Cancer Registry North-Rhine Westphalia, Bochum, Germany; Department of Nuclear Medicine, DKTK and NCT University Hospital Essen, Essen, Germany; Department of Nuclear Medicine, University Hospital Münster, Münster, Germany.
Cancer Registry North-Rhine Westphalia, Bochum, Germany.
Lancet Oncol. 2024 Sep;25(9):1188-1201. doi: 10.1016/S1470-2045(24)00326-7. Epub 2024 Jul 29.
Prostate-specific membrane antigen (PSMA)-PET was introduced into clinical practice in 2012 and has since transformed the staging of prostate cancer. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria were proposed to standardise PSMA-PET reporting. We aimed to compare the prognostic value of PSMA-PET by PROMISE (PPP) stage with established clinical nomograms in a large prostate cancer dataset with follow-up data for overall survival.
In this multicentre retrospective study, we used data from patients of any age with histologically proven prostate cancer who underwent PSMA-PET at the University Hospitals in Essen, Münster, Freiburg, and Dresden, Germany, between Oct 30, 2014, and Dec 27, 2021. We linked a subset of patient hospital records with patient data, including mortality data, from the Cancer Registry North-Rhine Westphalia, Germany. Patients from Essen University Hospital were randomly assigned to the development or internal validation cohorts (2:1). Patients from Münster, Freiburg, and Dresden University Hospitals were included in an external validation cohort. Using the development cohort, we created quantitative and visual PPP nomograms based on Cox regression models, assessing potential PPP predictors for overall survival, with least absolute shrinkage and selection operator penalty for overall survival as the primary endpoint. Performance was measured using Harrell's C-index in the internal and external validation cohorts and compared with established clinical risk scores (International Staging Collaboration for Cancer of the Prostate [STARCAP], European Association of Urology [EAU], and National Comprehensive Cancer Network [NCCN] risk scores) and a previous nomogram defined by Gafita et al (hereafter referred to as GAFITA) using receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) estimates.
We analysed 2414 male patients (1110 included in the development cohort, 502 in the internal cohort, and 802 in the external validation cohort), among whom 901 (37%) had died as of data cutoff (June 30, 2023; median follow-up of 52·9 months [IQR 33·9-79·0]). Predictors in the quantitative PPP nomogram were locoregional lymph node metastases (molecular imaging N2), distant metastases (extrapelvic nodal metastases, bone metastases [disseminated or diffuse marrow involvement], and organ metastases), tumour volume (in L), and tumour mean standardised uptake value. Predictors in the visual PPP nomogram were distant metastases (extrapelvic nodal metastases, bone metastases [disseminated or diffuse marrow involvement], and organ metastases) and total tumour lesion count. In the internal and external validation cohorts, C-indices were 0·80 (95% CI 0·77-0·84) and 0·77 (0·75-0·78) for the quantitative nomogram, respectively, and 0·78 (0·75-0·82) and 0·77 (0·75-0·78) for the visual nomogram, respectively. In the combined development and internal validation cohort, the quantitative PPP nomogram was superior to STARCAP risk score for patients at initial staging (n=139 with available staging data; AUC 0·73 vs 0·54; p=0·018), EAU risk score at biochemical recurrence (n=412; 0·69 vs 0·52; p<0·0001), and NCCN pan-stage risk score (n=1534; 0·81 vs 0·74; p<0·0001) for the prediction of overall survival, but was similar to GAFITA nomogram for metastatic hormone-sensitive prostate cancer (mHSPC; n=122; 0·76 vs 0·72; p=0·49) and metastatic castration-resistant prostate cancer (mCRPC; n=270; 0·67 vs 0·75; p=0·20). The visual PPP nomogram was superior to EAU at biochemical recurrence (n=414; 0·64 vs 0·52; p=0·0004) and NCCN across all stages (n=1544; 0·79 vs 0·73; p<0·0001), but similar to STARCAP for initial staging (n=140; 0·56 vs 0·53; p=0·74) and GAFITA for mHSPC (n=122; 0·74 vs 0·72; p=0·66) and mCRPC (n=270; 0·71 vs 0·75; p=0·23).
Our PPP nomograms accurately stratify high-risk and low-risk groups for overall survival in early and late stages of prostate cancer and yield equal or superior prediction accuracy compared with established clinical risk tools. Validation and improvement of the nomograms with long-term follow-up is ongoing (NCT06320223).
