T1 Colorectal Cancer After Local Excision: Decision Between Surgery and Active Surveillance (T1LDA Trial)

The goal of this two-arm clinical trial is to compare additional surgery with active surveillance in patients with high-risk pT1 colorectal cancer after local excision. The main questions it aims to answer are Does additional surgery result in lower rates of distant or extraluminal recurrence compared with active surveillance? How do the two treatment strategies differ in survival, complications, quality of life, and treatment-related costs? Participants will be randomly assigned to either additional surgery or active surveillance. Patients assigned to the surgery group will undergo standard preoperative assessment followed by additional surgery. Following surgery, patients will undergo surveillance according to the predefined follow-up protocol. Patients assigned to the active surveillance group will not receive any additional treatment. They will undergo surveillance according to a more intensive predefined follow-up protocol.

Inclusion Criteria: * Histopathologically confirmed diagnosis of pT1 colorectal cancer * Adenocarcinoma treated by endoscopic or transanal local excision * One to three risk factors for LNM or recurrence present Lymphovascular invasion (LVI) Intermediate or high tumor budding (grade 2-3) Close margin resection, defined as 100-1000 µm histologically non-cancerous resection margin, measured from the closest part of invasive adenocarcinoma to the resection line, without direct adenocarcinoma involvement at the margin The histological margin cannot be reliably assessed due to cautery artifact at the resection margin, where carcinoma is present at the evaluable edge, reflecting the involvement of cancer in margin. However, given the endoscopist's impression of complete excision Piecemeal resection, where the endoscopist's impression is that complete excision has been achieved (unclear resection margin after an endoscopic resection reported to have good macroscopic margin, e.g. a successful piecemeal resection) Adenoma involvement of the resection margin defined as 0 µm WHO high-grade adenocarcinoma Perineural invasion DSI (\>1000µm invasion or Haggitt level 4 or Kudo sm3) * Adequately performed primary colonoscopy, defined as a complete colonoscopy with visualization of the entire rectum and colon up to the cecum and no technical limitations compromising mucosal assessment or exclusion of synchronous disease * Patient age 18 or more * ECOG 0-2 Exclusion Criteria: * The patient is not eligible for either surgery or follow-up Multidisciplinary team (MDT) considers the surgical complication risk too high MDT considers the recurrence risk of surveillance strategy too high The patient is unable to understand information provided The patient is not willing to commit to the required follow-up * Either no high-risk factors are present or four or more high-risk factors are present * R1 resection, defined as noncancerous margin \< 100 µm without cautery artefact and not meeting criteria for piecemeal resection * Radiological involvement of lymph nodes (N+) in rectal cancer: Clearly pathologic nodes or suspicious nodes with additional risk factors, i.e. suspicious if: ≥9 mm or mucinous signal Smaller nodes 5-9 mm: Require 2 additional malignant features for cN+ classification. Nodes \10 mm * Radiological or histological EMVI+ (extramural vascular invasion) or radiological TD+ (tumor deposit) * Actively treated invasive cancer within 2 years * Any metastatic cancer * History of previous CRC * Hereditary CRC syndrome * Inflammatory bowel disease * Suspected M1 level metastases