Neoadjuvant Chemotherapy, Excision And Observation vs Chemoradiotherapy For Rectal Cancer

Inclusion Criteria:

• Histologically confirmed invasive, well-moderately differentiated rectaladenocarcinoma, mismatch repair proficient.

• MRI stage cT1 not eligible for transanal surgery or cT2-T3ab*. * T3a: <1mm depthinvasion, T3b: 1-5mm depth of invasion.

• cN0 stage based on pelvic MRI - including absence of radiographic evidence ofmesorectal nodal metastasis, tumour deposits or extramural venous invasion (EMVI).

• M0 stage based on no evidence of metastatic disease by CT imaging of chest, abdomenand pelvis.

• Mid to low-lying tumour eligible for transanal excision in the opinion of thetreating surgeon.

• Medically fit to undergo radical TME surgery as per treating surgeon's decision.

• Participant is able (i.e. sufficiently fluent) and willing to complete the qualityof life questionnaires in either English or French or Spanish.

• Age of at least 18 years.

• No contraindications to protocol chemotherapy.

• Adequate normal organ and marrow function: ANC ≥ x 10^9/L; platelet count ≥ 100 x 10^9/L; bilirubin < 1.5 UNL, excluding Gilbert's syndrome; Estimated creatinineclearance of ≥ 50ml/min

• Patient must have an ECOG performance of <2 (or Karnofsty ≥ 60%).

• Must be accessible for treatment and follow-up

• Males and females of reproductive potential must have agreed to use a highlyeffective contraceptive method during and for 6 months after completion ofchemotherapy.

• HIV-infected patients on effective anti-retroviral therapy with undetectable viralload within 6 months are eligible for this trial.

Exclusion Criteria:

• Pathologic high-risk factors on diagnostic biopsy: high histologic grade (poorlydifferentiated), mucinous or signet ring histology.

• Patients with visible pelvic sidewall nodes on MRI.

• Patients with unequivocal determination of nodal disease that, in the opinion of theinvestigator, would prohibit protocol therapy administration.

• Previous pelvic radiation for any reason, including brachytherapy alone.

• Patients who have had primary lesion excised prior to enrollment. If a patient hashad partial excision prior to enrollment, there must be gross residual diseaseendoscopically for patient to be eligible.

• Patients with a prior or concurrent malignancy whose natural history or treatmentdoes not have the potential to interfere with the safety or efficacy assessment ofthe investigational regimen are eligible for this trial.

• Prior treatment for rectal cancer.

• Patients with known dihydropyrimidine dehydrogenase deficiency (DYPD).

• Potential trial participants should have recovered from clinically significantadverse events of their most recent therapy/intervention prior to enrollment.

• Patients with known history or current symptoms of cardiac disease, or history oftreatment with cardiotoxic agents, should have a clinical risk assessment of cardiacfunction using the New York Heart Association Functional Classification. To beeligible for this trial, patients should be class 2B or better.

• Any contra-indications to undergo MRI imaging.

• Presence of anterior lesions above or near peritoneal reflection rendering thepatient ineligible for a transanal tumour excision.

• T3 tumours invading or abutting the internal sphincter.