KEY POINTS
- This retrospective analysis used a prospectively maintained institutional registry of 372 patients treated with Lu-PSMA-617 between 2022 and 2025; 88 patients (23.7%) had also received metastasis-directed EBRT for disease that was limited to ≤5 lesions at the time of radiation.
- The cohort had substantially greater disease burden by the time Lu-PSMA-617 was started: only 12/81 evaluable patients (14.8%) had 1–5 total metastases, while most had more extensive PSMA-PET-positive disease. Bone involvement was present in 94.3%.
- EBRT was delivered to a median of 3 metastatic sites per patient, most commonly bone (69.3%) and lymph nodes (64.8%). Of 202 irradiated lesions, 59.9% were treated alongside some form of systemic therapy.
- Among 84 patients with PSA follow-up, 55.7% achieved a ≥50% PSA decline, with a median time to response of 1.6 months. Receiving EBRT within three months of starting Lu-PSMA-617 was not associated with a different PSA response (p=0.46).
- With a median follow-up of 22.1 months among survivors, median overall survival from first Lu-PSMA-617 administration was 20.1 months. Neither baseline PSA, number of bone metastases, nor total metastatic burden showed a statistically significant association with OS in this small cohort.
- Grade ≥2 anemia occurred in 30.7%, including one grade 3 event; grade ≥2 leukopenia occurred in 9.1%, and no grade ≥2 thrombocytopenia was reported. Increasing numbers of previously irradiated metastatic sites were not associated with higher anemia (p=0.34) or leukopenia (p=0.08) rates.
- Sequencing was heterogeneous: 79.5% received EBRT only before Lu-PSMA-617, 11.4% only afterward, and 9% both before and after. These small subgroups cannot establish the preferred timing or sequence of the two modalities.
CLINICAL TAKEAWAY
Prior or intercurrent metastasis-directed EBRT does not appear to preclude subsequent Lu-PSMA-617 or create an obvious excess hematologic toxicity signal. The study supports feasibility rather than synergy: whether combining or sequencing these modalities improves disease control requires prospective testing.