1. CR07 results and informed patient consent David Sebag-Montefiore Leeds Cancer Centre

2. N=1350 Clinically operable adenocarcinoma of the rectum <15cm from anal verge; no metastases Adjuvant chemotherapy given as per local policy POST Post-op CRT 45Gy / 25F + concurrent 5FU PRE Pre-operative RT 25Gy / 5F Surgery Pathology Surgery Pathology CRM-ve CRM+ve No RT Trial Design

3. LR by treatment (ITT) 100 676594457333214115 POST 0 10 20 30 40 50 60 70 80 90 012345 Time (years) LR rate (%) At risk: 674587475338236134 PRE N Events3yr LR 5yr LR PRE67427 4% 5% POST6767110% 15% HR(95%CI)=2.50(1.66, 3.72) p<0.0001

4. 676557414309196109 POST DFS Rate (%) 0 10 20 30 40 50 60 70 80 90 100 Time (years) 012345 At risk: 674556436312219126 PRE N Events 3yr 5yr PRE674147 77% 73% POST676188 73% 65% HR(95%CI)=1.30 (1.05, 1.61) p=0.0154 DFS by treatment (ITT)

5. 100 676608484359232121 POST 0 10 20 30 40 50 60 70 80 90 012345 Time (years) Survival (%) 674593484343239136 PRE N Events 3yr OS 5yr OS PRE674153 81% 71% POST676173 80% 66% HR(95%CI)=1.12(0.90, 1.40) p=0.2886 Survival by treatment arm (ITT)

6. Subset analyses Treatment effect for:- Low mid and upper rectum Anterior resection and APER By stage (increased difference with higher stage Irrespective of plane of surgery achieved

7. Bowel problems Worse Better

8. Sexual problems Worse Better

9. Informed patient consent Clinical oncologist required! Planned operation important Perineal wound re APER Bowel funnction re AR Erectile dysfunction Sterility Small bowel stricture Pelvic insufficiency fractures

10. Three key issues Pre-operative radiotherapy works – the question is where to define the threshold where radiotherapy is considered If surgery first and node positive (irrespective of margin status), post- operative chemoradiation should be considered Radiation causes late toxicity

11. LR by stage III N3 yr5 yr PRE2529.0%10.2% POST27117.4%25.6% p=0.008

12. LR for node +ve CRM -ve N3 yr5 yr PRE2146.7%8.2% POST22117.1%24.5% p=0.0039

13. Which patients not to treat? T1/2 N0 CRM -ve T3++/T4 CRM +ve NNT= 18 X

14. Which patients to treat? T1/2 N0 CRM -ve T3++/T4 CRM +ve T3/4 Tany N0 N+ CRM -ve NNT= 9

15. Which patients to treat? T1/2 N0 CRM -ve T3++/T4 CRM +ve Tany N+ve CRM -ve NNT= 6

16. Different scenarios T1/2 N0 CRM -ve T3++/T4 CRM +ve CRT S SCPRT >2mm T3/N+ CRM-ve>5mm T3/N+ CRM-ve

17. LN+ rate by extramural spread of T 3 tumours (YCN data) n=4731 N=1948 N=1279 N=786N=718 41%59% 32% 68%

18. Use of radiotherapy according to selection criteria used for T3 tumours >2mm cut off>5mm cut off PrePostPrePost SCPRT5932 Receive SCPRT5630

19. Use of radiotherapy according to selection criteria used for T3 tumours >2mm cut off>5mm cut off PrePostPrePost SCPRT5932 Receive SCPRT5630 Surgery first4168 LN+ve1323 Receive post-op CRT916

20. Use of radiotherapy according to selection criteria used for T3 tumours >2mm cut off>5mm cut off PrePostPrePost SCPRT5932 Receive SCPRT5630 Surgery first4168 LN+ve1323 Receive post-op CRT916 RT courses6548 RT fractions505400

21. Yorkshire audit Network agreed MRI reporting proforma Includes the MRI T stage and N stage SCPRT criteria to agree (predicted CRM-ve) >2mm or 5mm (unit policy) N+ Document if SCPRT given or reasons why not given Histopathology

22. Conclusion Identify patients without threatened margins at significant risk of LR There is not a definitive answer! Share practice Prospective audit

23. Some need 5x5 in the middle! Its chemorads or nothing!