Mailed outreach raised HCC screening completion, but the absolute gain stayed small
Hepatocellular carcinoma screening in cirrhosis often fails long before a tumor is ever missed on imaging. Appointments are not completed, surveillance slips between visits, and the cancer care pathway fragments at exactly the point where early detection can still change outcomes. In this multicentre pragmatic randomized clinical trial, a simple systems intervention—mailed outreach paired with patient navigation—improved completion of the HCC screening process compared with usual visit-based care, but the final numbers showed how much room still exists for better implementation.
Between April 2018 and September 2021, 2,872 patients with cirrhosis at three US health systems were randomized in equal numbers to mailed outreach plus navigation or to usual care with screening offered during visits. The median age was 61.3 years, and 32.3% of participants were women. Every participant entered the intention-to-screen analysis, which gives the findings practical weight because the comparison reflects real-world care delivery rather than an idealized adherence setting.
Process completion improved across most prespecified subgroups
Screening process completion occurred in 6.6% of patients assigned to outreach and navigation, compared with 3.3% in usual care. The absolute difference was modest, but the relative effect was clear: the odds of completing the screening process were roughly doubled, with an odds ratio of 2.05. In a field where surveillance failure is common, even a low single-digit completion rate can represent a meaningful shift in delivery when the underlying barrier is access, reminders, or follow-through rather than medical contraindication.
The intervention worked across most examined strata, including age, sex, race and ethnicity, Child-Turcotte-Pugh class, and health system. That consistency matters because surveillance gaps often widen in populations already vulnerable to missed specialty care. A mailed invitation can move the first barrier out of the clinic and into the patient’s hands, while navigation addresses the more stubborn second barrier: the friction of actually getting to imaging, keeping appointments, and closing the loop after missed contact.
One sentence captures the practical signal: outreach improved completion, but it did not normalize screening.
The proportion of time covered also favored outreach
The secondary endpoint pointed in the same direction. Proportion of time covered by screening was significantly higher in the outreach arm than in usual care, with a mean of 37.5% versus 28.2% and a relative risk of 1.33. PTC is a particularly useful measure in surveillance studies because it reflects how much of the follow-up window patients are actually protected by being “in cycle” for screening, rather than just whether a single test was ever completed.
In cirrhosis, that distinction is clinically important. Hepatocellular carcinoma can emerge in a surveillance gap, and a one-time completed test does little good if the patient spends most of the next 36 months outside the screening rhythm. The better PTC in the intervention arm suggests that mailed outreach and navigation did more than trigger isolated visits; they helped sustain engagement across time.
Early-stage detection remained common despite low uptake
The trial also showed that most HCC cases in both study arms were detected at an early stage, even though overall screening use remained poor. That finding suggests that the screening process, once completed, still has value in identifying disease before it becomes advanced. It also implies that a substantial share of the challenge lies upstream, in getting cirrhotic patients into reliable surveillance rather than in the biological performance of the screening test itself.
The biology of the disease makes this especially consequential. Cirrhosis creates a chronic carcinogenic environment marked by inflammation, regenerative nodules, and architectural distortion of the liver. Once hepatocarcinogenesis takes hold, the window for curative treatment narrows quickly. Surveillance works best when it interrupts that progression early, before vascular invasion or multifocal disease makes treatment far more complex.
Usual care left too many patients outside the surveillance pathway
The contrast between 6.6% and 3.3% completion is statistically meaningful, but the absolute rates are still uncomfortably low for a cancer surveillance strategy. In a process designed to catch a lethal malignancy early, a completion rate in the single digits signals persistent operational failure, not just room for incremental improvement. The intervention helped, yet the care system still left most patients without completed screening over a 36-month period.
Patient navigation likely helped by reducing the practical obstacles that often derail surveillance: scheduling confusion, transportation issues, missed reminders, and uncertainty about next steps after a mailed invitation. In a pragmatic trial, those functions are not ancillary. They are the intervention’s clinical mechanism. A reminder without follow-through can generate intent but no imaging; navigation converts intent into completed care.
What this trial means for cirrhosis surveillance programs
This study provides a clear message for health systems managing cirrhosis: passive, visit-dependent screening misses too many patients. Mailed outreach plus navigation produced a consistent improvement in hepatocellular carcinoma screening completion and better time covered by surveillance, and the effect appeared across multiple demographic and clinical subgroups. The intervention is not a cure for underuse, but it is a workable systems-level step that can be deployed across diverse settings.
At the same time, the trial leaves a hard operational problem on the table. The intervention improved uptake without bringing completion anywhere near a level that would be reassuring for a high-risk cancer population. More intensive outreach, tighter tracking of missed appointments, embedded navigation resources, and better integration of surveillance into routine cirrhosis care may be needed to close the gap further.
For now, the strongest takeaway is straightforward: mailed outreach and patient navigation can move HCC surveillance forward, but they do not yet move it far enough. The trial registration number is NCT02582918.