Refining Risk Stratification of High-risk and Locoregional Prostate Cancer: A Pooled Analysis of Randomized Trials

IF 25.3 1区医学 Q1 UROLOGY & NEPHROLOGY

European urology Pub Date : 2025-02-01 DOI:10.1016/j.eururo.2024.04.038

Praful Ravi , Wanling Xie , Marc Buyse , Susan Halabi , Philip W. Kantoff , Oliver Sartor , Gert Attard , Noel Clarke , Anthony D'Amico , James Dignam , Nicholas James , Karim Fizazi , Silke Gillessen , Wendy Parulekar , Howard Sandler , Daniel E. Spratt , Matthew R. Sydes , Bertrand Tombal , Scott Williams , Christopher J. Sweeney

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引用次数: 0

Abstract

Background and objective

Radiotherapy (RT) and long-term androgen deprivation therapy (ltADT; 18–36 mo) is a standard of care in the treatment of high-risk localized/locoregional prostate cancer (HRLPC). We evaluated the outcomes in patients treated with RT + ltADT to identify which patients have poorer prognosis with standard therapy.

Methods

Individual patient data from patients with HRLPC (as defined by any of the following three risk factors [RFs] in the context of cN0 disease—Gleason score ≥8, cT3–4, and prostate-specific antigen [PSA] >20 ng/ml, or cN1 disease) treated with RT and ltADT in randomized controlled trials collated by the Intermediate Clinical Endpoints in Cancer of the Prostate group. The outcome measures of interest were metastasis-free survival (MFS), overall survival (OS), time to metastasis, and prostate cancer-specific mortality. Multivariable Cox and Fine-Gray regression estimated hazard ratios (HRs) for the three RFs and cN1 disease.

Key findings and limitations

A total of 3604 patients from ten trials were evaluated, with a median PSA value of 24 ng/ml. Gleason score ≥8 (MFS HR = 1.45; OS HR = 1.42), cN1 disease (MFS HR = 1.86; OS HR = 1.77), cT3–4 disease (MFS HR = 1.28; OS HR = 1.22), and PSA >20 ng/ml (MFS HR = 1.30; OS HR = 1.21) were associated with poorer outcomes. Adjusted 5-yr MFS rates were 83% and 78%, and 10-yr MFS rates were 63% and 53% for patients with one and two to three RFs, respectively; corresponding 10-yr adjusted OS rates were 67% and 60%, respectively. In cN1 patients, adjusted 5- and 10-yr MFS rates were 67% and 36%, respectively, and 10-yr OS was 47%.

Conclusions and clinical implications

HRLPC patients with two to three RFs (and cN0) or cN1 disease had the poorest outcomes on RT and ltADT. This will help in counseling patients treated in routine practice and in guiding adjuvant trials in HRLPC.

Patient summary

Radiotherapy and long-term hormone therapy are standard treatments for high-risk and locoregional prostate cancer. In this report, we defined prognostic groups within high-risk/locoregional prostate cancer and showed that outcomes to standard therapy are poorest in those with two or more “high-risk” factors or evidence of lymph node involvement. Such patients may therefore be the best candidates for intensification of treatment.

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完善高危和局部前列腺癌的风险分层：随机试验汇总分析》。

背景和目的：放疗（RT）和长期雄激素剥夺疗法（ltADT；18-36个月）是治疗高危局部/局部前列腺癌（HRLPC）的标准疗法。我们对接受 RT + LTADT 治疗的患者的预后进行了评估，以确定哪些患者接受标准疗法后预后较差：前列腺癌中期临床终点研究组整理了随机对照试验中接受RT和ltADT治疗的HRLPC患者（定义为cN0病变-格里森评分≥8、cT3-4和前列腺特异性抗原[PSA]>20纳克/毫升或cN1病变的以下三种危险因素[RF]中的任何一种）的个体数据。研究的结果指标包括无转移生存期（MFS）、总生存期（OS）、转移时间和前列腺癌特异性死亡率。多变量Cox和Fine-Gray回归估算了三种RF和cN1疾病的危险比（HRs）：共评估了来自十项试验的 3604 名患者，PSA 中位值为 24 ng/ml。Gleason评分≥8（MFS HR = 1.45；OS HR = 1.42）、cN1疾病（MFS HR = 1.86；OS HR = 1.77）、cT3-4疾病（MFS HR = 1.28；OS HR = 1.22）和PSA >20 ng/ml（MFS HR = 1.30；OS HR = 1.21）与较差的预后有关。有1个和2-3个RF的患者调整后的5年MFS率分别为83%和78%，10年MFS率分别为63%和53%；相应的10年调整后OS率分别为67%和60%。在cN1患者中，调整后的5年和10年MFS率分别为67%和36%，10年OS为47%：有两到三个RF（和cN0）或cN1疾病的HRLPC患者接受RT和ltADT治疗的效果最差。这将有助于为接受常规治疗的患者提供咨询，并为HRLPC的辅助试验提供指导：放疗和长期激素治疗是高危和局部前列腺癌的标准治疗方法。在这份报告中，我们定义了高危/局部前列腺癌的预后组别，并表明具有两个或两个以上 "高危 "因素或淋巴结受累证据的患者接受标准疗法的疗效最差。因此，这类患者可能是强化治疗的最佳人选。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European urology 医学-泌尿学与肾脏学

CiteScore

43.00

自引率

2.60%

发文量

1753

审稿时长

23 days

期刊介绍： European Urology is a peer-reviewed journal that publishes original articles and reviews on a broad spectrum of urological issues. Covering topics such as oncology, impotence, infertility, pediatrics, lithiasis and endourology, the journal also highlights recent advances in techniques, instrumentation, surgery, and pediatric urology. This comprehensive approach provides readers with an in-depth guide to international developments in urology.