Department of Urology, Helsinki University Hospital, Helsinki, Finland.
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Eur Urol Focus. 2018 Dec;4(6):867-873. doi: 10.1016/j.euf.2017.03.004. Epub 2017 Mar 22.
Active surveillance (AS) is an option for men with low-risk prostate cancer (PCa). PTEN and ERG have been considered as potential biomarkers of PCa progression and survival.
To study the role of ERG and PTEN status in the Prostate Cancer Research International: Active Surveillance (PRIAS) trial diagnostic biopsies (DBxs) in predicting surveillance discontinuation and adverse surgical findings in subsequent radical prostatectomy (RP).
DESIGN, SETTING, AND PARTICIPANTS: A total of 231 patients were recruited to the PRIAS between 2007 and 2013 in Helsinki. DBx tissue for immunohistochemistry (IHC) was available from 190 patients. Tissue microarrays (TMAs) were constructed from 57 specimens of subsequent RPs. DBxs containing grade group (GG) 1 PCa and RP TMA sections were stained with ERG and PTEN antibodies, and scored as either negative or positive.
Outcomes were followed up by biopsy GG upgrade (GG ≥ 2) and protocol-based treatment change, as well as adverse findings in RP (GG ≥ 3 or pathological stage≥3). Clinical variables and biomarker status in DBx were correlated in Cox regression analysis and cumulative survival in Kaplan-Meier analysis, and finally, Gray's competing risk analysis was performed and nonprotocol-based discontinuation was considered as a competing event.
In both uni- and multivariate Cox regression analyses, only the number of positive cores in the DBx, the number of rebiopsy sessions, and PTEN status at diagnosis were significantly associated with rebiopsy GG upgrade, treatment change, and adverse histopathology in RP. In Kaplan-Meier analysis, PTEN loss was associated with a shorter time to GG upgrade and treatment change. Patients with PTEN loss had a higher probability for protocol-based discontinuation but not for competing risk factors compared with patients with intact PTEN. Biopsy ERG status was concordant with RP TMA ERG status, while PTEN was not. Limitations include a retrospective analysis of prospective cohort data.
PTEN status at diagnosis is a potential biomarker for identifying patients with PCa on AS with a high risk for progression or adverse findings on subsequent RP.
A simple diagnostic biopsy-based analysis of PTEN status may help identify patients with high risk for prostate cancer progression.
主动监测（AS）是低危前列腺癌（PCa）患者的一种选择。PTEN 和 ERG 已被认为是 PCa 进展和生存的潜在生物标志物。
研究 ERG 和 PTEN 状态在前列腺癌研究国际：主动监测（PRIAS）试验诊断性活检（DBx）中预测后续根治性前列腺切除术（RP）中监测终止和不良手术结果中的作用。
设计、地点和参与者：2007 年至 2013 年，在赫尔辛基共招募了 231 名 PRIAS 患者。190 名患者的 DBx 组织可用于免疫组织化学（IHC）。从 57 份后续 RP 的标本中构建了组织微阵列（TMA）。DBx 包含 GG1 PCa 和 RP TMA 切片，用 ERG 和 PTEN 抗体染色，并分别标记为阴性或阳性。
通过活检 GG 升级（GG≥2）和基于方案的治疗改变以及 RP 中的不良发现（GG≥3 或病理分期≥3）来随访结果。在 Cox 回归分析中，在单变量和多变量 Cox 回归分析中，仅 DBx 中的阳性核心数、再活检次数和诊断时的 PTEN 状态与再活检 GG 升级、治疗改变和 RP 中的不良组织病理学显著相关。在 Kaplan-Meier 分析中，PTEN 缺失与 GG 升级和治疗改变的时间更短相关。与 PTEN 完整的患者相比，PTEN 缺失的患者更有可能基于方案停止治疗，但没有竞争风险因素。活检 ERG 状态与 RP TMA ERG 状态一致，而 PTEN 则不一致。局限性包括对前瞻性队列数据的回顾性分析。
诊断时的 PTEN 状态是识别 AS 中 PCa 进展风险较高或后续 RP 中发现不良结果的潜在生物标志物。
基于简单诊断性活检的 PTEN 状态分析可能有助于识别前列腺癌进展风险较高的患者。
