This is a prospective, multicentre, cohort study. For cohort 1, experimental cohort, older or Frail patients with inoperable localized colorectal cancer will receive Ultrafractionated Radiotherapy (RT) and Comprehensive Geriatric Assessment (CGA) Guided systemic treatment. All patients will receive Ultrafractionated RT and PD-1 antibody. Furthermore, CGA will assess all patients and classify them into Frail, Vulnerabe, or Fit. Frail patients will receive Best Supportive Care (BSC); Vulnerabe patients will receive Fluorouracil/Raltitrexed and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, and BSC.

For cohort 2, external control from real word, data of patients with the same baseline characteristics from the same period and the same institute will be prospectively collected.

The primary endpoint is complete response (CR, pathological complete response [pCR] plus clinical complete response [cCR]) rate. The secondary endpoints include the grade 3-4 acute adverse effects rate, anal preservation rate, survival etc.

This is a prospective, multicentre, cohort study. For cohort 1, experimental cohort, older or Frail patients with inoperable localized colorectal cancer will receive Ultrafractionated Radiotherapy (RT) and Comprehensive Geriatric Assessment (CGA) Guided systemic treatment. All patients will receive Ultrafractionated RT and PD-1 antibody. Furthermore, CGA will assess all patients and classify them into Frail, Vulnerabe, or Fit. Frail patients will receive Best Supportive Care (BSC); Vulnerabe patients will receive Fluorouracil/Raltitrexed and BSC; Fit patients will receive Fluorouracil/Raltitrexed, Oxaliplatin/Irinotecan, and BSC.

For cohort 2, external control from real word, data of patients with the same baseline characteristics from the same period and the same institute will be prospectively collected.

The primary endpoint is complete response (CR, pathological complete response [pCR] plus clinical complete response [cCR]) rate. The secondary endpoints include the grade 3-4 acute adverse effects rate, anal preservation rate, 1-year DFS rate, 1-year DSS rate, 1-year OS rate etc.

Inclusion Criteria:

1. ≥70y, or, ≥60 and <70y but ECOG≥2;
2. male or female;
3. Pathologically confirmed Colorectal adenocarcinoma;
4. any distance from anal verge;
5. Clinical stage ≥T2 and/or N+, without distance metastases;
6. refuse radical operation, physiologically or technically inoperable;
7. No previous radiotherapy in the same field；
8. No chemotherapy prior to enrollment;
9. No immunotherapy prior to enrollment;
10. With good compliance during the study
11. Signed written informed consent

Exclusion Criteria:

1. Known history of other malignancies within 3 years，except cured skin cancer, cervical cancer in situ or thyroid carcinoma.
2. Individuals with a history of uncontrolled epilepsy, central nervous system disease, or psychiatric disorders that, in the judgment of the investigator, are of such clinical severity that they may prevent the signing of an informed consent form or affect the patient's adherence to oral medications
3. Individuals with clinically serious (i.e., active) heart disease, such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmia requiring pharmacologic intervention, or history of myocardial infarction within the last 12 months
4. Individuals with a history of organ transplantation requiring immunosuppressive therapy and long-term hormone therapy
5. Individuals with autoimmune diseases
6. Individuals with severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases
7. Baseline hematology and biochemistry did not meet the following criteria: Hb≥90g/L; NEU ≥1.5×109/L; PLT ≥100×109/L; ALT, AST ≤2.5 times the upper limit of normal; ALP ≤2.5 times the upper limit of normal; TB <1.5 times the upper limit of normal; Cr <1 time the upper limit of normal; Alb ≥30g/L
8. Individuals allergic to any drug component of the study