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

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

LR by treatment (ITT) POST Time (years) LR rate (%) At risk: PRE N Events3yr LR 5yr LR PRE % 5% POST % 15% HR(95%CI)=2.50(1.66, 3.72) p<0.0001

POST DFS Rate (%) Time (years) At risk: PRE N Events 3yr 5yr PRE % 73% POST % 65% HR(95%CI)=1.30 (1.05, 1.61) p= DFS by treatment (ITT)

POST Time (years) Survival (%) PRE N Events 3yr OS 5yr OS PRE % 71% POST % 66% HR(95%CI)=1.12(0.90, 1.40) p= Survival by treatment arm (ITT)

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

Bowel problems Worse Better

Sexual problems Worse Better

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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