Repeated metastasis-directed radiotherapy in patients with oligorecurrent prostate cancer: outcomes and risk stratification from a large multinational PSMA PET-guided cohort.

BACKGROUND AND PURPOSE: Repeated metastasis-directed radiotherapy (MDRT) is increasingly used in patients with metachronous oligometastatic prostate cancer. However, the efficacy and optimal patient selection criteria remain insufficiently defined.

MATERIAL AND

METHODS

Within the multinational PORTAL consortium, we evaluated outcomes of repeated MDRT in patients with PSMA-PET-detected oligorecurrent hormone-sensitive prostate cancer undergoing ≥ 2 MDRT cycles. The primary endpoint was androgen deprivation therapy-free survival (ADT-FS), secondary endpoints included polymetastatic-free survival, next-line systemic therapy-free survival, and overall survival, all calculated from start of repeated MDRT. A multivariable Cox regression model was developed to predict ADT-FS, and its performance was evaluated by bootstrapped internal validation using discrimination (C-index) and calibration.

RESULTS

A total of 177 patients were included. Median follow-up after second MDRT was 26.1 months. During follow-up, 86 patients initiated ADT, 59 developed polymetastatic disease, 38 received next-line systemic therapy, and 17 deaths occurred. Two-year ADT-FS was 50.2 % (95 % CI 41.4-58.3). Two-year polymetastatic-free, next-line systemic therapy-free, and overall survival were 64.4 % (95 % CI 55.4-72.0), 83.5 % (95 % CI 76.0-88.9), and 94.2 % (95 % CI 88.2-97.2), respectively. In the multivariable Cox regression model, a longer interval between first and second MDRT (HR 0.96 per month, 95 % CI 0.94-0.99; p = 0.003) and treatment of a single versus ≥ 2 new lesions (HR for ≥ 2 lesions 1.88, 95 % CI 1.22-2.90; p = 0.006) were independently associated with ADT-FS. Model discrimination was moderate (optimism-corrected C-index 0.68) with good calibration.

CONCLUSIONS

In this multicentre cohort of patients with PSMA PET-detected metachronous oligorecurrent prostate cancer undergoing repeated MDRT, favourable ADT-FS outcomes were observed, with approximately half of patients remaining ADT-free two years after second MDRT. Given the absence of a comparator group, these outcomes may reflect both the effects of treatment and favourable disease biology of patients who remained eligible for repeated MDRT. The interval between MDRT cycles, and the number of metastases, independently predicted ADT-FS and may support patient selection.