This study hypothesizes that approximately 50% of rectal cancer patients can preserve their rectum using a watch-and-wait strategy if they achieve a complete or near-complete clinical response to total neoadjuvant therapy (TNT). The objective is to determine whether the complications, quality of life, and survival rates of rectal cancer patients who have achieved a complete or near-complete clinical response to TNT, followed by a watch-and-wait approach, are comparable to those of patients who undergo surgery first. Additionally, the study aims to identify potential prognostic and predictive markers for rectal cancer and examine survival rates and factors influencing responses to chemoradiotherapy (CRT) or TNT.
The study is divided into two parts:
\*\*Part One:\*\* Participants with cT1N1, T2-T3 N0-1 rectal cancer, MRF-, and EMVI-, with surgery as one of the possible first-line treatment options, will be randomized into two groups. The experimental group will consist of participants receiving TNT, including CRT and consolidation chemotherapy (Ch). If these participants achieve a complete or near-complete clinical response, they will be observed using a watch-and-wait strategy, which is a non-operative approach. The control group will consist of participants who undergo surgical treatment initially.
\*\*Part Two:\*\* All participants with rectal cancer who have received CRT or TNT will be included. Additionally, participants diagnosed with rectal cancer who are scheduled for CRT or TNT but declined to participate in Part One or do not meet the inclusion criteria will also be included.
Over 18 years of age.
Participants who agreed to participate in the study signed an informed consent form.
The Eastern Cooperative Oncology Group (ECOG) score ranges from 0 to 2.
Pathologically confirmed rectal adenocarcinoma.
Prior ST or Ch.
Participants who are not eligible for pelvic MRI.
Participants who have had a malignancy in the last 5 years, except for treatment for basal cell or squamous cell skin cancer or in situ cervical cancer.
ECOG status ≥ 3.
Parallel
Radiation Therapy
RadiationRadiation therapy (RT) is administered at a dose of 2 Gy per day for a total dose of 50 Gy delivered to the pelvis. This is done throughout 5 to 6 weeks.
Chemoradiotherapy
DrugCapecitabine: 825 mg/m² twice daily, prescribed 1-5 days per week, for 5 weeks during RT. Or Bolus 5-FU regimen: 5-fluorouracil (5-FU) 400 mg/m2/day intravenously, administered on days 1-4 and 33-35. Calcium folinate (folinic acid) 20 mg/m2/day intravenously on days 1-4 and 33-35.
Consolidation Chemotherapy
DrugXELOX: Oxaliplatin 130 mg/m² (day 1) + capecitabine 1000 mg/m² (days 1-14), every 3 weeks for 4 cycles. Or FOLFOX: Oxaliplatin - 85 mg/m2 intravenously (2-hour infusion), drip for 1 day. Calcium folinate (folinic acid) - 400 mg/m2/d. intravenously (2-hour infusion), started on day 1. F(5-fluorouracil) - 400 mg/m2/d. intravenously (bolus), started on day 1. Repeat every 2 weeks for 6 times.
Surgery
Procedure/SurgeryTransabdominal Resection: Abdominoperineal resection, low anterior resection, or coloanal anastomosis using total mesorectal excision.
Part two
Other interventionStandard treatment protocols and follow-up procedures are implemented in clinical practice.
Adjuvant treatment
Other interventionIf indicated, adjuvant therapy will be administered as usual in clinical practice.
Postoperative complications
Assessed based on the Clavien Dindo classification.
TNT toxicity
Local and systemic toxicity and (or) side effects will be recorded according to the general terminology criteria for adverse events version 5.0 (CTCAE v5.0).
Mortality rate
Mortality after TNT or surgery.
Quality of life
Quality of life Will be assessed using scoring manual of European Organisation For Research And Treatment Of Cancer of CR29 (Colorectal).
Rectal preservation rate
Percentage of participants achieving complete or near-complete clinical response and rectal preservation using a "watch and wait" approach.
Local regrowth rate
Percentage of participants with tumor regrowth after watch-and-wait when a complete or near-complete clinical response was achieved after TNT
Overall survival
The time between enrolment and death from any cause.
Disease-free survival
The time between enrolment and the first documented disease progression, i.e. local recurrence or metastasis, or death from any cause.
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National Cancer Center Affiliate of Vilnius University Hospital Santaros Klinikos
Lead sponsor
Vilnius University
Collaborator
Tomas Poskus, Faculty of Medicine, Vilnius University
Collaborator
Vilnius University Hospital Santaros Klinikos
Collaborator
Research Council of Lithuania
Collaborator
