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

2. Rectal cancer treatment
MRI staging
Stage Irradiation
Good; No
Bad; x 5 Gy
Ugly; Chemo-rad
or 5 x 5 ?

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

4. Advanced Rectal Cancer
Standard of care
Chemorad. 5 weeks
Time to surgery 8 weeks
Recovery after surgery; 4 weeks
In total > 4 months until patients receive decent chemotherapy !!

5. Neoadjuvant; Rectal cancer
The RAPIDO trial
Standard of care arm:
Chemorad. Surgery Chemo 4 m
Experimental arm:
5x5 Gy Chemo 5 m Surgery

6. The RAPIDO trial Inclusion 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

7. The RAPIDO trial Inclusion criteria Good quality MRI (T 3 c/d), T4 a/b
EMVI + N2
N+ (outside the fascia plane)
MRF +

8. At leased one of the criteria's
The RAPIDO trial
At 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

9. The RAPIDO trial Endpoints DFS at 3 years (Main endpoint)
880 patients (DFS %)
Toxicity + postop. complications
pCR
OS, Local recurrence rate
QoL

12. Experimental arm previous experience
The RAPIDO trial
Experimental 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 Abstract 427

13. The RAPIDO trial Experimental arm What are we treating ?
Local tumour Systemic
growth disease
Surgery Radioth. Chemoth.

14. Possible concerns The RAPIDO trial
Surgery difficult after > 20 weeks
Progressive disease during the delay

15. Local recurrence rate Trial / level Local recurrence RT - RT + p value
SRCT < 5 cm 27 % %
TME < 5 cm 11 % 12 %
CRO 7 < 5 cm 11 % 5 % < 0.001
SRCT cm 26 % 9 % < 0.001
TME cm 15 % 4 % < 0.001
CRO cm 10 % 5 % < 0.001
SRCT > 10 cm 12 % 8 %
TME > 10 cm 6 % 4 %
CRO 7 > 10 cm 6 % 1 % < 0.001

16. Swedish Rectal Cancer Registry

17. Dutch TME - trial Overall survival; eligible patients (n=1809)
TME alone
64.2% vs 63.4%
p = 0.87
RT + TME

18. CRO7 - Overall survival All patients%
100 90 80 70 60 50
Preop. RT
Postop. RT 40
p = 0.07 30 20 10 1 2 3 4 5
Years

19. Polish trial Trial design
Preop. chemorad x 2 Gy
Preop. radiotherapy x 5 Gy R a n d o m i s t L o c a l R e u r S u r v i a l S p h i n c t e r s v

20. Polish Trial Local Recurrences20
Chemo-radiation 15
16% 10
5 x 5 Gy
11% 5
p = 0.23 1 2 3 4 5
Years

21. Polish Trial - Overall Survival eligible patients (n=312)
Years 5 4 3 2 1
100 80 60 40 20
0,0
chemoradiation
5 x 5 Gy
p = 0.82

22. Short - course radiotherapy
Still an important option
Better than chemo-rad. ?
Polish trial !
Australian trial ?
Stockholm III !!!!

23. Ongoing trial in Sweden
Stockholm III Trial
Ongoing trial in Sweden
3-armed trial
25 Gy / 1 week immediate surgery
25 Gy / 1 week delayed surgery
50 Gy / 5 weeks delayed surgery

24. Non-resectable rectal cancer

25. Non-resectable rectal cancer

26. Advanced Rectal Cancer
Conclusion with 5x5 Gy
Delayed surgery is feasible
Delayed surgery gives down –sizing / staging !
Delayed surgery will not increase complication rates