Genomic Profiling of Small Cell Neuroendocrine Prostate Cancer and its Implications for Targeted Therapies.

Background/aim: This study aimed to investigate the genomic features of small cell neuroendocrine prostate cancer (SCPC) in Japanese patients, assess their relationships with platinum-based chemotherapy efficacy, and evaluate the potential treatment eligibility for therapies using cancer genomic profiling.

Patients and methods: This retrospective study included 21 patients diagnosed with SCPC between 2018 and 2022. An expert pathologist reviewed the biopsy specimens according to the World Health Organization prostate cancer classification. Biopsy samples from primary or metastatic lesions were analyzed using FoundationOne^® CDx to identify genomic mutations, focusing on DNA damage repair (DDR) mutations and other clinically relevant alterations. Platinum-based chemotherapy efficacy was assessed using progression-free survival (PFS) and overall survival (OS) outcomes.

Results: DDR mutations were detected in eight (38.1%) patients, and BRCA mutations were present in three (14.3%) cases. TP53 and RB1 mutations were identified in 15 (71.4%) and 12 (57.1%) cases, respectively. Three (14.8%) patients were identified with microsatellite instability-high or tumor mutational burden-high, making them eligible for immune checkpoint inhibitor treatment. PFS/OS rates suggested that the presence of these mutations did not significantly impact platinum-based chemotherapy efficacy. Six (28.6%) patients were eligible for treatments approved for prostate cancer in Japan as of 2024.

Conclusion: This study is the first to reveal the SCPC genomic landscape in Japanese patients. Although genomic mutations, including DDR mutations, were not predictive of platinum-based chemotherapy efficacy, active genomic testing may improve access to targeted therapies for this challenging malignancy, especially where treatment options are limited.