Thursday, May 19, 2011

AFP Predicts Outcome If Liver Cancer Recurs Posttransplant

Daniel M. Keller, PhD

AFP Predicts Outcome If Liver Cancer Recurs Posttransplant

May 19, 2011 (Philadelphia, Pennsylvania) — A low serum albumin or high alpha-fetoprotein (AFP) level independently predicted mortality when hepatocellular carcinoma (HCC) recurred after liver transplantation. The kind of treatment was also an independent predictor, with tumor resection and ablation being associated with better outcomes, Maarouf Hoteit, MD, instructor in medicine at the University of Pennsylvania School of Medicine in Philadelphia, reported here at the American Transplant Congress (ATC) 2011.
Dr. Hoteit and coworkers reviewed the charts of 333 patients who received liver transplants for HCC at the university between 1997 and 2009. Patients were followed every 6 months for 5 years to detect recurrent HCC, which was assessed using imaging of the chest and abdomen and measurements of AFP.
Dr. Hoteit reported that 44 patients (13.2%) had evidence of recurrent HCC on follow-up. Of these patients, 87% were men, the average age at baseline was 59.2 years (range, 54.7 to 62.8 years), and 66% had hepatitis C virus infection. The pretransplant peak AFP level averaged 191 ng/dL (range, 5 to 6342 ng/dL). One third of tumors were poorly differentiated, three quarters showed microvascular invasion, and 18% showed macrovascular invasion.

The average time to recurrence was 13.8 months (range, 8.8 to 29.6 months). At recurrence, median serum albumin level was 3.8 mg/dL, median International Normalized Ratio was 1.0, and median serum AFP was 15.5 ng/dL (range, 3.2 to 113 ng/dL). At recurrence, 45% of patients had a single lesion; the rest had multiple lesions.

Of the 44 patients with recurrent HCC, initial recurrence was in the lung in 19 patients, in the graft in 16, in the adrenal gland in 8, in abdominal lymph nodes in 7, in the peritoneum in 3, in bone in 3, in the pleura in 3, in the abdominal wall in 2, and in multiple sites in 15.

Median overall survival after recurrence was 8.2 months (95% confidence interval [CI], 5.6 to 13.7 months). The peak pretransplant serum AFP level and the level at recurrence were independent predictors of survival (P = .02 and P < .001, respectively). Median survival time after recurrence was 10.7 months if the pretransplant AFP level was less than 1000 ng/dL, but only 2.9 months if it was at or above that level. Similarly, if the AFP level at the time of recurrence was less than 1000 ng/dL, median survival was 11.2 months; for higher levels, it was only 4.3 months.

Resection or ablation was performed mainly for single lesions (15 single-lesion cases; 1 multiple-lesion case). Other forms of treatment were used mainly for multiple lesions. Median survival times were 28.3 months with resection, 16.7 months with ablation, 7.8 months with chemotherapy, 11.2 months with radiation, and about 3.7 months with transarterial chemoembolization or supportive care alone (P < .001).
There was trend toward longer survival if patients were exposed to sirolimus after or before and after recurrence, with a median survival of 12.8 months if patients received sirolimus and 5.8 months if patients did not (P = .08).

A multivariate analysis showed that there were statistically significant, independent predictive effects on mortality: an albumin level below 3.5 mg/dL (hazard ratio [HR], 3.8; 95% CI, 1.5 to 9.8; P = .03), AFP at recurrence of 1000 ng/dL or higher (HR, 5.4; 95% CI, 1.8 to 16.4; P = .01), supportive care alone compared with other treatments (HR, 7.54; 95% CI, 2.6 to 21.9; P < .001), and surgery or ablation vs other treatments (HR, 0.25; 95% CI, 0.11 to 0.55; P < .001). There was no statistically significant difference in survival related to tumor grade (poorly differentiated vs well or moderately differentiated).
Dr. Hoteit concluded that surgery or ablation is associated with the longest median survival, and reduces the risk for death by 75%. Whenever feasible, he said, surgery or ablation should be the treatment of choice for a recurrence of HCC after liver transplantation.

Session moderator Theodore Welling, III, MD, assistant professor of surgery at the University of Michigan in Ann Arbor, told Medscape Medical News that the variables shown to be independent predictors "were consistent with what a lot of other people have shown in other separate studies — that things like AFP and tumor size, which can be reflective of more aggressive disease biology, will increase your rate of recurrence."
Because the study was retrospective, the predictors are only prognostic indicators and cannot be used to determine therapy. "It's more of a statistical means of assessing risk, but it doesn't say for sure one way or the other [how] to stratify patients pretransplant [for any particular therapy]," Dr. Welling said.

Dr. Hoteit and Dr. Welling have disclosed no relevant financial relationships.
American Transplant Congress (ATC) 2011: Concurrent session 15. Presented May 1, 2011.

Authors and Disclosures
Daniel M Keller, PhD
Daniel M. Keller is a freelance writer for Medscape.

Daniel M. Keller has no disclosures.

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