DelveInsight’s ‘Biliary Tract Cancer (BTC) – Epidemiology Forecast—2030’ report delivers an in-depth understanding of the historical and forecasted epidemiology of biliary tract cancer in the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan.
Study Period: 2017–2030
Biliary Tract Cancer: Disease Understanding
Biliary Tract Cancer Overview
According to the Cholangiocarcinoma Foundation, about 8,000 people in the US are diagnosed with cholangiocarcinoma each year. It can occur at younger ages but is most common in older people, and the average age of diagnosis is 70–75. It is much more common in Asia and the Middle East, mostly because of the bile duct’s common parasitic infection
Biliary Tract Cancer constitutes epithelial malignancies of the biliary tree and include the following: gallbladder cancer (GBC), intrahepatic CCA (iCCA) and extrahepatic CCA (eCCA). The extrahepatic disease may be split into perihilar (Klatskin’s tumor) and distal CCA.
BTC constitutes approximately 3% of all gastrointestinal malignancies and is the most common hepatobiliary cancer after hepatocellular carcinoma. Primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), cirrhosis due to other causes, hepatitis C and congenital malformations such as choledochal cysts and multiple biliary papillomatosis are also associated with an increased risk of developing BTC. In addition, patients with germline mutations resulting in Lynch syndrome and BRCA1 and BRCA2 (breast cancer gene 1 and 2) genetic aberrations are also predisposed to BTC.
Gallbladder cancer originates in the cells of the gallbladder, and most are adenocarcinomas, which begin in the gland cells of the gallbladder lining. While, CCA is an epithelial malignancy originating from transformed cholangiocytes, with preclinical studies suggesting hepatic progenitor cells as the origin. iCCA can emerge at any point in the intrahepatic biliary tree, ranging from mian bile ducts to the segmental bile ducts. In contrast to HCC, iCCA usually develops in non-cirrhotic liver. pCCA can arise in the right and/or left hepatic duct and/or at their junction (so-called perihilar bile ducts), and dCCA involves the common bile duct. The current term extrahepatic cholangiocarcinoma (eCCA) is now discouraged from using as it combines subtypes with distinct clinicopathological features, origins, prognosis, and therapeutic options. Ampullary cancer originates in the area where the common bile duct meets the pancreatic duct, which is called the Ampulla of Vater.
Inflammation and cholestasis are key factors in cholangiocarcinogenesis. Next-generation sequencing has identified somatic mutations in oncogenes (i.e., KRAS), tumor suppressor (i.e., TP53 and SMAD4), and chromatin-modifying genes (i.e., ARID1A, BAP1, and PBMR1) in CCA. Furthermore, the tumor commonly metastasizes via lymphatic spread to the regional lymph nodes, followed by hematogenous metastasis to the liver, lungs, and peritoneum. The majority of cholangiocarcinomas are adenocarcinomas with variable grades of differentiation (mainly well-differentiated adenocarcinomas), although several uncommon types are also encountered, such as adenosquamous, squamous, mucinous, and anaplastic carcinomas. Jaundice and abdominal pain are the most common presentations of BTC.
A diagnosis of biliary tract cancer is usually based on the results of clinical examination of the abdomen, imaging scans using ultrasound, magnetic resonance imaging (MRI) or computed tomography (CT), and a biopsy. Further investigations can help to determine how advanced the cancer is (the ‘stage’). For example, MRI of the biliary tract, a CT scan of the chest and an ultrasound scan of the lymph nodes are commonly used to see how far cancer has spread. Biliary tract cancer is staged according to tumor size, whether it has spread to the lymph nodes and whether it has spread into the liver, lungs or other parts of the body. This information is used to help decide the best treatment.
Treatment options for the early-stage disease include surgery followed by adjuvant chemotherapy. For patients with locally advanced disease, locoregional therapies (e.g., trans-arterial chemoembolization (TACE) and external beam radiation therapy (EBRT) may be considered. However, these have not yet been validated in prospective randomized controlled trials, and therefore, their use is very variable. For patients with locally advanced and metastatic disease, the combination of gemcitabine and cisplatin has been shown to improve survival.
The Biliary Tract Cancer epidemiology division provides insights about the historical and current patient pool, along with the forecasted trend for every seven major countries. It helps recognize the causes of current and forecasted trends by exploring numerous studies and views of key opinion leaders. This part of the report also provides the diagnosed patient pool and their trends along with assumptions undertaken.
