Comparative outcomes of squamous and non-squamous penile cancers: Insights from SEER database.

e17031 Background: Penile cancer is a rare neoplasm in Western countries and is typically of squamous cell carcinoma (SCC) origin. Nonsquamous cell carcinomas (NSCC) constitute approximately 5% of penile malignancies, however, their clinicopathologic characteristics and prognostic implications remain poorly defined. Penile cancers are positively associated with human papillomavirus (HPV) infection and inversely associated with circumcision. Limited studies are done to see demographic patterns and population based survival outcomes in penile cancer. Our study aims to evaluate the trends, clinicopathologic differences, and survival outcomes between squamous and non-squamous penile cancers using the SEER database. Methods: A retrospective analysis was performed using SEER 17 registries (2000–2022). Adult patients (≥18 years) with histologically confirmed penile cancer (ICD-10 C60) were included. Variables analyzed included age, race, tumor site, stage, and treatment modality (surgery, chemotherapy, radiation). Survival was assessed using Kaplan–Meier estimates and log-rank testing using Graphpad Prism. Statistical significance was set at P < 0.05. Results: Among 7,719 patients (median age 68 years), 7,216 (93.5%) had SCC and 503 (6.5%) had NSCC. The cohort was predominantly White (62.9%), followed by Hispanic (21.8%), Black (8.7%), Asian/Pacific Islander (4.9%), and American Indian/Alaska Native (0.9%) patients. Median overall survival (OS) varied significantly by race (P < 0.0001), highest among Asian/Pacific Islanders (108 M) and lowest among Black patients (56 M). In terms of primary site, prepuce had the longest median OS (86 M), followed by glans (70M) and shaft (68M).Median OS was 73 M for SCC versus 43 M for NSCC (P < 0.0001). Median OS was 101 M for in situ/localized, 43 M for regional, and 8 M for distant disease (P value-0.0001). Surgery was associated with improved OS in both SCC (78M) and NSCC (89M), while chemotherapy or radiation demonstrated shorter survival, likely reflecting more advanced disease at presentation. Conclusions: Histologic subtype significantly impacts survival in penile cancer, with NSCC showing poorer outcomes than SCC. Surgical management remains the cornerstone of therapy and improves survival irrespective of histology. Chemotherapy and radiation were associated with worse outcomes, highlighting the need for early detection, individualized surgical strategies, and prospective studies for non-squamous variants.