80% 5

Coogan CL.JUrol. 1996; 156(5) :1656-1658.

75%-89% incidence of necrosis in lung if necrosis in RP.75%-89% incidence of necrosis in lung if necrosis in RP.

Brenner et.al. JCO 1996 14(6): 176524 patients with simultaneous PC-RP and chest + neck resection.

6 (25%) patients had discordent pathology.

Toginini et.al. JUrol 1998 159(6): 1833143 patients with simultaneous PC-RP and chest resection.

77.5% had the same pathological condition in the chest.7/40 patients showing RP necrosis has viable cancer in their chest.

Steyerberg et.al.JUrol 1997 158(2): 474159 patients undergoing PC-RP and thoracotomy.

Neither size nor degree of shrinkage was predicitive of chest pathology.Necrosis in RP correlated with necrosis in chest 89%.

Steyerberg et.al. Cancer 1997 79(2).215 patients, 6 centers (ReHit study).- Predictors of necrosis.

no teratoma in primary, normal prechemo markers and single unilateral mass.

RP histology is not sufficiently accurate to eliminate the need to resect chest masses.

Management of Post-Chemo Management of Post-Chemo Seminomatous Mass.-MSKCCSeminomatous Mass.-MSKCC

104 PC seminomas

Residual mass<3cmN=74

Residual mass=>3cmN=30

Observation n=3 Surgery n=27Surgery n=28 Observation n=46

Seminoma=6Teratoma=2

Necrosis=28Relapsed in RP

N=2No relapse

Herr et.al. JUrol 1997 157(3): 860Puc et.al JCO 1996 14(2): 454

Complete Resection is Important.Complete Resection is Important.• 55 patients PC-RPLND• 23 well defined masses

– 18 C. Resection.(78%)

– 6 positive histology.

• 32 poorly defined mass.– 14 C. Resection.(44%)

– 2 positive histology.

• Ravi et.al BJU 1999

Advocated not resecting ill defined masses.

All who relapse DODAll incomplete resections DOD

Management of Post-Chemo Management of Post-Chemo Seminomatous Mass.-Indiana UniversitySeminomatous Mass.-Indiana University

21 PC seminoma residual

mass

Residual mass<3cmN=12

Residual mass=>3cm

N=9

NED n=8 Relpase n=1NED n=11 relapse n=1

Schultz et.al. JCO 1990 8(4): 756

Approx 50% of non-resected masses completely resolved a median of 12 months form chemotherapy

Prospective studies show a low relapse rateProspective studies show a low relapse ratefor residual masses =>3cm.for residual masses =>3cm.

DeSantis. JCO 2004; 22:1034-1039

FDG-PET is useful in masses >3cm.FDG-PET is useful in masses >3cm.• FDG PET studies in 51 patients with metastatic pure seminoma who had

radiographically defined postchemotherapy residual masses, were correlated with either the histology of the resected lesion or the clinical outcome

• Supported by other studies in post induction chemotherapy patients.

DeSantis. JCO 2004; 22:1034-1039

Best Practise.Best Practise.

• Resect all radiographically visible NSGCT residual masses.

• Consider resecting normal RP if the primary tumor is teratoma positive.

• Modified template dissection is safe in small masses in the landing zone.

• Nerve sparing is safe, works and should be performed where possible.

• Surgery post salvage chemotherapy is very important.

• There is a place for desperation surgery.

Best Practise.Best Practise.• Retroperitoneal pathology will not sufficiently

accurately predict histology at other sites.

• PC seminoma residual masses <3cm should be observed.

• PC seminoma residual masses => 3cm should be imaged with FDG-PET.

• Complete resection is very important for outcome.