Pathologic and Prognostic Implications of Incidental versus Nonincidental Gallbladder Cancer: A 10-Institution Study from the United States Extrahepatic Biliary Malignancy Consortium

Abstract

Most gallbladder cancers (GBCs) are discovered incidentally after routine cholecystectomy. The influence of timing of diagnosis on disease stage, treatment, and prognosis is not known. Patients with GBC who underwent resection at 10 institutions from 2000 to 2015 were included. Patients diagnosed incidentally (IGBC) and nonincidentally (non-IGBC) were compared. Primary outcome was overall survival (OS). Of 445 patients with GBC, 266 (60%) were IGBC and 179 (40%) were non-IGBC. Compared with IGBC, non-IGBC patients were more likely to have R2 resections (43% vs 19%; P < 0.001), advanced T-stage (T3/T4: 70% vs 40%; P < 0.001), high-grade tumors (50% vs 31%; P < 0.001), lymphovascular invasion (64% vs 45%; P = 0.01), and positive lymph nodes (60% vs 43%; P = 0.009). Receipt of adjuvant chemotherapy was similar between groups (49% vs 49%). Non-IGBC was associated with worse median OS compared with IGBC (17 vs 32 months; P < 0.001), which persisted among stage III patients (12 vs 29 months; P < 0.001), but not stages I, II, or IV. Despite accounting for other adverse pathologic factors (grade, T-stage, lymphovascular invasion, margin, lymph node), adjuvant chemotherapy was associated with improved OS only in stage III IGBC, but not in non-IGBC. Compared with incidental discovery, non-IGBC is associated with reduced OS, which is most evident in stage III disease. Despite being well matched for other adverse pathologic factors, adjuvant chemotherapy was associated with improved survival only in stage III patients with incidentally discovered cancer. This underscores the importance of timing of diagnosis in GBC and suggests that these two groups may represent a distinct biology of disease, and the same treatment paradigm may not be appropriate.

Fig. 1

AJCC 7th edition anatomic staging for GBC.

Fig. 2

Kaplan-Meier survival curve for OS in patients with IGBC versus non-IGBC. Patients with non-IGBC had worse median OS (17 months) compared with patients with IGBC (32 months). Log-rank P = 0.001. Excludes 30-day mortalities and R2 resections.

Fig. 3

Kaplan-Meier survival curve for OS in patients with IGBC versus non-IGBCs, stratified by stage. (A) Stage I, log-rank P = 0.89. (B) Stage II, log-rank P = 0.16. (C) Stage III, log-rank P < 0.001. (D) Stage IV, log-rank P = 0.72. Excludes 30-day mortalities and R2 resections.

Fig. 4

Kaplan-Meier survival curve for OS in stage III patients who received adjuvant chemotherapy versus no adjuvant chemotherapy, stratified by timing of diagnosis. (A) IGBC, log-rank P = 0.03. (B) Non-IGBC, log-rank P = 0.23. Excludes 30-day mortalities and R2 resections.