Management Of Biliary Tract Cancer Research Articles

Facts and Hopes in the Systemic Therapy of Biliary Tract Carcinomas.

Biliary tract cancers (BTC) are a heterogeneous group of cancers that continue to present a particularly poor prognosis. BTC treatment is rapidly evolving yet facing many challenges to improve patient outcomes and maximize benefit from treatment. Only a minority of patients are diagnosed with early-stage disease and are suitable for curative resection. Current surgical strategies are limited by a high relapse rate, and despite extensive efforts focused on adjuvant strategies, the development of more effective adjuvant strategies remains a challenge. In addition, the role of locoregional strategies, liver transplant, and neoadjuvant treatment remains unclear. Systemic treatment in the advanced setting is based on three main pillars: first, cytotoxic chemotherapy options; second, the addition of immunotherapy to chemotherapy; and third, targeted therapies. The role of targeted therapies is oriented by many promising targets, including IDH1 mutations, FGFR2 fusions, BRAF-V600E mutations, and HER2 amplifications. The aim of this review is to provide an overview of current facts and future hopes in the management of BTC, including an overview of the unmet need, and particularly focus on systemic therapies.

Chinese expert consensus on the whole-course standardized management of biliary tract cancer(2023)

The early detection of biliary tract cancer remains challenging,with the majority of patients often presenting at an advanced stage,characterized by a low rate of radical surgery,limited comprehensive treatment options,and poor prognosis. Currently,the specialized diagnosis and treatment of biliary system diseases,as well as the establishment of multi-disciplinary collaboration strategy,are still developing in China. Given the increasing complexity of biliary tract cancer diagnosis and treatment,the Study Group of Biliary Surgery in Chinese Society of Surgery of Chinese Medical Association and the Biliary Surgeon Working Group of the Surgical Branch of the Chinese Medical Doctor Association have developed this "Chinese expert consensus on the whole-course standardized management of biliary tract cancer(2023)". This consensus has been based on current medical evidence and was reached through expert discussions. It comprehensively covers screening,diagnosis,treatment,and follow-up,providing clinicians with guidance on standardized and holistic management of biliary tract cancer.

Management of biliary tract cancers in early-onset patients: A nested multicenter retrospective study of the ACABI GERCOR PRONOBIL cohort.

Accumulating data has shown the rising incidence and poor prognosis of early-onset gastrointestinal cancers, but few data exist on biliary tract cancers (BTC). We aimed to analyse the clinico-pathological, molecular, therapeutic characteristics and prognosis of patients with early onset BTC (EOBTC, age ≤50 years at diagnosis), versus olders. We analysed patients diagnosed with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder adenocarcinoma between 1 January 2003 and 30 June 2021. Baseline characteristics and treatment were described in each group and compared. Progression-free survival, overall survival and disease-free survival were estimated in each group using the Kaplan-Meier method. Overall, 1256 patients were included, 188 (15%) with EOBTC. Patients with EOBTC demonstrated fewer comorbidities (63.5% vs. 84.5%, p < .0001), higher tumour stage (cT3-4: 50.0% vs. 32.3%, p = .0162), bilobar liver involvement (47.8% vs. 32.1%, p = .0002), and metastatic disease (67.6% vs. 57.5%, p = .0097) compared to older. Patients with EOBTC received second-line therapy more frequently (89.5% vs. 81.0% non-EOBTC, p = .0224). For unresectable patients with BTC, median overall survival was 17.0 vs. 16.2 months (p = .0876), and median progression-free survival was 5.8 vs. 6.0 months (p = .8293), in EOBTC vs. older. In advanced stages, fewer actionable alterations were found in EOBTC (e.g., IDH1 mutations [7.8% vs. 16.6%]; FGFR2-fusion [11.7% vs. 8.9%]; p = .029). Patients with EOBTC have a more advanced disease at diagnosis, are treated more heavily at an advanced stage but show similar survival. A distinctive molecular profile enriched for FGRF2 fusions was found.

Epidemiology of biliary tract cancer in China: A narrative review.

Biliary tract cancer (BTC) is a group of rare malignancies that affect the gallbladder and bile ducts. Although rare, BTC is becoming a significant public health burden in China, particularly among males and older individuals. The increasing trends in BTC incidence and mortality in China are influenced by various demographic, environmental, and lifestyle factors. In this review, we examine available epidemiological data on the incidence, mortality, prognosis, and trends of different BTC subtypes in China. We also discuss the challenges and opportunities for improving the prevention, diagnosis, and management of BTC in China, and identify areas for further research and intervention. The article aims to provide a better understanding of the epidemiological features of BTC in China and to inform public health strategies and clinical practice.

