A Population-Based Retrospective Study of Biliary Tract Cancers in Alberta, Canada

Abstract

Background: Biliary tract cancers (BTC) are uncommon malignancies and are underrepresented in the literature. Methods: We performed a retrospective population-based review of adult patients with biopsy-confirmed BTC in Alberta from 2000 to 2015. Demographic data, risk factors, symptoms, treatment, and staging data were collected and analyzed. Survival analyses were completed. Results: A total of 1604 patients were included in our study, of which 766 (47.8%) were male. The median age at diagnosis was 68 (range 19-99). There were 374 (23.3%) patients with resectable tumors at diagnosis versus 597 (37.2%) with unresectable tumors. Of the patients, 380 (21.5%) received chemotherapy (CT) and 81 (5.0%) underwent radiation therapy. There was a clear trend with worsening stage and performance status associated with shorter median overall survival (OS). Ampulla of Vater tumors had the best median OS (25.69 months), while intrahepatic bile duct cancers had the worst (5.78 months). First-line palliative CT regimens included gemcitabine+cisplatin (OS 14.98 months (mo), n = 212), single agent gemcitabine (OS 12.42 mo, n = 22), capecitabine (OS 8.12 mo, n = 8), and capecitabine+gemcitabine (OS 6.93 mo, n = 13). Patients with advanced or metastatic disease who received first-line gemcitabine+cisplatin had a median OS of 11.8 months (n = 119). Conclusion: BTCs have poor survival. Worse outcomes occur in higher stage and poorer Eastern Cooperative Oncology Group (ECOG) performance status patients across all tumor subtypes. Tumor resectability at diagnosis was associated with better OS. Our study supports the use of gemcitabine+cisplatin as a combination first-line palliative CT, as patients treated in Alberta have a comparable OS to that reported in the ABC-02 phase III study.

Keywords: biliary tract neoplasms; chemotherapy; cholangiocarcinoma; gallbladder cancer; survival outcomes.

Figure 1

Kaplan–Meier curves depicting median overall survival (OS) by BTC subtype. The ampulla of Vater tumor (AVT) subtype had the longest median OS, with 25.7 months (95% confidence interval (CI), 19.7 to 31.7), followed by the extrahepatic cholangiocarcinoma (EHC) group with 10.3 months (95% CI, 8.5 to 12.1), gallbladder (GB) group with 8.1 months (95% CI, 6.6 to 9.7), and intrahepatic cholangiocarcinoma (IHC) group with 5.8 months (95% CI, 4.7 to 6.9). The NOS subtype had a median OS of 3.1 months (95% CI, 0.75 to 5.4).

Figure 2

(a) Median OS by sex. The median OS in males for all subtypes was 9.8 months (95% CI, 8.4 to 11.2), while the median OS in females was 9.6 months (95% CI, 8.2 to 11.0; P = 0.306). (b) Median OS ECOG. Survival was higher among those with lower Eastern Cooperative Oncology Grou (ECOG) scores. An ECOG score of 0 had a median OS of 23.4 months (95% CI, 19.3 to 27.5), ECOG 1 of 14.5 months (95% CI, 11.7 to 17.3), ECOG 2 of 5.6 months (95% CI, 4.7 to 6.4), ECOG 3 of 3.3 months (95% CI, 2.4 to 4.1), and ECOG 4 of 1.1 months (95% CI, 0.7 to 1.6). (c) Median OS by stage. A similar trend was observed with stage. Patients classified as stage 1 had a median OS of 64.9 months 95% CI, 18.7 to 111.0), stage 2 of 24.2 months (95% CI, 18.2 to 30.3), stage 3 of 14.2 months (95% CI, 10.2 to 18.2), and stage 4 of 4.1 months (95% CI, 3.6 to 4.6). (d) Median OS by grade. The same trend was observed with overall survival when determined by grade at diagnosis. Those patients with grade 1 tumors at diagnosis had a median OS of 26.6 months (95% CI, 12.4 to 40.7), grade 2 of 18.7 months (95% CI, 15.1 to 22.3), grade 3 of 9.8 months (95% CI, 7.9 to 11.6), and grade 4 of 3.9 months (95% CI, 0.0 to 8.8).

Figure 2

(a) Median OS by sex. The median OS in males for all subtypes was 9.8 months (95% CI, 8.4 to 11.2), while the median OS in females was 9.6 months (95% CI, 8.2 to 11.0; P = 0.306). (b) Median OS ECOG. Survival was higher among those with lower Eastern Cooperative Oncology Grou (ECOG) scores. An ECOG score of 0 had a median OS of 23.4 months (95% CI, 19.3 to 27.5), ECOG 1 of 14.5 months (95% CI, 11.7 to 17.3), ECOG 2 of 5.6 months (95% CI, 4.7 to 6.4), ECOG 3 of 3.3 months (95% CI, 2.4 to 4.1), and ECOG 4 of 1.1 months (95% CI, 0.7 to 1.6). (c) Median OS by stage. A similar trend was observed with stage. Patients classified as stage 1 had a median OS of 64.9 months 95% CI, 18.7 to 111.0), stage 2 of 24.2 months (95% CI, 18.2 to 30.3), stage 3 of 14.2 months (95% CI, 10.2 to 18.2), and stage 4 of 4.1 months (95% CI, 3.6 to 4.6). (d) Median OS by grade. The same trend was observed with overall survival when determined by grade at diagnosis. Those patients with grade 1 tumors at diagnosis had a median OS of 26.6 months (95% CI, 12.4 to 40.7), grade 2 of 18.7 months (95% CI, 15.1 to 22.3), grade 3 of 9.8 months (95% CI, 7.9 to 11.6), and grade 4 of 3.9 months (95% CI, 0.0 to 8.8).

Figure 3

Kaplan–Meier survival curve based on resectability at diagnosis. Overall survival by resectability revealed the highest median OS in patients whose tumors were determined to be resectable at diagnosis with a median OS of 35.8 months (95% CI, 25.2 to 46.5) and was lower in those whose tumors were determined to be unresectable at diagnosis with a median OS of 4.4 months (95% CI, 3.9 to 5.0; P < 0.001).

Figure 4

Kaplan–Meier survival curves by regimen. In the palliative-intent chemotherapy group, the gemcitabine cisplatin combination chemotherapy group included 212 patients. Compared to all other chemotherapy regimens, the median OS was 15.0 months (95% CI, 12.8 to 17.1) versus 11.0 months (95% CI, 7.0 to 15.0).