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Recipients of solid-organ transplants more likely to die of cancer
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Individuals who underwent solid-organ transplants appeared more likely to die of cancer than those in the general population, according to a study conducted in Canada.
Solid-organ transplant recipients are at greater risk for developing some cancers. However, because transplant recipients are at greater risk for dying of causes other than cancer, the specific effects of transplantation on cancer mortality had not been established.
In this study, researchers determined cancer was the second-leading cause of death among transplant recipients.
“We didn’t expect to see this magnitude of the difference in cancer mortality,” Nancy N. Baxter, MD, PhD, associate professor in the department of surgery and the department of health policy, management and evaluation at St. Michael's Hospital and the University of Toronto, told HemOnc Today. “In spite of the increased incidence of cancer in transplant recipients and reports of worse cancer outcomes in this population, we were expecting a smaller excess in the risk of cancer mortality given the multiple competing causes of death in this population.
“It was also quite unexpected to see that the risk of cancer mortality was higher than that of the general population in older transplant recipients, and that the risk of cancer death was not limited to long-term survivors,” Baxter added. “[This shows] that the burden of cancer mortality was considerable soon after transplantation.”
Baxter and colleagues identified 11,061 people (median age, 49 years; range, 37-58; 63.8% men) in the province of Ontario who underwent solid-organ transplant between 1991 and 2010. The majority received transplants of the kidney, liver, heart or lungs.
Overall, researchers reported 3,068 deaths, of which 603 (20%) were cancer related.
The cancer-related mortality rate among transplant recipients was significantly higher than the general population in Ontario (standardized mortality ratio = 2.84; 95% CI, 2.61-3.07). The risk remained high even after excluding patients who had pre-existing cancers prior to transplantation (n = 1,124; standardized mortality ratio = 1.93; 95% CI, 1.75-2.13). The risk also was high regardless of transplanted organ.
Researchers reported a higher mortality rate in children (SMR = 84.61; 95% CI, 52-128.4) and a lower rate among patients aged older than 60 years (SMR = 1.88; 95% CI, 1.62-2.18). However, mortality rates for transplant recipients remained elevated compared with the general population at all age levels.
The most common cause of cancer death was lung cancer (21%), followed by liver cancers (18%), non-Hodgkin’s lymphoma (16%) and colorectal cancer (7%). Non-melanoma skin cancer accounted for 3% of the cancer-related deaths.
The investigators acknowledged study limitations. Because they determined cause of death by death certificates, transplant recipients who had comorbidities and then died could have led to misclassification and, thus, skewed the data. Additionally, non-melanoma skin cancer was not identified in the cancer registries used; therefore, those deaths were determined to be from new cancers diagnosed after transplant, even though they may have been pre-existing.
“Clinicians who care for transplant recipients should be aware that these patients are not only at increased risk of developing malignant neoplasms but also of dying of any cancer,” Sergio Acuna, MD, postdoctoral fellow at University of Toronto and St. Michael’s Hospital, told HemOnc Today. “It is critical to follow with the current recommendations for cancer screening in this population, starting early after transplantation, and have a high level of suspicion to identify malignancies at earlier stages. Clinicians involved in the care of transplant recipients should also counsel these patients to take every possible precaution to reduce their cancer risk, including limiting sun exposure, quitting smoking, reducing alcohol consumption, improving their diet and increasing their physical activity.”
In an accompanying editorial, Marianne Schmid, MD, of the department of urology at University Medical Center Hamburg-Eppendorf, and colleagues called the study “provocative” and said it raises even more questions about the association between transplants and cancer-related mortality. More importantly, it leaves the notion of what to do for these high-risk patients virtually unanswered, Schmid and colleagues wrote.
The “most sensible approach” would be to promote better preventive care, which includes cancer screening and lifestyle recommendations, they wrote.
“Although posttransplant care guidelines establish clear recommendations for preventive care, including cancer screening, the effectiveness and adherence to these recommendations remain unmeasured,” they wrote. “Moreover, the role of cancer screening in the general population, particularly for breast and prostate cancer, has come under scrutiny.
“Given the most recent United States Preventive Services Task Force recommendations against prostate-specific antigen–based screening for prostate cancer in all men, it may be even harder to justify screening in transplant recipients who have a more limited life expectancy than their general-population counterparts,” they wrote. “Conversely, given the findings of the study by Acuna [and colleagues], one may argue that this subset of patients is at increased risk of cancer mortality, which could serve to justify pursuing ‘targeted’ cancer screening.” – by Anthony SanFilippo
For more information:
Nancy N. Baxter, MD, PhD, can be reached at baxtern@smh.ca.
Sergio Acuna, MD, can be reached at Sergio.acuna@utoronto.ca.
Disclosure: Baxter reports research funding from Pfizer. Acuna, the other researchers, and Schmid and colleagues report no relevant financial disclosures.
Perspective
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Andreas Karachristos, MD, FACS
Several recent studies have documented increased risk for cancer among transplant recipients. Further, detailed matching between the U.S. transplant registry with regional cancer registries revealed that the 5-year post-transplant cumulative incidence of non-Hodgkin’s lymphomas, colon cancer, lung cancers and kidney cancers is significantly increased in transplant recipients compared with the general population. However, earlier large population-based studies did not show increased risk for cancer-related deaths in the transplant group compared with the general population due to competing cardiac or infectious-related deaths in transplant recipients or incomplete data.
The current study is very important because it shows the overall cancer mortality from new cancers in patients after organ transplantation is significantly increased compared with the general population regardless of sex, age or transplanted organ. Additionally, the investigators were able to calculate standardized mortality ratios for different cancers. Not surprisingly, skin cancers and lymphomas were most significantly prevalent.
However, increased risk for death also was observed in most solid organ cancers, including bone and soft tissue, stomach, lung, pancreas, bladder, prostate, gynecologic and liver cancers, among others. In fact, cancer was the second most common etiology for death, and the risk increases steadily with time, despite competing risk from heart events or infections.
These important data should be used to define guidelines for screening recommendations in the transplant population because there is no certainty the existing guidelines for the general population are effective in the transplant group. Further, we need guidelines for manipulation of immunosuppression, treatment and surveillance modification in this high-risk group of patients.
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