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.
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.
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.
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.
JCO precision oncology. 2024 Dec 06 [Epub]
Mike Wenzel, Florestan Koll, Benedikt Hoeh, Clara Humke, Henning Reis, Peter Wild, Thomas Steuber, Markus Graefen, Derya Tilki, Amir Sabet, Daniel Gröner, Felix K H Chun, Philipp Mandel
Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany., Dr Senckenberg Institute of Pathology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Department of Nuclear Medicine, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany.