Prognostic Implications and Precision Selection Criteria of Primary Tumor Resection in Metastatic Gallbladder Adenocarcinoma

Background Gallbladder cancer is recognized as one of the most aggressive malignancies within the biliary system, with adenocarcinoma being its predominant histological subtype. The gallbladder's concealed anatomical position, coupled with the nonspecific nature of early symptoms, significantly complicates early detection. As a consequence, the substantial part of patients are diagnosed at advanced stages, often with metastases to distant organs, which severely limits available therapeutic options. In cases of metastatic gallbladder adenocarcinoma, the potential benefit of primary tumor resection (PTR) in improving patient prognosis remains an unresolved issue that warrants further investigation. Patients and Methods We collected data to identify patients diagnosed with gallbladder cancer and concurrent metastases to the liver, lungs, bones, brain, or distant lymph nodes between 2004 and 2021 from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized into two groups based on whether they received surgical intervention: the surgical group and the non-surgical group. To visually represent the distribution of metastatic sites among these patients, a Venn diagram was constructed. Furthermore, the impact of primary tumor resection (PTR) on overall survival (OS) and cancer-specific survival (CSS) was evaluated using the Cox proportional hazards model. Kaplan-Meier survival curves were generated for additional clarity. Subgroup analyses were also conducted to identify patient groups that may derive significant survival benefit from PTR. Results A total of 1,968 patients diagnosed with metastatic gallbladder adenocarcinoma at the time of initial presentation between 2004 and 2021 were included in the analysis. Among these, liver metastasis was the most frequent site of metastasis (n=1,695, 86.12%). Of the total cohort, 600 patients (30.49%) underwent PTR, and these patients demonstrated a significant improvement in both OS (0.679 [0.612-0.752], P<0.001) and CSS (0.690 [0.619-0.768], P<0.001). Notably, PTR was associated with reduced overall mortality in patients with isolated liver or distant lymph node metastases (liver metastasis: 0.690 [0.612-0.778], P<0.001; distant lymph node metastasis: 0.498 [0.324-0.763], P<0.001), as well as reduced cancer-specific mortality (liver metastasis: 0.698 [0.616-0.791], P<0.001; distant lymph node metastasis: 0.522 [0.332-0.820], P=0.003). In addition, patients with one or two metastatic organs who underwent PTR experienced a similar reduction in both overall mortality (1 metastatic organ: 0.691 [0.619-0.771], P<0.001; 2 metastatic organs: 0.623 [0.434-0.895], P=0.005) and cancer-specific mortality (1 metastatic organ: 0.700 [0.624-0.785], P<0.001; 2 metastatic organs: 0.643 [0.439-0.940], P=0.013). Conclusion These results demonstrate that primary tumor resection (PTR) is an effective therapeutic option for patients with certain subtypes of metastatic gallbladder adenocarcinoma. Consequently, these findings offer valuable insights and guidance for the management of metastatic gallbladder adenocarcinoma, particularly in selecting patients who may benefit from surgical intervention.