Three androgen receptor signaling inhibitors (ARSIs), darolutamide (DAR), apalutamide (APA), and enzalutamide (ENZ), are standard treatments for non-metastatic castration-resistant prostate cancer (nmCRPC); comparative real-world data on treatment persistence and safety remain limited.
We retrospectively analyzed 343 Japanese patients with nmCRPC treated with DAR (n = 92), APA (n = 64), or ENZ (n = 187) across 16 institutions. Oncological outcomes, including PSA progression-free survival (PSA-PFS) and PFS, were compared using multivariable Cox regression to adjust for baseline imbalances. Treatment persistence was evaluated by time to treatment discontinuation (TTD) and reasons for discontinuation.
The ENZ group had significantly worse baseline characteristics than the other groups. After multivariable adjustment, DAR showed consistently favorable hazard ratios for PSA progression (HR, 0.55, P = .038) and disease progression (HR, 0.59, P = .047) compared with ENZ; however, these differences were attenuated and no longer statistically significant after PSM (PSA-PFS HR, 0.62, P = .119), suggesting broadly comparable oncological outcomes across agents. Median TTD was significantly shorter in the APA group (11.0 months) compared with the DAR (27.0 months) and ENZ (25.0 months) groups (P = .019). Discontinuation due to adverse events was significantly more frequent in APA (51.6%) than DAR (19.6%) or ENZ (18.8%), primarily due to skin rash. Among discontinuers, AEs were the primary reason in 82.5% of APA, 42.9% of DAR, and 41.7% of ENZ.
In this real-world cohort, all 3 ARSIs demonstrated broadly comparable oncological outcomes, consistent with PSM. The principal differentiator was treatment persistence: APA was limited by markedly shorter TTD (median 11.0 months), primarily driven by skin rash; this difference was numerically preserved after PSM, though it did not reach statistical significance in the smaller matched sample. The high frequency of APA-related rash (46.9%) is consistent with prior Japanese/East Asian reports, including the integrated SPARTAN/TITAN Japanese analysis, and should be prioritized in treatment selection and patient counseling.
Clinical genitourinary cancer. 2026 Mar 21 [Epub ahead of print]
Shuhei Hara, Keiichiro Mori, Masaki Hashimoto, Yuji Yata, Shiro Kurawaki, Yuya Iwamoto, Shota Kawano, Takashi Otsuka, Wataru Fukuokaya, Keiichiro Miyajima, Mimu Ishikawa, Gaku Kurokawa, Yu Imai, Minoru Nakazono, Mahito Atsuta, Fumihiko Urabe, Takafumi Yanagisawa, Shunsuke Tsuzuki, Tatsuya Shimomura, Hiroki Yamada, Takahiro Kimura
Department of Urology, The Jikei University School of Medicine, Tokyo, Japan; Department of Urology, Jikei Katsushika Medical Center, Tokyo, Japan. Electronic address: ., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan; Department of Urology, Jikei Katsushika Medical Center, Tokyo, Japan., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan; Department of Urology, Machida Municipal Hospital, Tokyo, Japan., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan; Department of Urology, Atsugi City Hospital, Kanagawa, Japan., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan; Department of Urology, Tokyo-Kita Medical Center, Tokyo, Japan., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan; Department of Urology, Nerima Hikarigaoka Hospital, Tokyo, Japan., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan; Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Ota Memorial Hospital, Gunma, Japan., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan; Department of Urology, Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan; Department of Urology, JR Tokyo General Hospital, Tokyo, Japan; Department of Urology, Saitama Northern Medical Center, Saitama, Japan., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan; Department of Urology, Fuji City General Hospital, Shizuoka, Japan., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan; Department of Urology, Kameda General Hospital, Chiba, Japan., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan; Department of Urology, Jikei Kashiwa Hospital, Chiba, Japan., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan; Department of Urology, Jikei the 3rd Hospital, Tokyo, Japan.