Department of Urology, The University of Texas Health San Antonio, San Antonio, Texas, United States of America.
Department of Epidemiology and Biostatistics, The University of Texas Health San Antonio, San Antonio, Texas, United States of America.
PLoS One. 2018 Oct 9;13(10):e0204823. doi: 10.1371/journal.pone.0204823. eCollection 2018.
Finasteride, a 5-alpha reductase inhibitor may have effects on biomarkers such as prostate-specific antigen (PSA) that could be leveraged to improve screening.
To determine the predictive characteristics of biomarkers for prostate cancer for cancer on biopsy following 3 months of finasteride use compared with placebo.
DESIGN, SETTING AND PARTICIPANTS: 383 men from multiple clinical sites with intermediate prostate cancer risk, without history of prostate cancer, were randomly allocated in a double-blinded manner, 4:1, to receive either finasteride or placebo for 90 days at which time a prostate biopsy was performed.
The primary outcomes were associations of biomarkers with prostate cancer that were tested using multiple logistic regression and area under the receiver operating curves (AUC). Biomarkers for PCA risk (PCA3, TMPRSS2:ERG (T2:ERG) gene product, and PSA) were measured at baseline and at biopsy in a blinded fashion to assess the predictive performance of baseline levels, 90-day levels, and measures of change relative to standard predictors.
A total of 292 (233 finasteride; 59 placebo) randomized patients underwent biopsy and were analyzed. On finasteride, baseline and 90-day measures of PCA3 and T2:ERG had similar moderate discrimination capacity with AUCs 62 to 65% (p-values < 0.001 and 0.001, respectively), but their rates of change had no discrimination ability (AUC 51%, (95% CI 43 to 60% p = 0.72) and 48% (95% CI 44 to 60%, p = 0.62), respectively).) Relative to baseline, the 90-day PCA3 and PSA decreased in the finasteride group by 25% and 50%, respectively (both p<0.001). T2:ERG had a smaller, non-significant change post finasteride treatment (p = 0.08).
Short-term finasteride therapy did not improve performance of the most commonly-employed prostate cancer biomarkers. Threshold values for new biomarkers of prostate cancer should be interpreted with caution in patients receiving finasteride until formal validation of test performance in these patients is conducted.
Three months of finasteride treatment did not increase the accuracy for predicting the outcome on prostate biopsy but did have a significant effect on biomarker values. Adjustments to thresholds for biopsy for men on finasteride are proposed.
ClinicalTrials.gov, NCT01296672.
5α-还原酶抑制剂非那雄胺可能对前列腺特异性抗原（PSA）等生物标志物产生影响，这些影响可被利用来改善筛查。
确定与接受安慰剂相比，使用非那雄胺 3 个月后活检前列腺癌的生物标志物的预测特征。
设计、地点和参与者：383 名来自多个临床地点的具有中等前列腺癌风险、无前列腺癌病史的男性以 4:1 的比例随机、双盲分配，分别接受非那雄胺或安慰剂治疗 90 天，然后进行前列腺活检。
主要结局是使用多元逻辑回归和受试者工作特征曲线（AUC）下面积来检验生物标志物与前列腺癌的相关性。使用盲法在基线和活检时测量 PCA 风险（PCA3、TMPRSS2:ERG（T2:ERG）基因产物和 PSA），以评估基线水平、90 天水平以及相对于标准预测因子的变化衡量标准的预测性能。
共有 292 名（233 名接受非那雄胺治疗；59 名接受安慰剂治疗）随机患者接受了活检并进行了分析。在接受非那雄胺治疗的患者中，基线和 90 天的 PCA3 和 T2:ERG 具有相似的中度区分能力，AUC 分别为 62%至 65%（p 值均<0.001），但它们的变化率没有区分能力（AUC 为 51%（95%CI 43%至 60%，p = 0.72）和 48%（95%CI 44%至 60%，p = 0.62））。与基线相比，非那雄胺组 90 天的 PCA3 和 PSA 分别降低了 25%和 50%（均<0.001）。T2:ERG 在接受非那雄胺治疗后变化较小，无统计学意义（p = 0.08）。
短期非那雄胺治疗并未提高最常用前列腺癌生物标志物的准确性。在对这些患者进行正式验证之前，应谨慎解释接受非那雄胺治疗的患者中新的前列腺癌生物标志物的截断值。
三个月的非那雄胺治疗并未增加预测前列腺活检结果的准确性，但确实对生物标志物值有显著影响。建议对正在接受非那雄胺治疗的男性进行活检的阈值进行调整。
ClinicalTrials.gov，NCT01296672。
