The goal of this clinical trial is to evaluate whether a total neoadjuvant therapy (TNT) regimen combining long-course chemoradiotherapy, sequential chemotherapy, and PD-1 inhibitor can improve response rates, enhance tolerability, and improve prognosis in patients with locally advanced, microsatellite-stable (MSS) rectal cancer.
The main questions it aims to answer are:
Does this TNT approach improve complete response (CR) rates?
How does selective reduction of clinical target volume (CTV) to S2/S3 level compare with conventional CTV irradiation in terms of efficacy and safety?
Researchers will compare a selective CTV reduction group and a conventional CTV irradiation group to assess differences in treatment outcomes, including complete response, tumor regression grading (TRG), organ preservation, R0 resection rates, and long-term survival.
Participants will:
Receive long-course chemoradiotherapy with either conventional or reduced CTV irradiation.
Undergo sequential chemotherapy.
Receive PD-1 inhibitor treatment.
Be monitored for safety, tumor regression, and long-term survival outcomes.
Voluntarily signs a written informed consent form.
Aged between 18 and 75 years at enrollment.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Expected survival of more than 2 years.
Presence of suspected metastatic lesions or locally advanced unresectable disease, regardless of disease stage.
Diagnosis of other malignancies within the past five years, except for patients with malignancies cured through local treatment (e.g., basal or squamous cell skin cancer, superficial bladder cancer, ductal carcinoma in situ of the breast).
Concurrent enrollment in another clinical study, unless it is an observational, non-interventional study or a follow-up phase of an interventional study.
Presence of intestinal obstruction, perforation, or bleeding requiring emergency surgery.
Parallel
Reduced CTV
Combination productLong-course radiotherapy with selective CTV reduction (lower to S2/S3 level) + CAPOX + PD-1 inhibitor. After treatment, patients will undergo TME surgery or a watch-and-wait approach, depending on response.
Conventional CTV
Combination productLong-course radiotherapy with conventional CTV irradiation + CAPOX + PD-1 inhibitor. After treatment, patients will undergo TME surgery or a watch-and-wait approach, depending on response.
Complete response (CR) rate
Evaluate whether total neoadjuvant therapy (TNT) with long-course chemoradiotherapy (selective vs. conventional CTV), sequential CAPOX chemotherapy, and PD-1 inhibitor improves the complete response (CR) rate in locally advanced MSS rectal cancer.
Tumor regression grade (TRG)
Tumor downstaging rate
Watch-and-wait rate
Sphincter preservation rate
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