This study is being done to answer the following questions: Is the chance of rectal cancer responding the same if chemotherapy alone is given before limited surgery compared to chemotherapy and radiation therapy given together before limited surgery? If radiation therapy is not given, is quality of life better?

This study is being done to find out if this approach is better or worse than the usual approach for early rectal cancer. The usual approach is defined as care most people get for early rectal cancer.

The usual approach for patients who are not in a study is surgery to remove the rectum or treatment with chemotherapy and radiation therapy, followed by surgery. There are several chemotherapy drugs approved by Health Canada that are commonly used with radiation therapy. For patients who get the usual approach for this cancer, about 90 out of 100 are free of cancer after 5 years.

If a patient decides to take part in this study, they will either get a combination of chemotherapy drugs called FOLFOX or CAPOX for up to 12 weeks or will get chemotherapy with radiation therapy for up to 6 weeks.

After finishing treatment, and even if treatment is stopped early, the study doctor will watch for side effects and determine which type of surgery would be best. After surgery, patients will be asked to come in every 4 months for 2 years, then every 6 months for an additional year. Then will be checked every year for 2 years. This means seeing the study doctor for up to 5 years after surgery. Patients may be seen more often if your study doctor thinks it is necessary.

Inclusion Criteria:

• Histologically confirmed invasive, well-moderately differentiated rectal adenocarcinoma, mismatch repair proficient.
• MRI stage cT1 not eligible for transanal surgery or cT2-T3ab*. * T3a: <1mm depth invasion, T3b: 1-5mm depth of invasion.
• cN0 stage based on pelvic MRI - including absence of radiographic evidence of mesorectal nodal metastasis, tumour deposits or extramural venous invasion (EMVI).
• M0 stage based on no evidence of metastatic disease by CT imaging of chest, abdomen and pelvis.
• Mid to low-lying tumour eligible for transanal excision in the opinion of the treating 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 quality of 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 creatinine clearance 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 highly effective contraceptive method during and for 6 months after completion of chemotherapy.
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

Exclusion Criteria:

• Pathologic high-risk factors on diagnostic biopsy: high histologic grade (poorly differentiated), 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 the investigator, 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 has had partial excision prior to enrollment, there must be gross residual disease endoscopically for patient to be eligible.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the 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 significant adverse events of their most recent therapy/intervention prior to enrollment.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible 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 the patient ineligible for a transanal tumour excision.
• T3 tumours invading or abutting the internal sphincter.