Posttransplant Outcomes in Older Patients With Hepatocellular Carcinoma Are Driven by Non–Hepatocellular Carcinoma Factors

Abstract

The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P = 0.004), and not HCC-related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a adeniji et al. liver transplantatiOn, vol. 27, no. 5, 2021 adeniji et al. Original article | 685higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.

Hepatocellular Carcinoma Staging: Differences Between Radiologic and Pathologic Systems and Relevance to Patient Selection and Outcomes in Liver Transplantation

“…Imaging technology continues to evolve to address the current gaps, and corresponding evolution in pathologic analysis may be warranted. Emerging evidence supports that scoring systems integrating imaging-based tumor characteristics and clinical variables are most predictive of prognosis and achieve better patient selection and risk stratification [36,48,52]. Further, incorporation of molecular data may help to inform biologic aggressiveness and individual risk of post-transplant recurrence and/or need for adjuvant therapies.…”

“…Ongoing research suggests that other imaging features may be important prognostic markers for recurrence and tumor aggressiveness, such as LR-M features [47]. Likewise, as the understanding of molecular alterations in HCC advances, it may be useful to revisit the utility of biopsy for prognostication even if the diagnosis of HCC is not in question, or to consider the combination of imaging and pathomolecular and clinical variables, rather than tumor size and number alone as in current management [36,48].…”

Association between bridging therapy and posttransplant outcomes in patients with HCC within Milan criteria: A systematic review and meta-analysis

“…Ciccarelli et al [24] reported no difference in RFS between patients with 1-2 or > 2 bridging LRTs (p = 0.24). Similarly, Adeniji et al [18] found RFS did not differ between patients who received 1-3 LRTs when compared to no LRT; however, patients who received 4 LRTs had worse RFS than patients without LRT (HR: 1.4, 95% CI: 1.1-1.8), although there was no difference in OS by number of LRTs. Agopian et al [19] reported an increased risk of recurrence with 3+ TACE (HR: 2.58, p = 0.001) or 3+ ablation (HR: 2.58, p < 0.001), compared to 1 session.…”

Outcomes in elderly patients undergoing hepatic resection compared to liver transplant for hepatocellular carcinoma

“…HCC remains the leading indication for LTs in the United States, with an increasing proportion of elderly patients receiving transplants. 13,14 Even as age cut-off levels fall out of favor for patients who can receive an LT across high-volume centers, concerns remain over the impact of older age on clinical outcomes. 15,16 In this study investigating survival outcomes among elderly patients with HCC, we found that most patients underwent HR.…”