In a retrospective study reported in The Lancet Oncology, Gafita et al developed nomograms for predicting overall survival and prostate-specific antigen (PSA) progression-free survival outcomes in men receiving lutetium-177–PSMA (LuPSMA) treatment for metastatic castration-resistant prostate cancer.
Study Details
The study included 270 men treated with LuPSMA between December 2014 and July 2019 as part of phase II trials or compassionate access programs at six sites in Germany, the United States, and Australia. Eligible patients had received 6.0 to 8.5 GBq LuPSMA once every 6 to 8 weeks for a maximum of four to six cycles, and had available baseline Ga-68–PSMA-11 positron-emission tomography/computed tomography (PET/CT) scans, clinical data, and survival outcomes.
Patients were divided into a development cohort (n = 196) and an external validation cohort (n = 74). Potential predictors for the models included 18 pretherapeutic clinicopathologic and Ga-86–PSMA-11 PET/CT variables. Primary outcomes for the nomograms were overall survival and PSA-based progression-free survival. An internal validation was performed using a bootstrap resampling process in the development cohort.
Key Findings
In the development cohort, the final predictors in the overall survival model were time since diagnosis of prostate cancer, chemotherapy status, baseline hemoglobin concentration, bone involvement status, liver involvement status, number of metastatic lesions, and tumor standardized uptake value (SUVmean). Predictors used in the PSA progression-free survival model were time since diagnosis of prostate cancer, chemotherapy status, pelvic nodal status, bone involvement status, liver involvement status, and tumor SUVmean.
In the development cohort, the C-index value for the overall survival model was 0.71 (95% confidence interval [CI] = 0.69–0.73), with values of 0.71 (95% CI = 0.69–0.73) with internal validation and 0.72 (95% CI = 0.68-0.76) in the external validation cohort.
The C-index value for the PSA progression-free survival model in the development cohort was 0.70 (95% CI = 0.68–0.72), with values of 0.70 (95% CI = 0.68–0.72) with internal validation and 0.71 (95% CI = 0.68–0.74) in the external validation cohort.
Stratification into low-risk vs high-risk groups based on calculated optimal cutoffs for the model risk scores showed a median overall survival of 19.1 months vs 8.4 months (P < .0001) in the development cohort, 24.9 vs 7.4 months (P < .0001) in the validation cohort, and 19.9 vs 8.2 months (P < .0001) in the complete set. Median PSA progression-free survival was 9.4 vs 3.3 months (P < .0001) in the development cohort, 6.6 vs 2.5 months (P = .022) in the validation cohort, and 8.8 vs 3.3 months (P < .0001) in the complete set.
The investigators concluded, “These externally validated nomograms that are predictive of outcomes after [LuPSMA] in patients with metastatic castration-resistant prostate cancer might help in clinical trial design and individual clinical decision-making, particularly at institutions where [LuPSMA] is introduced as a novel therapeutic option.”
Andrei Gafita, MD, of the Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was supported by the Prostate Cancer Foundation. For full disclosures of the study authors, visit thelancet.com.
