Liver Cancer: New Prognostic Tool for Liver Transplant Patients

Veronica Hackethal, MD

January 22, 2015

A tool that offers a better way to predict risk for liver cancer recurrence after liver transplantation has been developed by researchers at the University of California, Los Angeles (UCLA). It is based on results from an analysis of 30 years' worth of data, details of which were published online on December 26, 2014, in the Journal of the American College of Surgeons.

This is the first report of the new prognostic tool (or nomogram) and the largest single-center report of liver transplantation in liver cancer, the researchers note.

"This nomogram has an excellent ability to predict recurrence, and can be used to guide adjuvant therapy and the frequency of post-transplant surveillance," said first author Vatche Agopian, MD, assistant professor of surgery in the division of liver and pancreas transplantation at the David Geffen School of Medicine at UCLA.

"The selection of liver cancer patients for transplantation is improved by incorporating basic laboratory biomarkers in addition to radiologic criteria. The novel nomogram," Dr Agopian reported, "includes the pretransplant radiologic and laboratory biomarkers and the pathologic features of the diseased liver that can only be known post-transplant."

Patient selection plays an important role in deciding who might benefit from liver transplantation, the researchers write.

The Milan criteria were introduced in 1996 to assess candidates. They were a major step toward improving liver cancer outcomes and established liver transplantation as the gold standard for patients meeting the criteria.

In 2002, the Model for End-Stage Liver Disease (MELD) criteria, developed at the University of California, San Francisco, was introduced, resulting in a near doubling of liver transplantation in patients with liver cancer.

However, recurrence after transplantation remains a problem. There is growing consensus that the Milan and MELD criteria are too conservative. Both rely on radiographic tumor size alone, and neither takes into account other prognostic factors, such as tumor aggressiveness and serum biomarkers.

To develop the nomogram, Dr Agopian and colleagues analyzed data on 865 patients who had undergone liver transplantation for liver cancer from 1984 to 2013.

Median age in the cohort was 60 years, and 73% of the patients were male. Most were followed for nearly 30 months.

Overall survival was good. Disease recurred in 117 patients at a median of 15 months.

Table. Overall and Recurrence-free Survival

Years After Transplantation Overall Survival, % Recurrence-free Survival, %
1 83 79
3 68 63
5 60 56

 

The predictors of recurrence identified by the researchers include tumor grade and differentiation, micro- and macrovascular invasion, nonincidental tumors, pretransplant neutrophil-to-lymphocyte ratio, alphafetoprotein level, and total cholesterol level.

These predictors were used to develop the nomogram, which incorporated serum biomarkers, radiographic size, and pathologic tumor features. Analyses suggest that the nomogram significantly improves the ability to predict recurrences (c-statistic, 0.85; 95% confidence interval [CI], 0.82 - 0.89). In fact, it performed significantly better than the American Joint Committee on Cancer pathologic TNM staging system (c-statistic, 0.80; 95% CI, 0.75 - 0.83; P = .006).

Patients who did not originally meet the Milan criteria but who were successfully downstaged had about the same recurrence-free survival at 1, 3, and 5 years as patients who originally met the Milan criteria. These patients also had significantly better survival than patients who did not meet the Milan criteria and were not downstaged (P < .001).

These survival differences highlight the importance of successful downstaging and the need to adjust the selection criteria so that potentially lifesaving treatment is not denied on the basis of tumor size alone, the researchers note.

Because the nomogram used data from a single center, it will need to be validated in other settings. Such studies are in progress, according to Dr Agopian.

"[Validation] would significantly strengthen the generalizability of the nomogram. If validated with data from centers across the nation, it would be much more likely to gain widespread use," he explained.

"The main advantage of the nomogram is to give as accurate a prediction as possible about who is likely to develop liver cancer recurrence after transplantation. It really is a system to assess that risk, and seems to be better than any other system," he told Medscape Medical News.

The authors have disclosed no relevant financial relationships.

J Am Coll Surg. Published online December 26, 2014. Abstract

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