Response to ‘Monitoring for post-transplant hepatocellular carcinoma recurrence’

Sir, We appreciate the response from Ortiz et al. regarding recommendations for monitoring post-liver transplant (post-LTx) patients for recurrent hepatocellular carcinoma (HCC). The authors question the validity of our assertion that we have identified a group of patients at low risk for recurrent HCC after LTx and that these patients can be monitored using a less stringent surveillance strategy. Our report1 noted 13 recurrences in a population of 122 patients undergoing LTx for HCC. None of the 68 patients whose explants were shown by pathological staging to be within the Milan criteria experienced tumour recurrence. Our more recent experience includes an additional four patients with recurrence of HCC after LTx, in three of whom explants were staged as beyond the Milan criteria. The explant from the fourth patient was within the Milan criteria, but disease recurred 52 months after LTx. If we were to have applied an algorithm of scanning every 3 months for 1 year and every 6 months for a subsequent 2 years in the 69 patients whose explants were found to be within the Milan criteria, 552 scans (eight scans per patient) would have been performed over a 3-year period, but this protocol would still have missed the recurrence at 52 months. There are several important factors to consider in our study.1 Firstly, we used a cumulative staging process that included all viable and non-viable tumours in the explant. Secondly, waitlist time to transplant in our region is lengthy and many patients require multiple bridging treatments in order to maintain eligibility to remain on the list. This long wait time may itself separate patients into low- and high-risk groups based on the number of treatments required to maintain eligibility for transplant, and this is reflected in cumulative staging. For example, patients with favourable tumour biology who require only a single bridging treatment over a wait time of 12–15 months are often found to have completely necrotic nodules on explant and thus demonstrate disease that would be considered to fall within the Milan criteria, whereas patients who require two or more treatments often have residual viable tumour and may have vascular invasion, which puts them in a higher risk category based on explant. We maintain our assertion that patients with explant pathology within the Milan criteria are at very low risk for recurrent HCC after transplantation and therefore can be considered for less stringent imaging surveillance. We would agree, however, that other factors may have similar utility in stratifying patients into high- and low-risk groups, such as the alpha-fetoprotein (AFP) trajectory before transplant and the presence of vascular invasion. Indeed, our results1 demonstrated that vascular invasion and the presence of bilobar tumours were risk factors for recurrence. A very important component of any surveillance strategy is the premise that the timely detection of recurrence will lead to interventions that positively affect outcome. We and others have adopted an aggressive approach to recurrent HCC after LTx with the selective use of mTOR inhibitor-based immunosuppression, liberal use of sorafenib and frequent use of loco-regional modalities for solid organ recurrence. As such, we advocate aggressive screening for patients who are at medium to high risk of recurrence, such as those with disease outside the University of California San Francisco (UCSF) criteria with vascular invasion. By contrast with this group, in the low-risk group identified in our study,1 the yield of aggressive surveillance is quite low. Nevertheless, there remains little consensus on this matter and in fact the HCC Clinical Practice Guidelines cited by Dr Ortiz et al. state that after LTx for HCC, imaging should be performed only ‘as needed’.2 Defining this low-risk group and establishing a cost-effective and patient-friendly surveillance regimen represent ongoing challenges within the transplant community and continued dialogue is needed.