Risk of Cancer-Related Death Elevated in Solid-Organ Transplant Recipients

The cancer death rate was increased in recipients of a solid-organ transplant in a population-based cohort study conducted recently by Sergio A. Acuna, MD, and colleagues. The researchers reported study results online in JAMA Oncology [doi:10.1001/jamaoncol.2015.5137].

Previous studies have shown that compared with the general population, recipients of a solid-organ transplant have increased incidence of malignant neoplasm following transplantation. However, according to the researchers, there are few data from population-based studies on cancer mortality after transplantation. Further, the available findings have shown disparate results.

Relative to the general population, solid-organ transplant recipients have decreased cancer survival rates and are at higher risk of dying of causes not related to cancer. Common malignant neoplasms diagnosed in solid-organ transplant recipients are usually curable in the general population and have low mortality in the transplant population.

When a malignant neoplasm is diagnosed, outcomes among solid-organ transplant recipients are worse than in the general population. Possible explanations include malignant neoplasms occurring in an immunosuppressed environment may be more biologically aggressive, and patients may receive less aggressive cancer treatment because of comorbidities and the concern that treatment may trigger transplant rejection.

Dr. Acuna et al. designed the current study to determine the overall and site-specific risk for cancer mortality in a population-based cohort of recipients of solid-organ transplants in Ontario, Canada, over a 20-year period. The study included all solid-organ transplant recipients from January 1, 1991, through December 31, 2010, in Ontario, with 85,557 person-years of follow-up through December 31, 2011.

The study utilized data from the national transplant register that was linked to the provincial cancer registry and administrative databases. The analysis was conducted between November 2013 and February 2015. Standard mortality ratios (SMRs) were used to compare cancer mortality with that of the general population. Mortality and cause of death were identified by linkage between the Canadian Organ Replacement Register, the Ontario Cancer Registry, and the Office of the Registrar General of Ontario death database.

Of the 11,061 solid-organ transplant recipients identified, 59% (n=6516) were kidney, 24% (n=2606) were liver, 8% (n=929) were heart, and 6% (n=705) were lung. The median age of recipients was 49 years and 36.2% (n=4004) were female. Median follow-up time was 6.63 years.

Of the identified patients, 10% (n=1124) had a history of pretransplant malignant neoplasm. Among those, in 39% of the patients (n=442) malignant neoplasm was the underlying reason for the transplant, 21% (n=234) had a malignant neoplasm diagnosed near the time of the transplant, and 40% (n=448) had a malignant neoplasm in presumed remission. Post-transplant do novo malignant neoplasms occurred in 11% (n=1267) of patients. Median time from transplantation to post-transplant de novo cancer diagnosis was 5.16 years.

There were 3068 deaths in this study cohort, of which 603 were cancer related. The majority of the cancer-related deaths were secondary to post-transplant de novo malignant neoplasms (68%; n=411); 21% (n=127) were due to recurrent malignant neoplasms.

The age and sex SMR from cancer was statistically significantly increased for all transplant recipients compared with the general population (SMR, 2.84; 95% confidence interval [CI], 2.60-3.07). There were no differences in SMR by sex.

The increased risk remained following exclusion of deaths from malignant neoplasms that were the indication for transplantation (SMR, 2.38; 95% CI, 2.18-2.60) and when only mortality from post-transplant de novo malignant neoplasms was considered (SMR, 1.93; 95% CI, 1.75-2.13). The increased risk also remained regardless of the transplanted organ.

The overall SMR for cancer across all age groups was higher among solid-organ transplant recipients than in the general population. The risk of cancer-related death was highest in the pediatric transplant population (SMR, 84.61; 95% CI, 52.00-128.40) and lowest in transplant recipients >60 years of age (SMR, 1.88; 95% CI, 1.62-2.18) compared with the general population.

The researchers cited some limitations to the study, including the chance of misclassification of cause of death due to the multiple comorbidities in the transplant population; and because the incidence of non-melanoma skin cancer (NMSC) was not captured in the cancer registry, those deaths were considered to have arisen from new malignant neoplasms diagnosed post-transplantation, which may have led to an overestimation of the risk of de novo NMSC death.

“Despite the fact that solid-organ transplant recipients have shorter life expectancies and a higher risk of dying of non-cancer-related causes, these patients have an elevated risk of cancer death as compared with the general population. Addressing the cancer burden in solid-organ transplant recipients is critical to improving the survival of these patients. Cancer is a leading cause of death in this population, and its incidence is expected to increase in the next 10 years as the median age of transplant recipients increases and improvements in survival with a functioning transplant lengthen exposure in immunosuppression. Specific strategies for cancer prevention, screening, surveillance, and optimization of cancer treatment may be required to improve cancer outcomes for these patients,” the researchers concluded.

Takeaway Points

  1. Researchers conducted a study to examine whether solid-organ transplant recipients are at greater risk of cancer mortality by comparing cancer-related deaths in this population with those in the general population using standardized mortality ratios.
  2. Compared with the general population, cancer-related deaths in the population of solid-organ transplant recipients was significantly elevated, an increase in risk that remained when patients with pre-transplant malignant neoplasms were excluded.
  3. The risk was highest in the pediatric solid-organ transplant recipient population and lowest among those >60 years of age, but remained elevated compared with the general population at all ages.