In this study, we examined the prognosis between patients with nodules classified as LR-3 or -4 and those with LR-5 tumors. There was a significant difference in RFS in the comparison of all 64 cases. In particular, for BCLC A, we found that LR-5 had a worse RFS than LR-3 or -4. In contrast, there was no significant difference in OS between LR-3 or -4 and LR-5 stage tumors.
The influence of tumor size might be considered. When determining the LI-RADS classification, if conditions such as arterial enhancement and washout are the same, we will divide by tumor size . Larger tumors may have more vascular invasion of the tumor, and a higher probability of recurrence [14–16]. In addition, with a large tumor, some portions of the tumor that are not visible in the image may not be treatable, which may be related to the treatment results [17, 18]. It is possible that the drug did not reach the interior of the tumor with TACE, or that even if a sufficient safety margin were assumed, RFA did not sufficiently incinerate the tumor. Also, when the tumor has a capsule, the larger the size, the easier it is to infiltrate outside beyond the capsule, and thus the greater likelihood of metastasis [19, 20].
As indicated in Table 4, there were no significant differences in age, gender, or AFP values between patients with LR-3 or -4 and those with LR-5 stage tumors. However, there was a significant difference in PIVKA-II values. There is an association between PIVKA-II values and tumor vascular invasion . LR-5 tumors have high PIVKA-II values, and there might be microvascular invasion that is not visible on the pretreatment image. As a result, we considered that the risk of recurrence was high in our patients with high PIVKA-II values with LR-5 stage tumors.
Regarding the washout, previous reports revealed that washout of hypervascular HCC occurred earlier as the histological grade advanced, the histological architecture got closer to pure trabecular HCC, and hypervascular HCCs with thicker tumor plates showed worse histological grade and earlier washout pattern [22, 23]. Thus, clear washout may indicate an aggressive tumor, such as a moderately to poorly differentiated HCC with thicker tumor plates.
In contrast, there was no significant difference in OS. One of the possible reasons for this is that HCC can show multicentric development [24, 25]. Even if a tumor was treated completely, new HCC, not intrahepatic metastasis, can develop elsewhere in the liver, which significantly influences survival. Unfortunately, in many cases it is difficult to tell the difference between intrahepatic metastasis from the original tumor and a newly developed tumor. Other possible factors that affected patients’ prognosis included worsening liver function and cirrhosis, and these effects may have been greater than the tumor aggressiveness itself .
In this study, there was no significant difference between LR-3 or -4 and LR-5 in the BCLC 0 group. In the very early stage of HCC, if a tumor is well treated, the subsequent prognosis may depend on the likelihood of developing another HCC in the liver, or on the deterioration of underlying liver function . There may have been cases in which recurrence unrelated to the primarily treated tumor occurred.
This study had several limitations: (1) It was a retrospective study and selection bias which could have affected the results might therefore exist. (2) Data were collected from a single center, and samples from multiple regions were required for further validation. If we could have collected more cases, we would have been able to investigate in more detail. (3) Two anticancer drugs were used during TACE. There was no significant difference observed due to the difference in anticancer drugs, but the accuracy of the study might have been improved if comparisons could have been made under the same drug conditions . (4) Patients with BCLC 0 or A might be good surgical candidates; however, our hospital traditionally favored less invasive therapy such as TACE-RFA. Thus, patients who were eligible for surgery may have been included .
The LI-RADS classification is a classification of certainly, which is a tool for classifying images according to their major characteristics. Detailed tumor characteristics such as degree of differentiation are not included, and may be classified using other algorithms. Examining the LI-RADS classification by adding more detailed features of the tumor can provide a more detailed prognosis. It has also been reported that the combination of MRI diffusion-weighted image analysis and LI-RADS can improve confidence . In the future, by combining LIRADS with various factors, we will find it easier to predict the prognosis.
In conclusion, tumors categorized as LR-5 have a worse RFS than those classified as LR-3 or -4, especially in BCLC A. LI-RADS, originally created for use at the radiologist’s discretion in diagnosis, can predict patient prognosis. Tumors classified as LR-5 by LI-RADS require more attention to the patient’s course than tumors of other classifications.