Top Line: Results of the phase II EXTEND trial were initially presented in abstract form at last year’s ASTRO annual meeting.
The Study: We now have the full manuscript. Recall 334 patients with 1–5 metastases across six histology-specific baskets were randomized to standard-of-care systemic therapy with or without metastasis-direct therapy (hitherto referred to as ablative radiation as received by 98% in this arm). After a median follow-up of 53 months, ablative radiation significantly improved progression-free survival (HR 0.54,), with robust benefit even when excluding prostate cancers (HR 0.60). Among the prespecified individual histology baskets, breast and renal cell carcinoma were the only two that did not demonstrate a statistically significant benefit from the addition of ablative radiation. Overall survival was unchanged, likely reflecting frequent crossover as over half of those assigned to systemic therapy alone received radiation at progression. Translational analyses were equally compelling: detectable baseline circulating tumor DNA predicted inferior disease control and survival, whereas clearance at 3 months correlated with improved survival (HR 0.25). Radiation also induced measurable systemic immune activation—including expansion of proliferating CD8+ T cells and T-cell receptor remodeling—most prominently in tumor types demonstrating clinical benefit.
TBL: EXTEND reinforces ablative radiation as an important consideration for all oligometastatic patients, with anticipated benefit likely depending on biomarkers such as circulating tumor DNA as much as measurable radiographic disease. | Sherry, J Clin Oncol 2026
The Study: We now have the full manuscript. Recall 334 patients with 1–5 metastases across six histology-specific baskets were randomized to standard-of-care systemic therapy with or without metastasis-direct therapy (hitherto referred to as ablative radiation as received by 98% in this arm). After a median follow-up of 53 months, ablative radiation significantly improved progression-free survival (HR 0.54,), with robust benefit even when excluding prostate cancers (HR 0.60). Among the prespecified individual histology baskets, breast and renal cell carcinoma were the only two that did not demonstrate a statistically significant benefit from the addition of ablative radiation. Overall survival was unchanged, likely reflecting frequent crossover as over half of those assigned to systemic therapy alone received radiation at progression. Translational analyses were equally compelling: detectable baseline circulating tumor DNA predicted inferior disease control and survival, whereas clearance at 3 months correlated with improved survival (HR 0.25). Radiation also induced measurable systemic immune activation—including expansion of proliferating CD8+ T cells and T-cell receptor remodeling—most prominently in tumor types demonstrating clinical benefit.
TBL: EXTEND reinforces ablative radiation as an important consideration for all oligometastatic patients, with anticipated benefit likely depending on biomarkers such as circulating tumor DNA as much as measurable radiographic disease. | Sherry, J Clin Oncol 2026