Fukuokaya Wataru, Yanagisawa Takafumi, Mori Keiichiro, Urabe Fumihiko, Rajwa Pawel, Briganti Alberto, Shariat Shahrokh F, Kimura Takahiro
Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.
Eur Urol Oncol. 2025 Apr;8(2):263-269. doi: 10.1016/j.euo.2024.04.009. Epub 2024 Apr 30.
In prostate cancer treated with androgen deprivation therapy (ADT), the initial sign of treatment resistance is often prostate-specific antigen (PSA) progression, followed by radiographic progression. However, the association between these two forms of progression remains unclear, especially in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with androgen receptor pathway inhibitors. We sought to evaluate the association between radiographic progression, PSA progression, and outcomes of apalutamide therapy in mCSPC.
We analyzed individual participant-level data for patients randomized within the TITAN trial who experienced radiographic progression during follow-up (N = 326). This study investigated radiographic progression without simultaneous or preceding PSA progression, as defined by the Prostate Cancer Working Group 2 (discordant progression), and explored the association of such progression with radiographic progression-free survival.
Among the patients who developed radiographic progression, 115 (35.3%) had been treated with apalutamide plus ADT (the apalutamide group) and 211 (64.7%) with placebo plus ADT (the placebo group). Discordant progression occurred in 52.2% of patients (60 of 115) in the apalutamide group and 27.5% (58 of 211) in the placebo group (p < 0.001). A multivariable logistic regression analysis showed that discordant progression was associated with apalutamide treatment. We found evidence of an association between discordant progression and shorter radiographic progression-free survival.
This study found that nearly half of the patients with mCSPC treated with apalutamide who experienced radiographic progression developed it without corresponding PSA progression, suggesting that heavy reliance on PSA monitoring may be inadequate for assessing disease activity in this context.
In patients who have metastatic castration-sensitive prostate cancer (mCSPC) and are being treated with apalutamide, radiographic images may show cancer progression even if prostate-specific antigen tests indicate no change. This highlights the importance of regular imaging when using apalutamide to manage mCSPC.
在接受雄激素剥夺治疗（ADT）的前列腺癌患者中，治疗抵抗的初始迹象通常是前列腺特异性抗原（PSA）进展，随后是影像学进展。然而，这两种进展形式之间的关联仍不明确，尤其是在接受雄激素受体通路抑制剂治疗的转移性去势敏感性前列腺癌（mCSPC）患者中。我们试图评估mCSPC患者影像学进展、PSA进展与阿帕鲁胺治疗结局之间的关联。
我们分析了TITAN试验中随机分组且在随访期间出现影像学进展的患者的个体参与者水平数据（N = 326）。本研究调查了前列腺癌工作组2所定义的无同时或先前PSA进展的影像学进展（不一致进展），并探讨了这种进展与无影像学进展生存期的关联。
在出现影像学进展的患者中，115例（35.3%）接受了阿帕鲁胺加ADT治疗（阿帕鲁胺组），211例（64.7%）接受了安慰剂加ADT治疗（安慰剂组）。阿帕鲁胺组52.2%的患者（115例中的60例）出现不一致进展，安慰剂组为27.5%（211例中的58例）（p < 0.001）。多变量逻辑回归分析显示，不一致进展与阿帕鲁胺治疗相关。我们发现了不一致进展与较短的无影像学进展生存期之间存在关联的证据。
本研究发现，接受阿帕鲁胺治疗且出现影像学进展的mCSPC患者中，近一半患者出现影像学进展时无相应的PSA进展，这表明在这种情况下，过度依赖PSA监测可能不足以评估疾病活动。
对于患有转移性去势敏感性前列腺癌（mCSPC）且正在接受阿帕鲁胺治疗的患者，即使前列腺特异性抗原检测显示无变化，影像学检查仍可能显示癌症进展。这凸显了在使用阿帕鲁胺治疗mCSPC时定期进行影像学检查的重要性。
