Reports of Bone Scan Index (BSI) calculations as imaging biomarkers to predict survival in patients with metastatic castration-resistant prostate cancer (mCRPC) have been mainly from retrospective studies. To evaluate the effectiveness of enzalutamide (ENZ) in Japanese patients with mCRPC and bone metastases using BSI (bone scintigraphy) and circulating tumor cell (CTC) analysis. Prospective, single-arm study at Juntendo University affiliated hospitals, Japan. Patients were administered 160 mg ENZ daily, with 3 monthly assessments: BSI, prostate specific antigen (PSA), CTC and androgen receptor splicing variant-7 (AR-V7) status. Primary endpoint: BSI-decreasing rate after ENZ treatment. Secondary endpoints: PSA-decreasing rate and progression free survival (PFS). Statistical analyses included the Wilcoxon t-test, Cox proportional hazard regression analysis, and log-rank test. Median observation period: 17.9 months, and median PFS: 13.8 (2.0-43.9) months (n = 90 patients). A decrease in BSI compared to baseline as best BSI change on ENZ treatment was evident in 69% patients at the end of the observation period (29% patients showed a complete response, BSI 0.00). At 3 months 67% patients showed a ≥ 50% PSA reduction, and 70% after ENZ treatment. PSA decline (3 months) significantly associated with a prolonged median PFS: 18.0 (estimated) versus 6.4 months (HR 2.977 [95% CI 1.53-5.78], p = 0.001). Best BSI decline response significantly associated with a prolonged PFS: 18.1(estimated) versus 7.8 months (HR 2.045 [95% CI: 1.07-3.90], p = 0.029). CTC negative status (n = 20) significantly associated with a prolonged PFS: 13.4 [estimated] vs 8.6 months (HR 2.366, 95% CI 0.97-5.71, p = 0.041). CTC positive/AR-V7 positive status significantly associated with a shorter PFS: 5.9 months (HR 8.56, 95% CI 2.40-30.43, p = 0.0087). -reduction (3 months) and BSI-reduction (on ENZ treatment) were significant response biomarkers, and a negative CTC status was a predictive factor for ENZ efficacy in patients with mCRPC.
Scientific reports. 2023 May 29*** epublish ***
Hisashi Hirano, Masayoshi Nagata, Naoya Nagaya, So Nakamura, Takeshi Ashizawa, Yan Lu, Haruna Kawano, Kosuke Kitamura, Yoshiro Sakamoto, Kazuhiko Fujita, Hideyuki Isobe, Akira Tsujimura, Satoru Muto, Shigeo Horie
Department of Urology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo Bunkyo-Ku, Tokyo, 1138431, Japan., Department of Urology, Juntendo University Nerima Hospital, Tokyo, Japan., Department of Urology, Juntendo University Shizuoka Hospital, Shizuoka, Japan., Department of Urology, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan., Department of Urology, Juntendo University Urayasu Hospital, Chiba, Japan., Department of Urology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo Bunkyo-Ku, Tokyo, 1138431, Japan. .