Survival gap in gallbladder cancer: Bridging tumor biology and healthcare system logistics

Abstract

Gallbladder cancer (GBC) remains one of the most lethal gastrointestinal malignancies, characterized by aggressive biology and poor survival. Despite advances in molecular profiling and systemic therapies, innovations have not translated into proportional survival gains in many regions, suggesting underrecognized determinants of prognosis. In this opinion review, we argue that healthcare system logistics represent a critical, modifiable factor influencing GBC outcomes. In intermediate-incidence settings, such as Latin America, many cases are diagnosed incidentally following cholecystectomy. In this context, timely referral for radical re-resection represents a critical component of curative-intent management; however, delays in diagnosis and staging frequently compromise this therapeutic window. Emerging evidence indicates that system-level inefficiencies may impact survival more than traditional clinical variables. We explore the interplay between tumor biology and healthcare delivery, highlighting molecular stratification, surgical centralization, and multidisciplinary coordination. Additionally, we address controversies in incidental GBC, including optimal timing of re-resection and perioperative systemic therapy. We propose that healthcare logistics be formally recognized as a prognostic factor. Bridging the survival gap requires both oncologic advances and structural optimization of care pathways to ensure timely access to curative treatment.

Keywords: Gallbladder carcinoma; Incidental gallbladder cancer; Healthcare logistics; Referral pathways; Radical re-resection; Molecular stratification; Neoadjuvant therapy; Real-world evidence; Therapeutic window; Hepatobiliary surgery

Core Tip: Gallbladder cancer (GBC) prognosis is traditionally viewed through the lens of aggressive tumor biology. However, in intermediate-incidence regions like Brazil, systemic fragmentation often prevents curative intent. This opinion review proposes a paradigm shift: Classifying healthcare logistics as a modifiable prognostic factor. By integrating molecular stratification, focusing on TP53 and HER2, with logistical “auto-alerts” and neoadjuvant “biological filters”, we can bridge the survival gap. Optimizing the “therapeutic window” between incidental diagnosis and radical surgery is as crucial as the surgical technique itself in transforming GBC outcomes.