Bridging patients with hepatocellular cancer waiting for liver transplant: all the patients are the same?

Abstract

Hepatocellular carcinoma (HCC) is the fifth more frequent cancer worldwide and the most common primary liver tumor. Liver transplant (LT) is considered the best curative treatment for patients with cirrhosis and HCC within Milan criteria (1 tumor ≤5 cm and up to 3 tumors ≤3 cm). It removes all the liver affected by cancer and at the same time it treats the underlying liver disease, with a survival rate of 70% and a 5 years recurrence rate of less than 20%. Unfortunately, the applicability of LT for HCC patients is limited by the shortage of liver grafts, determining a longer time on waitlist and high dropout rate. Bridging treatments are neo-adjuvant antitumoral therapies given to patients on the waitlist for LT, affected by HCC within the criteria, with the aim to reduce the disease progression and therefore the dropout rate. Indeed, these treatments act as a "bridge" until a suitable donor organ becomes available. Most of bridging therapies are locoregional treatments (LRTs). Dropout rate for HCC progression increases in a time-dependent way (1) and evidences show higher dropout rates in patients with tumor >3 cm and an expected waiting time longer than 3-6 months (2). In different reports, if HCC is left untreated, the risk of drop out at 6 months and at 1 year has been estimated to be respectively 12% and 15-30% (3,4). Risk factors for dropout include: tumor diameter greater than 3 cm or multifocal disease, serum α-fetoprotein (AFP) level greater than 200 ng/mL, waiting time longer than 6 months and lack of response to bridging therapy (5). Although there are no randomized control trials (RCT) evaluating the efficacy of neo-adjuvant therapies in reducing dropout rate and improving survival after LT, LRT is accepted as the standard of care for patients expected to stay on the waitlist for more than 6 months. In patients with HCC within Milan criteria, bridging therapy is estimated to reduce dropout rate to 0-10%. A retrospective study

Cost-Utility Analysis of Imaging for Surveillance and Diagnosis of Hepatocellular Carcinoma

“…Primarily, TACE therapy aims to extend overall survival and avoid dropout of patients on the waiting list for LT [104,106].…”

Combined transarterial chemoembolization and stereotactic body radiation therapy as a bridge therapy to liver transplant for hepatocellular carcinoma

“…According to Milan criteria, the liver transplant (LT) is the treatment of choice for HCC patients with tumor less than 5 cm and up to 3 tumors ≤ 3 cm. The 5 years survival rate in these patients are 70% with less than 20% recurrence rate [2] . However, not all HCC patients can undergo transplantation due to a lack of liver donors, resulting in an extended time on the waiting list (WL) and a high dropout rate [3] .…”

“…These treatments act as a temporary "bridge" until a suitable donor is identified. Liver resection, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and stereotactic body radiation therapy (SBRT) are main bridge modalities to LT in patients with HCC [2] . The rates of drop out at 6 months and 1 year were estimated as high as 12% and 15%-30%, respectively, if HCC is left untreated [4,5] .…”

Embolotherapy for Hepatic Oncology: Current Perspectives and Future Directions

“…Bridging therapy is estimated to reduce dropout rate to 0 to 10% from up to 19.5% at 12 months. 43,44 All embolotherapies have shown similar safety and efficacy profiles for patients requiring bridging therapy. [45][46][47] Although there was no difference in OS, a prospective study of patients with either BCLC Stage A or B comparing SIRT to cTACE observed longer times to progression (TTPs) in the SIRT group in comparison to the cTACE group: >26 months in the SIRT group versus 6.8 months in the cTACE group, p ¼ 0.012 (hazard ratio [HR]: 0.122, 95% confidence interval [CI]: 0.027-0.557, p ¼ 0.007).…”