Radioligand therapy with lutetium-177-labeled prostate-specific membrane antigen 177Lu-PSMA-617 has demonstrated survival benefits in metastatic castration-resistant prostate cancer (mCRPC), yet prognostic markers in real-world settings remain poorly defined. Baseline hematologic parameters may influence both treatment safety and outcomes, but their prognostic role is uncertain.
We conducted a multi-institutional, retrospective cohort study of 180 patients with mCRPC treated with ≥ 1 cycle of 177Lu-PSMA-617 between March 2019 and September 2024 at Stanford University and Oregon Health and Science University. Clinical data, baseline laboratory values, and treatment outcomes were abstracted. Associations between hematologic parameters: absolute neutrophil count (ANC), hemoglobin, neutrophil-lymphocyte ratio (NLR), and platelet count with outcomes were assessed. Prostate-specific antigen (PSA) responses were compared with chi-squared testing. Overall survival (OS) was estimated and compared using Kaplan-Meier. Multivariable Cox regression adjusted for age, race, prior therapies, and taxane exposure.
Median age at treatment initiation was 65 years (interquartile range [IQR] 59-70), and median prior lines of therapy was 5 (IQR 3-6). PSA50 and PSA90 responses occurred in 51% and 24% of patients, respectively, without a significant association to baseline ANC, hemoglobin, or platelet counts. Median OS for the cohort was 13 months. On univariable analysis, hemoglobin < 10 g/dL was associated with shorter OS (median 8 vs. 15 months; hazard ratio [HR] 1.85, 95% CI, 1.17-2.91; P = .008), as was an ANC > 6500/µL (upper limit of normal) (median 11 vs. 14 months; HR 1.58, 95% CI, 1.04-2.38; P = .031). Platelet count and NLR were not associated with OS. In multivariable analysis, both hemoglobin < 10 g/dL and ANC > 6500/µL remained independently associated with increased shorter OS.
In this real-world multicenter cohort, baseline hemoglobin < 10 g/dL and ANC > 6500/µL were associated with shorter OS in patients with mCRPC treated with 177Lu-PSMA-617. Prospective validation integrating hematologic, imaging, and molecular biomarkers is warranted.