Short-course Radiotherapy Combined With CapeOx and PD-1 Inhibitor After Local Excision for High-risk Early Rectal Cancer (TORCH-LE)

A total of 60 patients with high-risk pathologic stage pT1 or pT2 cancer after local excision but refused radical surgery will be included.

Eligibility criteria include a histological diagnosis of adenocarcinoma located ≤7 cm from the anal verge, pT1 after local excision of the primary rectal cancer, with one of the high-risk features including margin positivity/very close margin (<1mm) at time of local excision, depth of invasion >1 mm or SM3 invasion (submucosal invasion to the lower third of the submucosal level), high grade or poorly differentiated, lymphovascular invasion, perineural invasion, tumour budding, or pT2 tumor.

They will receive 5*5Gy short-course radiotherapy, followed by 4 cycles of capecitabine plus oxaliplatin (CAPOX) chemotherapy and PD-1 antibody.

• Radiation (Radiation): Shor-course radiotherapy: 25Gy/5Fx
• PD-1 antibody (Drug), also known as Toripalimab: PD-1 antibody (Toripalimab): 240mg d1 q3w
• Capecitabine (Drug), also known as Xeloda: Capecitabine: 1000mg/m2 d1-14 q3w
• Oxaliplatin (Drug): Oxaliplatin: 130mg/m2 d1 q3w

Primary outcomes

• 3y LRFS [From date of initiation of treatment until the date of first documented pelvic failure, assessed up to 36 months.]: Rate of 3 year local recurrence free survival rate

Secondary outcomes

• 3y DFS [From date of initiation of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.]: Rate of 3 year disease free survival
• 3y OS [From date of initiation of treatment until the date of death from any cause, assessed up to 36 months.]: Rate of 3 year overall survival
• Grade 3-4 adverse effects rate [From date of initiation of treatment until the date of death from any cause, assessed up to 36 months.]: Rate of chemotherapy, radiotherapy and immunotherapy related adverse events

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

1. age 18-75 years old, female and male
2. pathological confirmed adenocarcinoma
3. the distance from anal verge ≤ 7 cm
4. pT1 after local excision of the primary rectal cancer, with at least one of the high-risk features including margin positivity/very close margin (<1mm) at time of local excision, depth of invasion >1 mm or SM3 invasion (submucosal invasion to the lower third of the submucosal level), high grade or poorly differentiated, lymphovascular invasion, perineural invasion, tumour budding, or pT2 tumor.
5. refuse radical surgery
6. without pelvic or distance metastases
7. KPS >=70
8. with good compliance
9. microsatellite repair status is MSS/pMMR
10. without previous anti-cancer therapy or immunotherapy
11. signed the inform consent

Exclusion Criteria:

1. pregnancy or breast-feeding women
2. pathological confirmed signet ring cell carcinoma
3. history of other malignancies within 5 years
4. serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc.
5. immunodeficiency disease or long-term using of immunosuppressive agents
6. baseline blood and biochemical indicators do not meet the following criteria: neutrophils≥1.5×10\^9/L, Hb≥90g/L, PLT≥100×10\^9/L, ALT/AST ≤2.5 ULN, Cr≤ 1 ULN
7. DPD deficiency
8. allergic to any component of the therapy