Bone Scan Index (BSI) scoring by using bone scintigraphy and circulating tumor cells (CTCs): predictive factors for enzalutamide effectiveness in patients with castration-resistant prostate cancer and bone metastases

Background: 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. Methods 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 and progression free survival (PFS). Statistical analyses included the Wilcoxon t-test, Cox proportional hazard regression analysis, and log-rank test. Results Median observation period: 17.9 months, and median PFS: 13.8 (2.0-43.9) months (n = 90 patients). At 3 months 67% patients showed a ≥ 50% PSA reduction, and 70% after ENZ treatment. At 3 months 20% patients showed a ≥ 50% BSI reduction (10% complete response [CR]; BSI value 0.00), and 38% patients (29% CR) at study end. PSA decline (3 months) significantly prolonged median PFS: 18.0 (estimated) vs 6.4 months (HR 2.977 [95% CI: 1.53–5.78], p =  0.001). Best BSI decline response significantly prolonged PFS: 18.1(estimated) vs 7.8 months (HR 2.045 [95% CI: 1.07–3.90], p =  0.029). CTC negative status (n = 20) significantly 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 reduced PFS: 5.9 months (HR 8.56, 95%CI: 2.40–30.43, p =  0.0087). Conclusions PSA reduction (3 months), BSI reduction (after ENZ), and a negative CTC status were significant predictive factors for ENZ efficacy in patients with mCRPC.