Cancer-Control Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer With Gene or Tumor Suppressor Mutations Undergoing 177-Lutetium Prostate-Specific Membrane Antigen Radioligand Therapy.

Purpose: Several tumor gene mutations are known for metastatic castration-resistant prostate cancer (mCRPC). The individual response to 177-lutetium prostate specific membrane antigen radioligand therapy (Lu-PSMA) is under current investigation regarding the genomic profile of patients with mCRPC.

Materials And Methods: We relied on the FRAMCAP database and compared progression-free survival (PFS) and overall survival (OS) rates of patients with mCRPC with breast cancer-related antigen () or tumor suppressor gene mutations (, , ). Specifically, subgroup analyses were performed for patients with Lu-PSMA-treated mCRPC.

Results: Of 194 patients with mCRPC, 22% was versus 14% versus 63% without one of these mutations. Patients with no mutation harbored a significantly lower Gleason score of 8-10, relative to and patients. In PFS analyses of first-line mCRPC, no difference between all three groups was observed, whereas the median OS differed significantly with 46.3 versus 48.7 versus 95.4 months for versus versus no mutated patients ( < .05). In univariable Cox regression models, BRCA-mutated patients were at higher risk of death (hazard ratio, 2.57; < .01), whereas patients were not ( = .4). Of 87 patients with Lu-PSMA-treated mCRPC, significant differences in PFS and OS were observed (both ≤ .02). In univariable and multivariable Cox regression models, BRCA-mutated Lu-PSMA patients were at higher risk of death, whereas patients had similar outcomes as no mutated patients.

Conclusion: In real-world setting, substantially lower OS in mCRPC is observed for - and -mutated patients, whereas no difference in first-line PFS could be computed. In Lu-PSMA-treated patients, worst outcomes were observed for patients.