In an adult patient with a controlled colorectal primary, limited (≤3–5) lung metastases, Eastern Cooperative Oncology Group (ECOG) performance status 0‑2 and adequate pulmonary reserve, what is the evidence supporting stereotactic ablative radiotherapy (SABR) as a curative‑intent treatment compared with surgery or systemic therapy?

Evidence for Lung SABR in Oligometastatic Colorectal Cancer

SABR is a safe and feasible treatment option for lung oligometastases from colorectal cancer in patients not amenable to surgery, though it should be recognized that local control rates are lower than for other primary tumor types, and decisions must be made through multidisciplinary team discussion. 1

Guideline-Based Recommendations

Patient Selection Criteria

SABR may be considered for patients with lung-only or oligometastatic disease (≤3-5 metastases) when resection is limited by comorbidity, extent of lung parenchyma resection required, or other factors. 1 The Pan-Asian adapted ESMO consensus guidelines specifically endorse this approach for colorectal cancer patients with controlled primary tumors and adequate performance status 1.

The definition of oligometastatic disease that should guide treatment decisions includes:

• One to five metastatic lesions 2, 3
• Controlled primary tumor (preferably) 2, 3
• All metastatic sites must be safely treatable 2, 3

Treatment Approach and Multidisciplinary Decision-Making

All treatment decisions should be made by a multidisciplinary team based on local experience, tumor characteristics, and patient preference. 1 This is critical because SABR represents an alternative to surgery rather than a clearly superior option, and the choice depends on multiple patient-specific and technical factors.

Clinical Outcomes Data

Local Control Rates

The evidence reveals a concerning pattern: colorectal cancer lung metastases demonstrate inferior local control compared to other primary tumor types when treated with SABR. 4, 5, 6

Specific local control rates from the research evidence:

• 2-year local control: 60-78% 4, 5, 6
• 3-year local control: 54-89% 6, 7
• Local recurrence occurred in approximately 36% of patients in one series 6

This represents notably worse outcomes than the 95-97% local control rates typically seen with SABR for primary lung cancer, highlighting the relative radioresistance of colorectal metastases 1.

Survival Outcomes

Despite suboptimal local control, overall survival outcomes are encouraging:

• Median overall survival: 38-46 months 1, 6, 8
• 2-year overall survival: 67-74% 6, 8
• 3-year overall survival: 51-73% 6, 7

These survival rates significantly exceed the 24.3 months median survival seen in patients with unresected metastases, supporting the value of local ablative therapy 1.

Critical Prognostic Factors for Treatment Personalization

Dose-Response Relationship

The most important modifiable factor is biological effective dose (BED), with BED ≥125 Gy significantly reducing local progression risk (HR 0.24,95% CI 0.11-0.51). 4 This represents a critical threshold:

• BED <100 Gy: 76.1% 2-year local control 4
• BED 100-124 Gy: 70.6% 2-year local control 4
• BED ≥125 Gy: 94% 2-year local control 4

Higher BED also significantly prolonged time to polymetastatic conversion, suggesting dose escalation may delay systemic progression 4.

Tumor-Related Factors

Rectal primary site is associated with significantly worse local control compared to colon primary (multivariate analysis P=0.001), despite receiving higher radiation doses 5. This paradox may relate to higher rates of KRAS mutations in rectal lesions (73.3% vs 40.4%) 5.

Number of metastases is a critical prognostic factor:

• Single metastasis: Better outcomes across all endpoints 5, 6
• 2-3 metastases: Intermediate outcomes 4

• 2 metastases: Significantly worse local control and overall survival 5

• 4-5 simultaneous oligometastases: Median time to polymetastatic disease only 9.8 months 4

Tumor size matters: Lesions >20mm had 66.6% 2-year local control versus 79.7% for lesions ≤10mm 4. Gross tumor volume ≥3266 mm³ was associated with worse overall survival on multivariate analysis 5.

Disease Timing

Metachronous oligometastatic disease (developing after initial treatment) is associated with significantly better progression-free survival compared to synchronous disease. 6 This likely reflects more indolent tumor biology.

Comparison with Surgery

Surgery remains the historical standard for oligometastatic colorectal cancer, but no randomized trials directly compare SABR versus surgery. 1 The choice between modalities should consider:

Surgery is preferred when:

• Histologic confirmation of metastasis is required 1
• Solitary lung metastasis in younger, fitter patients 1
• Complete macroscopic excision is feasible without excessive morbidity 1

SABR is preferred when:

• Multiple low-volume metastases are present 1
• Surgical morbidity would be excessive 1
• Oligoprogressive disease requires treatment without interrupting systemic therapy 1
• Medical comorbidities preclude surgery 1

Treatment Algorithm

For patients with controlled colorectal primary and ≤5 lung metastases:

1. Multidisciplinary tumor board evaluation to assess resectability, patient fitness, and treatment goals 1

2. If surgically resectable and patient fit: Consider surgery as first option, particularly for solitary metastasis 1

3. If surgery contraindicated or patient refuses: SABR is appropriate alternative 1

4. Dose selection: Target BED ≥125 Gy when safely achievable to maximize local control 4

5. Risk stratification:

   • Favorable: Single metastasis, colon primary, metachronous presentation, lesion <20mm → Proceed with SABR 4, 5, 6
   • Intermediate: 2-3 metastases, mixed features → SABR reasonable with close surveillance 4
   • Unfavorable: >3 metastases, rectal primary, synchronous disease, large volume → Consider more aggressive systemic therapy; SABR may still delay polymetastatic conversion 4, 5

Critical Caveats and Common Pitfalls

Do not assume SABR for colorectal lung metastases will achieve the same excellent local control seen with primary lung cancer SABR. The 60-78% 2-year local control is substantially inferior to the 95-97% rates in early-stage NSCLC 1, 4, 5, 6.

Rectal primary tumors are particularly radioresistant, and even dose escalation may not overcome this biological disadvantage 5. These patients require especially close surveillance and consideration of systemic therapy intensification.

KRAS mutation status predicts for worse metastasis-free survival (0% vs 37.5% at 1 year) but not local control, suggesting it reflects systemic disease biology rather than radiosensitivity 5.

The median progression-free survival is only 8-10 months despite local therapy, emphasizing that most patients will develop new metastases and SABR is buying time rather than providing cure 6, 8. This should inform patient counseling about realistic expectations.

Patients with 4-5 simultaneous oligometastases have a median time to polymetastatic disease of only 9.8 months, questioning whether aggressive local therapy is appropriate in this subset 4. These patients may be better served by systemic therapy alone.

Safety Profile

SABR for lung metastases demonstrates favorable toxicity: No Grade ≥3 toxicities were reported in the colorectal-specific series, with no major pulmonary toxicity, chest pain, or rib fractures 6, 7. This safety profile supports its use even in patients with limited pulmonary reserve, provided dosimetric constraints are met 1.