Key Findings
The disease epidemiology covered in the report provides historical and forecasted Biliary Tract Cancer epidemiology segmented as the total incident cases of biliary tract cancer, age-specific cases of biliary tract cancer, stage-specific cases of biliary tract cancer and mutation-specific cases of biliary tract cancer. The report includes the incident scenario of biliary tract cancer in the 7MM covering the United States, EU5 countries (Germany, France, Italy, Spain, and the United Kingdom), and Japan from 2017 to 2030.
Country-wise Biliary Tract Cancer Epidemiology
The epidemiology segment also provides the biliary tract cancer epidemiology data and findings across the United States, EU5 (Germany, France, Italy, Spain, and the United Kingdom), and Japan.
The total incident population of biliary tract cancer in the 7MM countries was estimated to be 70,111 cases in 2017.
As per the estimates, in 2017, the United States had the highest incident population of biliary tract cancer. Among the EU5 countries, Germany had the highest incident population of biliary tract cancer with 6,918 cases, followed by Italy in 2017. On the other hand, Spain had the lowest incident population of 2,908 cases in 2017.
We interview KOLs and obtain SME’s opinion through primary research to fill the data gaps and validate our secondary research. The opinion helps understand the total patient population and current treatment pattern. This will support the clients in potential upcoming novel treatment by identifying the overall scenario of the indications.
Biliary Tract Cancer Epidemiology report will allow the user to:
1. Key Insights
2. Biliary Tract Cancer (BTC): Patient Overview at a Glance
2.1. Patient Share (%) Distribution of BTC in 2017
2.2. Patient Share (%) Distribution of BTC in 2030
3. Executive Summary
4. Organizations
5. Biliary tract cancer (BTC): Disease Background and Overview
5.1. Introduction
5.2. Classification of Cholangiocarcinomas
5.3. Staging
5.3.1. Intrahepatic CCA (iCCA)
5.3.2. Perihilar CCA
5.3.3. Distal extrahepatic
5.3.4. Gall Bladder Cancer
5.4. Symptoms
5.5. Etiology
5.6. Pathogenesis
5.7. Biomarkers
5.8. Diagnosis
5.8.1. Diagnosis of Intrahepatic CCA
5.8.2. Diagnosis of Perihilar and Distal CCA
5.8.3. Diagnosis of Gall Bladder Cancer
5.8.4. Guidelines for the diagnosis of intrahepatic cholangiocarcinoma
5.8.5. ESMO Clinical Practice Guidelines for diagnosis for Biliary tract Cancer
6. Epidemiology and Patient Population
6.1. Key Findings
6.2. 7MM Total Incident Patient Population of BTC
6.3. Assumptions and Rationale: 7MM
6.4. United States Epidemiology
6.4.1. Total Incident Cases of Biliary tract cancers (BTC) in the United States
6.4.2. Age-specific Cases of Biliary tract cancers (BTC) in the United States
6.4.3. Mutation-specific Cases of Biliary tract cancers (BTC) in the United States
6.4.4. Stage-specific Cases of Biliary tract cancers (BTC) in the United States
6.5. Germany Epidemiology
6.5.1. Total Incident Cases of Biliary tract cancers (BTC) in Germany
6.5.2. Age-specific Cases of Biliary tract cancers (BTC) in Germany
6.5.3. Mutation-specific Cases of Biliary tract cancers (BTC) in Germany
6.5.4. Stage-specific Cases of Biliary tract cancers (BTC) in Germany
6.6. France Epidemiology
6.6.1. Total Incident Cases of Biliary tract cancers (BTC) in France
6.6.2. Age-specific Cases of Biliary tract cancers (BTC) in France
6.6.3. Mutation-specific Cases of Biliary tract cancers (BTC) in France
6.6.4. Stage-specific Cases of Biliary tract cancers (BTC) in France
6.7. Italy Epidemiology
6.7.1. Total Incident Cases of Biliary tract cancers (BTC) in Italy
6.7.2. Age-specific Cases of Biliary tract cancers (BTC) in Italy
