Over recent years, Biliary Tract Cancer (BTC) has claimed the life of many individuals. BTC is an epithelial malignancy of the biliary tree. Around 3% of all gastrointestinal malignancies are established by BTC, and after hepatocellular carcinoma, BTC is the most common hepatobiliary cancer.
Biliary Tract Cancer is a complex disease because of its heterogeneous nature. Many classification systems have been outlined since the introduction of the disease, but the most recent NCCN and ESMO guidelines classify BTC as Gallbladder cancer (GBC), and Cholangiocarcinoma (CCA). The CCA further divided into intra-hepatic CCA, perihilar (Klatskin’s tumor), and distal CCA. Furthermore, CCA can also be classified based on the growth pattern of the tumor as mass-forming, periductal infiltrating, and intraductal. The mass-forming type is most commonly witnessed for intrahepatic Cholangiocarcinoma and is associated with a high rate of lymph node metastasis. The periductal infiltrating type is commonly seen in perihilar Cholangiocarcinoma. In another clinical classification system proposed by Bismuth, these tumors are classified by anatomic location as type I – confined to the common hepatic duct, type II –involving the common hepatic duct bifurcation, type IIIa –affecting the hepatic duct bifurcation and the right hepatic duct, type IIIb – affecting the hepatic duct bifurcation and the left hepatic duct and type IV – located at the biliary confluence with both the right and left hepatic ducts involvement or has multifocal distribution. Lastly, concerning the occurrence segmentation, Gallbladder cancer is the most common among all BTC, followed by perihilar and then distal common bile duct cholangiocarcinoma.
As far as incidence is concerned, DelveInsight estimates the total Biliary tract cancer incidence in the US as 16,653 cases, Germany as 6,918 cases, Italy as 6,423 cases, Spain as 2,908 cases, and Japan as 28,907.
Despite being a common cancer, the carcinogenesis remains to be poorly understood. Studies suggest that BTC involves the malignant transformation of epithelial cells. Gallbladder cancer originates in the cells of the gallbladder, and most are adenocarcinomas, which begin in the gland cells of the gallbladder lining. CCA malignancy originates from transformed cholangiocytes. Inflammation and cholestasis are considered as key factors in cholangiocarcinogenesis. At any point in the intrahepatic tree, stretching from main bile ducts to the segmental bile ducts, iCCA can emerge. In contrast to HCC, iCCA usually advances 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 dejected to use 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. Mutated driver genes in BTC cases appear moderately analogous to that of Hepatocellular carcinoma (TP53, ARID1A, and ARID2) and pancreatic cancer (TP53, KRAS, and SMAD4). By contrast, characteristically, alterations in WNT signaling and TERT were infrequent, and IDH1 mutations (3%) were unique in BTC.
The disease is heralded as a silent killer as the symptoms presented are often camouflaged and misinterpreted, which results in misdiagnosis, and eventually, the patient is pushed to late-stage. Moreover, in recent times and ages, little progress has been made in the treatment for this aggressive disease; consequently, the need for superior treatment options continues to prevail. This makes the diagnosis of BTC challenging, however, the latest technology enables conclusive diagnosis. Patients usually undergo endoscopic retrograde cholangiopancreatography and more than a few procedures, namely chromoendoscopy, cytology, brushing, biopsy, ultrasonography, choledochoscopy, cholangioscopy, confocal endoscopy, narrow-band imaging, and FISH (fluorescence in situ hybridization)-polisomy. MRI, CT, endoscopic ultrasonography or 18FDG PET-CT cannot conclusively establish the stricture’s neoplastic nature.
The Biliary Tract Cancer market remains to lack effective treatment as most patients currently with advanced-stage disease fail to seek a qualitative cure. However, for early-stage disease, surgery followed by adjuvant chemotherapy is the mainstay. Whereas for patients with locally advanced disease, loco-regional therapies (e.g., trans-arterial chemoembolization (TACE) and external beam radiation therapy (EBRT)) may be considered. For patients with locally advanced and metastatic disease, the combination of gemcitabine and cisplatin has also been demonstrated to improve survival.
DelveInsight estimates that owing to vast unmet needs, especially for the treatment for the BTC patients and the onset of technological advancements, the Biliary tract cancer market would evolve in the upcoming years. Promising entrants for targeted, personalized therapy have emerged, including prospective driver FGFR gene fusions and somatic mutations in IDH 1/2 in iCCA, PRKACA, or PRKACB gene fusions in pCCA, and ELF3 mutations in dCCA/ampullary carcinoma. In addition, with continuous efforts in research and development, few companies are developing therapies, Ivosidenib (Agios Pharmaceuticals), Infigratinib (QED Therapeutics), Melphalan Hydrochloride (Delcath Systems), Futibatinib (Taiho Oncology), Bintrafusp Alfa (Merck Sharp & Dohme), Melphalan Hydrochloride (Delcath Systems), Durvalumab (AstraZeneca), Nanoliposomal Irinotecan (Ipsen), Zanidatamab (BeiGene), Pembrolizumab (Merck Sharp & Dohme), Nab-paclitaxel (Celgene), Fimaporfin (PCI Biotech), Lenvatinib (Eisai), Nivolumab (Bristol-Myers Squibb), Regorafenib (Bayer), Derazantinib (Basilea Pharmaceutica) and others that are expected to enter the market by 2030, which will fuel the growth of the Biliary tract cancer market size.