Involve-site Radiotherapy Combined With Chemotherapy and Immunotherapy as Neoadjuvant Treatment for Locally Advanced Rectal Cancer

Surgery is the primary treatment for rectal cancer. However, in patients with locally advanced disease, direct surgery often fails to achieve complete tumor resection. In such cases, neoadjuvant therapy is required to downstage the tumor before surgery. The current standard neoadjuvant approach consists of preoperative radiotherapy and then surgery. Although effective, standard radiotherapy uses large target volumes, which results in significant toxicities, increased surgical complications, and reduced patient compliance and quality of life. In addition, excessive radiation fields can compromise the intensity and timing of systemic therapy, potentially increasing the risk of distant metastasis. This may be one of the key reasons why current neoadjuvant radiotherapy mainly improves local control but has not translated into prolonged overall survival. Emerging evidence suggests that combining immunotherapy with radiotherapy may further enhance treatment efficacy. However, large radiation fields may impair the effectiveness of immunotherapy. Therefore, reducing the radiotherapy target volume may not only decrease treatment-related toxicity but also augment the immunotherapy response. This clinical study is designed to evaluate whether reducing the radiotherapy target volume, when combined with chemotherapy and immunotherapy prior to surgery, can decrease radiotherapy-related toxicities and reduce the risk of distant metastasis, without increasing the local recurrence rate, compared with the current standard radiotherapy fields. The ultimate goal is to improve the efficacy of neoadjuvant therapy in locally advanced rectal cancer while minimizing treatment toxicity, thereby providing new strategies and evidence for preoperative management.

Sex

All

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

* Voluntarily agrees to participate and provides written informed consent
* Age 18 to 75 years, male or female
* Histologically confirmed rectal adenocarcinoma
* MRI confirms that the upper margin of the tumor is ≤12 cm from the anal verge
* ECOG performance status of 0-1
* Clinical stage T3-T4 or N+ and circumferential resection margin (CRM) positive by imaging evaluation; lateral lymph nodes negative
* Immunohistochemistry or genetic testing indicates pMMR or MSS status
* Adequate organ function and bone marrow reserve

Exclusion Criteria:

* Presence of distant metastasis
* Prior pelvic radiotherapy
* Chemotherapy or immunotherapy within the past 3 months
* Refusal to undergo radical surgery for rectal cancer
* Concurrent active malignancy other than rectal cancer
* Positive antinuclear antibody (ANA)
* History of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, autoimmune hepatitis)
* Elevated troponin above the normal range
* Active tuberculosis
* Positive hepatitis B surface antigen (HBsAg) or detectable HBV DNA
* Positive for hepatitis C virus (HCV), syphilis, or HIV
* Severe comorbid conditions (e.g., serious infection, severe bone marrow suppression, psychiatric disorder) deemed unsuitable for participation by the investigator
* Pregnant or breastfeeding women
* Any other contraindications to radiotherapy, chemotherapy, or immunotherapy