A “silent” neoplasm, with vague and often underestimated symptoms, for which diagnosis is often late. A multidisciplinary team and the experience of surgeons are decisive for choosing therapeutic strategies
It mainly affects men and in particular after the age of 70. In Italy every year there are about 5,400 new cases of cholangiocarcinoma, a rare tumor of the biliary tract particularly difficult to treat, precisely due to the late discovery of the disease in the vast majority of patients. It is, in fact, a “silent” neoplasm, often characterized by generic symptoms (such as abdominal pain, weight loss, nausea, a general sense of weakness and fatigue) that can be easily underestimated or confused with those of other pathologies. Precisely to raise awareness of this pathology and inform about symptoms, risk factors and treatment opportunities, World Cholangiocarcinoma Day is celebrated on 12 February, a world day dedicated to giving greater visibility to a type of cancer that is still little talked about.
Cases on the rise in Italy
Biliary tract tumors are a heterogeneous group of different liver cancers: cholangiocarcinoma originates from cholangiocytes, the cells that line the bile ducts, the channels that transport bile from the liver to the intestine. The various subtypes are distinguished on the basis of their site of onset: intrahepatic, if they develop within the liver, and extrahepatic, if they arise from the extrahepatic biliary tract. And the cases are increasing (in our country they have increased by 14% in 5 years, going from 4700 in 2015 to 5400 in 2020). “There are some liver diseases that are very well recognized as risk factors – explains Filippo de Braud, full professor of Medical Oncology at the University of Milan and director of the Department and Division of Medical Oncology of the IRCCS National Cancer Institute of Milan Foundation -: Gallstones and primary sclerosing cholangitis, a severe chronic inflammatory disease of the liver, increase the odds for intrahepatic forms. As well as obesity, smoking, chronic inflammatory bowel diseases, excessive alcohol consumption and exposure to carcinogenic chemicals, toxins and various environmental agents (dioxins, nitrosamines, radon and asbestos) “.
In particular, with regard to asbestos, data are accumulating: “Retrospective and prospective case control studies (the latter being published in 2022) suggest that the risk of intrahepatic cholangiocarcinomas increases at least 5 times in the exposed – adds Giovanni Brandi, director of the School of Specialization of Medical Oncology at the University of Bologna -. All this has already led to definitive sentences by Italian courts that have accepted the correlation between asbestos and the development of intrahepatic cholangiocarcinomas ».
Late stage diagnosis in 70% of patients
To date, precisely because the disease is usually asymptomatic for a long time (and the first signs appear if the neoplasm is advanced) and since to date there are no methods for early diagnosis,
lsurveillance in higher-risk patients increases the likelihood of an early-stage diagnosis as the disease is still amenable to complete surgical resection. “In the extrahepatic form, 90% of patients present to the specialist with jaundice (yellow color of the skin and sclerae, due to the accumulation of bile in the blood) with dark urine, whitish stools and itching (due to increased levels of bile salts in the blood) without pain, and only in 10% of cases are symptoms referable to cholangitis, such as pain and fever – says Nicola Silvestris, Member of the National Board of AIOM (Italian Association of Medical Oncology) and associate professor of Medical Oncology at the ‘IRCCS John Paul II Cancer Institute of Bari -. In intrahepatic cholangiocarcinoma, non-specific disorders can be felt and for this reason 70% of patients present at diagnosis with a disease already in an advanced stage, with few possibilities of treatment, even if today innovative weapons capable of improving survival are emerging ” . Unfortunately, at the moment, cholangiocarcinoma remains a difficult neoplasm and in Italy the survival five years from diagnosis is equal to 17% in men and 15% in women.
The therapies
Surgery is the first fundamental step to be able to hope for recovery, but it is not always practicable due to late diagnosis. In any case, it is essential to be treated in a center with experience, both in the intervention (not simple due to the very complexity of the area in which the neoplasm is located) and in the diagnosis and treatment, which require a multidisciplinary team of professionals expert in this specific pathology. “Only 25% of patients are candidates for surgery, but the operation, if carried out in the early stage of the disease, can have a resolutive outcome – Silvestris underlines -. In many cases, precautionary chemotherapy is indicated after surgery. Nonetheless, even after radical and potentially curative surgical resection, recurrence occurs in 60% of cases within two years. In patients who cannot be operated on or in whom there is a relapse, the treatment of first choice is chemotherapy, which can help control the evolution of the tumor, albeit with limited efficacy. In fact, most patients at some point no longer respond to first-line chemotherapy ».
New treatments are being studied
“This is why new weapons are needed – highlights de Braud -. In recent years, much attention has been paid to the molecular characterization of the disease through gene sequencing techniques, which have made it possible to identify alterations targeting specific drugs. And there are numerous studies aimed at understanding the role of targeted therapies in advanced or metastatic cholangiocarcinoma, in particular in tumors with intrahepatic genesis. Overall, about half of cholangiocarcinomas have one or more mutations potentially treatable with molecularly targeted drugs “. In particular, translocations of FGFR2 (fibroblast growth factor receptor 2) are present in approximately 7% of intrahepatic cholangiocarcinomas in Europe. “In the multi-center phase II clinical trial FIGHT-202, pemigatinib, a new targeted therapy, demonstrated an overall response rate of 37% and a median duration of response of 8 months in patients with FGFR2 fusions or rearrangements – continues de Braud -. Pemigatinib has a higher activity than that of other molecules used in second or subsequent lines of treatment. The results are important and, in a small percentage of patients, complete responses have even been observed, so the disease has disappeared ». Based on the results of the FIGHT-202 study, last year the European Commission approved pemigatinib in locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements and with disease progression after at least one previous line of systemic therapy.
Also raise awareness among general practitioners
The purpose of the World Day is to shed light on a rare disease that is still too little talked about. “The path leading to diagnosis is very complex for extrahepatic cholangiocarcinomas, but it is often late also for intrahepatic cholangiocarcinomas, where the diagnostic path would be easier if the signs / symptoms of suspicion were detected early – concludes Giovanni Brandi, founder of Italian Cholangiocarcinoma Patients Association (APiC) and of the Italian Cholangiocarcinoma Group (GICO) -. For this reason, even family doctors must be sensitized, so that they are able to detect the first suspicious symptoms. Sometimes a simple laboratory alteration, such as an increase in alkaline phosphatase, is enough to induce suspicion to be investigated. In addition, it is essential that patients are referred early to referral centers where complete care is possible by a dedicated multidisciplinary team, consisting of the medical oncologist, the hepatobiliary surgeon, the diagnostic radiologist and interventionist, hepatologist, endoscopist and radiotherapist, able to better define the diagnostic and therapeutic path “.
February 11, 2022 (change February 11, 2022 | 13:05)
© Time.News