Abstract

Simple Summary Hepatobiliary cancers (that include hepatocellular carcinoma, intrahepatic or extrahepatic cholangiocarcinoma and gallbladder cancer) are usually treated with systemic oncological treatments (i.e., chemotherapy, immunotherapy and biological or targeted therapies) mainly due to their improvement in survival. However, the trade-off between these therapies and usual practice supportive care is not clear, and other outcomes beyond survival should be considered in advanced stages, such as quality of life or symptom control. The present study is part of a wider project aiming to conduct broad evidence syntheses assessing the effects of systemic oncological treatments versus usual practice supportive care for patients with advanced non-intestinal digestive cancers. We performed an overview of systematic reviews assessing the effects of systemic oncological treatments versus usual practice supportive care for patients with primary advanced hepatobiliary cancer. We found evidence that for these patients (specifically for advanced hepatocellular carcinoma), systemic oncological treatments tend to improve survival at the expense of greater toxicity. Much of systematic reviews included was of low quality and highly overlapped. Nevertheless, the evidence we found failed to report other important outcomes that could be critical for decision making, including quality of life or symptom control. Future research assessing these patient-important outcomes is needed. Background: The trade-off between systemic oncological treatments (SOTs) and UPSC in patients with primary advanced hepatobiliary cancers (HBCs) is not clear in terms of patient-centred outcomes beyond survival. This overview aims to assess the effectiveness of SOTs (chemotherapy, immunotherapy and targeted/biological therapies) versus UPSC in advanced HBCs. Methods: We searched for systematic reviews (SRs) in PubMed, EMBASE, the Cochrane Library, Epistemonikos and PROSPERO. Two authors assessed eligibility independently and performed data extraction. We estimated the quality of SRs and the overlap of primary studies, performed de novo meta-analyses and assessed the certainty of evidence for each outcome. Results: We included 18 SRs, most of which were of low quality and highly overlapped. For advanced hepatocellular carcinoma, SOTs showed better overall survival (HR = 0.62, 95% CI 0.55-0.77, high certainty for first-line therapy; HR = 0.85, 95% CI 0.79-0.92, moderate certainty for second-line therapy) with higher toxicity (RR = 1.18, 95% CI 0.87-1.60, very low certainty for first-line therapy; RR = 1.58, 95% CI 1.28-1.96, low certainty for second-line therapy). Survival was also better for SOTs in advanced gallbladder cancer. No outcomes beyond survival and toxicity could be meta-analysed. Conclusion: SOTs in advanced HBCs tend to improve survival at the expense of greater toxicity. Future research should inform other patient-important outcomes to guide clinical decision making.