Colorectal cancer (CRC) is the third most common cancer worldwide. Surgical resection is one of the primary treatment options for CRC; however, postoperative recurrence remains a significant clinical challenge for both the medical community and patients. Postoperative chemotherapy, as an important adjuvant therapy, is widely used in CRC patients aiming to reduce the risk of recurrence. Despite extensive research on the efficacy of postoperative chemotherapy in CRC, the mechanisms of postoperative recurrence, predictive factors, and strategies to enhance chemotherapy effectiveness remain unclear. For colorectal cancer patients who have achieved NED (No Evidence of Disease), the decision to either reinitiate or change the systemic chemotherapy regimen for newly developed pulmonary oligometastases remains controversial. Local treatment options for diagnosing oligometastases include surgery, radiotherapy, and radiofrequency ablation. However, whether systemic treatment should be added after local treatment in patients who have achieved NED remains uncertain , and this issue requires urgent resolution.

Colorectal cancer (CRC) is the third most common cancer worldwide. Surgical resection is a primary treatment option; however, postoperative recurrence remains a significant challenge. Postoperative chemotherapy is commonly used as an adjuvant treatment to reduce recurrence risk, but the mechanisms of recurrence, predictive factors, and strategies to enhance chemotherapy efficacy remain unclear.For CRC patients who have achieved No Evidence of Disease (NED), the decision to reinitiate or modify systemic chemotherapy for newly developed pulmonary oligometastases is still debated. Local treatment options for pulmonary oligometastases include surgery, radiotherapy, and radiofrequency ablation. However, whether systemic therapy should follow local treatment in NED patients is uncertain.This issue is actively debated in multidisciplinary team (MDT) consultations both in our hospital and across the country. Some experts argue that pulmonary oligometastases signify disease progression, requiring systemic treatment, while others suggest that these metastases may not indicate high malignancy and that observation, with possible delayed systemic treatment, could be sufficient.This study will include CRC patients who have achieved NED for at least six months and then develop pulmonary oligometastases, treated exclusively with destructive local therapies (surgery, radiotherapy, or ablation) without systemic therapy. The study will assess the timing of transitioning to the next line of systemic therapy through imaging and ctDNA monitoring.

Inclusion Criteria:

• Patients with a pathologically confirmed diagnosis of colorectal cancer with the following disease conditions:

  1. The patient has achieved No Evidence of Disease (NED) after undergoing EMR, surgery, radiofrequency ablation, or radiotherapy.
  2. NED has been maintained for ≥ 6 months.
  3. The patient has not received chemotherapy, or has only received postoperative adjuvant chemotherapy or first-line systemic therapy.
  4. Oligometastatic lung lesions (defined as 5 or fewer lesions) detected after ≥ 6 months of NED maintenance, eligible for destructive therapy.
  5. No prior radiotherapy to the lungs.

• RECIST 1.1 criteria: The patient must have measurable lesions, defined as at least one nodal lesion with a longest diameter > 1.5 cm, or at least one nodal lesion > 1 cm with an accurately measurable pendulous diameter.

• ECOG performance status: ≤ 2 (Eastern Cooperative Oncology Group general condition score).

• The patient's expected survival must be ≥ 3 months.

• Adequate hematologic function: Absolute neutrophil count ≥ 1.6 x 10⁹/L, with no growth factor support for at least 7 days prior to testing.

• Normal organ function: The patient must be able to tolerate at least one of the local destructive treatments, as assessed by the corresponding department's physician, based on normal hepatic, renal, pulmonary, and cardiac function.

• Reproductive age: Female patients of childbearing potential must agree to use a reliable method of contraception with their partner from the time of informed consent until 1 year after treatment completion.

• The patient must have voluntarily provided informed consent to participate in the study.

Exclusion Criteria:

• First diagnosis of advanced colorectal cancer with metastatic disease.
• Multiple lung metastases (> 5 lesions), liver metastasis, bone metastasis, or lymph node metastasis.
• Lung metastases that are not amenable to radiotherapy, as determined by the investigator.
• Previously received second-line or higher systemic treatment.
• Liver or kidney dysfunction: Alanine aminotransferase (ALT) > 3 times the upper limit of normal; Aspartate aminotransferase (AST) > 3 times the upper limit of normal; Total bilirubin (TBIL) > 2 times the upper limit of normal; Serum creatinine > 1.5 times the upper limit of normal.
• Elevated tumor marker: CEA ≥ 50 ng/mL.
• Serious medical conditions that may interfere with the study (e.g., uncontrolled diabetes, gastric ulcers, severe cardiopulmonary diseases), at the discretion of the researchers.
• Severe or uncontrolled infections.
• Active autoimmune disease.
• Clinically significant central nervous system dysfunction.
• Recent major surgery (excluding lymph node biopsy) within the last 30 days.
• Pregnant or breastfeeding women of childbearing age who are not using contraception.
• Drug allergy to study treatments.
• Other reasons, as determined by the researchers, that make the patient unsuitable for participation.