Prognostic Value of Interim PSMA-PET Total Tumor Volume for Overall Survival Within ENZA-p, A Randomized Phase 2 Trial of Enzalutamide Versus Enzalutamide Plus [177Lu] Lu-PSMA-617 (ANZUP1901)

IF 29.1 1区医学 Q1 UROLOGY & NEPHROLOGY

European urology Pub Date : 2026-10-01 Epub Date: 2026-04-08 DOI:10.1016/j.eururo.2026.03.026

Louise Emmett, Nathan Papa, Oliver Sartor, Michael J. Morris, Shalini Subramaniam, Megan Crumbaker, Narjess Ayati, Jeffrey Chen, Ken Herrmann, Andrei Gafita, Mina Swiha, Anthony M. Joshua, Andrew Weickhardt, Sze-Ting Lee, Siobhan Ng, Roslyn J. Francis, Jeffrey C. Goh, David A. Pattison, Bao Ho, Sobia Khan, Ian D. Davis

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引用次数: 0

Abstract

Background and objective

Interim [⁶⁸Ga]Ga-prostate-specific membrane-antigen positron emission tomography/computed tomography (PSMA-PET/CT) has prognostic potential for overall survival (OS) in metastatic castrate-resistant prostate cancer (mCRPC), although evidence is limited. This ENZA-p sub-study evaluated 3-mo PSMA-total-tumor-volume (PSMA-TTV) as a prognostic biomarker for OS with enzalutamide ± [¹⁷⁷Lu]Lu-PSMA-617.

Methods:

ENZA-p is a randomized, phase 2 trial. Participants with mCRPC and risk factors for early treatment failure with enzalutamide were randomized (1:1) to enzalutamide or enzalutamide + [¹⁷⁷Lu]Lu-PSMA-617. Participants underwent baseline and 3-mo [⁶⁸Ga]Ga-PSMA-11-PET/CT, quantified to derive PSMA-TTV. We evaluated the prognostic value of PSMA-TTV change, and residual PSMA-TTV at 3-mo for OS (NCT04419402).

Key findings and limitations:

This sub-study included 152/162 (94%) randomized participants with a 3-mo PSMA-PET. Median OS was 27 mo (95% confidence interval [CI] 23–30). Baseline median PSMA-TTV 230 ml (interquartile range [IQR] 75–635) and 3-mo PSMA-TTV 103 ml (IQR 24–457). The median change in PSMA-TTV from baseline was –34% (IQR –76% to 16%) with 50/152 (33%) participants with increase in PSMA-TTV. Any increase versus decrease in PSMA-TTV at 3-mo was associated with shorter OS (HR 2.52, 95% CI 1.65–3.85) and decreased 2-yr survival 30% (95% CI 17–43) versus 67% (95% CI 56–75) (log-rank p < 0.0001). Residual 3-mo PSMA-TTV higher versus lower than the median (103 ml) was associated with shorter OS (HR 3.76, 95% CI 2.39–5.92) and lower 2-yr survival 34% (95% CI 23–45) versus 76% (95% CI 64–84) (log-rank p < 0.0001). This association was independent of treatment arm and prostate-specific antigen (PSA) response.

Conclusions and clinical implications:

PSMA-TTV at 3 mos was prognostic for OS independent of study treatment and PSA response in ENZA-p, warranting further prospective validation of interim PSMA-PET response criteria.

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中期PSMA-PET肿瘤总体积对ENZA-p总生存期的预后价值，ENZA-p是一项Enzalutamide与Enzalutamide Plus的随机2期试验[177Lu] Lu-PSMA-617 （ANZUP1901）。

背景与目的：虽然证据有限，但Interim [68Ga] ga -前列腺特异性膜抗原正电子发射断层扫描/计算机断层扫描（PSMA-PET/CT）对转移性去势抵抗性前列腺癌（mCRPC）的总生存期（OS）具有预后潜力。这项ENZA-p亚研究评估了3个月psma总肿瘤体积（PSMA-TTV）作为enzalutamide±[177Lu]Lu-PSMA-617治疗OS的预后生物标志物。设计、环境和参与者：ENZA-p是一项随机的2期试验。具有mCRPC和enzalutamide早期治疗失败危险因素的参与者被随机（1:1）分配到enzalutamide或enzalutamide + [177Lu]Lu-PSMA-617。参与者接受基线和3个月[68Ga]Ga-PSMA-11-PET/CT，量化得出PSMA-TTV。我们评估了PSMA-TTV变化和3个月时残余PSMA-TTV对OS的预后价值（NCT04419402）。结果和局限性：该亚研究纳入了152/162（94%）随机接受3个月PSMA-PET检查的参与者。中位OS为27个月（95%可信区间[CI] 23-30）。基线PSMA-TTV中位数为230 ml（四分位数范围[IQR] 75-635）， 3个月PSMA-TTV中位数为103 ml （IQR 24-457）。PSMA-TTV较基线的中位变化为-34% (IQR为-76%至16%),50/152（33%）参与者PSMA-TTV升高。3个月时PSMA-TTV的任何升高或降低与较短的OS相关（HR 2.52, 95% CI 1.65-3.85）， 2年生存率降低30% （95% CI 17-43）对67% (95% CI 56-75) （logrank p）。结论：3个月时PSMA-TTV是独立于研究治疗和ENZA-p中PSA反应的OS预后，需要进一步前瞻性验证PSMA-PET中期反应标准。

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.