120P Management of biliary tract cancers in early onset patients: A French multicenter real-life study from the ACABI-PRONOBIL cohort

120P Management of biliary tract cancers in early onset patients: A French multicenter real-life study from the ACABI-PRONOBIL cohort

Current Role and Future Perspectives of Immunotherapy and Circulating Factors in Treatment of Biliary Tract Cancers.

Biliary tract cancers (BTCs) are a heterogenous group of malignancies arising from the epithelial cells of the biliary tree and the gallbladder. They are often locally advanced or already metastatic at the time of the diagnosis and therefore prognosis remains dismal. Unfortunately, the management of BTCs has been limited by resistance and consequent low response rate to cytotoxic systemic therapy. New therapeutic approaches are needed to improve the survival outcomes for these patients. Immunotherapy, one of the newest therapeutic options, is changing the approach to the oncological treatment. Immune checkpoint inhibitors are by far the most promising group of immunotherapeutic agents: they work by blocking the tumor-induced inhibition of the immune cellular response. Immunotherapy in BTCs is currently approved as second-line treatment for patients whose tumors have a peculiar molecular profile, such as high levels of microsatellites instability, PD-L1 overexpression, or high levels of tumor mutational burden. However, emerging data from ongoing clinical trials seem to suggest that durable responses can be achieved in other subsets of patients. The BTCs are characterized by a highly desmoplastic microenvironment that fuels the growth of cancer tissue, but tissue biopsies are often difficult to obtain or not feasible in BTCs. Recent studies have hence proposed to use liquid biopsy approaches to search the blood circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) to use as biomarkers in BTCs. So far studies are insufficient to promote their use in clinical management, however trials are still in progress with promising preliminary results. Analysis of blood samples for ctDNA to research possible tumor-specific genetic or epigenetic alterations that could be linked to treatment response or prognosis was already feasible. Although there are still few data available, ctDNA analysis in BTC is fast, non-invasive, and could also represent a way to diagnose BTC earlier and monitor tumor response to chemotherapy. The prognostic capabilities of soluble factors in BTC are not yet precisely determined and more studies are needed. In this review, we will discuss the different approaches to immunotherapy and tumor circulating factors, the progress that has been made so far, and the possible future developments.

Current status and tasks of management of biliary tract cancer

Current status and tasks of management of biliary tract cancer

Immunotherapy in Biliary Tract Cancers: Where Are We?

Biliary tract cancers (BTCs) are a heterogenous group of cancers arising from the biliary tract. The hallmark of these cancers is the advanced stage of presentation and a paucity of durable treatment options. Despite the advances in targeted therapy and immunotherapy in solid tumors, systemic cytotoxic chemotherapy has remained the mainstay for cholangiocarcinomas. With advances in the understanding of the tumor microenvironment, genetic features, and inflammatory milieu, have led to the identification of tumor-infiltrating immune cells as indicators of prognosis and response to treatment in BTC. Through an improved comprehension of immunology, immuno-oncology is becoming another pillar of treatment along with traditional radiation, surgery, cytotoxic chemotherapy, and targeted therapies. This article reviews the evidence for immunotherapy use in cholangiocarcinoma, which still being in infancy, and offers promising new novel options for the management of biliary tract cancers.

Health care resource utilization (HCRU) and costs in patients with biliary tract cancer (BTC) treated with systemic therapy in the United States (US).

