SAN FRANCISCO – The indication for liver transplant, the selection of immunosuppression therapy, and smoking status influence the long-term risk of new solid organ malignancies after liver transplantation, Dr. Sebastian Rademacher reported at the 2014 World Transplant Congress.
Multivariate analysis showed that recipients’ risk of a new solid organ cancer was elevated for those who had a history of smoking (1.89). Risk was reduced for recipients who received tacrolimus, compared with cyclosporine A (0.56), and for patients who had primary biliary cirrhosis/primary sclerosing cholangitis (0.47) or hepatitis C infection (0.21) as the indication for transplantation.
"I think we have to reoptimize and reevaluate the currently used immunosuppressive regimens," Dr. Rademacher said. "We have to adapt cancer surveillance programs for high-risk patients. Further studies into surveillance protocols and surrogate markers and long-term outcomes are recommended."
Researchers led by Dr. Rademacher, a surgeon at the Campus Virchow Clinic, Charité, Berlin, retrospectively studied 1,179 consecutive adults who underwent liver transplantation between 1988 and 2002 and had follow-up evaluations until 2013. Patients were 47 years old, on average, at the time of transplantation, and the median follow-up was 13.3 years.
Their 20-year cumulative incidence of solid organ cancers was 14%, he reported at the congress, which was sponsored by the American Society of Transplant Surgeons. The mean age at cancer diagnosis was 56 years.
The researchers used age- and sex-matched individuals from the German general population for comparison. The standardized incidence ratio in transplant recipients was 1.2 for breast cancer, 9.4 for cancer of the oropharynx and larynx, 1.7 for cancers of the colon and rectum, 3.0 for lung cancer, 3.9 for esophageal and stomach cancers, 4.5 for kidney and bladder cancers, and 4.6 for cancers of the female genitourinary system.
"We tried to evaluate the different immunosuppressive regimens and, over time, we had, I think, 27 different primary regimens," Dr. Rademacher said. Steroid-free regimens and low-dose steroid were part of that consideration, "but we segregated them out. For the five most frequent regimens, there was no significance. We assessed immunosuppressive regimens given over at least 2 years, but there was no difference between the regimens. Also, the trough levels of tacrolimus did not have any significant influence," he said.
The investigators did not have data on cumulative immunosuppression or mTOR [mammalian target of rapamycin] inhibitors, which were introduced late in the study period, according to Dr. Rademacher, who disclosed no relevant conflicts of interest. A surrogate marker of immunosuppression, rejection frequency, did not significantly predict the development of solid organ malignancies.