A new review article notes efforts to diagnose cholangiocarcinoma (CCA) early are hampered by a lack of biomarkers.
People who have cholangiocarcinoma (CCA) often receive a diagnosis when their cancer has already advanced, and although surgery and/or chemotherapy are options in some cases, the current state of treatment means the prognosis for patients remains poor.
Those are some of the key takeaways from a new review article published in Annals of Hepatology.
In western countries, CCA is relatively rare, the investigators noted, making up just 1% of cancers and 10% to 15% of primary liver cancers. Yet, its incidence has more than doubled worldwide over the past decade.
Risk factors for CCA can vary significantly from patient to patient and region to region, but the study investigators said one common risk factor is chronic inflammation of biliary epithelium and bile stasis. Such inflammation could be triggered by several causes, including viruses, parasites, and environmental factors.
“Despite this, most cases are sporadic and occur without any accepted or known risk factors,” the authors wrote. “Thus, the adoption of surveillance protocol is limited, and early diagnosis remains challenging.”
They said surgery is considered the only curative possibility, although it is often difficult to preoperatively determine if a case is resectable, “as conventional radiology can underestimate the actual extent of the disease and the definitive decision to resect or not is generally made at surgical exploration.”
When resection is possible, it is usually followed by systemic chemotherapy with capecitabine, the authors said. Still, 5-year survival in CCA following resection has been found to be in the range of 25% to 40%, they added.
In cases of intrahepatic CCA that are diagnosed very early, a liver transplant may be a treatment option, the authors said, and when patients are not candidates for surgery, systemic chemotherapy with gemcitabine and cisplatin is the first treatment option, the authors said, “but the prognosis remains poor.”
However, there is reason to hope that new therapies might soon become available.
“Recent advances in immunotherapy have changed the therapeutic chances in biliary tract cancer, which are considered ‘immune-cold’ due to low-moderate tumor mutational burden,” the authors wrote. “Moreover, the tumor microenvironment encourages the immune escape and inhibition of immune response.”
The authors said several targeted therapies are being developed or investigated for CCA, either alone or in combination. Among them are immune checkpoint inhibitors targeting programmed cell death protein-1, programmed death-ligand 1, and cytotoxic T-lymphocyte antigen-4. Other strategies under investigation include chimeric antigen receptor T-cell therapies and tumor vaccines.
The authors concluded that even though research into the disease has been increasing, “the prognosis of CCA is still invariably poor.”
Despite a better understanding of some of the drivers of CCA, they said the triggers of factors like biliary inflammation are not always known and therefore are not preventable.
“In the subgroup of patients with recognized risk factors for CCA, lack of biomarkers for early diagnosis is a critical issue,” they wrote.
Biomarkers also remain an issue with regard to new potential therapies, since pretreatment biomarkers will likely be necessary in order to choose the most effective therapy.
“Therefore, more scientific and clinical efforts are warranted in order to identify targetable molecular mechanisms of cholangiocarcinogenesis, develop innovative therapeutic strategies, and improve our ability to stratify patients to offer them the best therapeutic strategy available,” they concluded.
Reference:
Elvevi A, Laffusa A, Scaravaglio M, et al. Clinical treatment of cholangiocarcinoma: an updated comprehensive review. Ann Hepatol. Published online July 6, 2022;. doi:10.1016/j.aohep.2022.100737
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