SCARLET - Italian proSpeCtionAl obseRvationaL multicEntre Study on Treatment for recTal pT1 Cancer

Inclusion Criteria:

1. Age 18 years or older.
2. Good performance status (Eastern Cooperative Oncology Group \[ECOG\] performance status 0 or 1).
3. Primary tumor of the distal rectum (clinical T1) amenable to local endoscopic resection using Endoscopic Submucosal Dissection (ESD) or local surgical resection using Transanal Endoscopic Microsurgery (TEM) or Transanal Minimally Invasive Surgery (TAMIS).
4. High-risk pathological T1 rectal cancer meeting at least one of the following conditions:

   i) Poorly differentiated adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma.

   ii) Pathological submucosal invasion greater than 1000 micrometers. iii) Positive lymphatic invasion or positive venous invasion confirmed by immunohistochemistry.

   iv) Tumor budding grade 2 or 3. v) Positive lateral or vertical resection margin (tumor within 1 mm of the surgical margin) or non-assessable resection margin.
5. No lymph node or distant metastases confirmed by computed tomography of the chest, abdomen, and pelvis (clinical N0, M0 disease).
6. Radiotherapy or chemoradiotherapy initiated within 12 weeks after local endoscopic or surgical resection.
7. No previous rectal resection (other than local excision) or pelvic irradiation for any malignancy.
8. Adequate organ function as assessed by the treating physician.
9. The treating surgeons have explained to the patient that the current standard of care is Total Mesorectal Excision (TME) with D2 lymph node dissection and the patient has declined this treatment.
10. Candidate for adjuvant chemoradiotherapy according to routine clinical practice.
11. Written informed consent provided.

Exclusion Criteria:

1. Synchronous or metachronous malignancy diagnosed within the previous 5 years.
2. Infection requiring systemic treatment.
3. Requirement for continuous systemic treatment with corticosteroids or immunosuppressive agents.
4. Diagnosis of a hereditary colorectal cancer syndrome, including familial adenomatous polyposis or Lynch syndrome, or diagnosis of inflammatory bowel disease, including ulcerative colitis or Crohn disease.
5. Squamous cell carcinoma, neuroendocrine neoplasm, or mixed neuroendocrine-non-neuroendocrine neoplasm histology.