Lim Daniel M, Gulati Roman, Aleshin-Guendel Serge, Gawne Agnes, Wingate Jonathan T, Cheng Heather H, Etzioni Ruth, Yu Evan Y
Department of Medicine, Division of Oncology, University of Washington, Seattle Cancer Care Alliance, Seattle, Washington.
Biostatistics and Biomathematics, Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Prostate. 2018 Jul 10. doi: 10.1002/pros.23666.
Optimal utilization of novel therapies for advanced prostate cancer is challenging without a validated surrogate efficacy endpoint. Ongoing trials are using durable undetectable prostate-specific antigen (PSA) levels as a marker of efficacy. The clinical relevance of prolonged undetectable PSA after a short course of androgen deprivation therapy (ADT) is uncertain.
The University of Washington Caisis database was queried for radical prostatectomy patients who received 6-12 months of ADT after biochemical recurrence (BCR), defined as PSA ≥0.2 ng/mL and no radiographically detectable metastasis. Proportions of men with undetectable PSA 12 and 24 months after ending ADT were compared to a hypothesized 5% rate using exact binomial tests. Associations with patient and tumor characteristics were examined using logistic regression, and associations with risk of subsequent metastasis and death were evaluated by log-rank tests.
After ineligibility exclusions, 23/93 (25%; 95%CI 16-35%; P < 0.001) and 14/93 (15%; 95%CI 9-24%; P < 0.001) had undetectable PSA 12 and 24 months after ending ADT, respectively. Detectable PSA at 12 months was associated with increased risk of metastasis (P = 0.006), prostate cancer-specific death (P = 0.028), and death from any cause (P = 0.065). Being 1 year older at diagnosis was associated with a 14% (95%CI 5-24%; P = 0.006) decrease in the odds of having a detectable PSA after controlling for PSA at diagnosis, PSA doubling time, grade group, and time from initial therapy to BCR.
This single-institution retrospective analysis shows that it is not uncommon to have undetectable PSA 12 or 24 months after a short course of ADT. No baseline prognostic characteristic other than age was associated with a durable (12 month) undetectable PSA. Because a durable undetectable PSA was associated with lower risks of metastasis and prostate cancer-specific death, it may be a reasonable clinical trial endpoint.
在没有经过验证的替代疗效终点的情况下，优化晚期前列腺癌新疗法的使用具有挑战性。正在进行的试验将持续不可检测的前列腺特异性抗原（PSA）水平用作疗效标志物。短期雄激素剥夺治疗（ADT）后PSA持续不可检测的临床相关性尚不确定。
查询华盛顿大学Caisis数据库，以获取生化复发（BCR）后接受6至12个月ADT的前列腺癌根治术患者，BCR定义为PSA≥0.2 ng/mL且无影像学可检测到的转移。使用精确二项式检验将ADT结束后12个月和24个月PSA不可检测的男性比例与假设的5%发生率进行比较。使用逻辑回归检查与患者和肿瘤特征的关联，并通过对数秩检验评估与后续转移和死亡风险的关联。
在排除不符合条件的患者后，分别有23/93（25%；95%CI 16-35%；P<0.001）和14/93（15%；95%CI 9-24%；P<0.001）在ADT结束后12个月和24个月PSA不可检测。12个月时可检测到的PSA与转移风险增加（P=0.006）、前列腺癌特异性死亡（P=0.028）和任何原因导致的死亡（P=0.065）相关。在控制诊断时的PSA、PSA倍增时间、分级组以及从初始治疗到BCR的时间后，诊断时年龄每增加1岁，可检测到PSA的几率降低14%（95%CI 5-24%；P=0.006）。
这项单机构回顾性分析表明，短期ADT后12个月或24个月PSA不可检测并不罕见。除年龄外，没有其他基线预后特征与持久（12个月）不可检测的PSA相关。由于持久不可检测的PSA与较低的转移风险和前列腺癌特异性死亡风险相关，它可能是一个合理的临床试验终点。
