Post-heart transplant cancer rates are climbing

More than 10 percent of heart transplant recipients developed cancer between one and five years post-transplantation—most commonly skin cancer—according to a study published in the Journal of the American College of Cardiology.

Survival in transplant patients with de novo malignancy—the first occurrence of cancer in the body—is markedly shorter than those with no malignancy, reported lead author Jong-Chan Youn, MD, PhD, and colleagues.

“Importantly, the increased risk of mortality was sizeable even for patients diagnosed with skin cancer; this finding is in contrast to the general population, in whom survival after skin cancer is typically favorable,” Youn et al. wrote.

People undergoing organ transplants typically have their immune systems suppressed to help the new organ survive. But immunosuppression has direct carcinogenic effects, and no current guidelines exist to adjust it in different at-risk populations, the authors noted.

Previous studies have suggested cardiac transplant recipients are at particularly high risk of developing de novo malignancies due to more intense immunosuppression, but those were single-center or single-country studies and lacked analysis of temporal trends. Therefore, the researchers sought to analyze the incidence of, types of, and time to de novo malignancy in an international registry over two eras (2000 through 2005 and 2006 through 2011).

The retrospective analysis included 17,587 adult heart transplant recipients who were followed for up to five years postoperation. Patients with a previous history of cancer, those who received multiple organ transplants and those who died or had unknown survival one year after surgery were excluded.

The incidence of any de novo malignancy was 10.7 percent one to five years after transplantation, with higher prevalence in the more recent era (12.4 percent versus 10 percent). The cumulative incidence of skin cancer in the more recent group was 8.4 percent versus 6.4 percent in the 2000-2005 cohort.

Despite this difference, the median time from transplant to diagnosis was similar for the two eras—899 days in 2001 to 2005 and 900 days in 2006 to 2011.

“Considering the increased burden of de novo malignancy in cardiac transplant recipients, additional effort needs to be directed toward formulating evidence-based cancer screening recommendations and optimized immunosuppression protocols for these patients,” Youn and colleagues wrote. “Relevant stakeholders, including oncologists, primary care physicians, and public health experts, as well as transplant cardiologists and immunologists, might be involved in the formulation of screening recommendations. In addition, it may be reasonable to consider the risk of de novo post-transplant malignancy in older patients when making decisions regarding candidacy for heart transplant versus left ventricular assist device as destination therapy.”

The researchers said the increasing incidence of post-transplant cancer in their study is especially notable considering early survival is improving in these patients. Cutting back de novo malignancy could extend these short-term gains to the intermediate and long term.

However, they acknowledged the increasing trend of skin cancer in heart transplant recipients could simply be mirroring the rising trend found in the general population.

In an accompanying editorial, Donna Mancini, MD, took issue with the researchers’ finding that skin cancer—despite a favorable survival rate in the general population—was associated with significantly worse survival in heart transplant recipients. She said the statistical methods used by Youn et al. could explain the disparity between their results and what Mancini has experienced clinically.

“In my own practice, where I have had the privilege of caring for more than 2,000 heart transplant recipients, although I have seen innumerable skin cancers, there were only two patients whose deaths could be directly linked to metastatic squamous cell skin cancer,” wrote Mancini, who coauthored the editorial with Val Rakita, MD, another physician with Mount Sinai Medical Center in New York.

“Clearly, the factors predisposing to skin cancer, such as increased age, smoking history, male sex, and diabetes, are all associated with decreased survival, and without the advantage of having propensity matching of this cohort, the conclusions may be flawed.”

The editorialists agreed with the study authors that patient-specific immunosuppression targets should be considered, and that surveillance for post-transplantation malignancies could improve. But they also pointed out tradeoffs in medicine are unavoidable.

“No matter how vigilant we and our patients ultimately become, society must recognize and accept that, although we can alleviate one problem, we cannot solve them all,” Mancini and Rakita wrote. “After all, there is a cost for long-term immunosuppression and allograft survival, and as we all know, ‘there is no such thing as a free lunch.’”