Tumor Debulking Predicts Liver Transplant Success

MAINZ, Germany, Aug. 2 -- The success of chemoembolization tumor debulking is a better indicator of which liver cancer patients will do well with a transplant than the current standard of size and number of lesions, according to investigators here.

In fact, the so-called Milan criteria of size and number of lesions appeared to have no impact on recurrence in a study of 96 consecutive patients with hepatocellular carcinoma, according to Gerd Otto, M.D., of Johannes Gutenberg University.

Instead, only two factors predicted recurrence - the response to transarterial chemoembolization and the number of tumor nodules found in a surgical specimen, Dr. Otto and colleagues reported in the August issue of Liver Transplantation.

Transarterial chemoembolization is usually used as a bridging therapy while patients await an orthotopic liver transplant and to downstage the tumor in order to render patients eligible for a transplant under the Milan criteria, Dr. Otto said.

"Our results suggest that large and even multifocal hepatocellular carcinoma can be successfully treated by [liver transplant] if they show a good response and remain stable during the sequential pretreatment by transarterial chemoembolization," the researchers concluded.

"This observation may form a basis of biologically more plausible selection criteria rather than simple tumor size or tumor number," they added.

Of the 96 patients treated with transarterial chemoembolization in the study, 34 met the Milan criteria and were immediately listed for transplant although seven were delisted for various reasons. In the end, 23 of these patients were transplanted and four remain on the waiting list.

Of the 62 patients who did not meet the Milan criteria, 28 were downstaged and listed for transplant; 27 were transplanted and one remains on the waiting list.

The study found:

• Overall, five-year survival in the 96 patients was 51.9%, but it was 80.9% in those who had a transplant and 0% for those who did not - a difference that was highly statistically significant at P<0.0001.
• Freedom from recurrence was 94.5% in the 39 patients who had no progression during transarterial chemoembolization in the pretransplant period, but 35.4% in the 11 patients who initially responded but then had some progression before transplant. The difference was significant at P=0.0017.

In a univariate analysis of various possible predictors of freedom from recurrence, only grade (one or two versus three), number of nodules in a surgical specimen (one, two, or three versus multiple), and progression (on transarterial chemoembolization) while waiting for a transplant achieved statistical significance.

In a multivariate analysis, grade was no longer statistically significant, but having three or fewer nodules conferred a relative risk of progression of 0.166 compared to having four or more. The 95% confidence interval was 0.034 to 0.796; P=0.025.

And progressing while on transarterial chemoembolization increased the risk of recurrence by more than 11 times. The relative risk was 11.134, with a 95% confidence interval from 2.01 to 61.46; P=0.006.

The study "raises the intriguing possibility of looking beyond tumor size and number in selecting patients for transplant," commented Francis Yao, M.D., of the University of California San Francisco.

But he noted that an "all-comers" transplant policy - in which any tumor burden would be acceptable as long as the patient responded to transarterial chemoembolization - is unlikely to be useful. "An upper limit in tumor size and number therefore probably still exists beyond which orthotopic liver transplant will likely yield poor results despite preoperative loco-regional therapy," Dr. Yao said in an accompanying editorial.

Rather than replacing the Milan criteria, Dr. Yao said, the factors identified by Dr. Otto and colleagues should be used in conjunction with tumor burden.