4090 Background: BTC is associated with poor prognosis and limited treatment choices. There is limited evidence on HCRU and costs among BTC patients receiving systemic treatments (ST). This study examined HCRU and total direct cost of care among BTC patients treated with ST to understand the disease burden in management of BTC. Methods: A retrospective cohort study of BTC patients who received first line (1L) ST was conducted, using US private payer Cancer Care Quality Program data and administrative claims from the HealthCore Integrated Research Database between 07/01/2014 - 03/31/2021. Patients with ampullary cancer, brain/ CNS metastases, other primary cancer before BTC diagnosis were excluded. Per patient per month (PPPM) costs in 2020 USD were calculated during 1L, 2L, and 3L treatments associated with HCRU from inpatient, emergency room, and outpatient visits as well as outpatient pharmacy dispensing. Results: Among 298 BTC patients (biliary tract, n=203; gallbladder, n=65; bile duct, n=30; stage IV, n=231; stage III, n=28; stage I/II, n=39) who received ST, mean (SD) age was 61.7 (9) years at 1L treatment initiation, and the majority were female (58%). Following 1L treatment, 44% received 2L treatment, and 16% received 3L treatment. Median follow-up was 7.6 months. Among 201 (67%) patients who had hospitalization in the follow-up period, mean (SD) number of hospitalizations was 2.5 (2), and the average length of stay was 7.0 (5) days. Total PPPM all-cause costs were the lowest during 1L treatment (mean [SD]: $19,589 [$22,603]), and increased as the treatment advanced (2L: $22,617[$19,302]; 3L: $33,534[$40,588]). Similar trend was observed in BTC-related total costs with $16,237 ($22,452) in 1L, $19,083 ($18,670) in 2L and $27,609 ($39,949) in 3L. The table summarizes BTC-related HCRU and PPPM cost during each line of therapy. Conclusions: Study findings suggest significant resource use burden and high total direct medical costs for BTC patients receiving ST. Hospitalizations and outpatient visits represent important HCRU and cost for BTC. These data indicate a need for future newer innovative therapies in the management of BTC.[Table: see text]

Galectin-9 expression and decreased survival in advanced biliary tract cancers.

465 Background: Biliary tract cancers (BTCs) are a group of rare and aggressive malignancies often refractory to chemotherapeutic or targeted therapies, carrying an overall poor prognosis and high mortality. Identifying prognostic biomarkers and effective therapeutic targets for this disease therefore remains a high priority. T-cell immunoglobulin mucin domain-containing protein 3 (TIM-3), a negative regulatory immune checkpoint receptor, is known to induce immune tolerance and inhibit T-cell antitumor immunity. Its ligand, galectin-9 (Gal-9), has been shown to play a paradoxical role in tumorigenesis in a number of disease states. However, the role of Gal-9 in the setting of BTCs is not completely understood. Methods: We examined expression patterns of total cellular Gal-9 and TIM-3 in a panel of human BTC cell lines with diverse molecular profiles via immunoblot. Soluble Gal-9 (sGal-9) was measured by enzyme-linked immunoassay (ELISA). Tetrazolium-based MTT assay was utilized to evaluate cell viability following Ab-mediated Gal-9 neutralization. Pre-treatment peripheral blood was obtained from patients with metastatic BTCs enrolled in a randomized phase II clinical trial (NCI10139) and sGal-9 levels were measured. ROC curve analysis was employed to identify an optimal concentration cut-point value. Kaplan-Meier models were used to assess the association between sGal-9 levels and overall survival. Results: Human BTC cells demonstrate detectable and differential expression levels of total Gal-9 and TIM-3 proteins in vitro, with greater expression among intrahepatic cell lines (HUCCT-1, HUH28, SNU478). TIM-3 expression was not detected among extrahepatic (MzChA-1) and gallbladder cancer (WITT) cell lines. sGal-9 is secreted at variable levels between cell lines and its neutralization does not affect viability. Pre-treatment peripheral blood was obtained from 73 patients with metastatic BTCs (53% (n = 39) intrahepatic cholangiocarcinoma, 22% (n = 16) extrahepatic cholangiocarcinoma, 25% (n = 18) gallbladder cancer). There was no significant difference in sGal-9 levels between disease sites (p = 0.08). Patients were dichotomized by low and high sGal-9 levels. High baseline plasma levels of sGal-9 were associated with worse overall survival among patients with advanced BTCs (p = 0.03). Conclusions: Biliary tract cancer cells differentially express galectin-9 and its ligand, TIM-3, in vitro. Higher plasma levels of soluble galectin-9 are associated with worse overall survival, suggesting galectin-9 expression may be related to a more aggressive disease state. Additional work is needed to better inform the mechanistic role of the galectin-9/TIM-3 axis on disease progression and how best to leverage this pathway as a therapeutic target in the management of biliary tract cancers.

Diagnosis and Management of Biliary Tract Cancer

Biliary tract cancer (BTC) are highly aggressive and fatal malignancies. As one of the leading cause of death in Republic of Korea, BTC amoung various malignancies has been one of major public health concerns in the country. Although BTCs, including intrahepatic, perihilar, and distal cholangiocarcinoma, are relatively low-incidence malignancies compared to other cancer, but they represent a major health problem in endemic areas like Korea and Asia contries; moreover, the incidence of intrahepatic cholangiocarcinoma is rising globally. Surgery is the only curative treatment. The optimal surgical approach depends on the anatomical site of the primary tumour, and the best outcomes are achieved through management by specialist multidisciplinary team. Unfortunately, most patients present with locally advanced or metastatic disease. Only up to 20% of patients are diagnosed in early-stage, suitable for the curative surgery. Despite the surgery performed with potentially-curative intent, recurrence rates are high, around 60-70% of patients expected to have disease recurrence. In this review, we present an update of the causes, diagnosis, and treatment with a focus on chemotherapy of BTC.

