Background: Platinum compounds are active in pts with metNEPC/CRPC. The neutrophil-to-lymphocyte ratio (NLR) is a simple clinical metric of systemic inflammation with prognostic and predictive value in advanced PC treated with FDA-approved therapies (doc, abi, enza, cabaz, mitox). We hypothesized that pretreatment NLR may be associated with clinical outcomes of platinum-treated pts. Methods: Records were reviewed from NEPC/CRPC platinum-treated pts with available information to enable pretreatment NLR calculation. Kaplan Meier curves, Cox regression analyses were used to predict PSA-PFS, radiographic PFS and OS after platinum initiation. For NLR, a cutoff of ≤5 was used as previously described (Leibowitz-Amit et al. 2014). Results: 108 men, median age 64 yrs (range 46-80), were studied. 28 pts (26%) were NEPC based on histological features. 54 had visceral mets (39 liver, 31 lung, 8 brain). 100 received carboplatin, 17 received cisplatin (9 received both sequentially, with initial platinum used for this analysis). Most received platinum in combination with other drugs, most commonly paclitaxel (N = 71) and etoposide (N = 20). 51 (47.2%) had low NLR ≤5 and 57 (52.7%) had high NLR > 5. Median PSA-PFS was 5 months in the low NLR group versus 3 months in the high NLR group (log-rank P = 0.07). Median rPFS did not differ between the two NLR groups (log-rank P = 0.36). Median OS of pts with NLR ≤5 was 15 months vs only 9 months in the high NLR ( > 5) subgroup (log-rank P = 0.06). There was no significant difference in NLR or OS status between NEPC and CRPC pts. On multivariate analysis (adjusted for age at platinum, Gleason, PSA, ALP, LDH, Hb, measurable disease, visceral mets, ECOG PS, use of opioids), NLR emerged as an independent prognostic factor for OS (HR 5.39, 95% CI 1.25-23.33, P = 0.02), together with PSA (P = 0.03) and visceral mets (P = 0.02). Conclusions: NLR is associated with shorter OS in men with advanced PC who receive platinum-based chemotherapy. It may serve as a useful clinical indicator of systemic inflammatory response and is more prognostic than standard NEPC vs adenocarcinoma histology. Prospective validation studies in such pts are needed to confirm these findings.