6.7.3. Mutation-specific Cases of Biliary tract cancers (BTC) in Italy
6.7.4. Stage-specific Cases of Biliary tract cancers (BTC) in Italy
6.8. Spain Epidemiology
6.8.1. Total Incident Cases of Biliary tract cancers (BTC) in Spain
6.8.2. Age-specific Cases of Biliary tract cancers (BTC) in Spain
6.8.3. Mutation-specific Cases of Biliary tract cancers (BTC) in Spain
6.8.4. Stage-specific Cases of Biliary tract cancers (BTC) in Spain
6.9. UK Epidemiology
6.9.1. Total Incident Cases of Biliary tract cancers (BTC) in UK
6.9.2. Age-specific Cases of Biliary tract cancers (BTC) in UK
6.9.3. Mutation-specific Cases of Biliary tract cancers (BTC) in UK
6.9.4. Stage-specific Cases of Biliary tract cancers (BTC) in UK
6.10. Japan Epidemiology
6.10.1. Total Incident Cases of Biliary tract cancers (BTC) in Japan
6.10.2. Age-specific Cases of Biliary tract cancers (BTC) in Japan
6.10.3. Mutation-specific Cases of Biliary tract cancers (BTC) in Japan
6.10.4. Stage-specific Cases of Biliary tract cancers (BTC) in Japan
7. Therapies and Treatment strategies
7.1.1. Treatment Recommendations – British Society of Gastroenterology guidelines
7.1.2. Guidelines for the treatment of Intrahepatic Cholangiocarcinoma
7.1.3. ESMO Clinical Practice Guidelines for Treatment and Follow-up for Biliary Tract Cancer
7.1.4. NCCN Guidelines for Hepatobiliary Cancer 2020
7.1.5. Treatment Algorithm
8. Patient Journey
9. Research Priorities
10. Unmet Needs
11. Reimbursement and Market Access
12. SWOT Analysis
13. Case studies
13.1. A Case Report of Intrahepatic Cholangiocarcinoma in a Young Male
13.2. A new potential immunotherapy drug for solid tumor: A case study
13.3. A case of distal extrahepatic cholangiocarcinoma with two positive resection margins
14. KOL Views
15. Appendix
16. Report Methodology
17. DelveInsight Capabilities
18. Disclaimer
19. About DelveInsight
List of Table
Table 1: TNM and AJCC/UICC Staging Systems for iCCA
Table 2: AJCC staging of iCCA: Comparison of 7th and 8th editions
Table 3: TNM and AJCC/UICC Staging Systems for Perihilar and Distal CCA
Table 4: TNM and AJCC/UICC Staging Systems for Gall Bladder Cancer
Table 5: Risk Factors for BTC
Table 6: Host genetic polymorphism associated with cholangiocarcinoma
Table 7: Recommendations of ICCA for Diagnosis
Table 8: ESMO Clinical Practice Guidelines for treatment and follow-up
Table 9: Total Incident Cases of Biliary tract cancers in the 7MM (2017–2030)
Table 10: Total Incident Cases of BTC in the US (2017–2030)
Table 11: Age-specific Cases of BTC in the US (2017–2030)
Table 12: Mutation-specific Cases of BTC in the US (2017–2030)
Table 13: Stage-specific Cases of BTC in the US (2017–2030)
Table 14: Total Incident Cases of BTC in Germany (2017–2030)
Table 15: Age-specific Cases of BTC in Germany (2017–2030)
Table 16: Mutation-specific Cases of BTC in Germany (2017–2030)
Table 17: Stage-specific Cases of BTC in Germany (2017–2030)
Table 18: Total Incident Cases of BTC in France (2017–2030)
Table 19: Age-specific Cases of BTC in France (2017–2030)
Table 20: Mutation-specific Cases of BTC in France (2017–2030)
Table 21: Stage-specific Cases of BTC in France (2017–2030)
Table 22: Total Incident Cases of BTC in Italy (2017–2030)
Table 23: Age-specific Cases of BTC in Italy (2017–2030)
Table 24: Mutation-specific Cases of BTC in Italy (2017–2030)
Table 25: Stage-specific Cases of BTC in Italy (2017–2030)
Table 26: Total Incident Cases of BTC in Spain (2017–2030)
Table 27: Age-specific Cases of BTC in Spain (2017–2030)
Table 28: Mutation-specific Cases of BTC in Spain (2017–2030)
Table 29: Stage-specific Cases of BTC in Spain (2017–2030)
Table 30: Total Incident Cases of BTC in UK (2017–2030)
Table 31: Age-specific Cases of BTC in UK (2017–2030)
