Cancer-Control Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer With BRCA 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 ( BRCA ) or tumor suppressor gene mutations ( TP53 , PTEN , RB1 ). Specifically, subgroup analyses were performed for patients with Lu-PSMA–treated mCRPC. RESULTS Of 194 patients with mCRPC, 22% was BRCA1/2 versus 14% PTEN/TP53/RB1 versus 63% without one of these mutations. Patients with no mutation harbored a significantly lower Gleason score of 8-10, relative to BRCA and PTEN/TP53/RB1 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 BRCA versus PTEN/TP53/RB1 versus no mutated patients ( P < .05). In univariable Cox regression models, BRCA-mutated patients were at higher risk of death (hazard ratio, 2.57; P < .01), whereas PTEN/TP53/RB1 patients were not ( P = .4). Of 87 patients with Lu-PSMA–treated mCRPC, significant differences in PFS and OS were observed (both P ≤ .02). In univariable and multivariable Cox regression models, BRCA-mutated Lu-PSMA patients were at higher risk of death, whereas PTEN/TP53/RB1 patients had similar outcomes as no mutated patients. CONCLUSION In real-world setting, substantially lower OS in mCRPC is observed for BRCA - and PTEN/TP53/RB1 -mutated patients, whereas no difference in first-line PFS could be computed. In Lu-PSMA–treated patients, worst outcomes were observed for BRCA patients.