Biliary Tract Cancers: Treatment Updates and Future Directions in the Era of Precision Medicine and Immuno-Oncology.

The effective management of biliary tract cancers (BTCs) has been hampered by limited options for systemic therapy. In recent years, the focus on precision medicine has made technologies such as next-generation sequencing (NGS) accessible to clinicians to identify targetable mutations in BTCs in tumor tissue (primarily) as well as blood, and to treat them with targeted therapies when possible. It has also expanded our understanding of functional pathways associated with genetic alterations and opened doors for identifying novel targets for treatment. Recent advances in the precision medicine approach allowed us to identify new molecular markers in BTCs, such as epigenetic changes (methylation and histone modification) and non-DNA markers such as messenger RNA, microRNA, and long non-coding RNA. It also made detecting these markers from non-traditional sources such as blood, urine, bile, and cytology (from fine-needle aspiration and biliary brushings) possible. As these tests become more accessible, we can see the integration of different molecular markers from all available sources to aid physicians in diagnosing, assessing prognosis, predicting tumor response, and screening BTCs. Currently, there are a handful of approved targeted therapies and only one class of immunotherapy agents (immune checkpoint inhibitors or ICIs) to treat BTCs. Early success with new targets, vascular endothelial growth factor receptor (VEGFR), HER2, protein kinase receptor, and Dickkopf-1 (DKK1); new drugs for known targets, fibroblast growth factor receptors (FGFRs) such as futabatinib, derazantinib, and erdafitinib; and ICIs such as durvalumab and tremelimumab is encouraging. Novel immunotherapy agents such as bispecific antibodies (bintrafusp alfa), arginase inhibitors, vaccines, and cellular therapy (chimeric antigen receptor—T cell or CAR-T, natural killer cells, tumor-infiltrating lymphocytes) have the potential to improve outcomes of BTCs in the coming years.

Potential utility of liquid biopsies in the management of patients with biliary tract cancers: A review.

Biliary tract cancer, comprising gallbladder cancer, cholangiocarcinoma and ampullary cancer, represents a more uncommon entity outside high-endemic areas, though global incidence is rising. The majority of patients present at a late stage, and 5-year survival remains poor. Advanced stage disease is incurable, and though palliative chemotherapy has been shown to improve survival, further diagnostic and therapeutic options are required in order to improve patient outcomes. Although certain subtypes of biliary tract cancer are relatively rich in targetable mutations, attaining tumour tissue for histological diagnosis and treatment monitoring is challenging due to locoregional anatomical constraints and patient fitness. Liquid biopsies offer a safe and convenient alternative to invasive procedures and have great potential as diagnostic, predictive and prognostic biomarkers. In this review, the current standard of care for patients with biliary tract cancer, future treatment horizons and the possible utility of liquid biopsies within a variety of contexts will be discussed. Circulating tumour DNA, circulating microRNA and circulating tumour cells are discussed with an overview of their potential applications in management of biliary tract cancer. A summary is also provided of currently recruiting clinical trials incorporating liquid biopsies within biliary tract cancer research.

Novel approaches for the management of biliary tract cancer: today and tomorrow

In this interview, we ask Dr. Alessandro Rizzo, Guest Editor of this special issue on biliary tract cancers and member of the Steering Committee of the GICO (Italian Cholangiocarcinoma Group) to of...

Is there any place for novel agents in treating biliary tract cancer?

Biliary tract cancer is an uncommon cancer in developed countries. In localized stages, surgery is the cornerstone of treatment with curative purpose. Conversely in advanced stages, chemotherapy with platinum-gemcitabine combination is the standard of care. Biliary tract cancers are a biologically heterogeneous group of malignancies, which perhaps explains the failure of targeted therapies in unselected patient populations to demonstrate benefit in advanced disease, although there are promises in selected populations (e.g. PD1/PD-L1 positive, BRAFV600E-mutated or IDH1-mutant). In view of the limited benefit of second line therapies in metastatic biliary tract cancer, various targeted agents have been tested in progressive disease. Furthermore, several ongoing trials are using next-generation sequencing of multiple genes to identify molecular abnormalities in the tumors of patients with refractory cancers that may potentially be used in pretreated disease (e.g. FGFR or IDH genes). Immunotherapy with immune checkpoint inhibitors may be interesting for patients whose tumors have programmed cell death 1 ligand 1 (PD-L1) overexpression. Ongoing and future trials will further advance our knowledge toward the optimal treatment strategy for the management of biliary tract cancer in its different stages, starting from metastatic and then reaching early stages of disease. We here provided an overview of these novel treatment strategies for advanced biliary tract cancers not amenable of curative treatment modalities.

