The ENABLE study, an investigator-initiated, multicenter, randomized controlled trial, demonstrated comparable survival benefits between enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) for castration-resistant prostate cancer (CRPC). Because randomized controlled trials typically exclude patients with a history of other cancers (HOCs), we evaluated the efficacy of these agents in this population.
This sub-analysis was conducted as a post hoc analysis using data from the ENABLE study. Endpoints included time to PSA progression, radiographic progression-free survival, overall survival (OS), prostate cancer-specific survival, and safety. Outcomes were compared between patients with and without a HOC+ versus HOC- and between treatment arms within each group.
The HOC+ group included 35 patients (13 ENZ, 22 ABI), whereas the HOC- group included 149 patients (79 ENZ, 70 ABI). The most frequent malignancy was gastric cancer (n = 10, 29%). HOC+ patients had significantly worse OS than HOC- patients (median 24.7 vs. 37.4 months; HR 1.96; 95% CI 1.02-3.77; p = 0.0426), while other survival endpoints did not differ between the groups. Within the HOC+ group, OS was significantly worse with ENZ than with ABI (median 16.0 vs. 30.5 months; HR 3.27; 95% CI 1.08-9.89; p = 0.0354), whereas no significant differences were observed between the arms in the HOC- group.
Although OS was poorer in HOC+ patients, other outcomes were similar, supporting the feasibility of ENZ and ABI regardless of cancer history. The longer OS with ABI in HOC+ patients represents a hypothesis-generating observation and should be interpreted with particular caution.
International journal of urology : official journal of the Japanese Urological Association. 2026 May [Epub]
Seiji Hoshi, Kouji Izumi, Satoru Meguro, Takashi Shima, Yuki Kato, Koji Mita, Takehiko Okamura, Shogo Inoue, Shuichi Tatarano, Nobumichi Tanaka, Yuko Yoshio, Manabu Kamiyama, Ippei Chikazawa, Noriyasu Kawai, Kohei Hashimoto, Takashi Fukagai, Kazuyoshi Shigehara, Shizuko Takahara, Atsushi Mizokami
Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Fukushima, Japan., Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan., Department of Urology, Toyama Prefectural Central Hospital, Toyama, Japan., Department of Urology, Fukui-ken Saiseikai Hospital, Fukui, Fukui, Japan., Department of Urology, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima, Hiroshima, Japan., Department of Urology, Anjo Kosei Hospital, Anjo, Aichi, Japan., Department of Urology, Kobatake Hospital, Fukuyama, Hiroshima, Japan., Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Kagoshima, Japan., Department of Urology, Nara Medical University, Kashihara, Nara, Japan., Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Mie, Japan., Department of Urology, University of Yamanashi Graduate School of Medical Sciences, Chuo, Yamanashi, Japan., Department of Urology, Kanazawa Medical University, Kahoku, Ishikawa, Japan., Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan., Department of Urology, School of Medicine, Sapporo Medical University, Sapporo, Hokkaido, Japan., Department of Urology, Showa University School of Medicine, Tokyo, Japan., Innovative Clinical Research Center, Kanazawa University, Kanazawa, Ishikawa, Japan.