Abstract Introduction: Penile carcinoma is a rare malignancy accounting for 1% of cancers in men in the U.S. Although the overall 5-year survival rate is 83% for those with localized disease, this survival rate is reduced to 48% for those with regional lymph node involvement. Thus, there is an unmet need to identify prognostic factors for those at high risk of poor outcomes. Methods: Demographic and clinical information was obtained from electronic medical records among 230 men diagnosed with penile carcinoma between 1986 and 2013. The log-rank test was used to test for differences in overall survival (censored at 12, 36, and 60 months) by demographic and clinical variables. Overall survival was defined as date of cancer diagnosis to date of event or date of last follow-up. Modeling building approaches were utilized to identify the most informative variables associated with overall survival including backward elimination analysis and classification and regression tree (CART) analysis. Results: Following univariable analyses, a full multivariable model was generated and reduced to the most informative covariates using backward elimination analysis. The reduced model revealed penile tumors located on the penis glans (HR =0.48, 95% CI=0.27-0.85) or NOS (HR=0.45, 95% CI=0.25-0.84) and undetermined tumor differentiation (HR=0.48, 95% CI=0.27-0.86) was associated with a reduced risk of dying and late stage disease (III/IV) was associated with an increased risk of death (HR=2.83, 95% CI=1.68-4.75). To identify potential novel prognostic factors, the full model was subjected to CART analysis which identified four subgroups based on three covariates: tumor stage, tumor site, and marital status. Compared to risk-group 1 (Stage 0-II and penis glans/NOS), men in risk-group 3 (Stage 0-II, prepuce/penis corpus/overlapping lesion, single/widowed/divorced) exhibited a 4.9-fold increased risk of death (HR =4.87; 95% CI 2.28-10.42) and men in risk-group 4 (Stages III/IV) had a slightly attenuated increased risk of death (HR =4.62; 95% CI 2.68-7.98). When CART risk-groups were included into a single model and adjusted for alcohol use, ethnicity, and tumor differentiation, the point estimates were slightly somewhat attenuated but the overall trend was the same. Conclusion: This analysis of a cohort of patients diagnosed with penile cancer identified prognostic models with the most informative covariates significantly associated with overall survival. Using a decision tree approach, we identified four novel patient risk subgroups that demonstrated early stage patients who were not married had significantly worse 5-year survival (18.2%) compared to late stage patients (38.2%). These data may suggest that social support network has a beneficial impact on patient outcomes even among late stage patients. Citation Format: Monica E. Reyes, Heloise Borges, Muhamed S. Adjao, Nisha Vijayakumar, Philippe E. Spiess, Matthew B. Schabath. A novel prognostic model demonstrates social support has a beneficial impact on penile carcinoma outcomes [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3526.