External Validation and Addition of Prostate-specific Membrane Antigen Positron Emission Tomography to the Most Frequently Used Nomograms for the Prediction of Pelvic Lymph-node Metastases: an International Multicenter Study,European Urology

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External Validation and Addition of Prostate-specific Membrane Antigen Positron Emission Tomography to the Most Frequently Used Nomograms for the Prediction of Pelvic Lymph-node Metastases: an International Multicenter Study
European Urology ( IF 25.3 ) Pub Date : 2021-05-21 , DOI: 10.1016/j.eururo.2021.05.006
Dennie Meijer ₁ , Pim J van Leeuwen ₂ , Matthew J Roberts ₃ , Amila R Siriwardana ₄ , Andrew Morton ₅ , John W Yaxley ₆ , Hemamali Samaratunga ₇ , Louise Emmett ₈ , Peter M van de Ven ₉ , Henk G van der Poel ₂ , Maarten L Donswijk ₁₀ , Thierry N Boellaard ₁₁ , Ivo G Schoots ₁₁ , Daniela E Oprea-Lager ₁₂ , Geoffrey D Coughlin ₁₃ , André N Vis ₁₄

Affiliation

Department of Urology, Prostate Cancer Network Netherlands, Amsterdam University Medical Center, VU University, Amsterdam, The Netherlands; Department of Radiology & Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Center, VU University, Amsterdam, The Netherlands.
Department of Urology, Prostate Cancer Network Netherlands, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Australia; University of Queensland Centre for Clinical Research, Herston, Australia; Department of Urology, Redcliffe Hospital, Brisbane, Australia.
Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Australia.
Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia.
Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia; Department of Urology, Wesley Hospital, Brisbane, Australia.
Faculty of Medicine, University of Queensland, Brisbane, Australia; Department of Pathology, Aquesta Uropathology, Brisbane, Australia.
St. Vincent's Clinical School, University of New South Wales, Kensington, Australia; Department of Theranostics and Nuclear Medicine, St. Vincent's Hospital Sydney, Darlinghurst, Australia.
Department of Epidemiology and Data Science, Amsterdam University Medical Center, VU University, Amsterdam, The Netherlands.
Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Radiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Radiology & Nuclear Medicine, Cancer Center Amsterdam, Amsterdam University Medical Center, VU University, Amsterdam, The Netherlands.
Faculty of Medicine, University of Queensland, Brisbane, Australia; Department of Urology, Wesley Hospital, Brisbane, Australia.
Department of Urology, Prostate Cancer Network Netherlands, Amsterdam University Medical Center, VU University, Amsterdam, The Netherlands; Department of Urology, Prostate Cancer Network Netherlands, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Background

Different nomograms exist for the preoperative prediction of pelvic lymph-node metastatic disease in individual patients with prostate cancer (PCa). These nomograms do not incorporate modern imaging techniques such as prostate-specific membrane antigen (PSMA) positron emission tomography (PET).

Objective

To determine the predictive performance of the Briganti 2017, Memorial Sloan Kettering Cancer Center (MSKCC), and Briganti 2019 nomograms with the addition of PSMA-PET in an international, multicenter, present-day cohort of patients undergoing robot-assisted radical prostatectomy (RARP) and extended pelvic lymph-node dissection (ePLND) for localized PCa.

Design, setting, and participants

All 757 eligible patients who underwent a PSMA-PET prior to RARP and ePLND in three reference centers for PCa surgery between January 2016 and November 2020 were included.

Outcome measurements and statistical analysis

Performance of the three nomograms was assessed using the receiver operating characteristic curve–derived area under the curve (AUC), calibration plots, and decision curve analyses. Subsequently, recalibration and addition of PSMA-PET to the nomograms were performed.

Results and limitations

Overall, 186/757 patients (25%) had pelvic lymph-node metastatic (pN1) disease on histopathological examination. AUCs of the Briganti 2017, MSKCC, and Briganti 2019 nomograms were 0.70 (95% confidence interval [95% CI]: 0.64–0.77), 0.71 (95% CI: 0.65–0.77), and 0.76 (95% CI: 0.71–0.82), respectively. PSMA-PET findings showed a significant association with pN1 disease when added to the nomograms (p < 0.001). Addition of PSMA-PET substantially improved the discriminative ability of the models yielding cross-validated AUCs of 0.76 (95% CI: 0.70–0.82), 0.77 (95% CI: 0.72–0.83), and 0.82 (95% CI: 0.76–0.87), respectively. In decision curve analyses, the addition of PSMA-PET to the three nomograms resulted in increased net benefits.

Conclusions

The addition of PSMA-PET to the previously developed nomograms showed substantially improved predictive performance, which suggests that PSMA-PET is a likely future candidate for a modern predictive nomogram.

Patient summary

Different tools have been developed to individualize the prediction of prostate cancer spread to lymph nodes before surgery. We found that the inclusion of modern imaging (prostate-specific membrane antigen positron emission tomography) improved substantially the overall performance of these prediction tools.

中文翻译：

前列腺特异性膜抗原正电子发射断层扫描的外部验证和添加到最常用的列线图预测盆腔淋巴结转移：一项国际多中心研究

背景

存在不同的列线图用于术前预测个别前列腺癌 (PCa) 患者的盆腔淋巴结转移性疾病。这些列线图不包含现代成像技术，例如前列腺特异性膜抗原 (PSMA) 正电子发射断层扫描 (PET)。

客观的

为了确定 Briganti 2017、纪念斯隆凯特琳癌症中心 (MSKCC) 和 Briganti 2019 列线图以及 PSMA-PET 在当今接受机器人辅助根治性前列腺切除术 (RARP) 的国际多中心患者队列中的预测性能) 和扩展盆腔淋巴结清扫术 (ePLND) 用于局部 PCa。

设计、设置和参与者

纳入了 2016 年 1 月至 2020 年 11 月期间在三个 PCa 手术参考中心在 RARP 和 ePLND 之前接受 PSMA-PET 的所有 757 名符合条件的患者。

结果测量和统计分析

三个列线图的性能使用接收器操作特征曲线导出的曲线下面积 (AUC)、校准图和决策曲线分析进行评估。随后，对列线图进行重新校准和添加 PSMA-PET。

结果和局限性

总体而言，186/757 名患者 (25%) 在组织病理学检查中患有盆腔淋巴结转移 (pN1) 疾病。Briganti 2017、MSKCC 和 Briganti 2019 列线图的 AUC 分别为 0.70（95% 置信区间 [95% CI]：0.64–0.77）、0.71（95% CI：0.65–0.77）和 0.76（95% CI：0.71– 0.82），分别。当添加到列线图中时，PSMA-PET 发现显示与 pN1 疾病显着相关（p < 0.001）。添加 PSMA-PET 显着提高了模型的判别能力，产生 0.76（95% CI：0.70–0.82）、0.77（95% CI：0.72–0.83）和 0.82（95% CI：0.76–）的交叉验证 AUC 0.87），分别。在决策曲线分析中，将 PSMA-PET 添加到三个列线图导致净收益增加。