Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Prostate Cancer Program and Radiation Oncology 1, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy.
Eur Urol. 2016 Dec;70(6):954-960. doi: 10.1016/j.eururo.2016.06.007. Epub 2016 Jun 19.
The Prostate Cancer Research International Active Surveillance (PRIAS) study was initiated a decade ago to study the most optimal selection and follow-up of men on active surveillance (AS).
We report on 10 yr of follow-up of men on AS in the PRIAS study and evaluate if criteria used to recommend a switch to active treatment truly predict unfavorable outcome on subsequent radical prostatectomy (RP).
DESIGN, SETTING, AND PARTICIPANTS: Men with low-risk prostate cancer were included and followed prospectively on AS. Follow-up consisted of regular prostate-specific antigen (PSA) tests, digital rectal examinations, and biopsies. Men with Gleason >3+3, more than two positive biopsy cores, or stage higher than cT2 were advised to switch to active treatment (until 2014, a PSA doubling time [PSA DT] of 0-3 yr was also used).
Reclassification rates, treatment after discontinuation, and outcome on RP after discontinuing AS were reported. Regression analysis on the outcome of RP was used to evaluate the predictive value of criteria currently used to recommend a switch to active treatment. Kaplan-Meier and competing risk analysis were used to report discontinuation rates over time and long-term oncologic end points.
A total of 5302 men were included in PRIAS across 18 countries. Reclassification rates remained stable on all subsequent biopsies, with 22-33% of men having either Gleason >3+3 or more than two positive cores on any repeat biopsy. At 5 and 10 yr of follow-up, 52% and 73% of men, respectively, had discontinued AS, most of them because of protocol-based reclassification. A third of men undergoing subsequent RP had favorable pathologic tumor features (Gleason 3+3 and pT2). Of the criteria used to recommend a switch to active treatment, more than two positive cores and a PSA DT of 0-3 yr were not predictive of unfavorable pathologic outcome on RP.
A substantial group of men discontinued AS without subsequent unfavorable tumor features on RP; therefore, we propose Gleason upgrading and cT3 as the only indicators for an immediate switch to active treatment. Surrogate indicators (eg, more than two positive cores and a fast-rising PSA) should not trigger immediate active treatment but rather further investigation to confirm the suspicion of higher risk disease.
We confirmed the safety of active surveillance as a treatment option for men with low-risk prostate cancer; however, some changes could be made to the follow-up protocol to safely increase the number of men who remain on active surveillance.
前列腺癌研究国际主动监测（PRIAS）研究于十年前启动，旨在研究对主动监测（AS）男性进行最优化选择和随访。
我们报告了 PRIAS 研究中接受 AS 治疗的男性 10 年的随访结果，并评估用于推荐转为主动治疗的标准是否真正预测了随后根治性前列腺切除术（RP）的不良结局。
设计、地点和参与者：纳入低危前列腺癌患者，并前瞻性接受 AS 治疗。随访包括定期前列腺特异性抗原（PSA）检测、直肠指检和活检。Gleason >3+3、两个以上阳性活检核心或 cT2 以上的患者被建议转为主动治疗（直到 2014 年，PSA 倍增时间[PSA DT]为 0-3 年也被使用）。
报告再分类率、停止治疗后的治疗情况以及停止 AS 后的 RP 结局。对 RP 结局进行回归分析，以评估目前用于推荐转为主动治疗的标准的预测价值。使用 Kaplan-Meier 和竞争风险分析报告随时间推移的停药率和长期肿瘤学终点。
共有 5302 名男性来自 18 个国家参加了 PRIAS 研究。所有后续活检的再分类率保持稳定，22-33%的男性在任何重复活检中均出现 Gleason >3+3 或两个以上阳性核心。在 5 年和 10 年的随访中，分别有 52%和 73%的男性停止了 AS，其中大多数是基于方案的再分类。三分之一接受后续 RP 的男性具有有利的病理肿瘤特征（Gleason 3+3 和 pT2）。用于推荐转为主动治疗的标准中，两个以上阳性核心和 PSA DT 为 0-3 年均不能预测 RP 的不良病理结局。
相当一部分男性在 RP 上未出现不良肿瘤特征后停止了 AS；因此，我们建议 Gleason 升级和 cT3 作为立即转为主动治疗的唯一指标。替代指标（例如，两个以上阳性核心和 PSA 快速上升）不应立即触发主动治疗，而应进一步调查以确认对更高风险疾病的怀疑。
我们证实了主动监测作为低危前列腺癌治疗选择的安全性；然而，可以对随访方案进行一些更改，以安全地增加继续接受主动监测的男性数量。
