Skeletal-related events are significant complications in prostate cancer patients with bone metastases. While bone-modifying agents are established in metastatic castration-resistant prostate cancer (mCRPC), their role in metastatic castration-sensitive prostate cancer (mCSPC) remains unclear. This study characterized symptomatic skeletal events (SSEs) and identified factors predicting their onset in mCSPC patients treated with denosumab.
We retrospectively analyzed 318 mCSPC patients with bone metastases who received denosumab between 2015 and 2024. The primary endpoint was the probability of SSE occurrence, defined as symptomatic pathologic fracture, spinal cord compression, symptoms requiring orthopedic surgery, or external beam radiotherapy (EBRT) due to bone complications. Predictive factors were assessed using multivariate Cox regression and logistic regression analyses. The optimal serum alkaline phosphatase (ALP) cutoff for predicting SSEs was determined with receiver operating characteristic (ROC) analysis.
Over a median follow-up of 25 months, 32 patients (10.1%) developed SSEs, most commonly symptoms requiring EBRT (7.9%). The 3-year probability of SSE occurrence was 15.4%. Multivariate analysis identified elevated ALP as an independent predictor of SSEs (hazard ratio per 50-U increase: 1.03; 95% confidence interval, 1.01-1.04; P = .002). The ROC-derived ALP cutoff of 127.75 U/L was significantly associated with increased SSE risk. The most common reasons for denosumab discontinuation were death (19.0%) and osteonecrosis of the jaw (19.0%).
In this real-world mCSPC cohort, SSEs occurred in ∼15% of patients within 3 years of denosumab initiation. Elevated ALP was a significant predictor, supporting the need for individualized bone management strategies in mCSPC.
Clinical genitourinary cancer. 2026 Mar 11 [Epub ahead of print]
Yuzo Inaba, Fumihiko Urabe, Yu Imai, Juria Nakano, Kensuke Fujiwara, Masaki Hashimoto, Yuhei Koike, Yuya Iwamoto, Shuhei Hara, Keiichiro Miyajima, Wataru Fukuokaya, Kosuke Iwatani, Mahito Atsuta, Masaya Murakami, Kojiro Tashiro, Masato Yamaguchi, Tatsuya Shimomura, Jun Miki, Takahiro Kimura, JIKEI-YAYOI Collaborative Group
Department of Urology, The Jikei University School of Medicine, Minato City, Tokyo, Japan; Department of Urology, Fuji City General Hospital, Fuji, Shizuoka, Japan., Department of Urology, The Jikei University School of Medicine, Minato City, Tokyo, Japan; Department of Urology, Jikei University West Medical Center, Komae-shi, Tokyo, Japan. Electronic address: ., Department of Urology, The Jikei University School of Medicine, Minato City, Tokyo, Japan., Department of Urology, JR Tokyo General Hospital, Shibuya, Tokyo, Japan., Department of Urology, Machida Municipal Hospital, Machida, Tokyo, Japan., Department of Urology, The Jikei University School of Medicine, Minato City, Tokyo, Japan; Department of Urology, Jikei Katsushika Medical Center, Katsushika City, Tokyo, Japan., Department of Urology, The Jikei University School of Medicine, Minato City, Tokyo, Japan; Department of Urology, Atsugi City Hospital, Atsugi, Kanagawa, Japan., Department of Urology, The Jikei University School of Medicine, Minato City, Tokyo, Japan; Department of Urology, Jikei Kashiwa Hospital, Kashiwa, Chiba, Japan., Department of Urology, Fuji City General Hospital, Fuji, Shizuoka, Japan., Department of Urology, Atsugi City Hospital, Atsugi, Kanagawa, Japan., Department of Orthopedics, The Jikei University School of Medicine, Minato City, Tokyo, Japan.