Active Monitoring, Surgery, and Radiotherapy for Cribriform-Positive and Cribriform-Negative Prostate Cancer: A Secondary Analysis of the PROTECT Randomized Clinical Trial.

Background

To retrospectively analyze the results of the PROTECT randomized clinical trial to establish the association between cribriform-positive and cribriform-negative prostate cancer and 15-year risk of metastasis in patients who underwent active monitoring, surgery, or radiotherapy.

回顾性分析PROTECT随机临床试验的结果，以确定筛状阳性与筛状阴性前列腺癌与接受主动监测、手术或放疗的患者15年转移风险之间的关联。

DESIGN, SETTING, AND PARTICIPANTS: Between 1999 and 2009, the PROTECT phase 3 randomized clinical trial enrolled 1643 men with clinically localized prostate cancer who were randomly assigned to receive active monitoring, surgery, or radiotherapy with neoadjuvant androgen deprivation therapy (ADT).

设计、设置和参与者：在1999年至2009年间，PROTECT第三阶段随机临床试验招募了1643名患有临床局限性前列腺癌的男性，这些患者被随机分配接受主动监测、手术或新辅助雄激素剥夺治疗（ADT）的放疗。

In this secondary analysis of the PROTECT trial, a centralized histopathologic review was conducted on available diagnostic biopsy slides to classify patients as cribriform-positive if they had invasive cribriform carcinoma and/or intraductal carcinoma.

在这项PROTECT试验的二次分析中，对可用的诊断活检切片进行了集中组织病理学审查，如果患者有侵袭性筛状癌和/或导管内癌，则将其分类为筛状阳性。

Data were collected from January 25, 2024, to October 11, 2024, and were analyzed from October 14, 2024, to January 30, 2025.

数据收集时间为2024年1月25日至2024年10月11日，并于2024年10月14日至2025年1月30日进行分析。

exposures

Age, prostate-specific antigen (PSA), Gleason score, and cribriform status.

年龄、前列腺特异性抗原（PSA）、Gleason评分和筛状状态。

main_outcomes_and_measures

The primary outcome was progression to metastatic disease (bony, visceral, or lymph node metastases on imaging or PSA >100 ng/mL).

主要结果是进展为转移性疾病（影像学上出现骨转移、内脏转移或淋巴结转移，或 PSA >100 ng/mL）。

Multivariable Cox proportional hazards regression models, adjusted for randomization variables, were incorporated to assess 15-year metastasis risk.

通过调整随机化变量的多变量Cox比例风险回归模型，评估了15年的转移风险。

Cumulative incidencecurves were compared using the Gray test.

使用Gray检验比较累积发生率曲线。

Both intention-to-treatand per-protocol analyses were performed.

进行了意向治疗分析和按方案分析。

Results

Among 712 men (mean [SD] age, 62.0 [5.0] years) whose biopsies were retrospectively reviewed, 93 (13.1%) had cribriform-positive disease and 42 (5.9%) developed metastasis.

在回顾性审查的712名男性（平均年龄[标准差]为62.0[5.0]岁）中，93人（13.1%）的活检显示有筛状阳性病变，其中42人（5.9%）发展为转移。

In the intention-to-treatcohort, cribriform-positive disease significantly increased the risk of metastasis (hazard ratio[HR], 3.61 [95% CI, 1.60-8.11]; P = .003).

在意向治疗队列中，筛状阳性病变显著增加了转移的风险（风险比[HR]，3.61 [95% 置信区间，1.60-8.11]；P = .003）。

Radiotherapy with neoadjuvant ADT significantly reduced metastasis risk (HR, 0.35 [95% CI, 0.16-0.78]; P = .04) (15-year cumulative incidencein patients with cribriform-positive disease, 8%), while surgery delayed metastasis but did not significantly improve long-term outcomes compared with active monitoring (HR, 0.52 [95% CI, 0.25-1.08]; P = .09) (15-year cumulative incidencein patients with cribriform-positive disease, 26% for surgery and 25% for active monitoring).

新辅助ADT放疗显著降低了转移风险（HR，0.35 [95% CI，0.16-0.78]；P = .04）（在cribriform阳性疾病患者中，15年累积发生率为8%），而手术延迟了转移，但与积极监测相比，并没有显著改善长期结果（HR，0.52 [95% CI，0.25-1.08]；P = .09）（在cribriform阳性疾病患者中，手术的15年累积发生率为26%，积极监测为25%）。

Among patients with cribriform-negative disease, incidenceof metastasis was low and did not differ by treatment.

在cribriform阴性疾病患者中，转移发生率低，且治疗方式之间无差异。

Similar per-protocol results were noted.

类似的结果在按方案分析中被注意到。

conclusions_and_relevance

The findings of this secondary analysis of the PROTECT randomized clinical trial suggest that cribriform morphology was a strong, independent predictor of 15-year metastasis among patients with prostate cancer and that radiotherapy with neoadjuvant ADT was associated with a reduced long-term risk of metastasis.

这项PROTECT随机临床试验的次要分析结果表明，筛状形态是前列腺癌患者15年转移的强有力的独立预测因素，并且放疗联合新辅助雄激素剥夺治疗（ADT）与降低长期转移风险相关。

Conversely, outcomes were favorable for most patients with cribriform-negative disease, supporting their eligibility for active surveillance.

相反，对于大多数筛状阴性疾病的患者来说，结果是有利的，这支持了他们接受积极监测的资格。

trial_registration

ClinicalTrials.gov Identifier: NCT02044172.

ClinicalTrials.gov 注册号：NCT02044172。