Bryce A H, Alumkal J J, Armstrong A, Higano C S, Iversen P, Sternberg C N, Rathkopf D, Loriot Y, de Bono J, Tombal B, Abhyankar S, Lin P, Krivoshik A, Phung D, Beer T M
Division of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, USA.
OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Prostate Cancer Prostatic Dis. 2017 Jun;20(2):221-227. doi: 10.1038/pcan.2016.71. Epub 2017 Jan 24.
Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested.
Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups.
Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26-2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar.
Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.
晚期前列腺癌是一种表型多样的疾病，会经历多种临床病程。前列腺特异性抗原（PSA）水平是疾病监测中使用最广泛的参数，但它存在公认的局限性。与临床试验不同，在实际临床中，医生可能仅依靠PSA监测来确定治疗中的疾病状态。这种方法尚未得到充分验证。
对在PREVAIL研究中接受雄激素受体抑制剂恩杂鲁胺治疗的872例初治的无症状或轻度症状的转移性去势抵抗性前列腺癌（mCRPC）男性患者进行事后分析，以观察在影像学进展时PSA水平是升高还是未升高（经验性定义为高于或低于3个月前PSA水平的1.05倍）。比较PSA升高组和未升高组的临床特征和疾病转归。
在恩杂鲁胺治疗组中，265例有影像学进展且PSA水平可评估的PREVAIL患者中，近四分之一的患者PSA未升高。该队列中，PSA未升高组的中位无进展生存期为8.3个月，而PSA升高组为11.1个月（风险比1.68；95%置信区间1.26 - 2.23）；两组的总生存期相似，尽管两组中均不到一半的患者在24个月时仍处于风险中。两组的基线临床特征相似。
在接受恩杂鲁胺治疗的mCRPC患者中，影像学进展时PSA未升高是一种常见现象。由于晚期前列腺癌患者的再分期通常以PSA水平升高为指导，我们的结果表明，恩杂鲁胺治疗期间疾病进展可能不伴随PSA水平升高。因此，一种不完全依赖于连续血清PSA测量的影像学疾病监测策略可能更准确地识别疾病进展。
