Aspirin for cholangiocarcinoma prevention: New targets to shift the dogma from ascertained risk to possible prevention
Authors: Giovanni Brandi, Stefania De Lorenzo, Andrea Palloni, Guido Biasco, Francesco Tovoli
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. To the Editor: We read with interest the recent article by Choi et al.1 published in your journal. This retrospective study included 2,395 patients with cholangiocarcinoma (CC) at the Mayo Clinic and 4,769 controls. Using a case–control design, the authors found that CC cases were significantly less likely to report use of aspirin than controls (adjusted odds ratio after propensity analyses = 0.38, 95% confidence interval 0.33‐0.44; P < 0.001). The authors should be commended for these interesting findings, which pave the way for future innovative studies of chemoprevention for CC. Should we expect large trials of chemoprevention? Both the authors1 and Bagante et al.2 in their editorial agree on the futility of such trials in the general population (as CC is a relatively rare condition) and about the need for future studies limited to high‐risk categories. But who are these high‐risk patients, and how can we identify them? Choi and colleagues declare their intention to perform a case–control study in patients with primary sclerosing cholangitis, the population with the highest risk of CC.1 However, other categories are also at risk and may benefit from targeted studies. First, a radical surgical resection of early‐stage CC in the setting of a multidisciplinary evaluation can lead to a sustained disease‐free survival.3 Relapse due to recurrence of resected tumor or de novo emergence of new CC, however, occurs in a proportion of patients as high as 60%, even after adjuvant chemotherapies.3 Similar to what is described for hepatocellular carcinoma, an accurate differential diagnosis between de novo neoplasia and actual recurrence is not easy. Therefore, a question has to be raised: may patients who suffered from CC and are currently disease‐free also benefit from aspirin prevention? Second, exposure to asbestos may be a hidden player for the development of intrahepatic CC. Confirming this line of thought, we described an increased risk of developing CC in a cohort of 155 workers exposed to asbestos compared to matched controls (adjusted odds ratio = 4.81, 95% confidence interval 1.73‐3.33).4 Interestingly, asbestos was the only known risk factor in about one third of patients who developed CC.4 Therefore, professionally exposed workers may be candidates for both screening and chemoprevention. In this regard, however, aspirin has not proven effective at preventing other asbestos‐related malignancies in an animal model and in a human cohort.5 In conclusion, the Choi et al. study represents an innovation in the fields of hepatology and oncology and identifies a possible preventive role of aspirin in the development of CC. The results of this retrospective study need validation through prospective studies on selected high‐risk populations. Primary sclerosing cholangitis patients are natural candidates for this kind of study, but a possible benefit should be assessed also in patients with resected CC or those exposed to asbestos (as no valid preventive strategies are available for them, to date). Clinical trials dedicated to these conditions may help broaden the series of patients benefiting from chemoprevention, eventually shifting the focus of research from risk to prevention.