Multinational validation of distant metastasis velocity as a post-progression prognostic score in patients with oligometastatic cancer treated with metastasis-directed stereotactic body radiotherapy.

Background: Distant progression is the predominant failure pattern after metastasis-directed stereotactic body radiotherapy (SBRT) for oligometastatic disease, but prognostic tools to guide post-progression management are lacking. We aimed to validate the prognostic value of distant metastasis velocity (DMV) for overall survival (OS) and widespread failure-free survival (WFFS) after distant progression.

Methods: Two independent international cohorts of patients with extracranial oligometastatic disease (≤5 lesions) who developed distant progression after SBRT were analyzed. The primary outcome was OS; secondary outcome was WFFS in the subgroup of patients with repeat oligometastasis at distant progression. DMV was defined as the number of new or progressing metastases per month after initial metastasis-directed SBRT.

Results: Among 563 patients (median age 68 years, 56 % male), DMV stratified prognosis in both cohorts. In the prospective cohort (n = 221), median OS was 35.7 months for patients with DMV ≤ 0.5 metastases/month versus 20.6 months for DMV > 0.5 (P = 0.0001). In the retrospective cohort (n = 342), OS was 32.8 vs. 12.1 months (P < 0.0001). Similar trends were observed for WFFS (prospective cohort, n = 91: 6.8 vs. 3.0 months, p = 0.42; retrospective cohort, n = 341: 18.8 vs. 6.1 months, p < 0.0001).

Conclusion: Higher DMV was consistently associated with worse outcomes after progression in oligometastatic disease. Its reproducibility across tumor types and independent cohorts supports DMV as a simple, dynamic, and clinically relevant prognostic marker. DMV should be further explored as a component of multimodal prognostic models to refine patient selection and guide post-progression treatment strategies.