Goss Louisa B, Liu Menghan, Zheng Yingye, Guo Boya, Conti David V, Haiman Christopher A, Kachuri Linda, Catalona William J, Witte John S, Lin Daniel W, Newcomb Lisa F, Darst Burcu F
Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington.
Institute of Public Health Genetics, University of Washington, Seattle.
JAMA Oncol. 2025 Feb 1;11(2):168-171. doi: 10.1001/jamaoncol.2024.5398.
Active surveillance is the preferred management strategy for patients with low- or favorable intermediate-risk prostate cancer (PCa); however, frequent health care visits can be costly and burdensome to patients. Identifying patients who may benefit from intensive vs passive surveillance could reduce these burdens.
To investigate associations between a polygenic risk score (PRS) and risk of upgrading and other prostate tumor features in patients receiving active surveillance.
DESIGN, SETTING, AND PARTICIPANTS: This prospective multicenter cohort study across 10 US sites included 1220 patients from the Canary Prostate Active Surveillance Study (PASS) enrolled from July 2008 to November 2017, with follow-up (median, 5.3 years) through August 2022. Participants were those with clinically localized PCa (cT1-T2) receiving active surveillance. Analyses took place from January 2023 to April 2024.
Multi-ancestry PRS of 451 PCa risk variants (PRS-451) and 400 PCa risk variants (PRS-400) after excluding prostate-specific antigen (PSA)-associated variants.
The primary outcome was PCa upgrading (any Gleason grade increase) vs no upgrading. Secondary outcomes included prostate volume, PSA, PSA density, percentage of biopsy cores with cancer, and Gleason grade group at diagnosis.
The median (IQR) age at diagnosis of the 1220 patients receiving active surveillance was 63 (58-67) years. During follow-up, 470 patients upgraded; the 2- and 5-year risks of upgrading were 17.7% (95% CI, 15.5%-19.9%) and 33.3% (95% CI, 30.5%-36.3%), respectively. Each 1-SD unit increase in PRS-451 was associated with 23% increased hazard of upgrading (95% CI, 1.11-1.35; P < .001), whereas PRS-400 was associated with 27% increased hazard (95% CI, 1.15-1.39; P < .001) at any point in time during follow-up. Except for PSA, associations with remaining outcomes were similar or stronger using PRS-400. Higher PRS-400 was associated with smaller prostate volume, a higher percentage of biopsy cores with cancer, and higher PSA density. A model with clinical risk factors had a C-index of 0.64 (95% CI, 0.62-0.67); adding PRS-400 led to a C-index of 0.65 (95% CI, 0.63-0.68).
In this cohort study, among patients receiving active surveillance, high PRS was associated with risk of upgrading and possibly tumor multifocality. Excluding PSA variants from the PRS revealed an association with smaller prostate size, which has been previously associated with more aggressive tumors. Although PRS may inform active surveillance, it is yet to be seen whether they improve clinical decisions.
主动监测是低风险或预后良好的中风险前列腺癌（PCa）患者的首选管理策略；然而，频繁的医疗就诊对患者来说可能成本高昂且负担沉重。识别可能从强化监测与被动监测中获益的患者可以减轻这些负担。
研究多基因风险评分（PRS）与接受主动监测患者的疾病升级风险及其他前列腺肿瘤特征之间的关联。
设计、设置和参与者：这项在美国10个地点开展的前瞻性多中心队列研究纳入了1220名来自加那利前列腺主动监测研究（PASS）的患者，这些患者于2008年7月至2017年11月入组，随访至2022年8月（中位随访时间为5.3年）。参与者为临床局限性PCa（cT1-T2）且接受主动监测的患者。分析于2023年1月至2024年4月进行。
排除前列腺特异性抗原（PSA）相关变异后，451个PCa风险变异的多血统PRS（PRS-451）和400个PCa风险变异的PRS（PRS-400）。
主要结局为PCa升级（任何Gleason分级增加）与未升级。次要结局包括前列腺体积、PSA、PSA密度、癌组织活检核心的百分比以及诊断时的Gleason分级组。
1220名接受主动监测患者的诊断时中位（IQR）年龄为63（58-67）岁。随访期间，470名患者疾病升级；2年和5年疾病升级风险分别为17.7%（95%CI，15.5%-19.9%）和33.3%（95%CI，30.5%-36.3%）。PRS-451每增加1个标准差单位与疾病升级风险增加23%相关（95%CI，1.11-1.35；P＜0.001），而PRS-400在随访期间的任何时间点均与疾病升级风险增加27%相关（95%CI，1.15-1.39；P＜0.001）。除PSA外，使用PRS-400与其余结局的关联相似或更强。较高的PRS-400与较小的前列腺体积、较高比例的癌组织活检核心以及较高的PSA密度相关。包含临床风险因素的模型C指数为0.64（95%CI，0.62-0.67）；加入PRS-400后C指数为0.65（95%CI，0.63-0.68）。
在这项队列研究中，在接受主动监测的患者中，高PRS与疾病升级风险以及可能的肿瘤多灶性相关。从PRS中排除PSA变异显示与较小的前列腺大小相关，而较小的前列腺大小此前与更具侵袭性的肿瘤相关。尽管PRS可能为主动监测提供信息，但它们是否能改善临床决策还有待观察。
