Cited by 273Radiopharmaceutical Chemistry and ApplicationsProstate Cancer Treatment and ResearchProstate Cancer Diagnosis and Treatment

Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study

Open access
Gafita, Andrei, Calais, Jeremie, Grogan, Tristan R, Hadaschik, Boris, Wang, Hui, Weber, Manuel, Sandhu, Shahneen, Kratochwil, Clemens +17 more·2021·The Lancet Oncology

Abstract

Background Lutetium-177 ( 177 Lu) prostate-specific membrane antigen ( 177 Lu-PSMA) is a novel targeted treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). Predictors of outcomes after 177 Lu-PSMA to enhance its clinical implementation are yet to be identified. We aimed to develop nomograms to predict outcomes after 177 Lu-PSMA in patients with mCRPC. Methods In this multicentre, retrospective study, we screened patients with mCRPC who had received 177 Lu-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 177 Lu-PSMA once every 6–8 weeks, for a maximum of four to six cycles, and had available baseline [ 68 Ga]Ga-PSMA-11 PET/CT scan, clinical data, and survival outcomes. Putative predictors included 18 pretherapeutic clinicopathological and [ 68 Ga]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 [ 68 Ga]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 177 Lu-PSMA in patients with mCRPC might help in clinical trial design and individual clinical decision making, particularly at institutions where 177 Lu-PSMA is introduced as a novel therapeutic option. Funding Prostate Cancer Foundation.

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Authors
Gafita, A., Calais, J., Grogan, T. R., Hadaschik, B., Wang, H., Weber, M., Sandhu, S., Kratochwil, C., Esfandiari, R., Tauber, R., Zeldin, A., Rathke, H., Armstrong, W. R., Robertson, A., Thin, P., D'Alessandria, C., Rettig, M. B., Delpassand, E. S., Haberkorn, U., Elashoff, D., Herrmann, K., Czernin, J., Hofman, M. S., Fendler, W. P., & Eiber, M.
Affiliations
  • University of California, Los Angeles (US)
  • Essen University Hospital (DE)
  • TUM Klinikum (DE)
  • The University of Melbourne (AU)
  • University Hospital Heidelberg (DE)
  • Excel Diagnostics Imaging (US)
  • Ronald Reagan UCLA Medical Center (US)
Corresponding author
Gafita, Andrei
Venue
The Lancet Oncology
Publisher
Elsevier BV
Published
2021-08
Volume
22
Issue
8
Pages
1115-1125
ISSN
1470-2045 (ISSN-L)
OpenAlex
W3180641083
Cited by
271
References
35
Citations by year
2026: 49 · 2025: 61 · 2024: 50 · 2023: 63 · 2022: 37 · 2021: 10
FWCI
21.14
Type
journal article
Language
en
Open access
Locations
  • The Lancet Oncology (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion, cc-by-nc-nd)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, other-oa)
Funders
Prostate Cancer Foundation
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Diagnosis and Treatment
Keywords
177Lu-PSMA, metastatic castration-resistant prostate cancer, nomogram, outcome prediction, overall survival, PSA progression-free survival, prognostic factors, risk stratification, targeted radionuclide therapy, LASSO feature selection, model validation
MeSH terms
Humans, Lutetium, Male, Retrospective Studies, Treatment Outcome, Prostate-Specific Antigen, Nomograms, Prostatic Neoplasms, Castration-Resistant

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