# Drastic Response to Olaparib in a Patient With Metastatic Castration‐Resistant Prostate Cancer Harboring BRCA2 Alterations and Near‐Threshold Tumor Mutational Burden

## TL;DR

A patient with prostate cancer and specific genetic changes responded well to a targeted drug, offering insights for similar cases.

## Contribution

Demonstrates a rare case where olaparib effectively treats prostate cancer with BRCA2 and near-TMB-H markers.

## Key findings

- Olaparib led to significant tumor regression and PSA reduction in a patient with BRCA2 and near-TMB-H.
- The coexistence of BRCA2 and near-TMB-H is rare but may guide treatment in prostate cancer.
- Early discontinuation of chemohormonal therapy allowed for successful PARP inhibitor use.

## Abstract

BRCA2 alterations and high tumor mutational burden (TMB‐H) are responsible for prostate cancer; however, their co‐occurrence is uncommon, and evidence for PARP inhibition in the castration‐sensitive setting remains limited. We describe a case of metastatic castration‐resistant prostate cancer (CRPC) harboring both biomarkers, showing a marked response to olaparib.

A 74‐year‐old man presented with urinary retention. Initial prostate‐specific antigen (PSA) level was 11 ng/mL. Follow‐up MRI revealed bilateral PI‐RADS 5 lesions with seminal‐vesicle invasion. Biopsy confirmed adenocarcinoma (Gleason score 5 + 5 = 10). Staging revealed osseous and 30‐mm right internal iliac nodal metastasis. Genomic profiling identified a pathogenic BRCA2 mutation and near‐threshold TMB. Chemohormonal therapy was discontinued early owing to severe infection, and olaparib was initiated. Over 3 months, MRI showed further regression of the primary lesion and nodal disease, and PSA and SCC decreased.

In metastatic CRPC harboring a BRCA2 mutation and near‐threshold TMB, olaparib produced clear radiological and serological responses.

In this report, we describe a case of metastatic castration‐resistant prostate cancer (mCRPC) with both BRCA2 alteration and near‐threshold tumor mutational burden, in which the PARP inhibitor olaparib showed a remarkable response. The coexistence of BRCA2 alteration and TMB‐H is rare in prostate cancer, but in this case, their presence was related to treatment selection. We present this case in the hope that it will serve as a reference for therapeutic decision‐making in similar patients.