Introduction: Treatment of testicular cancer is based on stage and the distinctions between seminoma and non-seminoma. However, within non-seminoma germ cell tumors (NSGCT) presence of potentially higher risk histological subtypes, such as presence of teratoma or even more so, presence of pure teratoma received limited consideration in treatment and follow-up guidelines based on the rarity of this histological subtype. Moreover, it is unknown to what extent the presence of pure teratoma increases the risk of mortality relative to mixed germ cell tumors (GCT) in metastatic, regional or localized stages. The aim of this study was to test for survival differences between testicular pure teratoma vs. mixed GCT patients within stages I, II and III. Methods: We relied on the Surveillance, Epidemiology and End Results (SEER) database (2004-2019) to identify testicular pure teratoma and mixed GCT patients. Kaplan-Meier curves depicted five-year overall survival (OS) and subsequently, cumulative incidence plots depicted cancer-specific mortality (CSM) and other-cause mortality (OCM) in a stage-specific fashion. Multivariable competing risks regression (CRR) models tested for independent predictor status of pure teratoma vs. mixed GCT. Results: Of 9183 patients, 433 (5%) had pure teratoma vs. 8750 (95%) mixed GCT. Median age was 28 years in both groups and median follow-up was 70 months. Pure teratoma differed from mixed GCT patients regarding higher clinical stage (stage III 27 vs. 19%), higher rate of retroperitoneal lymph node dissection (RPLND, 28 vs. 19%) and higher proportions of International Germ Cell Cancer Collaborative Group (IGCCCG) poor prognosis group (49 vs. 39%). Conversely, pure teratoma patients exhibited a lower rate of lung metastases than mixed GCT (21 vs. 43%; p<0.001). In stage I and III, five-year OS rates differed between pure teratoma and mixed GCT (stage I: 92.3 vs. 97.2%, p<0.001; stage III: 66.8 vs. 77.8%; p=0.03), but not in stage II (96.3 vs. 95.9%). In stage I, survival differences originated from higher OCM in pure teratoma vs. mixed GCT (6.4 vs. 1.2%; p<0.001). Conversely in stage III, survival differences originated from higher CSM in pure teratoma vs. mixed GCT (29.4 vs. 19.0%; p=0.03). In multivariable CRR models, pure teratoma was associated with higher OCM in stage I (Hazard Ratio (HR): 3.97; p<0.01). Conversely, in stage III in multivariable CRR models pure teratoma was associated with higher CSM (HR: 1.71; p=0.01). Conclusions: In testicular pure teratoma, the survival disadvantage in stage I patients was previously unknown and relates to OCM. The survival disadvantage in stage III pure teratoma originates from higher CSM that was also previously unknown. SOURCE OF Funding: None
