Differential Response to 177Lu-PSMA-617 in Patients with Tumor Suppressor Gene-Mutated Metastatic Castration-Resistant Prostate Cancer.

Genomic alterations are common in metastatic castration-resistant prostate cancer (mCRPC), but limited data exist on the response to 177Lu-PSMA-617 (LuPSMA) in patients with these aberrations. We aimed to characterize oncologic outcomes of patients with mCRPC and germline or somatic aberrations after treatment with LuPSMA.

Methods

The medical record was surveyed for all patients with mCRPC treated with LuPSMA between October 2022 and October 2024. All patients who had received at least 1 cycle of LuPSMA and underwent either germline or somatic testing were included.

Results

Seventy-two patients were included. Patients with TP53/PTEN/RB1 mutations demonstrated inferior overall survival, even after adjustment for age and race. TP53/PTEN/RB1, BRCA1/2, and CHEK2/PALB2/ATM were not associated with inferior progression-free survival. No individual mutation was significantly associated with changes in the percentage decline in prostate-specific antigen levels from baseline.

Conclusion

TP53, PTEN, and RB1 mutations were linked to inferior overall survival in LuPSMA-treated patients and may serve as prognostic biomarkers. Prospective validation is required to establish their predictive value.