Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer

• Verfasst von: Gafita, Andrei [VerfasserIn]
• Verfasst von: Calais, Jeremie [VerfasserIn]
• Verfasst von: Grogan, Tristan R [VerfasserIn]
• Verfasst von: Hadaschik, Boris [VerfasserIn]
• Verfasst von: Wang, Hui [VerfasserIn]
• Verfasst von: Weber, Manuel [VerfasserIn]
• Verfasst von: Sandhu, Shahneen [VerfasserIn]
• Verfasst von: Kratochwil, Clemens [VerfasserIn]
• Verfasst von: Esfandiari, Rouzbeh [VerfasserIn]
• Verfasst von: Tauber, Robert [VerfasserIn]
• Verfasst von: Zeldin, Anna [VerfasserIn]
• Verfasst von: Rathke, Hendrik [VerfasserIn]
• Verfasst von: Armstrong, Wesley R [VerfasserIn]
• Verfasst von: Robertson, Andrew [VerfasserIn]
• Verfasst von: Thin, Pan [VerfasserIn]
• Verfasst von: D'Alessandria, Calogero [VerfasserIn]
• Verfasst von: Rettig, Matthew B [VerfasserIn]
• Verfasst von: Delpassand, Ebrahim S [VerfasserIn]
• Verfasst von: Haberkorn, Uwe [VerfasserIn]
• Verfasst von: Elashoff, David [VerfasserIn]
• Verfasst von: Herrmann, Ken [VerfasserIn]
• Verfasst von: Czernin, Johannes [VerfasserIn]
• Verfasst von: Hofman, Michael S [VerfasserIn]
• Verfasst von: Fendler, Wolfgang P [VerfasserIn]
• Verfasst von: Eiber, Matthias [VerfasserIn]
• Titel: Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer
• Titelzusatz: an international, multicentre, retrospective study
• Verf.angabe: Andrei Gafita, Jeremie Calais, Tristan R Grogan, Boris Hadaschik, Hui Wang, Manuel Weber, Shahneen Sandhu, Clemens Kratochwil, Rouzbeh Esfandiari, Robert Tauber, Anna Zeldin, Hendrik Rathke, Wesley R Armstrong, Andrew Robertson, Pan Thin, Calogero D'Alessandria, Matthew B Rettig, Ebrahim S Delpassand, Uwe Haberkorn, David Elashoff, Ken Herrmann, Johannes Czernin, Michael S Hofman, Wolfgang P Fendler, Matthias Eiber
• E-Jahr: 2021
• Jahr: July 8, 2021
• Umfang: 11 S.
• Teil: volume:22
• Teil: year:2021
• Teil: number:8
• Teil: month:08
• Teil: pages:1115-1125
• Teil: extent:11
• Fussnoten: Im Text ist "177" hochgestellt ; Gesehen am 18.10.2021
• Titel Quelle: Enthalten in: The lancet <London> / Oncology
• Ort Quelle: London : The Lancet Publ. Group, 2000
• Jahr Quelle: 2021
• Band/Heft Quelle: 22(2021), 8 vom: Aug., Seite 1115-1125
• ISSN Quelle: 1474-5488
• DOI: doi:10.1016/S1470-2045(21)00274-6
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 177433447X

Abstract

Background - Lutetium-177 (177Lu) prostate-specific membrane antigen (177Lu-PSMA) is a novel targeted treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). Predictors of outcomes after 177Lu-PSMA to enhance its clinical implementation are yet to be identified. We aimed to develop nomograms to predict outcomes after 177Lu-PSMA in patients with mCRPC. - Methods - In this multicentre, retrospective study, we screened patients with mCRPC who had received 177Lu-PSMA between Dec 10, 2014, and July 19, 2019, as part of the previous phase 2 trials (NCT03042312, ACTRN12615000912583) or compassionate access programmes at six hospitals and academic centres in Germany, the USA, and Australia. Eligible patients had received intravenous 6·0-8·5 GBq 177Lu-PSMA once every 6-8 weeks, for a maximum of four to six cycles, and had available baseline [68Ga]Ga-PSMA-11 PET/CT scan, clinical data, and survival outcomes. Putative predictors included 18 pretherapeutic clinicopathological and [68Ga]Ga-PSMA-11 PET/CT variables. Data were collected locally and centralised. Primary outcomes for the nomograms were overall survival and prostate-specific antigen (PSA)-progression-free survival. Nomograms for each outcome were computed from Cox regression models with LASSO penalty for variable selection. Model performance was measured by examining discrimination (Harrell's C-index), calibration (calibration plots), and utility (patient stratification into low-risk vs high-risk groups). Models were validated internally using bootstrapping and externally by calculating their performance on a validation cohort. - Findings - Between April 23, 2019, and Jan 13, 2020, 414 patients were screened; 270 (65%) of whom were eligible and were divided into development (n=196) and validation (n=74) cohorts. The median duration of follow-up was 21·5 months (IQR 13·3-30·7). Predictors included in the nomograms were time since initial diagnosis of prostate cancer, chemotherapy status, baseline haemoglobin concentration, and [68Ga]Ga-PSMA-11 PET/CT parameters (molecular imaging TNM classification and tumour burden). The C-index of the overall survival model was 0·71 (95% CI 0·69-0·73). Similar C-indices were achieved at internal validation (0·71 [0·69-0·73]) and external validation (0·72 [0·68-0·76]). The C-index of the PSA-progression-free survival model was 0·70 (95% CI 0·68-0·72). Similar C-indices were achieved at internal validation (0·70 [0·68-0·72]) and external validation (0·71 [0·68-0·74]). Both models were adequately calibrated and their predictions correlated with the observed outcome. Compared with high-risk patients, low-risk patients had significantly longer overall survival in the validation cohort (24·9 months [95% CI 16·8-27·3] vs 7·4 months [4·0-10·8]; p<0·0001) and PSA-progression-free survival (6·6 months [6·0-7·1] vs 2·5 months [1·2-3·8]; p=0·022). - Interpretation - These externally validated nomograms that are predictive of outcomes after 177Lu-PSMA in patients with mCRPC might help in clinical trial design and individual clinical decision making, particularly at institutions where 177Lu-PSMA is introduced as a novel therapeutic option. - Funding - Prostate Cancer Foundation.