Cancer Registry North-Rhine Westphalia.
前列腺特异性膜抗原（PSMA）-PET 于 2012 年引入临床实践，自此改变了前列腺癌的分期。前列腺癌分子影像学标准化评估（PROMISE）标准被提出，以规范 PSMA-PET 报告。我们旨在比较 PROMISE（PPP）分期的 PSMA-PET 与在具有总生存随访数据的大型前列腺癌数据集的既定临床列线图的预后价值。
在这项多中心回顾性研究中，我们使用了来自德国埃森、明斯特、弗莱堡和德累斯顿大学医院的任何年龄的经组织学证实的前列腺癌患者的数据，这些患者在 2014 年 10 月 30 日至 2021 年 12 月 27 日期间接受了 PSMA-PET 检查。我们将患者医院记录的一部分与来自德国北莱茵-威斯特法伦癌症登记处的患者数据（包括死亡率数据）进行了链接。埃森大学医院的患者被随机分配到发展或内部验证队列（2:1）。明斯特、弗莱堡和德累斯顿大学医院的患者被纳入外部验证队列。我们使用发展队列，基于 Cox 回归模型创建了定量和可视化的 PPP 列线图，评估了总体生存的潜在 PPP 预测因素，以整体生存的最小绝对收缩和选择算子惩罚为主要终点。在内部和外部验证队列中，使用 Harrell 的 C 指数来衡量性能，并与既定的临床风险评分（国际分期协作组用于前列腺癌 [STARCAP]、欧洲泌尿外科学会 [EAU] 和国家综合癌症网络 [NCCN] 风险评分）和 Gafita 等人定义的先前列线图（以下简称 GAFITA）进行比较，使用接收器工作特征（ROC）曲线和 ROC 曲线下面积（AUC）估计值。
我们分析了 2414 名男性患者（1110 名纳入发展队列，502 名纳入内部队列，802 名纳入外部验证队列），其中 901 名（37%）患者截至数据截止日期（2023 年 6 月 30 日；中位随访时间为 52.9 个月[33.9-79.0]）死亡。定量 PPP 列线图的预测因素为局部区域淋巴结转移（分子影像学 N2）、远处转移（盆外淋巴结转移、骨转移[弥漫或弥漫性骨髓累及]和器官转移）、肿瘤体积（以 L 计）和肿瘤平均标准化摄取值。可视化 PPP 列线图的预测因素为远处转移（盆外淋巴结转移、骨转移[弥漫或弥漫性骨髓累及]和器官转移）和总肿瘤病变计数。在内部和外部验证队列中，定量列线图的 C 指数分别为 0.80（95%CI 0.77-0.84）和 0.77（0.75-0.78），可视化列线图的 C 指数分别为 0.78（0.75-0.82）和 0.77（0.75-0.78）。在联合发展和内部验证队列中，定量 PPP 列线图在初始分期时（n=139，有可用分期数据）优于 STARCAP 风险评分，用于预测总生存（AUC 0.73 与 0.54；p=0.018），在生化复发时优于 EAU 风险评分（n=412；0.69 与 0.52；p<0.0001），在 NCCN 全期风险评分（n=1534；0.81 与 0.74；p<0.0001），但在转移性激素敏感前列腺癌（mHSPC；n=122；0.76 与 0.72；p=0.49）和转移性去势抵抗性前列腺癌（mCRPC；n=270；0.67 与 0.75；p=0.20）方面与 GAFITA 列线图相似。可视化 PPP 列线图在生化复发时优于 EAU（n=414；0.64 与 0.52；p=0.0004）和 NCCN 在所有分期（n=1544；0.79 与 0.73；p<0.0001），但在初始分期时与 STARCAP 相似（n=140；0.56 与 0.53；p=0.74），在 mHSPC 时与 GAFITA 相似（n=122；0.74 与 0.72；p=0.66），在 mCRPC 时与 GAFITA 相似（n=270；0.71 与 0.75；p=0.23）。
我们的 PPP 列线图准确地对前列腺癌早期和晚期的高风险和低风险组进行分层，与既定的临床风险工具相比，具有同等或更高的预测准确性。正在对列线图进行长期随访的验证和改进（NCT06320223）。
北莱茵-威斯特法伦癌症登记处。
