Prognostic factors and survival outcomes in adrenocortical carcinoma: A comprehensive analysis of the SEER and TCGA databases.

Abstract

e16620 Background: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy characterized by high recurrence rates and poor response to treatment, leading to high mortality. Prognostic factors for these patients are poorly defined due to the rarity of the disease. This study aims to investigate the prognostic factors and survival outcomes based on clinical, pathological, and molecular characteristics through a combined analysis of the Survival, Epidemiology, and End Results (SEER) and Cancer Genome Atlas (TCGA) databases. Methods: Using SEER data from 2000-2021, we identified 1,654 patients with ACC through ICD-O-3 code 8370/3. Demographic and pathological variables including age, gender, race, laterality, tumor grade, stage, and treatment type were examined. Univariate and multivariate analyses were performed using the log-rank test and Cox regression. The cBioPortal for Cancer Genomics was used to obtain data on commonly mutated genes, and associated clinical survival information was assessed. Results: The median age at diagnosis was 56 years. 60.9% of patients were female, and 68.9% were White. The median tumor size was 10.5 cm, and the median overall survival (OS) was 23 months. In univariate analysis, factors associated with improved OS included female sex (p = 0.03), age < 56 years (p < 0.0001), and surgical intervention (p < 0.0001). Poor prognostic factors included tumor grade 3 or 4 (p < 0.0001), AJCC Stage IV (p < 0.0001), and chemotherapy (p < 0.0001). No differences in median OS were observed based on tumor laterality, tumor size, or radiotherapy. In multivariate analysis, age < 56 years (HR 0.72, p < 0.0001) and surgical treatment (HR 0.23, p < 0.0001) were independent predictors of survival. The TCGA database included 92 patients. The most common driver mutations were ZFPM1 (53%), ZNRF3 (22%), TP53 (20%), CTNNB1 (16%), TERT (15%), PRKAR1A (12%), and CDKN2A (11%). No survival differences were observed based on these mutations. The median tumor mutational burden (TMB) was 3.03 mutations/Mb for the entire cohort, averaging 2.98 mutations/Mb for the queried genes. Conclusions: This study identifies several factors influencing survival in ACC. Age under 56 years and surgical treatment were associated with improved survival, while higher tumor grade, Stage IV disease, and chemotherapy were linked to poorer survival outcomes. No significant impact of tumor size or laterality was found. Although common mutations were identified, none correlated with survival. The low TMB suggests a limited potential for response to immunotherapy. These findings contribute to a broader understanding of the demographic, clinical, and genomic factors affecting survival in patients with adrenocortical carcinoma.