Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.

The efficacy of neoadjuvant therapy (NT) versus surgery first (SF) for pancreatic ductal adenocarcinoma (PDAC) remains controversial. A random-effects meta-analysis of only prospective randomized controlled trials (RCTs) comparing NT versus SF for potentially resectable (PR) or borderline resectable (BR) PDAC was performed. Among six RCTs including 850 patients, 411 (48.3%) received NT and 439 (51.6%) SF. In all included trials, NT was gemcitabine-based: four using chemoradiation and two chemotherapy alone. Based on an intention-to-treat analysis, NT resulted in improved overall survival (OS) compared to SF (HR 0.73, 95% CI 0.61–0.86). This effect was independent of anatomic classification (PR: hazard ratio (HR) 0.73, 95% CI 0.59–0.91; BR: HR 0.51 95% CI 0.28–0.93) or NT type (chemoradiation: HR 0.77, 95% CI 0.61–0.98; chemotherapy alone: HR 0.68, 95% CI 0.54–0.87). Overall resection rate was similar (risk ratio (RR) 0.93, 95% CI 0.82–1.04, I² = 39.0%) but NT increased the likelihood of a margin-negative (R0) resection (RR 1.51, 95% CI 1.18–1.93, I² = 0%) and having negative lymph nodes (RR 2.07, 95% CI 1.47–2.91, I² = 12.3%). In this meta-analysis of prospective RCTs, NT significantly improved OS in an intention-to-treat fashion, compared with SF for localized PDAC. Randomized controlled trials using contemporary multi-agent chemotherapy will be needed to confirm these findings and to define the optimal NT regimen.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and third leading cause of cancer-related mortality worldwide. While surgical resection and transplantation are the standard first-line treatments for early-stage HCC, most patients do not fulfill criteria for surgery. Fortunately, catheter-directed and percutaneous locoregional approaches have evolved as major treatment modalities for unresectable HCC. Improved outcomes have been achieved with novel techniques which can be employed for diverse applications ranging from curative-intent for small localized tumors, to downstaging or bridging to resection and transplantation for early and intermediate disease, and locoregional control and palliation for advanced disease. This review explores recent advances in liver-directed techniques for HCC including bland transarterial embolization, chemoembolization, radioembolization, and ablative therapies, with a focus on patient selection, procedural technique, periprocedural management, and outcomes.

Liver-directed hepatic arterial therapies are associated with improved survival and effective symptom control for patients with unresectable neuroendocrine liver metastases (NELM). Whether transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) with yttrium-90 (y-90) are associated with improved short- or long-term outcomes is unknown. A retrospective review was performed of all patients with NELM undergoing transarterial therapies, from 2000 to 2018, at 2 academic medical centers. Postoperative morbidity, radiographic response according to response evaluation criteria in solid tumors (RECIST) criteria, and long-term outcomes were compared between patients who underwent TACE vs TARE. Among 248 patients with NELM, 197 (79%) received TACE and 51 (21%) received TARE. While patients who underwent TACE were more likely to have carcinoid syndrome, larger tumors, and higher chromogranin A levels, there was no difference in tumor differentiation, primary site, bilobar disease, or synchronous presentation. Nearly all TARE treatments (92%) were performed as outpatient procedures, while 99% of TACE patients spent at least 1 night in the hospital. There were no differences in overall morbidity (TARE 13.7% vs TACE 22.6%, p = 0.17), grade III/IV complication (5.9% vs 9.2%, p = 0.58), or 90-day mortality. The disease control rate (DCR) on first post-treatment imaging (RECIST partial/complete response or stable disease) was greater for TACE compared with TARE (96% vs 83%, p < 0.01). However, there was no difference in median overall survival (OS, 35.9 months vs 50.1 months, p = 0.3) or progression-free survival (PFS, 15.9 months vs 19.9 months, p = 0.37). In this retrospective multi-institutional analysis, both TACE and TARE with Y-90 were safe and effective liver-directed therapies for unresectable NELM. Although TARE was associated with a shorter length of hospital stay, TACE demonstrated improved short-term DCR, and both resulted in comparable long term outcomes.