Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Urology, Aichi Medical University Hospital, Nagakute, Japan.
Prostate. 2023 Mar;83(4):307-315. doi: 10.1002/pros.24462. Epub 2022 Nov 24.
In recent years, the usefulness of androgen receptor axis-targeted agents (ARATs) such as abiraterone, enzalutamide, and apalutamide for the upfront treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has been demonstrated. However, it remains unclear which patients would truly benefit from these treatments. Furthermore, intraductal carcinoma of the prostate (IDC-P) is a known poor prognostic factor in patients with prostate cancer. We investigated the association between the presence of IDC-P and response to therapy in patients with mHSPC.
This retrospective analysis included 318 patients with mHSPC who received treatment at Nagoya University and its 12 affiliated institutions between 2014 and 2021. Their biopsy specimens were evaluated for the presence of IDC-P. The patients were classified according to their first-line treatment into the ARAT (n = 100, receiving a combination of androgen-deprivation therapy [ADT] and ARAT) or conventional therapy (n = 218, receiving ADT with or without standard antiandrogen agents) group. We compared the overall survival (OS) and second progression-free survival (PFS2) between the ARAT and conventional groups according to the presence of IDC-P to evaluate whether presence of IDC-P predicts the response to each treatment. PFS2 was defined as the period from mHSPC diagnosis to disease progression on second-line treatment or death. Propensity score matching with one-to-one nearest-neighbor matching was used to minimize the potential effects of selection bias and confounding factors. The clinicopathological variables of the patients were well-balanced after propensity score matching.
Most patients in the ARAT (79%) and conventional therapy (71%) groups were ICD-P positive. In the propensity score-matched cohort, the OS and PFS2 of IDC-P-positive patients were significantly longer in the ARAT group than in the conventional group (OS: hazard ratio [HR], 0.36; p = 0.047; PFS2: HR, 0.30; p < 0.001). In contrast, no difference in OS and PFS2 was observed between the ARAT and conventional groups in IDC-P-negative patients (OS: HR, 1.09; p = 0.920; PFS2: HR, 0.40; p = 0.264).
The findings highlight a high prevalence of IDC-P among patients with mHSPC and suggest that IDC-P positivity may be a reliable indicator that ARAT should be implemented as first-line treatment.
近年来，雄激素受体轴靶向药物（ARATs）如阿比特龙、恩扎鲁胺和阿帕鲁胺在转移性激素敏感前列腺癌（mHSPC）的一线治疗中的有效性已得到证实。然而，仍不清楚哪些患者真正受益于这些治疗。此外，前列腺导管内癌（IDC-P）是前列腺癌患者预后不良的已知因素。我们研究了 mHSPC 患者中 IDC-P 的存在与治疗反应之间的关系。
本回顾性分析纳入了 2014 年至 2021 年在名古屋大学及其 12 家附属医院接受治疗的 318 例 mHSPC 患者。对他们的活检标本进行 IDC-P 评估。根据一线治疗将患者分为 ARAT 组（n=100，接受雄激素剥夺治疗[ADT]和 ARAT 联合治疗）或常规治疗组（n=218，接受 ADT 联合或不联合标准抗雄激素药物治疗）。我们比较了 IDC-P 阳性和阴性患者在 ARAT 和常规组之间的总生存期（OS）和第二次无进展生存期（PFS2），以评估 IDC-P 是否预测每种治疗的反应。PFS2 定义为从 mHSPC 诊断到二线治疗或死亡时疾病进展的时间。采用 1:1 最近邻匹配的倾向评分匹配法，以最小化选择偏倚和混杂因素的潜在影响。经过倾向评分匹配后，患者的临床病理变量得到很好的平衡。
ARAT 组（79%）和常规治疗组（71%）的大多数患者 IDC-P 阳性。在倾向评分匹配队列中，IDC-P 阳性患者在 ARAT 组的 OS 和 PFS2 明显长于常规组（OS：风险比[HR]，0.36；p=0.047；PFS2：HR，0.30；p<0.001）。相反，IDC-P 阴性患者在 ARAT 组和常规组之间的 OS 和 PFS2 无差异（OS：HR，1.09；p=0.920；PFS2：HR，0.40；p=0.264）。
研究结果突出了 mHSPC 患者中 IDC-P 的高患病率，并表明 IDC-P 阳性可能是 ARAT 作为一线治疗的可靠指标。
