Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study
Open accessAbstract
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
- ORCID
- 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
- hybrid
- doi.org
- Licence
- 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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