Department of Pharmacy, Kindai University Nara Hospital, 1248-1 Otodacho, Ikoma, Nara, 630-0293, Japan.
School of Pharmacy, Hyogo Medical University, 1-3-6 Minatojima, Chuo-ku, Hyogo, 663- 8530, Japan.
Sci Rep. 2024 Oct 4;14(1):23119. doi: 10.1038/s41598-024-73197-y.
Hormone therapy, especially androgen deprivation therapy (ADT), is effective against prostate cancer (PC), whereas long-term ADT is a risk for metabolic/cardiovascular disorders including diabetes (DM), hypertension (HT) and dyslipidemia (DL), and might result in progression to castration-resistant prostate cancer (CRPC). We thus conducted a multicenter retrospective cohort study to ask whether CRPC progression would be associated positively with HT, DM or DL and negatively with statins prescribed for treatment of DL. In this study, 1,112 nonmetastatic PC patients undergoing ADT were enrolled. Univariate statistical analyses clearly showed significant association of HT or DM developing after ADT onset, though not preexisting HT or DM, with early CRPC progression. On the other hand, preexisting DL or statin use, but not newly developed DL or started statin prescriptions following ADT, was negatively associated with CRPC progression. Multivariate analysis revealed significant independent association of the newly developed DM or HT, or preexisting statin use with CRPC progression [adjusted hazard ratios (95% confidence intervals): 3.85 (1.65-8.98), p = 0.002; 2.75 (1.36-5.59), p = 0.005; 0.25 (0.09-0.72), p = 0.010, respectively]. Together, ADT-related development of HT or DM and preexisting statin use are considered to have positive and negative impact on CRPC progression, respectively.
激素治疗，尤其是雄激素剥夺治疗（ADT），对前列腺癌（PC）有效，而长期 ADT 是代谢/心血管疾病的风险因素，包括糖尿病（DM）、高血压（HT）和血脂异常（DL），并可能导致去势抵抗性前列腺癌（CRPC）进展。因此，我们进行了一项多中心回顾性队列研究，以了解 CRPC 进展是否与 HT、DM 或 DL 呈正相关，与用于治疗 DL 的他汀类药物呈负相关。在这项研究中，纳入了 1112 例接受 ADT 的非转移性 PC 患者。单因素统计分析清楚地表明，ADT 后发生的 HT 或 DM 与早期 CRPC 进展显著相关，尽管 ADT 前的 HT 或 DM 无此相关性。另一方面，DL 的预先存在或他汀类药物的使用，而不是 ADT 后新发生的 DL 或开始他汀类药物处方，与 CRPC 进展呈负相关。多因素分析显示，新发生的 DM 或 HT，或预先存在的他汀类药物使用与 CRPC 进展有显著的独立相关性[调整后的危险比（95%置信区间）：3.85（1.65-8.98），p=0.002；2.75（1.36-5.59），p=0.005；0.25（0.09-0.72），p=0.010]。总之，ADT 相关的 HT 或 DM 发展和预先存在的他汀类药物使用分别对 CRPC 进展有积极和消极的影响。
