Inflammatory biomarkers have a prognostic role in patients with metastatic castration-resistant prostate cancer treated with Lutetium-177-PSMA-617.

Abstract

This study evaluates baseline inflammatory biomarkers prognostic of clinical outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with Lutetium-177 (¹⁷⁷Lu)-PSMA-617. A retrospective review of patients treated with ¹⁷⁷Lu-PSMA-617 at Emory Winship Cancer Institute was conducted. Baseline inflammatory markers obtained included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and hemoglobin-to-platelet ratio (HPR). Cox proportional hazards models assessed overall survival (OS) and progression-free survival (PFS), and a logistic regression model assessed ≥50% decline in prostate-specific antigen (PSA) from baseline (PSA50). A prognostic biomarker composite score was generated using best-subset variable selection from a multivariate Cox model. In this cohort of 163 patients (median age 73; 51.6% White, 43.6% Black) with mCRPC treated with ¹⁷⁷Lu-PSMA-617, elevated NLR, PLR, PIV, SII, and reduced HPR were independent prognostic biomarkers of shortened OS (NLR hazard ratio [HR], 2.7, p = .002; PLR HR, 2.08, p = .015, PIV HR, 2.86, p = .002, SII HR, 2.5, p = .003; and HPR HR, 0.43, p = .011). Higher NLR, PLR, and SII values were independently prognostic of shortened PFS (NLR HR, 1.82, p = .012; PLR, 1.6, p = .036; and SII HR, 1.85, p = .009). Patients with elevated HPR and hemoglobin (Hgb) had higher odds of PSA50 response (HPR: 84.8% vs. 15.2%, p = .032, median Hgb of PSA50 response: 11.5 vs. 10.7, p = .01). The biomarker composite score stratified overall survival with good discrimination (C-index = 0.732), demonstrating a reduction in mortality risk from the high-tercile group to intermediate-tercile (HR, 0.40, p = .022) and low-tercile (HR, 0.16, p < .001). Baseline inflammatory markers are associated with clinical outcomes for patients treated with ¹⁷⁷Lu-PSMA-617.