Inclusion Criteria:
This study consists of four cohorts. Inclusion and exclusion criteria comprise general inclusion criteria, cohort-specific inclusion criteria, general exclusion criteria, and cohort-specific exclusion criteria.
General Inclusion Criteria Age 18-75 years, male or female; Pathologically confirmed squamous cell carcinoma of the anal canal or perianal region; ECOG performance status 0-1 and life expectancy ≥ 3 months; Adequate organ function:(1) Absolute neutrophil count ≥ 1.5 ×10⁹/L; platelet count ≥ 100 ×10⁹/L; hemoglobin ≥ 9 g/dL; serum albumin ≥ 3 g/dL;(2) Thyroid-stimulating hormone (TSH) ≤ 1 × upper limit of normal (ULN), with normal T3 and T4;(3) Bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2 × ULN;(4) Serum creatinine ≤ 1.5 × ULN, creatinine clearance ≥ 60 mL/min;(5) International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN, unless the patient is on anticoagulation with PT within the expected therapeutic range; activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN; No severe comorbidities expected to limit survival to \< 5 years; Female subjects: negative pregnancy test (if of childbearing potential) or permanently non-childbearing potential; Sexually active males and females of childbearing potential must agree to use effective contraception during the entire study period and for 12 months after completion of study treatment; Written and dated informed consent indicating the patient has been informed of all relevant aspects of the study; No concurrent medical condition requiring mandatory hormone replacement therapy; Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Inclusion Criteria for Cohort 1 In addition to the general inclusion criteria:（1）Tumor \< 5 cm (T1-2) and negative regional lymph nodes (N-) on physical examination or contrast-enhanced pelvic MRI;(2) No prior anti-tumor therapy.
Inclusion Criteria for Cohort 2 In addition to the general inclusion criteria:(1) No residual tumor detectable on physical examination or imaging after local excision;(2) No prior anti-tumor therapy including radiotherapy, chemotherapy, targeted therapy, or immunotherapy.
Inclusion Criteria for Cohort 3 In addition to the general inclusion criteria:(1) Tumor ≥ 5 cm (T3), or invasion of adjacent organs (T4), or regional lymph node positivity (N+) in mesorectal, presacral, internal/external iliac, or inguinal lymph node regions on physical examination or contrast-enhanced pelvic MRI;(2) No prior anti-tumor therapy.
Inclusion Criteria for Cohort 4 In addition to the general inclusion criteria:(1) Initial distant metastasis (M1) (liver, lung, bone, distant lymph nodes, etc.) confirmed by chest/abdominal CT or PET-CT,or pelvic recurrence after prior treatment, with or without distant metastasis.
Exclusion Criteria:
Patients with any of the following criteria are ineligible for this study:
Pathological diagnosis of other anal tumors, such as gastrointestinal stromal tumor, lymphoma, melanoma, etc.; Prior treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies; Previous or concurrent malignancy, except adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, and papillary thyroid carcinoma; Active autoimmune disease or history of autoimmune disease (including but not limited to interstitial lung disease, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism); excluding: autoimmune-mediated hypothyroidism on a stable dose of thyroid replacement therapy; type 1 diabetes mellitus on a stable dose of insulin; vitiligo; childhood asthma/allergy that resolved with no intervention required in adulthood; History of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency disorders, history of organ transplantation or allogeneic bone marrow transplantation; History of interstitial lung disease (excluding radiation pneumonitis not requiring corticosteroid therapy) or non-infectious pneumonitis; Active pulmonary tuberculosis confirmed by medical history or CT scan, active tuberculosis within 1 year prior to enrollment, or inactive tuberculosis for more than 1 year without standard anti-tuberculosis treatment; Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10⁴ copies/mL) or active hepatitis C (positive anti-HCV antibody with HCV RNA above the lower limit of detection); Severe cardiac, pulmonary, hepatic, or renal dysfunction; History of psychoactive substance abuse, alcoholism, or drug addiction; Any other conditions judged by the investigator that may compromise patient safety or study compliance, including severe medical or psychiatric disorders requiring concurrent treatment, significant laboratory abnormalities, or other social or family factors.
