RAPIDO Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation Lars Påhlman Dept. Surgery, Colorectal unit, University Hospital,

RAPIDORectal cancer And Preoperative Induction therapy followed by Dedicated Operation

Lars Påhlman

Dept. Surgery, Colorectal unit,

University Hospital, Uppsala, Sweden

Rectal cancer treatmentMRI staging

Stage Irradiation

Good; No

Bad; 5 x 5 Gy

Ugly; Chemo-rad or 5 x 5 ?

Advanced Rectal CancerProblems !

Local recurrences solved ! Occult metastases the problem ! Survival not improved Chemo-rad. standard of care Chemotherapy too weak !

Advanced Rectal CancerStandard of care

Chemorad. 5 weeks Time to surgery 8 weeks Recovery after surgery; 4 weeks In total > 4 months until patients

receive decent chemotherapy !!

Neoadjuvant; Rectal cancer

The RAPIDO trial

Standard of care arm:

Chemorad. Surgery Chemo 4 m

Experimental arm:

5x5 Gy Chemo 5 m Surgery

The RAPIDO trialInclusion criteria

Biopsy proven rectal cancer Staging 5 weeks prior treatment No contra indication to chemotherapy ECOG performance < 1 Written informed consent 18 years Adequate for follow up

The RAPIDO trialInclusion criteria

Good quality MRI (T 3 c/d), T4 a/b EMVI + N2 N+ (outside the fascia plane) MRF +

The RAPIDO trialAt leased one of the criteria's

T4 overgrowth to adjacent organs T4b peritoneal involvement EMVI + vascular invasion N2 > 4 nodes which looks abnormal N+ lateral nodes > 1 cm MRF + threatened mesorectal fascia

The RAPIDO trialEndpoints

DFS at 3 years (Main endpoint) 880 patients (DFS 50 60 %) Toxicity + postop. complications pCR OS, Local recurrence rate QoL

The RAPIDO trialExperimental arm previous experience

Dutch M 1 Study

50 patients M1 (75% T3/4N+)5x5 Gy + XELOX + Bevacizumab (6 cycles) + surgery

83% received all chemo (90% >4 cycles)Low/acceptable toxicity

pCR in 26% of specimens‘No progression was seen on chemotherapy’

van Dijk et al. JCO 2009: p. ASCO GI 2010. Abstract 427

The RAPIDO trialExperimental armWhat are we treating ?

Local tumour Systemicgrowth disease

Surgery Radioth. Chemoth.

The RAPIDO trial

Possible concerns

Surgery difficult after > 20 weeks

Progressive disease during the delay

Local recurrence rateTrial / level Local recurrence

RT - RT + p value

SRCT < 5 cm 27 % 10 % 0.003TME < 5 cm 11 % 12 % 0.53CRO 7 < 5 cm 11 % 5 % < 0.001

SRCT 6 - 10 cm 26 % 9 % < 0.001TME 6 - 10 cm 15 % 4 % < 0.001CRO 7 6 - 10 cm 10 % 5 % < 0.001

SRCT > 10 cm 12 % 8 % 0.3TME > 10 cm 6 % 4 % 0.15CRO 7 > 10 cm 6 % 1 % < 0.001

Swedish Rectal Cancer Registry %

10

Dutch TME - trial Overall survival; eligible patients (n=1809)

Years since surgery

86420

Cu

m S

urv

iva

l

1,0

,9

,8

,7

,6

,5

,4

,3

,2

,1

0,0

64.2% vs 63.4% p = 0.87

TME alone

RT + TME

CRO7 - Overall survivalAll patients

Years

0

10

20

30

40

50

60

70

80

90

100

0 1 2 3 4 5

Preop. RT

Postop. RT p = 0.07

%

Polish trial

Trial design

Preop. chemorad. 25 x 2 Gy

Preop. radiotherapy 5 x 5 Gy

Randomisation

Local

Recurr

Survival

Sphincter

preserv

Polish Trial Local Recurrences

Years

54321

20

15

10

5

Chemo-radiation

5 x 5 Gy

p = 0.23

16%

11%

Polish Trial - Overall Survival eligible patients (n=312)

p = 0.82

Years

543210

100

80

60

40

20

0,0

chemoradiation

5 x 5 Gy

Short - course radiotherapyStill an important option

Better than chemo-rad. ? Polish trial ! Australian trial ? Stockholm III !!!!

Stockholm III TrialOngoing trial in Sweden

3-armed trial

25 Gy / 1 week immediate surgery

25 Gy / 1 week delayed surgery

50 Gy / 5 weeks delayed surgery

Non-resectable rectal cancer

Non-resectable rectal cancer

Advanced Rectal CancerConclusion with 5x5 Gy

Delayed surgery is feasible Delayed surgery gives down –

sizing / staging ! Delayed surgery will not

increase complication rates