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

Abstract Background This study evaluates baseline inflammatory biomarkers prognostic of clinical outcomes for patients with metastatic castration‐resistant prostate cancer (mCRPC) treated with Lutetium‐177 ( 177 Lu)–PSMA‐617. Methods A retrospective review of patients treated with 177 Lu–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. Results In this cohort of 163 patients (median age 73; 51.6% White, 43.6% Black) with mCRPC treated with 177 Lu–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). Conclusions Baseline inflammatory markers are associated with clinical outcomes for patients treated with 177 Lu–PSMA‐617.