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

Abstract

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.

The Detection and Negative Reversion of Circulating Tumor Cells as Prognostic Biomarkers for Metastatic Castration-Resistant Prostate Cancer with Bone Metastases Treated by Enzalutamide

“…In our previous study, we demonstrated the efficacy of ENZ in treating mCRPC with bone metastases and showed that the presence or absence of CTCs at baseline correlated with the prolongation of PFS by ENZ treatment [10]. In this study, by analyzing a subgroup from the previous study, we first demonstrated that the absence of CTC detection at baseline might contribute to prolonged OS (Figure 2) and showed the efficacy of chronological analyses of CTC in 43 patients with mCRPC.…”

“…Therefore, we conducted this study to evaluate the usefulness of CTC analysis in the clinical setting of mCRPC. In a previous study conducted at our facilities and affiliated hospitals, we analyzed PFS in mCRPC patients with bone metastases treated with ENZ and demonstrated that a negative CTC status at baseline before ENZ treatment was a significant predictor for ENZ efficacy [10]. It has already been reported that chronological monitoring of CTCs is very effective for evaluating possible treatments and their efficacy in mCRPC [15][16][17].…”

“…CTC-negative patients at the time of treatment administration demonstrate superior clinical outcomes to those of CTC-positive patients [8,10]. Androgen receptor splice variant 7 (AR-V7) in CTCs of patients with mCRPC is a potential biomarker to predict the development of drug resistance to ENZ and abiraterone [8,10,11]. Unlike antiandrogen treatments, taxanes are effective for mCRPC, irrespective of AR-V7 status [12,13], which has been confirmed in the Asian population as well [14].…”

“…Liquid biopsies allow the carrying out of analyses using non-solid biological tissues and are thereby less invasive, painless, and inexpensive compared to tissue biopsies and can be carried out repeatedly [9]. CTC-negative patients at the time of treatment administration demonstrate superior clinical outcomes to those of CTC-positive patients [8,10]. Androgen receptor splice variant 7 (AR-V7) in CTCs of patients with mCRPC is a potential biomarker to predict the development of drug resistance to ENZ and abiraterone [8,10,11].…”

Recent advances and future perspectives in the therapeutics of prostate cancer

“…For PC cells, PSA and FGF2 are target proteins for identification [ 113 ]. Another CTC biomarker under clinical investigation is AR-V7 [ 114 ].…”