Editorial for “Comparing Survival Outcomes of Patients With LI‐RADS‐M Hepatocellular Carcinomas and Intrahepatic Cholangiocarcinomas”

Editorial for “Comparing Survival Outcomes of Patients With LI-RADS-M Hepatocellular Carcinomas and Intrahepatic Cholangiocarcinomas” Hepatocellular carcinoma (HCC) is the most common primary liver cancer followed by intrahepatic cholangiocarcinoma (iCCA) and combined HCC-CCA (cHCC-CCA). Once HCC and CCA were thought to be independent disease categories from different cell origins. However, recent study results support that HCC and CCA may represent two extreme ends of continuing disease spectrum. Therefore, it is not surprising that there are overlaps of imaging features between the two diseases. Liver Reporting and Data System (LI-RADS) is one of metrics, which can measure the overlaps of imaging features between HCC and CCA, since it provides a unique diagnostic category of LR-M. LR-M indicates high probability of malignancies but not necessarily HCC, whereas LR-5 and LR-4 mean “definite” and “probable” HCCs, respectively. Observations with targetoid appearance or those not meeting LR-5 criteria and showing nontargetoid M features fall into this category. The criteria have been increasingly used for primary liver cancer differential diagnosis as well as its prognostication. According to prior studies, HCCs with LR-M features demonstrated early recurrence than those with LR-4 or 5 HCCs after curative hepatic resection. Furthermore, LR-M tumors showed shorter overall survival and progression free survival than tumors with LR-4 or 5, regardless of pathologic diagnoses in primary liver cancers. These studies strongly suggest that the imaging phenotype is related to the tumor biology in primary liver cancers. In this issue of JMRI, Kierans et al reported a comparison between clinical outcomes of HCC and iCCA with’ LR-M’ features. The hypothesis is that primary liver cancers with similar imaging features may show a similar clinical outcome. Authors retrospectively collected 120 patients with histologically confirmed either HCC (n = 65) and iCCA (n = 55) from eight centers. All patients were at risk of developing HCC and lesions were categorized as LR-M at CT or MRI. During the follow-up period (median 744–1087 days), 52.3% of HCC patients (34/65) and 52.7% of iCCA patients (29/55) deceased (P = 0.96). There was no significant difference of overall survival between patients having HCC with LR-M features and iCCA with LR-M features (median 738 days vs. 769 days, respectively, P = 0.58). Disease-specific survival was not significantly different either (P = 0.35). Histologic diagnosis was not associated with overall survival. Only treatment option (nonsurgical), poor liver function (high model for end-stage liver disease MELD score), and large tumor size were significantly associated with decreased overall survival. Although patients having iCCA with LR-M features showed shorter progression free survival compared with those having HCC with LR-M features (310 days vs. 533 days, respectively, P = 0.04), pathologic diagnosis was not significantly associated with progression free survival. Only treatment option (nonsurgical) and large tumor size were significantly associated with progression free survival. iCCA is known to show poor prognosis than HCCs, but it is also known that HCCs with LR-M features show worse prognosis than HCCs with LR-4 or -5. Therefore, it would be interesting to directly compare the prognosis between atypical HCCs (LR-M) and iCCA, which is rarely studied yet. Interestingly, the study reveals that no significant difference between overall survival of the two primary liver cancers. This observation is not clearly explained, but we could surmise some possible explanations. First, included HCCs might have poor prognostic subtypes: HCCs with LR-M features often include scirrhous HCC, HCC with stemness-related markers, poorly differentiated HCC and sarcomatoid HCC that are related to poor prognosis. Second, there may be a possibility that small duct type iCCA with relatively better prognosis in iCCA group since small duct type iCCA is more common in patients at risk of developing HCC. Third, both HCC and iCCA groups had cirrhosis with different hepatic function which might affect their treatment option. Interestingly, a recent large-scale database study also reported that tumor type (HCC vs. iCCA) was not significantly associated with overall survival after adjusting factors: only tumor size, treatment option and staging were related to the prognosis. Although