(UroToday.com) The 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between February 13th and 15th 2025, was host to the Poster Session A: Prostate Cancer. Dr. Mike Wenzel presented Abstract 71: Cancer-control outcomes of metastatic castration resistant prostate cancer patients with BRCA-gene or tumor suppressor mutations undergoing 177-lutetium PSMA radioligand therapy.
There are several tumor gene mutations known for metastatic castration-resistant prostate cancer (mCRPC). However, the individual response to ¹⁷⁷Lu-PSMA therapy is under investigation and is likely associated with the genomic profile of mCRPC patients.
Dr. Wenzel and colleagues utilized the Frankfurt Metastatic Cancer Database of the Prostate (FRAMCAP) database to compare progression-free survival (PFS) and overall survival (OS) in mCRPC patients with BRCA or tumor suppressor gene (TSG) mutations, including TP53, PTEN, and RB1. Subgroup analyses were specifically conducted for patients treated with ¹⁷⁷Lu-PSMA therapy.
A total of 194 patients with mCRPC were identified and studied. Of these, 22% had BRCA1/2 mutations, 14% had tumor suppressor gene (TSG) mutations, and 63% had neither mutation. Notably, and as expected, patients without mutations had significantly lower rates of Gleason score 8–10 prostate cancer compared to those with BRCA or TSG mutations.
In terms of PFS analyses, no significant differences were observed among the three groups in the first-line mCRPC treatment setting. However, median OS differed significantly, with 46.3 months for BRCA-mutated patients, 48.7 months for tumor suppressor gene-mutated patients, and 95.4 months for patients without mutations (p<0.05).
Moreover, in univariable Cox regression models, BRCA-mutated patients had a significantly higher risk of death (HR: 2.57, p<0.01), whereas tumor suppressor gene-mutated patients did not (p=0.4). Among the 87 patients with mCRPC treated with Lu-PSMA, significant differences in both PFS and OS were observed (both p≤0.02).
Notably, after sensitivity analysis, a significant difference in PFS and OS remained to be observed in patients without mutations vs. those with BRCA and TP53/RB1/PTEN mutations, as illustrated below.
In both univariable and multivariable Cox regression models, BRCA-mutated patients treated with Lu-PSMA had a higher risk of death, while tumor suppressor gene-mutated patients had similar outcomes to those without mutations.
Dr. Wenzel concluded his presentation by highlighting the following key points:
- In the real-world setting, patients with BRCA and tumor suppressor gene (TP53/RB1/PTEN) mutations have significantly lower OS in mCRPC.
- Among Lu-PSMA-treated patients, BRCA-mutated patients experienced the worst OS outcomes and preferential treatment with PARPi for this group of patients should be consider.
Presented by: Mike Wenzel, MD, Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany.
Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.