New Recommendations Issued for Transplantation in Patients With Hepatocellular Carcinoma

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New Recommendations Issued for Transplantation in Patients With Hepatocellular Carcinoma

March 17, 2010 — Liver transplantation and resection continue to be the mainstay of curative treatment for patients with liver cancer, and new recommendations addressing liver transplantation for hepatocellular carcinoma (HCC) have now been issued.

The expert panel behind the new guidelines reports that there was general consensus among the members for a need to develop a "calculated continuous HCC priority score for ranking HCC candidates" who are awaiting liver transplants. Measures taken into consideration would include tumor size and rate of tumor growth.

In addition, the new allocation policy set out to ensure that there would be similar outcomes for HCC and non-HCC transplant recipients.

"Ultimately, we agreed that the allocation policy should result in similar risks of removal from the waiting list and comparable transplant rates for HCC and non-HCC candidates alike," said A. Pomfret, MD, PhD, from the Lahey Clinic Medical Center in Burlington, Massachusetts, in a statement.

The details of the recommendations appear in the March issue of Liver Transplantation; Dr. Pomfret is first author of the report.

National Conference Convened

The recommendations were compiled during a national conference that was convened — under the auspices of the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS), the American Society of Transplant Surgeons, the American Society of Transplantation, and the International Liver Transplantation Society — to address liver transplantation as a treatment option for patients with HCC.

The conference participants were more than 180 transplant physicians, surgeons, and other medical specialists, representing the 50 most active transplant centers in the United States.

In an accompanying editorial, Neuberger, MD, from the Queen Hospital in Birmingham, the United Kingdom, and medical director of organ donation and transplantation at NHS Blood and Transplant, writes that "it is very much to be hoped" that these new recommendations will not be the final word on the subject, but rather the first in a series that will refine the role of liver transplantation in the management of patients with HCC.

"With the advent of more robust markers to define the tumor natural history, the introduction of newer agents to treat the tumor, the better use of immunosuppression to slow the natural history of recurrent disease, will mean that these considerations may well become of little more than historical interest in a few years' time," he notes. But for now, these recommendations "remain a valuable step in optimizing the management of the waiting lists."

Conference Objectives

The objectives of the conference, according to the report, were to address issues specific to HCC as they relate to liver allocation; to develop a standardized pathology report form for the assessment of the explanted liver; to develop more specific imaging criteria for HCC, which is designed to qualify transplant candidates for automatic Model for End-Stage Liver Disease (MELD) exception points without the need for biopsy; and to develop a standardized pretransplant imaging report form for the assessment of patients with liver lesions.

To best fulfill the objectives of the conference, 6 work groups reviewed and defined what they believe are the key issues:

Pathology. Currently, reporting of HCC pathology components in liver transplant patients to UNOS is inconsistent and heavily dependent on clinical circumstances. These inconsistencies, the authors note, severely limit the usefulness of these data.

Imaging. The current OPTN policy in the United States specifically permits a pretransplant diagnosis of HCC solely on the basis of imaging criteria. The authors write that there is "considerable concern" that the limited imaging criteria in the current policy is inadequate.

The rationale for the expansion of the Milan criteria. The Milan criteria for transplantation in HCC patients are based on tumor size and number, but the cutoffs for the size and number at which the risk for recurrence is considered to be acceptable are not well established.

The role of local-regional therapy in the treatment of HCC. This therapy is increasingly being used to prevent list dropout, to improve posttransplant survival, and to downstage advanced disease.

The role of downstaging in liver transplant candidates with HCC. Patients with tumors that do not meet the Milan criteria can potentially undergo transplantation after showing a response to treatment. But in the majority of studies, the authors note, not only were there no upper limits for the tumor size and number before downstaging treatments were applied, but the criteria for a response varied among these studies.

Organ allocation for liver transplantation candidates with HCC. Data suggest that HCC candidates have increased access to deceased donor livers, compared with standard MELD candidates, but that adjusted 3-year survival data show that these patients (who receive a transplant with HCC exceptions) have inferior 3-year survival. HCC candidates appear to have an advantage, the authors note, but there is a reduction in system utility as a result of this advantage.

Key Recommendations

The leaders of each working group reported their findings during a plenary presentation and provided a summary of their evidence-based recommendations. Their main recommendations are as follows:

Priority should be maintained for candidates with HCC who meet the Milan criteria. There should be no regional adjustment in assigned priority for HCC candidates in this iteration.

A calculated continuous HCC priority score should be developed that incorporates calculated MELD, alpha-fetoprotein (AFP), tumor size, and rate of tumor growth. Only candidates with at least stage T2 tumors will receive additional HCC priority-score points.

The candidate must meet the Milan criteria for a minimum of 3 months before additional priority-score points are assigned.

Time is calculated from the date of the first imaging study that indicates that the Milan criteria are met if the liver tumor meets class 5A imaging criteria.

Patients with a diagnosis of HCC who meet the Milan criteria and who have a calculated MELD score of less than 15 will start with a MELD/HCC priority score of 15 until they have had the HCC diagnosis for 3 months, afterwhich they will receive a calculated MELD/HCC priority score.

Patients with a calculated MELD score of more than 15 will receive a calculated MELD score for the first 3 months after the diagnosis of HCC in which they meet the Milan criteria, afterwhich they will receive a calculated MELD/HCC priority score.

The MELD/HCC priority score will be recalculated every 3 months and can increase or decrease according to changes in tumor characteristics, underlying MELD score, and time meeting the Milan criteria.

Allocation points will be based on candidate's calculated MELD score plus the following factors: an AFP level below 500 ng/mL (no points will be added if AFP is greater than 500 ng/mL); tumor size within the Milan criteria; and time within the Milan criteria, including patients downstaged to within the Milan criteria.

Patients with elevated AFP levels and no tumor on imaging will no longer receive additional MELD points.

In the editorial, Dr. Neuberger explains that the main question for liver transplant clinicians is not, primarily, "what are the indications for liver transplantation in those with HCC." The main questions, he maintains, are: What is the best pathway for management? When should replacement be considered? and How should the needs of the patient with HCC be balanced against those with other liver diseases that affect either quality or quantity of life?

Liver Transpl. 2010;16:249-251, 262-278. Abstract, Abstract

http://www.medscape.com/viewarticle/718650