New nomogram accurately predicts hepatocellular carcinoma recurrence

Last Updated: 2015-01-22

By Will Boggs MD

NEW YORK (Reuters Health) - A new nomogram that includes seven clinicopathologic variables accurately predicts recurrence of hepatocellular carcinoma (HCC) after liver transplant, researchers say.

"We finally have a clinic-pathologic nomogram with a C-statistic of 0.85, indicating a high degree of accuracy, which identifies prognosis after transplant for HCC and which is superior to size and number of tumors alone," Dr. Ronald W. Busuttil, of the David Geffen School of Medicine at the University of California at Los Angeles, told Reuters Health by email.

Nearly a quarter of liver transplants in the United States go to patients with HCC, and HCC recurrence after transplantation affects 8% to 18% of those recipients.

Dr. Busuttil's team sought to develop a prognostic nomogram incorporating radiographic, laboratory, and pathologic characteristics that could be used to predict the risk of post-transplant HCC recurrence and guide adjuvant therapy and post-transplant surveillance.

Their retrospective review of 865 adult patients with HCC who underwent liver transplant, including 117 who subsequently had recurrence of HCC, identified seven prognostic variables in multivariable analysis: nuclear grade, vascular invasion, downstaging to Milan criteria, radiologic maximum tumor diameter, pretransplant maximum alpha-fetoprotein level, neutrophil-lymphocyte ratio, and total cholesterol.

The C-statistic associated with a risk score based on these variables (0.85) demonstrated significantly superior to the ability of the American Joint Committee on Cancer T (AJCC T)-staging system (0.80), the Milan Criteria (0.64), and the University of California San Francisco criteria (0.64) to predict HCC recurrence, according to the December 26th Journal of the American College of Surgeons online report.

"Of the seven prognostic variables, the one that seemed to have a great positive effect on prevention of HCC recurrence after transplant was downstaging," Dr. Busuttil said. "Specifically, our study showed that recipients originally beyond Milan Criteria (MC) and successfully down staged to MC had equivalent survival to those patients originally in MC. This may reflect a more favorable tumor biology in those that are able to be successfully downstaged."

"In the time of limited donors, we would recommend that the nomogram be used to select patients for transplant as opposed to size and number of tumors alone," Dr. Busuttil said. "Of course this would require in some cases pre-op biopsies, which should only be done by those experienced with a technique that has essentially a zero chance of cancer seeding."

"Despite the fact that biopsies are known not to provide 100% certainty of microvascular invasion or nuclear grade in the majority of cases, they will add to our knowledge of tumor biology and help in better selecting patients for transplant," he added.

Dr. María �ngeles Vázquez Millán, of the Liver Transplant Unit, A Coruña Hospital, A Coruña, Spain, told Reuters Health by email, "If the results are validated prospectively, the pretransplant nomogram could be used in a similar way to Milan Criteria in clinical practice, but with greater reliability. Once validated, the post-transplant nomogram could have implications in follow-up protocols (number and periodicity of radiological studies) and maybe in therapy."

"The most surprising result in my opinion is that patients successfully downstaged to Milan Criteria had equivalent recurrence-free survival to patients originally within Milan Criteria and significantly superior to patients beyond Milan Criteria who were not downstaged," Dr. Vázquez Millán said. "To the best of my knowledge, no group has demonstrated this point. In case these results are confirmed, this could allow transplant in patients in whom transplant is currently denied."

This paper was presented at the 126th Annual Meeting of the Southern Surgical Association, Palm Beach, Florida, December 2014.

The authors report no external funding or disclosures.

SOURCE: http://bit.ly/1yNvMRQ

J Am Coll Surg 2014.