Date Published: January 14, 2019
Publisher: Public Library of Science
Author(s): Dong Hyun Sinn, Gyu-Seong Choi, Hee Chul Park, Jong Man Kim, Honsoul Kim, Kyoung Doo Song, Tae Wook Kang, Min Woo Lee, Hyunchul Rhim, Dongho Hyun, Sung Ki Cho, Sung Wook Shin, Woo Kyoung Jeong, Seong Hyun Kim, Jeong Il Yu, Sang Yun Ha, Su Jin Lee, Ho Yeong Lim, Kyunga Kim, Joong Hyun Ahn, Wonseok Kang, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Jae-Won Joh, Hyo Keun Lim, Seung Woon Paik, Seung Up Kim.
Given the complexity of managing hepatocellular carcinoma (HCC), a multidisciplinary approach (MDT) is recommended to optimize management of HCC patients. However, evidence suggesting that MDT improves patient outcome is limited.
We performed a retrospective cohort study of all patients newly-diagnosed with HCC between 2005 and 2013 (n = 6,619). The overall survival (OS) rates between the patients who were and were not managed via MDT were compared in the entire cohort (n = 6,619), and in the exactly matched cohort (n = 1,396).
In the entire cohort, the 5-year survival rate was significantly higher in the patients who were managed via MDT compared to that of the patients who were not (71.2% vs. 49.4%, P < 0.001), with an adjusted hazard ratio (HR) of 0.47 (95% confidence interval [CI]; 0.41–0.53). In the exactly matched cohort, the 5-year survival rate was higher in patients who were managed via MDT (71.4% vs. 58.7%, P < 0.001; HR [95% CI] = 0.67 [0.56–0.80]). The survival benefit of MDT management was observed in most pre-defined subgroups, and was especially significant in patients with poor liver function (ALBI grade 2 or 3), intermediate or advanced tumor stage (BCLC stage B or C), or high alphafetoprotein levels (≥200 ng/ml). MDT management was associated with improved overall survival in HCC patients, indicating that MDT management can be a valuable option to improve outcome of HCC patients. This warrants prospective evaluations.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide with increasing mortality rate in many countries [1–3]. HCC usually develops in patients with liver disease that compromises liver function . Many HCC patients suffer from decreased liver function, and sometimes liver failure is the cause of mortality without cancer progression . Hence, the prognosis of patients with HCC is complex by the interplay of tumor burden and liver function [6,7]. HCC management is complex, as one should carefully assess not only the risks and benefits of treatment on tumor, but also its effect on liver function. HCC is also notorious for its high recurrence rate even after curative treatment for early-stage tumor . Hence, while managing patients with HCC, one should consider possibility of recurrence and available therapeutic option at the time of recurrence. Liver transplantation (LT) is a highly effective treatment option for HCC , and can dramatically change the prognosis of patients. However, donor availability differs by patient and regions, making things more complex. Recent advances in HCC treatment provided multiple potentially efficacious treatments, but, randomized controlled trials comparing between treatments are largely limited . Several HCC guidelines have been published to facilitate the selection of optimal management [6,7,10], however, these guidelines have both similarities and dissimilarities due to the geographic differences, available resources, and lack of high level of evidences , and are not followed well in real-life clinical practice .
The baseline characteristics of 6,619 HCC patients (median age: 57.0 years, men: 5,287 [79.9%], hepatitis B: 5,029 [76.0%]) are summarized according to the MDT management in Table 1. Patients who had MDT management were older, and included a higher number of men, had more preserved liver function, less advanced tumor stage, lower levels of AFP and PIVKA-II levels. Proportions of the patients who underwent resection, ablation or LT as a first-line treatment were similar for those who were managed via MDT than those who did not (49.2% vs.50.3%), but more patients received transarterial chemoembolization or other treatments (50.7% vs. 43.2%), and less patients received the best supportive care (0.1% vs. 6.4%) for those who were managed via MDT. There was no difference in terms of etiology and LT during follow-up.
In this study, we observed better OS in HCC patients who had MDT management. Those received MDT management had different baseline characteristics than those who did not. Those received MDT management showed more preserved liver function, earlier tumor stage, lower levels of serum tumor markers, managed at more recent years, and had received more active treatment. However, MDT management was an independent factor associated with better OS in multivariable-adjusted model in the entire cohort. Also, MDT management was associated with better OS in the matched cohort, where the key factors related to patient outcome were exactly matched between patients who were and were not managed via MDT. The benefit of MDT management was observed across most pre-defined subgroups; especially, it was greater in those with poor liver function (ALBI grade 2 or ALBI grade 3), intermediate or advanced BCLC stage (BCLC stage B or C), or high AFP levels (≥200 ng/ml).