Our present study indicated that the number of patients in group VE increased in the late period (2009–2017) and that there was a higher proportion of patients with HCV and patients without HBV and HCV.
The incidence of PVI and fibrosis was lower in group VE than in group Y. The number of surgical procedures was not significantly different between groups. Group VE showed significantly fewer cancer-related deaths and more noncancer-related deaths than group Y. The surgical outcomes and morbidities of group VE were almost the same as those of the other two groups. These three groups showed similar OS and RFS results. Regarding the prognostic factors, tumor factors such as tumor size and tumor number had a smaller influence on the prognosis of patients in group VE than on that of patients in groups E and Y.
According to the nationwide survey of HCC patients in Japan, the rate of nonviral HCC was 32.5% in 2015 [19]. In this study, the rate in group VE was 59%. This rate was high. Previous studies have reported that the number of elderly patients with HCC is increasing [20] and that elderly patients have higher rates of HCV or NBNC than nonelderly patients [14, 15, 20, 21], which is consistent with our results. HCV infections generally occur in adulthood, in contrast to HBV infections, which are generally acquired through mother-child transmission [22]. The reason why there are more elderly NBNC-HCC patients is thought to be because non-alcoholic fatty liver disease and non-alcoholic steatohepatitis-related HCC with metabolic syndromes are more likely to occur in elderly patients than in young patients [23, 24]. Regarding liver function, elderly patients tend to develop HCC without cirrhosis or liver fibrosis [21]. Paradis et al. reported that HCC patients with metabolic syndromes showed less significant fibrosis than those without metabolic syndromes [23]. Tokushige et al. reported that cryptogenic HCC patients aged 80 years or older tended to develop HCC without cirrhosis [25]. Regarding oncological features, some reports have shown a higher frequency of tumor encapsulation and lower vascular invasion in elderly patients than in young patients [26, 27]. These results were consistent with our results. Katsuta et al. reported an age-related upregulation of the androgen and phosphatidylinositol 3-kinase pathways in tumor tissue and a downregulation of fibrosis-related pathways in noncancerous liver tissue [28]. Thus, compared to those of HCC in young patients, the characteristics of HCC in elderly patients could be somewhat different, such as a slightly lower degree of malignancy and relatively better liver function. In this study, prognostic factors such as tumor size and tumor number had less influence on the prognoses of patients in group VE than on those of patients in groups E and Y. This result might be explained by these biological differences. The liver function reserve might be more important in group VE than in group E or Y. Interestingly, the patients with an FRLR ≥ 50% showed significantly more favorable survival than the patients with an FRLR < 50% in group VE according to the univariate analysis. Furthermore, there were no significant differences in recurrence. During hepatectomy for very elderly patients, surgeons might have to make a maximum effort to preserve the remnant liver as much as possible.
The prognoses of pretty elderly patients with HCC are under investigation. Many reports have claimed that the prognoses after hepatectomy are not different between elderly patients and nonelderly patients [15, 20, 26]. Oishi et al. reviewed 23 papers and reported that the 5-year OS rates after hepatectomy in elderly HCC patients ranged from 26–75.9%, whereas those in young patients ranged from 31.4–68%. Tsukioka et al. reported that in the early stage, patients with HCC aged 80 years or older had a poorer prognosis than nonelderly patients with HCC, although there were no differences in all stages; additionally, their study included not only hepatectomy but also other treatments [14]. Huang et al. reported that elderly patients had a better 5-year OS rate than younger patients (43.2% and 31.4%, respectively) [27]. In this study, the OS and RFS rates of very elderly patients were not different from those of elderly or young patients.
Hepatic resection is the main therapeutic method for HCC, even in elderly patients. However, hepatectomy is a highly invasive surgical procedure with a high morbidity rate [7]. Therefore, the indications for hepatectomy in elderly patients with HCC represent an important consideration because these patients frequently have systemic comorbidities and low activities of daily living. Most previous studies have shown that the morbidity rates after hepatectomy are not significantly different between elderly and nonelderly patients. These studies reported that the morbidities after hepatectomy in elderly patients ranged from 9–58% [27, 29, 30]. However, Ferrero et al. showed that elderly patients aged 70 years had lower complication rates after hepatectomy than young patients (23.4% vs. 42.4%), particularly in terms of liver failure (1.6% vs. 12.9%) [31]. The authors considered that this result was due to elderly patients undergoing more meticulous patient selection and less aggressive surgery than young patients. Kondo et al. reported that only the incidence of pneumonia after hepatectomy was significantly higher in elderly patients than in young patients, although the total complication rate and the rates of other complications were not different between the groups [32]. In our study, these rates were not significantly different. Recent technological developments for hepatectomy and perioperative management have resulted in decreased mortality rates [7]. Hepatectomy should not be avoided in very elderly patients with HCC if the patients have a good general status. In our institute, we have empirically confirmed that cognitive function was well maintained and that patients were walking on their own at the outpatient consultation for the selection of elderly patients receiving hepatectomy.
Regarding treatment after recurrence, re-hepatectomy was not performed in group VE in this cohort. This strategy was considered to be due to the conservative patient selection. However, laparoscopic surgery might be a useful tool for re-hepatectomy in very elderly patients.
The limitations of the study are as follows. First, the number of patients aged 80 years or older was small (n = 49). Second, elderly patients had a possibility of selection bias when they were referred from internal medicine.