Tumor location is a strong predictor of tumor progression and survival in T2 gallbladder cancer: an international multicenter study

Abstract

Objective: To determine the prognostic impact of tumor location in gallbladder cancer.

Background: Depth of tumor is a strong predictor of survival after curative resection of gallbladder cancer. However, the gallbladder has a unique anatomical relationship with the liver, and the clinical significance of tumor location remains unclear.

Methods: For 437 patients with gallbladder cancer who underwent resection at 4 international institutions, clinicopathologic characteristics and their association with survival were analyzed. Tumor location was defined as "hepatic side" or "peritoneal side," and the prognostic significance of tumor location was evaluated.

Results: Among the 252 patients with T2 disease, patients with tumors on the hepatic side (T2h, n = 99) had higher rates of vascular invasion, neural invasion, and nodal metastasis than patients with tumors on the peritoneal side (T2p, n = 153) (51% vs 19%, 33% vs 8%, and 40% vs 17%, respectively; P < 0.01 for all). After a median follow-up of 58.9 months, 3-year and 5-year survival rates were 52.1% and 42.6%, respectively, for T2h tumors and 73.7% and 64.7%, respectively, for T2p tumors (P = 0.0006). No such differences were observed in T1 or T3 tumors. Multivariate analysis confirmed the independent association of hepatic-side location with survival in T2 tumors (hazard ratio, 2.7; 95% confidence interval, 1.7-4.2; P < 0.001). This subclassification of T2 tumors predicted recurrence in the liver (23% vs 3%; P = 0.003) and distant lymph nodes (16% vs 3%; P = 0.019) even after radical resection.

Conclusions: After curative resection of T2 gallbladder cancer, tumor location predicts the pattern of recurrence and survival.

Figure 1

Definition of tumor location of gallbladder cancer.

Figure 2

Prognostic influence of tumor location after resection of gallbladder cancer according to T stage.

Figure 3

Histopathologic evidence of tumor invasion and incidence of nodal/liver metastases. A. Histopathological evidence of vascular or neural invasion. B. Incidences of nodal involvement and liver metastases. Vascular or neural invasion was assessed in 377 evaluable specimens excluding indeterminate cases due to the effect of adjuvant therapy or low quality of the specimens. The incidences of nodal involvement and macroscopic liver metastases were actual incidences based on the histopathologic data only from the patients who underwent liver resection or lymphadenectomy for curative intent.

Figure 4

Survival after resection of gallbladder cancer A. Comparison of survival according to T stage with subclassification of T2 tumors by tumor location. B. Comparison of survival according to conventional TNM classification with subclassification of T2 tumors by tumor location. N factor and M factor were clinically determined based on either histopathologic findings or radiographic evaluation.

Figure 5

Prognostic impact of radical resection for T2 peritoneal-side tumors and T2 hepatic-side tumors.

Figure 6

Efficacy of additional resection after simple cholecystectomy in T2 gallbladder cancer. A. T2 peritoneal-side tumors. B. T2 hepatic-side tumors.