Baseline Hematological Parameters and Outcomes in Patients With Prostate Cancer Treated With Lu-177 PSMA Radioligand Therapy (RLT): A Multicenter Real-World Analysis.
Baseline hemoglobin levels below 10 g/dL and absolute neutrophil counts above 6500/µL are associated with shorter overall survival in patients with metastatic castration-resistant prostate cancer treated with lutetium-177-PSMA-617.
Where it sits
this study against the rest of the vipivotide corpusSummary and findings
This study examined baseline hematological parameters in 180 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with lutetium-177-labeled PSMA-617. The study found that a hemoglobin level of less than 10 g/dL and an absolute neutrophil count (ANC) greater than 6500/µL were associated with shorter overall survival (OS). Median OS for the cohort was reported as 13 months.
Abstract
Background 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. Patients and methods 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. Results 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. Conclusion 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.
Background
This paper addresses the prognostic role of baseline hematologic parameters in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing radioligand therapy with lutetium-177-labeled PSMA-617. Prior studies have shown survival benefits with this treatment, but the influence of hematologic markers on outcomes remains poorly defined. Understanding these associations could help refine prognostic assessments and treatment strategies in real-world settings.
Methods
This was a multi-institutional, retrospective cohort study involving 180 patients treated with at least one cycle of lutetium-177-PSMA-617 between March 2019 and September 2024. Clinical data and baseline laboratory values were collected, and associations between hematologic parameters and treatment outcomes were assessed. Primary outcomes included overall survival (OS) and prostate-specific antigen (PSA) responses, analyzed using chi-squared testing and Kaplan-Meier methods.
Results
The median overall survival (OS) for the cohort was 13 months. Hemoglobin levels below 10 g/dL were associated with a median OS of 8 months compared to 15 months for those with higher levels (HR 1.85, 95% CI, 1.17-2.91; P = .008). An ANC greater than 6500/µL was associated with a median OS of 11 months compared to 14 months for lower counts (HR 1.58, 95% CI, 1.04-2.38; P = .031).
Interpretation
The findings suggest that low hemoglobin and high ANC may serve as negative prognostic indicators in patients with mCRPC treated with lutetium-177-PSMA-617. While these associations are statistically significant, the clinical relevance of the effect sizes should be interpreted cautiously, especially given the retrospective nature of the study and potential confounding factors. Further research is warranted to validate these findings in prospective studies.
Key findings
- Median OS for the cohort was 13 months.
- PSA50 and PSA90 responses occurred in 51% and 24% of patients, respectively.
- Hemoglobin < 10 g/dL was associated with shorter OS (median 8 vs. 15 months; HR 1.85, 95% CI, 1.17-2.91; P = .008).
- ANC > 6500/µL was associated with shorter OS (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.
Limitations
- Retrospective cohort study design.
- Potential confounding factors not controlled for.
- Single-site data collection may limit generalizability.
- Short follow-up period for assessing long-term outcomes.