Prognostic utility of neutrophil:lymphocyte ratio (NLR) in patients receiving 177Lu-PSMA-617 (LuPSMA) for metastatic castration resistant prostate cancer (mCRPC).

Abstract

207 Background: LuPSMA has a proven clinical benefit in mCRPC, but there is a need to develop predictive and prognostic biomarkers of response. Neutrophil:lymphocyte ratio (NLR) has shown prognostic value across a range of therapies for solid tumors, but there is limited data on its utility in mCRPC patients receiving LuPSMA. Methods: Patients with mCRPC who received ≥2 cycles (C) of LuPSMA therapy at Dana-Farber Cancer Institute between June 2022 and December 2024 were included. NLR at C1 and C2 of LuPSMA was categorized as ≤3 or >3, based on the cutoff used in the VISION trial (Wei et al, ESMO 2023). Efficacy endpoints included PSA50 (≥50% reduction in PSA from C1) and overall survival (OS). The association of NLR with outcomes was evaluated by logistic regression for PSA50 and Cox regression for OS, adjusted for age, visceral disease, number of prior taxanes and log-transformed C1 PSA. For C2 NLR or the change from C1 to C2, OS was calculated from the C2 date under a landmark analysis. Results: 265 patients were included, all of whom had received ≥1 taxane and ≥1 androgen receptor pathway inhibitor (ARPI). Median age was 72 years (IQR, 66-78), 80 (30%) had received 2 taxanes, 149 (56%) had received ≥2 ARPIs and 29 (11%) had liver metastases at baseline. Overall, 133 patients (50%) achieved a PSA50; with no significant difference in PSA50 rates based on NLR >3 (n=178) versus ≤3 (n=87) at C1 (OR=0.79 [0.47-1.35], p =0.39) or C2 (OR=0.69 [0.40-1.19], p =0.18). In the entire cohort, 63 deaths were observed, with a 6-month OS rate of 87% (95% CI 82-91). High NLR (>3) at C1 was associated with shorter OS compared to those with NLR ≤3 (6-month OS: 84% vs 93%, adjusted HR=1.87 [1.02–3.45], p=0.04); a similar trend was observed for elevated NLR at C2 (6-month OS from C2: 78% vs. 83%, adjusted HR=1.72 [0.93–3.18], p=0.08). When assessing change in NLR between C1 and C2, patients with persistently elevated NLR (>3 at C1 and C2) had the poorest outcomes, intermediate in those with change from >3 to ≤3 and best in those with NLR ≤3 at C1 (Table). Conclusions: In this large institutional cohort, baseline NLR was prognostic in patients receiving LuPSMA, with elevated NLR (>3) at C1 and C2 associated with the poorest outcomes to therapy. Baseline and early NLR dynamics may be helpful in identifying patients with poor outcomes on LuPSMA, for whom early treatment modification or intensification may be warranted. Change in NLR between C1 and C2 N OS (landmark analysis from C2) 6-mos OS from C2 (%, 95% CI) Adjusted HR (95% CI) <3 to <3 60 84 (71-92) Ref. >3 to ≤3 19 76 (41-92) 1.57 (0.42-5.85) ≤3 to >3 27 92 (57-99) 1.04 (0.29-3.78) >3 to >3 159 77 (69-84) 2.00 (1.00-4.00)