Clinical outcomes of stage IV mucinous adenocarcinoma based on primary sites

Background: Mucinous adenocarcinoma (MAC) is an uncommon adenocarcinoma subtype that arises in multiple organs. Its biology and prognosis vary by site, and evidence supporting treatment benefit in stage IV MAC is limited. This study compared clinical features and survival outcomes of stage IV MAC across primary sites with emphasis on pulmonary MAC. Methods: Clinical data were extracted from the Surveillance, Epidemiology, and End Results (SEER) 17 registries from 2000 to 2021. Patients initially diagnosed with stage IV MAC using the seventh or eighth TNM classification were included. Four major primary sites were analyzed: colorectal, lung, pancreas, and stomach. Exclusions were adenocarcinoma in situ, minimally invasive adenocarcinoma, stage I to III, and missing survival information. Demographic and clinicopathologic variables including age, sex, tumor stage, and socioeconomic factors were assessed with Cox proportional hazard regression to evaluate risk factors for overall survival. Survival differences by treatment were compared across sites by Kaplan Meier lwith log-rank test. Results: A total of 1,036 patients were included: colorectal (n = 489), pulmonary (n = 160), pancreas (n = 331), and stomach (n = 56). Median age differed across sites (p < 0.001), with pulmonary MAC presenting at the oldest age and showing the highest proportion of advanced nodal disease (p < 0.001). Survival varied by primary site: Compared with colorectal MAC, pulmonary MAC (hazard ratio [HR] 1.66; 95% confidence interval [CI] 1.31-2.11; p < 0.0001) and stomach MAC (HR 1.64; 95% CI 1.13-2.37; p = 0.009) had worse outcomes, while pancreatic MAC had the poorest prognosis (HR 2.78; 95% CI 2.36-3.29; p < 0.0001). Surgery plus chemotherapy improved survival compared with chemotherapy alone in most sites (colorectal, HR 0.38, p < 0.001; lung, HR 0.49, p = 0.024; pancreas, HR 0.66, p = 0.003). Additionally, Higher income level was associated with better survival (HR 0.61; 95% CI 0.44-0.85; p = 0.003). Conclusions: Stage IV MAC shows marked site specific survival differences. Pulmonary MAC has more favorable outcomes than pancreatic MAC, particularly with multimodal therapy. Tumor related macro/microenvironmental features and molecular profiles may contribute to these differences. The benefit of surgery plus chemotherapy was observed in most MAC. Prospective studies that integrate genomic and treatment related data are needed to guide personalized management.