前列腺特异性抗原谷底与癌症控制结局在实际应用中阿帕鲁胺治疗转移性激素敏感性前列腺癌患者中的单中心分析

目前可用的基于第三阶段试验后分析数据表明，在达到了（超）低前列腺特异性抗原（PSA）谷底的阿帕鲁胺治疗的转移性激素敏感性前列腺癌（mHSPC）患者中，癌症控制结局更佳。本研究旨在验证超低PSA谷底的临界值。依托机构前列腺癌数据库，筛选出107例符合条件的患者。对现有的PSA谷底临界值（SWOG试验：<0.2 ng/ml；TITAN试验的超低：≤0.02 vs 0.02-0.2 vs >0.2 ng/ml）以及PSA反应（≥99%）进行了测试，以评估接受阿帕鲁胺治疗的mHSPC患者的抗去势抵抗性前列腺癌（ttCRPC）时间和总生存期（OS）。最后，将结果与阿比特龙治疗的患者进行比较。总体而言，研究纳入了以中位年龄68岁、基线PSA为29 ng/ml的107例接受阿帕鲁胺治疗的mHSPC患者。最高比例（40.2%）的患者达到了≤0.02 ng/ml的超低PSA谷底。达到SWOG 9346定义的<0.2 ng/ml PSA谷底和超低PSA谷底（≤0.02 ng/ml）患者具有最长的抗去势抵抗性前列腺癌（mCRPC）发病时间和OS（均p < 0.05）。此外，80%的患者在接受阿帕鲁胺治疗后获得了≥99%的PSA反应。这些患者的mCRPC发病时间和OS均优于PSA反应<99%的患者（两者均p < 0.05）。在第二步分析中，与阿比特龙患者的比较显示，达成超低PSA谷底（≤0.02 ng/ml）的比例显著更高：阿帕鲁胺组为40.2%，而阿比特龙组为8.8%，导致阿帕鲁胺组的ttCRPC显著更长（37个月对比22个月，p = 0.001），即使经过多变量调整及对高危mHSPC患者的敏感性分析亦如此。该研究受限于其回顾性设计。在实际应用中，大多数接受阿帕鲁胺治疗的mHSPC患者都能达成超低PSA谷底，这与更好的癌症控制结局相关。此外，PSA反应≥99%预示着更佳的预后。在直接比较中，阿帕鲁胺在PSA动力学和ttCRPC结局方面优于阿比特龙。前列腺特异性抗原（PSA）谷底<0.02 ng/ml及PSA反应≥99%与接受阿帕鲁胺治疗的转移性激素敏感性前列腺癌患者的更好癌症控制结局相关。

Currently available post hoc phase 3 trial-derived data suggest better cancer-control outcomes in apalutamide-treated metastatic hormone-sensitive prostate cancer (mHSPC) patients achieving an (ultra)low prostate-specific antigen (PSA) nadir. This study aims to validate ultralow PSA nadir cutoffs.Relying on an institutional prostate cancer database, 107 eligible patients were yielded. The currently available PSA nadir cutoffs (SWOG trial: <0.2 ng/ml; ultralow TITAN trial: ≤0.02 vs 0.02-0.2 vs >0.2 ng/ml) and PSA responses (≥99%) were tested for time to castration-resistant prostate cancer (ttCRPC) and overall survival (OS) in mHSPC patients treated with apalutamide. Finally, comparisons were made against abiraterone mHSPC treatment.Overall, 107 mHSPC patients treated with apalutamide at a median age of 68 yr and baseline PSA of 29 ng/ml were included. The highest proportion of included patients (40.2%) achieved an ultralow PSA nadir of ≤0.02 ng/ml. Patients reaching the SWOG 9346-defined PSA nadir of <0.2 ng/ml and ultralow PSA nadir of ≤0.02 ng/ml harbored the longest time to metastatic castration-resistant prostate cancer (mCRPC) and OS (all p < 0.05). Moreover, 80% of mHSPC patients treated with apalutamide achieved a PSA response of ≥99%. These patients also harbored better time to mCRPC and OS outcomes, relative to patients with a <99% PSA response (both p < 0.05). In the second step of analyses, a comparison against abiraterone patients showed a significantly higher rate of achieving an ultralow PSA nadir of ≤0.02 ng/ml: 40.2% versus 8.8% for apalutamide versus abiraterone, resulting in a significantly longer ttCRPC for the apalutamide-treated (37 mo) than for the abiraterone-treated (22 mo) group (p = 0.001), even after multivariable adjustment and in sensitivity analyses for high-risk mHSPC patients only. The study is limited by its retrospective design.In the real-world setting, most mHSPC patients treated with apalutamide achieve an ultralow PSA nadir, which is associated with better cancer-control outcomes. Moreover, a PSA response of ≥99% predicts better outcomes. In head-to-head comparisons, apalutamide achieves better PSA kinetics and ttCRPC outcomes than abiraterone.A prostate-specific antigen (PSA) nadir of <0.02 ng/ml and PSA responses ≥99% are associated with better cancer-control outcomes in metastatic hormone-sensitive prostate cancer patients treated with apalutamide.