Improving access to screening and treatment of hepatocellular carcinoma in the United States

INTRODUCTION

HCC is the third leading cause of cancer-related mortality worldwide. The incidence of HCC is growing. Ideal screening and treatment of HCC requires navigation of a fractured health care system and access to specialty care. We will review gaps and effective interventions in the screening and treatment of HCC.

Gaps in screening

Screening for HCC has been shown to increase early-stage detection and curative treatment and reduce mortality related to HCC.¹ Screening is cost-effective.² Despite the established impact of screening for HCC, screening remains inadequate globally. In the United States, one recent large trial showed rates of <30% even within a safety net system.³ Many factors contribute to the lack of screening—inadequate access to health care, lack of recognition of the need for screening by providers in high-risk groups leading to late-stage diagnosis, lack of specialty care, insufficient sensitivity of current screening tests, and fractured health care for those with abnormal screenings. For patients with access to HCC screening, the rate of detection remains low. Screening tests for other common cancers—colorectal cancer, breast cancer, and prostate cancer are 70%–90% sensitive, while the current American Association for the Study of Liver Diseases–recommended semiannual ultrasound and alpha fetal protein have sensitivity of 63% for detection of early HCC.⁴ MRI has improved sensitivity for the detection of early HCC but is not cost-effective nor universally available. Additional blood markers for screening are in development, but none are widely available nor recommended by current guidelines (Figure 1).

FIGURE 1.

Gaps in screening and treatment of liver cancer. Created with BioRender.com. Abbreviations: LRT, locoregional therapy; RCT, randomized clinical trial.

Gaps in treatment

The treatment landscape of HCC has expanded over the past few years.⁵ A key step in treatment decision-making is access to a multidisciplinary liver tumor board. Liver cancer is unique in that it occurs in a sick organ, so the severity of liver disease, as well as the performance status of the patient, plays a major role in deciding treatment options.

Curative treatment options, including surgical resection, ablation, and transplant, are significantly underutilized.⁶ Locoregional therapies, although widely available, suffer from a lack of randomized clinical trials as well as dependency on local expertise. This all points toward the importance of multidisciplinary care, which has been shown to improve survival and access to care.⁷ The Veterans Health Administration has been at the forefront of such efforts, given the ability to incorporate telemedicine services and create regional tumor boards.⁸

Another challenging aspect of liver cancer treatment is the role of systemic chemotherapy and its evolution over recent years. Traditionally, systemic chemotherapy was limited to the most advanced stage of disease; however, with the use of immune checkpoint inhibitors, the role of systemic chemotherapy now includes intermediate and early-stage cancers. Close collaboration between oncology and hepatology, especially with respect to those patients who might qualify for transplant after systemic chemotherapy, is critical in the future care of patients with liver cancer. However, hepatology has been on the sidelines with respect to administering systemic chemotherapy to these patients. Transplant hepatology fellowship does not address this need for special training or familiarity with systemic chemotherapy (Figure 1).

Effective interventions for gaps in screening

To have the largest impact on mortality, HCC screening should be targeted, convenient, cost-effective, highly sensitive, and reasonably specific. Several strategies are available that will bring us toward this ideal and reduce gaps in HCC screening. On a systemic level, increased access to health insurance coverage and education of patients and primary care providers of the need for HCC screening would increase patient access to screening tests. Multiple studies have shown that outreach and patient education can increase population screening rates. Automated letters, phone calls, and reviews of quality dashboards on a population level are all impactful.³ Telemedicine has also been shown to increase rates of adequate HCC screening and extend the reach of a relatively small number of specialty providers to patients whose need for screening may otherwise go unrecognized.⁹ Personalized medicine will also improve HCC screening; with several risk calculators available, providers can better identify patients who are at the highest risk of HCC and focus outreach efforts on this population.¹⁰

In addition to increasing access to regular screening, several promising changes to screening testing to improve sensitivity and specificity are under development. The use of abbreviated MRI has improved sensitivity and specificity and is cost-effective.² A large national study of abbreviated MRI in the VA population is underway (NCT05486572). While not yet ready for clinical use, DNA-based blood testing has excellent sensitivity for HCC detection, and a large observational trial is currently recruiting subjects (NCT05064553). Blood-based testing has the advantage of streamlining care for “one-stop shopping.” Taken together, increased outreach to targeted populations along with improved screening tests has the potential to meaningfully reduce mortality from liver cancer (Figure 2).

FIGURE 2.

Interventions to improve gaps in screening. Created with Biorender.com.

Effective interventions for gaps in treatment

Increasing access to tumor boards and bridging the gap between tertiary transplant centers and nonacademic high-volume centers is key to ensuring that patients with liver cancer are discussed in a multidisciplinary fashion. This ensures access to curative treatment options, transplantation, and clinical trials for those who might have failed first-line systemic chemotherapy. Given the multiple modalities of treatment available to patients with liver cancer, including surgery, ablative procedures, intra-arterial locoregional therapy, radiation, and treatment, the role of hepatologist as the backbone of this structure and as the provider who usually has the most continuity with patient care is key.

Randomized clinical trials to include newer locoregional treatment options, specifically stereotactic beam radiation therapy, in comparison with transarterial chemoembolization or transarterial radioembolization would improve our understanding of how these modalities can contribute to different stages of Barcelona clinical liver cancer staging. This would provide more objective evidence with respect to patient tolerance and survival rather than relying on local expertise and availability.

Lastly, Hepatology involvement in the administration of systemic chemotherapy would have the potential of reducing wait time given that hepatology involvement would be an additional resource and not replacing oncology care. Development of this expertise would require involvement by major societies and support of fellowship programs to educate the workforce on the intricacies of the administration of systemic chemotherapy.

DISCUSSION

Liver cancer remains deadly cancer, with low screening rates and a wide range of treatment options are now available, choosing among which is mainly achieved by local expertise as opposed to objective data.

There are multiple strategies that can be used to increase screening rate, access to treatment as well as more individualized plans for screening and treatment for our patients with chronic liver disease as summarized in Table 1.

TABLE 1.

Suggested action items to improve screening and treatment of HCC in the United States

Action Items
Screening	Treatment
• Increase health insurance coverage • Recognition of high-risk patients by providers • Perform patient outreach • Use risk calculators • Improve convenience and sensitivity of screening tests	• Increase tumor board access • RCT comparing LRT modalities • Hepatology involvement in systemic therapy • Access to early referral to transplant center

Abbreviations: LRT, locoregional therapy; RCT, randomized controlled trial.

This requires commitment from major societies for liver disease, hepatologists, scientists, and a close collaboration between hepatology and other subspecialties that offer treatment for liver cancer.