Table 32: Mutation-specific Cases of BTC in UK (2017–2030)
Table 33: Stage-specific Cases of BTC in UK (2017–2030)
Table 34: Total Incident Cases of BTC in Japan (2017–2030)
Table 35: Age-specific Cases of BTC in Japan (2017–2030)
Table 36: Mutation-specific Cases of BTC in Japan (2017–2030)
Table 37: Stage-specific Cases of BTC in Japan (2017–2030)
Table 38: Recommendations of the British Society of Gastroenterology guidelines
Table 39: Recommendations of iCCA for management
Table 40: Levels of evidence and grades of recommendation
Table 41: ESMO Clinical Practice Guidelines for treatment and follow-up
Table 42: ESMO Clinical Practice Guidelines for treatment and follow-up
Table 43: NCCN Guidelines for Hepatobiliary Cancer 2020
Table:44 NCCN Guidelines for Principles of Systemic Therapy**
List of Figures
Figure 1: Risk factors and molecular alterations of BTC
Figure 2: Possible Risk Factor and Symptoms
Figure 3: Cells of origin in Cholangiocarcinoma (CCA)
Figure 4: Chronic Inflammation Cycle
Figure 5: Components of the tumor microenvironment in CCA
Figure 6: Factors secreted by cancer-associated fibroblasts
Figure 7: Intracellular pathways involved in CCA proliferation and apoptosis
Figure 8: Common driver genes in HCC and CCA
Figure 9: Molecular genetics of BTC
Figure 10: Algorithm for management and diagnosis of intrahepatic CCA
Figure 11: Algorithm for management and diagnosis of perihilar cholangiocarcinoma
Figure 12: Total Cases of Biliary tract cancers (BTC) in the 7MM (2017–2030)
Figure 13: Total Incident Cases of BTC in the US (2017–2030)
Figure 14: Age-specific Cases of BTC in the US (2017–2030)
Figure 15: Mutation-specific Cases of BTC in the US (2017–2030)
Figure 16: Stage-specific Cases of BTC in the US (2017–2030)
Figure 17: Total Incident Cases of BTC in Germany (2017–2030)
Figure 18: Age-specific Cases of BTC in Germany (2017–2030)
Figure 19: Mutation-specific Cases of BTC in Germany (2017–2030)
Figure 20: Stage-specific Cases of BTC in Germany (2017–2030)
Figure 21: Total Incident Cases of BTC in France (2017–2030)
Figure 22: Age-specific Cases of BTC in France (2017–2030)
Figure 23: Mutation-specific Cases of BTC in France (2017–2030)
Figure 24: Stage-specific Cases of BTC in France (2017–2030)
Figure 25: Total Incident Cases of BTC in Italy (2017–2030)
Figure 26: Age-specific Cases of BTC in Italy (2017–2030)
Figure 27: Mutation-specific Cases of BTC in Italy (2017–2030)
Figure 28: Stage-specific Cases of BTC in Italy (2017–2030)
Figure 29: Total Incident Cases of BTC in Spain (2017–2030)
Figure 30: Age-specific Cases of BTC in Spain (2017–2030)
Figure 31: Mutation-specific Cases of BTC in Spain (2017–2030)
Figure 32: Stage-specific Cases of BTC in Spain (2017–2030)
Figure 33: Total Incident Cases of BTC in UK (2017–2030)
Figure 34: Age-specific Cases of BTC in UK (2017–2030)
Figure 35: Mutation-specific Cases of BTC in UK (2017–2030)
Figure 36: Stage-specific Cases of BTC in UK (2017–2030)
Figure 37: Total Incident Cases of BTC in Japan (2017–2030)
Figure 38: Age-specific Cases of BTC in Japan (2017–2030)
Figure 39: Mutation-specific Cases of BTC in Japan (2017–2030)
Figure 40: Stage-specific Cases of BTC in Japan (2017–2030)
Figure 41: Algorithm for diagnosis and management of Biliary Tract Cancer
Figure 42: A suggested algorithm for the diagnosis and treatment of cholangiocarcinomas
Figure 43: A suggested treatment algorithm for patients with iCCA
Figure 44: Algorithm for diagnosis and management of dCCA
Figure 45: Flowchart – Management and treatment of patients suspected of perihilar CCA
Figure 46: A suggested diagnosis and treatment algorithm for Gallbladder Cancer
Figure 47: Unmet Needs of Cholangiocarcinoma (CCA)
Figure 48: SWOT Analysis of Biliary Tract Cancer
