The goal of this clinical trial is to learn if close follow-up alone (active surveillance) works as well as radiation combined with chemotherapy (chemoradiotherapy) after removing early rectal cancer in adults. The main questions it aims to answer are:
1. Does active surveillance cause fewer serious adverse events than chemoradiotherapy within 3 years? Serious adverse events include a permanent or temporary ostomy (a surgical opening in the belly to pass stool), major bowel problems, or severe treatment-related complications. 2. Is active surveillance as safe as chemoradiotherapy in preventing cancer from coming back or spreading within 3 years?
Researchers will compare active surveillance to chemoradiotherapy to see if surveillance causes fewer serious adverse events while keeping cancer outcomes comparable.
To join this study, participants must be adults who had an early-stage rectal cancer (T1) removed by an endoscopic procedure, and whose removed tumor showed certain features that raise the risk of cancer cells remaining nearby.
Participants will be randomly placed in one of two groups:
1. Active surveillance group: Participants will have regular checkups, blood tests, flexible camera exams of the bowel (rectoscopy), scans of the pelvis and abdomen, and colonoscopy on a set schedule for 5 years. If cancer comes back, doctors will propose further treatment options. 2. Chemoradiotherapy group: Participants will receive radiation to the pelvis along with a chemotherapy pill (capecitabine) or an intravenous (IV) chemotherapy drug (5-FU) for about 5 weeks. After treatment, they will have regular checkups and scans for 5 years.
Pathologically confirmed rectal cancer located extraperitoneally.
Complete tumour resection (R0) by means of ESD or IMD (endoscopic or TAMIS).
Endoscopic images or video of the tumour before local excision.
Maximum cancer diameter ≤ 30 mm based on the pathological assessment.
Suspicion of distant metastases on computed tomography of the abdomen or thorax or lymph node involvement (lymph nodes >9mm in short axis); In case of isolated enlarged nodes biopsy will be required before exclusion.
Mesorectal tumour involvement on pelvic MRI.
Synchronous colorectal cancer in screening colonoscopy.
Known genetic cancer syndrome, including, but not limited to adenomatous or serrated polyposis syndrome; Lynch or Lynch-like syndrome.
Parallel
Active surveillance
Other interventionActive surveillance includes physical examination, and carcinoembryonic antigen (CEA) testing every 3 months during years 1-2 and every 6 months during years 3-5. Rectoscopy is performed every 3 months during years 1-2 and every 6 months during years 3-5. Pelvic MRI is performed every 6 months for 5 years. Thoracic and abdominal CT scans are performed annually for 5 years. Colonoscopy is performed at 1 year after local excision and subsequently according to findings. Recurrences are managed according to multidisciplinary team recommendations.
Adjuvant chemoradiotherapy
RadiationAdjuvant long-course pelvic chemoradiotherapy will be initiated within 12 weeks after local excision. Radiotherapy consists of 45 Gy delivered in 25 fractions of 1.8 Gy once daily, 5 days per week, over approximately 5 weeks. Concurrent chemotherapy consists of either oral capecitabine 825 mg/m² twice daily on radiotherapy days or continuous intravenous 5-fluorouracil 225 mg/m²/day throughout radiotherapy. After treatment, follow-up includes history, physical examination, CEA testing, and flexible sigmoidoscopy every 6 months for 5 years; pelvic MRI every 6 months during the first 3 years; annual thoracic and abdominal CT for 5 years; pelvic CT after discontinuation of MRI surveillance; and colonoscopy at 1 year and thereafter according to findings.
Disease-related treatment failure
Time from randomisation to the first occurrence of: 1. Cancer specific death. 2. Non-salvageable locoregional recurrence. 3. Distant metastases.
Composite severe treatment-related adverse event
Occurrence of any of the following: 1. Stoma (permanent or temporary). 2. Major LARS (score ≥30). 3. CTCAE grade ≥3 toxicity. 4. Clavien-Dindo ≥3b complications.
Disease-free survival
Time from randomisation to first event: death (any cause), distant metastases, or locoregional recurrence
Overall Survival
Time from randomization to death from any cause.
Stoma formation rate
Proportion of patients with a colostomy or ileostomy (permanent or temporary) present at assessment. Stoma rates will be evaluated at predefined follow-up intervals.
Incidence of Major Low Anterior Resection Syndrome (LARS)
Proportion of patients with a LARS Questionnaire score of 30 points or greater, indicating major low anterior resection syndrome.
Click on the lead sponsor to view all of their trials.
Medical University of Gdansk
Lead sponsor
University of Oslo
Collaborator
Maria Sklodowska-Curie National Research Institute of Oncology
Collaborator
Centre Hospitalier Universitaire Dupuytren de Limoges (CHUL)
Collaborator
Vestre Viken Hospital Trust
Collaborator
Universitätsklinikum Hamburg-Eppendorf
Collaborator
Karolinska Institutet
Collaborator
University Hospital, Akershus
Collaborator
University of Roma La Sapienza
Collaborator
Hospital Clinic of Barcelona
Collaborator
Leuven University Medical Center
Collaborator
University Hospital, Ghent
Collaborator
Sorlandet Hospital HF
Collaborator
Northern Norway Regional Health Trust
Collaborator
Helse Stavanger HF
Collaborator
Haukeland University Hospital
Collaborator
St. Olavs Hospital
Collaborator
