Prognostic factors of gallbladder cancer (GBC) in patients diagnosed over a period of 20 years: A Canadian province experience.
Authors: Toussi Nima Hamidi , Daida Krishna , Alsafar Noura , Ahmed Osama , Chalchal Haji I. , Dueck Dorie-Anna , Gitlin Joshua , Gowrishankar Branawan , Hagel Kimberly Marie , Haider Kamal , Iqbal Mussawar , Kanthan Rani , Le Duc , Mahmood Shazia , Moore Jocelyn , Moser Michael , Ravi Deepti , Shaw John , Zaidi Adnan , Ahmed Shahid 
Published: January 2024

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Background: GBC is an uncommon but often fatal gastrointestinal cancer. The poor prognosis of GBC may in part be due to lack of effective screening tools and a delay in diagnosis that leads to presentation in the latter stages of the disease. The current study aims to determine outcomes of patients with GBC in relation to contextual, demographic and clinical factors in a Canadian province over a span of 20 years. Methods: In this population-based retrospective cohort study patients with GBC diagnosed in Saskatchewan, Canada from 2000-2019 were evaluated. Cox proportional multivariate regression analyses was performed to determine factor correlated with inferior outcomes. Results: 331 patients with median age of 74 yrs and M:F of 1:2 were identified. 92% had a pathological diagnosis of GBC & 80% had adenocarcinoma. 49% were diagnosed >year 2010. 217 (66%) of those diagnosed with GBC were rural residents. 149 (45%) patients were referred to a cancer center. In patients with documented stage, 64% had stage IV disease & >90% were symptomatic with a median time from the onset of symptoms to the diagnosis of 7 months. Rural residents have a significantly high rate of smoking history whereas urban residents have significantly high rates of pathological diagnosis, low serum albumin and elevated platelet count. Median overall survival (OS) of patients with stage I-III GBC was 20 months (95% CI:10.9-29.1) vs. 4.0 months (3.0-5.0) with stage IV GBC (<0.001). No significant differences were noted in OS in relation to residence and time-period of diagnosis. Patients who were not referred for a cancer center had a median OS of 3 months (1.98-4.0) vs. 13 months (9.9-16.1), p<0.001. Median disease-free survival (DFS) of patients with stage I-III GBC was 20 months (95%CI: 10-30.1) with 5-year DFS of 36%. Patients with stage I-III GBC who received adjuvant chemotherapy had 5-yr DFS of 43% vs. 33% without adjuvant chemotherapy (p=0.73). 5-year DFS of urban patients was 25% vs. 42% of rural patients (p=0.016). On multivariate analysis for patients with Stage I-III GBC, stage III disease, HR (hazard ratio), 2.63 (1.09-6.34) and urban residence, HR, 2.20 (1.1-4.39) were correlated with inferior DFS whereas for all patients, stage IV disease, HR, 3.02 (1.85-4.94); no referral to cancer center, HR, 2.64 (1.51-4.62); lack of surgery, HR, 1.63 (1.03-2.57); neutrophil:lymphocyte of >3.2, HR, 1.57 (1.05-2.36); and age ≥70, HR, 1.51 (1.04-2.19) were correlated with inferior OS. Conclusions: In a real-world setting, most patients with GBC are diagnosed with late-stage disease and were not referred to cancer center. For early-stage GBC, urban residence and stage III disease were correlated with inferior outcome, whereas for all stage GBC, stage IV disease, old age, lack of surgery, lack of referral to cancer center, and high neutrophil to lymphocyte ratio were correlated with inferior survival.