-Original-

The Current Status of Comprehensive Genomic Profiling in the Management of Metastatic Castration-Resistant Prostate Cancer: A Study from a Cooperative Hospital for Cancer Genomic Medicine in Japan

Jun Akatsuka¹, Go Kimura¹, Mami Takadate^1,2,5, Sayuri Hiraoka³, Tomoko Sahara³, Takuma Iwai⁴, Hiroya Hasegawa¹, Hikaru Mikami¹, Kotaro Obayashi¹, Hayato Takeda¹, Yuki Endo¹, Yuka Toyama¹, Yoichiro Yamamoto^1,2,5, Takeshi Yamada^3,4 and Yukihiro Kondo¹

¹Department of Urology, Nippon Medical School, Tokyo, Japan
²Pathology Informatics Team, RIKEN Center for Advanced Intelligence Project, Tokyo, Japan
³Department of Genetics, Nippon Medical School, Tokyo, Japan
⁴Department of Digestive Surgery, Nippon Medical School, Tokyo, Japan
⁵Mathematical Intelligence for Medicine, Graduate School of Medicine, Tohoku University, Miyagi, Japan

Background: Several effective treatment modalities against metastatic castration-resistant prostate cancer (mCRPC) are available; however, an unmet clinical need persists for mCRPC treatment because resistance to these therapies is inevitable. This study aimed to evaluate the status of comprehensive genomic profiling (CGP) and its impact on subsequent treatments for patients with mCRPC at our hospital.
Methods: Between December 2020 and August 2023, we assessed 41 patients with mCRPC who underwent CGP testing at the Nippon Medical School Hospital. The testing comprised FoundationOne^® CDx for 30 patients and FoundationOne^® Liquid CDx for 11 patients, following the procedures outlined by the Japanese Urological Association.
Results: CGP testing was successfully conducted in 40 out of 41 patients (97.6%), which resulted in the identification of 140 actionable genomic alterations. The most common alteration was TP53 in 12 patients (30.0%). Twenty-three patients (57.5%) with druggable gene alterations were identified; 21 were recommended for clinical trials, four for patient-proposed healthcare services, and six for insurance-covered drugs. Consequently, genotype-matched therapy with insurance-covered drugs was administered to five patients (12.5%) with a BRCA2 mutation. Notably, none of the patients underwent clinical or prospective trials based on patient-suggested medical services.
Conclusions: Our results offer insights into the real-world application of CGP testing for patients with mCRPC at a cooperative hospital for cancer genomic medicine in Japan. Thus, urologists require a comprehensive understanding of the current status of CGP testing to enhance mCRPC management.

J Nippon Med Sch 2024; 91: 472-479

Keywords
prostate cancer, next-generation sequencing, metastatic castration-resistant prostate cancer

Correspondence to
Jun Akatsuka, MD, PhD, Department of Urology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
s00-001@nms.ac.jp

Received, March 26, 2024
Accepted, July 12, 2024