Prognostic significance of risk stratification in CHAARTED and LATITUDE studies among Japanese men with de novo metastatic prostate cancer

DOI: 10.1111/iju.13870 Upfront docetaxel and abiraterone have each become standard therapies for metastatic HSPC. In the CHAARTED trial, upfront docetaxel showed significant survival benefit in the highvolume group (defined as the presence of visceral metastasis or ≥4 bone metastases with metastasis beyond the vertebrae and pelvis), but survival benefit was not yet shown in the low-volume group. Similarly, in the LATITUDE trial, upfront abiraterone showed significant survival prolongation in the high-risk group (defined as having at least 2 of [i] Gleason score ≥8, [ii] ≥3 bone metastases, or [iii] visceral metastasis). Thus, risk stratifications in the CHAARTED and LATITUDE trials are important criteria in deciding whether to introduce these upfront therapies or not. Recently, sensitivity to androgen deprivation therapy among patients with HSPC has been shown to vary by race; Asian men show better survival than men of African or European origin. However, the prognosis as stratified by CHAARTED and LATITUDE criteria has not been shown in Asian men, although each individual parameter has already been shown. Therefore, the present study investigated the prognostic significance in Japanese men with metastatic HSPC when stratified by the criteria in the CHAARTED and LATITUDE trials. The present study retrospectively enrolled 91 Japanese men with de novo metastatic prostate cancer at Kyushu University Hospital, Fukuoka, Japan, from 2007 to 2013. This study was approved by the institutional review board. A total of 77 men who were biopsied at Kyushu University Hospital and 14 men who were biopsied at another institution (from which seven of the biopsy specimens were reviewed at our institution) were included. All patients were primarily treated with surgical castration, or medical castration using a luteinizing hormone-releasing hormone agonist/antagonist (goserelin acetate, leuprorelin acetate or degarelix acetate) and/or an antiandrogen agent (bicalutamide or flutamide); 89 men were primarily treated with combined androgen blockade and two men were treated with castration alone. Progression was judged by PCWG2 criteria. All statistical analyses were carried out using JMP 13 (SAS Institute, Cary, NC, USA). Continuous and categorical data were analyzed using the Wilcoxon rank-sum test and Pearson’s vtest, respectively. Survival analyses were carried out using the Kaplan–Meier method and log–rank test. The Cox proportional hazards model was used to estimate HR. P < 0.05 was considered significant. A total of 50 men and 59 men were considered to be in the “high” groups by CHAARTED and LATITUDE criteria, respectively (Fig. S1). Prostate-specific antigen level, biopsy Gleason score, visceral metastasis, and EOD scores were worse in the “high” groups (Table S1). Using the CHAARTED criteria, the median PFS was 32.9 months (95% CI 24.0–57.3 months) in the low-volume group and 11.3 months (95% CI 8.3–18.5 months, P = 0.0008; Fig. 1a) in the high-volume group. Using the LATITUDE criteria, the median PFS was 36.8 months (95% CI 24.0 months–not reached) in the low-risk group and 13.1 months (95% CI 9.6–18.7 months, P = 0.0006; Fig. 1b) in the high-risk group. Thus, the “high” groups by the CHAARTED and LATITUDE criteria showed approximately 2.5-fold higher risk of progression to castration-resistant prostate cancer both on univariate and multivariate analyses (Table S2). Similar results were obtained for OS. Using the CHAARTED criteria, the median OS was 90.5 months (95% CI 68.9 months–not reached) in the low-volume group and 49.0 months (95% CI 29.7–69.7 months, P = 0.0033; Fig. 1c) in the high-volume group. Using LATITUDE criteria, the median OS was 90.5 months (95% CI 61.9 months–not reached) in the low-risk group and 60.4 months (95% CI 36.7–75.6 months, P = 0.0038; Fig. 1d) in the high-risk group. The “high” groups by the CHAARTED and LATITUDE criteria thus showed 2.5to threefold higher risk of death from any cause both on univariate and multivariate analyses (Table S3). The present study showed that the CHAARTED and LATITUDE risk criteria could apply to Japanese patients. Furthermore, prognoses in clinical trials including GETUG-AFU