Background: Penile squamous cell carcinoma (pSCC) is a rare neoplasm with a poor prognosis and a need for biomarkers to guide treatment selection. We report an association of baseline inflammatory markers with outcomes in pSCC treated with immune checkpoint inhibitors (ICI). Methods: We performed a retrospective review of patients with pSCC from 2012-2022 at the Winship Cancer Institute at Emory University. Demographics, disease characteristics, and optimal cutoffs of biomarkers prior to ICI initiation were described. Neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), and neutrophil-to-eosinophil ratios (NER) were obtained from complete blood count data. Clinical benefit with ICI was defined as complete response, partial response, or stable disease based on RECIST 1.1 criteria. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan-Meier method and univariate Cox regression (UVA) using SAS software with significance level set at p<0.05. Results: Twenty-one patients were included in which 71.4% were white and 28.6% were black. Median age at ICI initiation was 56 years (38-76). Most patients (65%) had an ECOG PS ≥2. Four patients (19.1%) had clinical benefit at best response to ICI. Most patients (76.2%) had disease progression and 14.3% were alive at last contact. Median OS was 8.4 months (mo) (95%CI: 2.3-15.7), and median PFS was 2.0 mo (95%CI: 1.3-3.2). Of 9 patients with available HPV status, 8 were HPV+. Of 12 patients with available PD-L1 status, 8 were PD-L1+. Median follow-up was 8.4 mo and median time to ICI treatment from diagnosis was 15.6 mo. High baseline NLR, MLR, PLR, and NER above optimal cut were significantly associated with shorter OS on UVA (Table,all p<0.05). High baseline NLR was associated with shorter PFS (p=0.003). Baseline NLR groups were similar except for age and without differences in race, ECOG, BMI, PD-L1, and HPV status. Conclusions: Our real-world analysis reports a potential association of baseline inflammatory biomarkers with clinical outcomes in ICI-treated pSCC. More prospective and multicenter studies are needed for further confirmation.

^aCompared with its respective lower optimal cut group. Significance level set at alpha <0.05. ^bHigh NLR ≥6.74 (n=9, 42.8%), Low NLR <6.74 (n=12, 57.2%). ^cHigh MLR ≥1.13 (n=3, 14.3%), Low MLR <1.13 (n=18, 85.7%). ^dHigh PLR ≥346.5 (n=7, 33.3%), Low PLR <346.5 (n=14, 66.7%). ^eHigh NER ≥49.4 (n=10, 47.6%), Low NER <49.4 (n=11, 52.4%).