Clinical practice guidelines for the management of biliary tract cancers 2019: The 3rd English edition.

The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract cancers (cholangiocarcinoma, gallbladder cancer, and ampullary cancer) in 2007, then published the 2nd version in 2014. In this 3rd version, clinical questions (CQs) were proposed on six topics. The recommendation, grade for recommendation, and statement for each CQ were discussed and finalized by an evidence-based approach. Recommendations were graded as Grade 1 (strong) or Grade 2 (weak) according to the concepts of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The 31 CQs covered the six topics: (a) prophylactic treatment, (b) diagnosis, (c) biliary drainage, (d) surgical treatment, (e) chemotherapy, and (f) radiation therapy. In the 31 CQs, 14 recommendations were rated strong and 14 recommendations weak. The remaining three CQs had no recommendation. Each CQ includes a statement of how the recommendations were graded. This latest guideline provides recommendations for important clinical aspects based on evidence. Future collaboration with the cancer registry will be key for assessing the guidelines and establishing new evidence.

Biliary Tract Cancers: Molecular Heterogeneity and New Treatment Options.

Simple SummaryIncidence of biliary tract cancer is increasing, and patients are frequently diagnosed with unresectable or metastatic disease, when therapeutic options are limited. Due to these reasons, prognosis remains poor and new systemic treatment options are urgently needed. This article reviews the new available data on molecular heterogeneity of biliary tract cancer and especially intrahepatic cholangiocarcinoma and the novel therapeutic strategies offered by the improved knowledge of the biology of this disease. For these reasons, this topic is of relevant interest for the oncology and hepatology community.Most patients with biliary tract cancer (BTC) are diagnosed with advanced disease, relapse rates are high in those undergoing surgery and prognosis remains poor, while the incidence is increasing. Treatment options are limited, and chemotherapy is still the standard of care in both adjuvant and advanced disease setting. In recent years, different subtypes of BTC have been defined depending on the anatomical location and genetic and/or epigenetic aberrations. Especially for intrahepatic cholangiocarcinoma (iCCA) novel therapeutic targets have been identified, including fibroblast growth factor receptor 2 gene fusions and isocitrate dehydrogenase 1 and 2 mutations, with molecularly targeted agents having shown evidence of activity in this subgroup of patients. Additionally, other pathways are being evaluated in both iCCA and other subtypes of BTC, alongside targeting of the immune microenvironment. The growing knowledge of BTC biology and molecular heterogeneity has paved the way for the development of new therapeutic approaches that will completely change the treatment paradigm for this disease in the near future. This review provides an overview of the molecular heterogeneity of BTC and summarizes new targets and emerging therapies in development. We also discuss resistance mechanisms, open issues, and future perspectives in the management of BTC.

Genetic analysis in the clinical management of biliary tract cancer.

Biliary tract cancer (BTC) is clinically and pathologically heterogeneous and responds inadequately to treatment. A small section of patients develop resectable disease, although the relapse rates are high; the benefits of adjuvant capecitabine chemotherapy for BTC are now understood, and gemcitabine‐based combination chemotherapy is the first line of therapeutic strategy for BTC; however, alternative therapy for BTC is not known. Genomic profiling can provide detailed information regarding the carcinogenesis, identification, and therapy for BTC. Currently, confirmed restorative targets for BTC are lacking. In this review, we aimed to analyze the preclinical and clinical implications of a spectrum of genomic alterations associated with new potentially remedial targets. We focused on eight draggable genes for BTC, which were described as having evidence of therapeutic impact (evidence level 2A‐3B) based on the clinical practice guidance for next‐generation sequencing in cancer diagnosis and treatment; these include ERBB2, NTRK1, RNF43, CDK6, CDKN2B, FGFR2, IDH1, and IDH2. Moreover, some of the BTC present microsatellite instability, hypermutation, and germline variants, which we also reviewed. Finally, we discussed the therapeutic options based on the next‐generation sequencing findings in BTC. Studies have demonstrated that BTC includes subgroups with individually distinct driver mutations, most of which will be targeted with new treatment plans.

