Examination of The Characteristics of Long-Term Survivors Among Patients With Gallbladder Cancer With Liver Metastasis Who Underwent Surgical Treatment: A Retrospective Multicenter Study (ACRoS1406)

Background: Gallbladder cancer (GBC) with liver metastasis is considered unresectable. However, there have been infrequent reports of long-term survival in patients with GBC and liver metastases. Therefore, we examined the characteristics of long-term survivors of gallbladder cancer with liver metastasis. Methods: : A retrospective multicenter study of 503 patients with GBC (mean age, 68.6 years; female, 52%) was performed. Although patients with pre-operatively diagnosed GBC and liver metastasis were generally excluded from resection, some cases identified during surgery were resected. Result: In patients with resected stage III/IV GBC (n = 228), the period 2007–2013 (vs. 2000–2006, hazard ratio 0.55), other type histology (vs. well/moderate histology, hazard ratio 2.34), ≥2 liver metastases (vs. one liver metastasis, hazard ratio 4.30), and positive margin resection (vs. complete resection with a negative margin, hazard ratio 1.57) were independent prognostic factors for overall survival, whereas one liver metastasis (vs. no liver metastasis) was not. The 5-year overall survival and median survival times in those with one liver metastasis with complete resection and a negative margin (40.9%, 28.3 months) were significantly better than those in patients with ≥2 liver metastases with complete resection and a negative margin (0%, 11.0 months, p = 0.025), and comparable to those in patients with liver metastasis with complete resection and a negative margin (37.0%, 33.0 months). According to the univariate analysis of resected patients with GBC and liver metastases (n=24), minor hepatectomy, less blood loss, less surgery time, papillary adenocarcinoma, T2, morbidity of Clavien–Dindo classification ≤ 2, and adjuvant chemotherapy were significantly associated with longer survival. Long-term survivors (n = 5) had a high frequency of T2 tumors (4/5), had small liver metastases near the gallbladder during or after surgery, underwent minor hepatectomy without post-operative complications, and received post-operative adjuvant chemotherapy. Conclusions: : Although there is no surgical indication for GBC with liver metastasis diagnosed pre-operatively, minor hepatectomy and post-operative chemotherapy may be an option for selected patients with T2 GBC and liver metastasis identified during or after surgery who do not have other poor prognostic factors.