APHRODITE

• Biopsy confirmed adenocarcinoma of the rectum

• Age 18 or over

• Able to provide written informed consent

• Non-surgical management is deemed appropriate due to one of the following three reasons:

·         Unsuitable for radical TME surgery, due to increased surgical risk from TME (for example due general frailty or due to specific co-morbidities which make anaesthetic or surgery hazardous, such as cardiac disease, pulmonary disease, renal failure, previous anaesthetic problems or previous pelvic surgery), OR

·         Anticipated difficulty managing a stoma post-operatively (including physical causes such as arthritis, Dupuytren’s contracture and visual problems).

·         Suitable for radical TME surgery in terms of performance status and general medical condition, but where the patient strongly prefers an attempt at organ preservation, aiming to try and avoid TME surgery.

• Patient is suitable for either pelvic radiotherapy or chemoradiation in the opinion of the treating oncologist

• ECOG PS 0-2

• Primary tumour is visible on MRI

• Primary tumour is ≤ 5 cm in maximum diameter

• Primary tumour is staged at T1-T3b. (TNM staging as per UICC 8th Edition (Appendix B), with additional T3 subdivisions)

• Superior aspect of tumour is at or below a horizontal line drawn from the anterior aspect of the S2/3 junction on pre-treatment MRI

• Nodal disease is staged at N0-N1b i.e. a maximum of three involved mesorectal lymph nodes is permitted. Involved lymph nodes are defined morphologically i.e. demonstrating irregular margins and or heterogeneous signal on high resolution MRI.

·         Nx nodal disease is also permitted i.e. nodes are equivocal for involvement.

·         Superior aspect of involved lymph nodes is at or below a horizontal line drawn from the anterior aspect of the S2/3 junction on pre-treatment MRI

• Mesorectal fascia or levator ani are clear (>1 mm from primary tumour or contiguous EMVI or nodal disease to mesorectal fascia or levator ani)

• For patients intended to receive radiotherapy alone, or concurrent 5-Fluorouracil, there is no required level of renal function. Patients intended to receive capecitabine require an estimated creatinine clearance ≥ 30 ml/min (estimated using a validated creatinine clearance calculation e.g. Cockroft and Gault (Appendix D) or Wright formula)

·         Absolute neutrophil count > 1.5 x 109/l; platelets > 100 x 109/l

·         Serum transaminase concentration < 3 x Upper Limit Normal (ULN)

• Bilirubin concentration < 1.5 x ULN 

• N2 disease; i.e. 4 or more involved mesorectal lymph nodes

• Presence of discontinuous tumour deposits / discontiguous EMVI (N1c)

• Dominant mucinous tumour on MRI

• Signet ring carcinoma or tumours histopathologically containing a neuroendocrine component

• Tumour threatens (≤ 1mm), involves or breaches the mesorectal fascia or levator ani

• Involvement of anal intersphincteric plane or external anal sphincter or adjacent organs (If the participant has a low rectal tumour extending inferior to the puborectalis sling, involvement of the internal anal sphincter is permitted) 

• Undergone an attempt at complete local resection of their cancer

• Previous pelvic radiotherapy

• Definite distant metastases (equivocal distant metastases on the CT scan are permitted, e.g. indeterminate lung nodules, sub-centimetre retroperitoneal nodes or indeterminate liver lesions)

• Defunctioning colostomy or ileostomy has been fashioned

• Prior invasive malignancy unless disease free for a minimum of 3 years (excluding basal cell carcinoma of the skin or other in situ carcinomas)

• Prior systemic chemotherapy for colorectal cancer

• Women who are pregnant, breastfeeding or a women of child bearing potential who are unwilling to use effective contraceptive methods

Research Nurse: Rashmi Madan (x4656) Rashmi.Madan@LTHTR.nhs.uk

Administrator: Yecora Lecanda-Swarbrick (x3766)