Modern gastrointestinal endoscopic techniques for biliary tract cancers.

Biliary tract cancers, specifically cholangiocarcinomas (CCAs), arise from the epithelial cells of the biliary tree. They can be divided into three groups based on their location: intra-hepatic, peri-hilar or distal extra-hepatic CCAs. Traditionally, the main role of endoscopy in the management of biliary tract cancers was diagnosis and biliary decompression. For diagnosis, endoscopic retrograde cholangiopancreatography (ERCP) can be used to obtain either brushings or intra-ductal biopsies however both techniques have poor sensitivity. The introduction of cholangioscopy has allowed endoscopists to perform both targeted biopsies and also obtain a visual diagnosis. Similarly, with the spread of endoscopic ultrasound (EUS), the ability to obtain tissue by fine-needle aspiration is another avenue available, but concerns regarding tumor seeding still persist. For biliary decompression, with the advent of neo-adjuvant therapy, the role of early decompression is growing. Nevertheless, it is still not clear whether endoscopic decompression is superior to percutaneous decompression, especially in advanced hilar tumors. When possible, at least 50% of viable liver should be drained, and that will determine whether unilateral or bilateral stents are required. Additionally, there is growing evidence on the benefits of metal stents over plastic stents, but care should be taken as metal stents are generally permanent. Finally, although not widely available or adopted, with the growing use of radiofrequency ablation and the introduction of drug-eluting metal stents, the near-future might allow newer techniques to treat the disease itself.

18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) for patients with biliary tract cancer: Systematic review and meta-analysis

The role of 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) in the diagnosis and staging of patients with biliary tract cancers (BTCs) remains controversial, so we aimed to provide robust information on the utility of 18FDG-PET in the diagnosis and management of BTC. This systematic review and meta-analysis explored the diagnostic test accuracy of 18FDG-PET as a diagnostic tool for diagnosis of primary tumour, lymph node invasion, distant metastases and relapsed disease. Subgroup analysis by study quality and BTC subtype were performed. Changes in management based on 18FDG-PET and impact of maximum standardised uptake values (SUVmax) on prognosis were also assessed. A random effects model was used for meta-analyses. A total of 2,125 patients were included from 47 eligible studies. The sensitivity (Se) and specificity (Sp) of 18FDG-PET for the diagnosis of primary tumour were 91.7% (95% CI 89.8-93.2) and 51.3% (95% CI 46.4-56.2), respectively, with an area under the curve (AUC) of 0.8668. For lymph node invasion, Se was 88.4% (95% CI82.6-92.8) and Sp was 69.1% (95% CI 63.8-74.1); AUC 0.8519. For distant metastases, Se was 85.4% (95% CI 79.5-90.2) and Sp was 89.7% (95% CI86.0-92.7); AUC 0.9253. For relapse, Se was 90.1% (95% CI 84.4-94.3) and Sp was 83.5% (95% CI 74.4-90.4); AUC 0.9592. No diagnostic threshold effect was identified. Meta-regression did not identify significant sources of heterogeneity. Sensitivity analysis revealed no change in results when analyses were limited to studies with low risk of bias/concern. The pooled proportion of change in management was 15% (95% CI 11-20); the majority (78%) due to disease upstaging. Baseline high SUVmax was associated with worse survival (pooled hazard ratio of 1.79; 95% CI 1.37-2.33; p <0.001). There is evidence to support the incorporation of 18FDG-PET into the current standard of care for the staging (lymph node and distant metastases) and identification of relapse in patients with BTC to guide treatment selection; especially if the identification of occult sites of disease would change management, or if diagnosis of relapse remains unclear following standard of care imaging. The role for diagnosis of the primary tumour remains controversial due to low sensitivity and 18FDG-PET should not be considered as a replacement for pathological confirmation in this setting. A positron emission tomography (PET scan), using 18F-fluorodeoxyglucose (18FDG), can help doctors identify areas of cancer in the body by highlighting "hot spots". These hotspots may be cancerous (true positive) but may also be non-cancerous, like inflammation (false positive). We show that PET scans are useful to assess how far advanced the cancer is (by assessing spread to lymph glands and to other organs) and also to identify if the cancer has recurred (for example after surgery), thus helping doctors to make treatment decisions. However, a biopsy is still needed for the initial diagnosis of a biliary tract cancer, because of the high chance of a "false positive" with PET scans.