Screening and Early Detection: Cancer in the Kidney Transplant Recipient

Life expectancy in the kidney transplant population is only about half that in the general population.[1] Although cardiovascular disease is the most common cause of death (42%) in patients who die with a functioning graft,[2] malignancy is a significant cause of mortality, especially in older patients who are the most likely group to die with a functioning transplant. A recent review of Medicare patients in the United Network for Organ Sharing database[3] and several other registries[4-8] provides convincing evidence of the higher risk of cancer in the end-stage renal disease (ESRD) and kidney transplant populations.

Of the 38% of kidney transplant recipients who die with a functioning transplant, malignancy is the cause of death in 9.2%. Furthermore, the mortality rate from cancer increases linearly with age such that at ages 50-59 years, the mortality rate is 4 deaths per 1000 patient years; and after age 65, the mortality rate increases to 7.1 deaths per 1000 patient years.[9] The Clinical Practice Guidelines Committee of the American Society of Transplantation (AST) published guidelines for outpatient evaluation of adult and pediatric kidney transplant candidates.[10] Included in these guidelines are recommendations for cancer screening and early detection.
Cancer Screening and Early Detection in the Patient With ESRD: Room for Improvement

Although an increase incidence of cancer has been documented in dialysis patients,[3,11] compliance with cancer screening recommendations in this population is low.[12] One explanation may be that the cost-effectiveness of screening has been questioned, given that dialysis patients have a much shorter life expectancy than the general population and therefore, are perceived as unlikely to benefit from screening and early detection.[13,14] However, incorporating screening and early detection into the pretransplant evaluation of patients with ESRD potentially serves 2 important purposes: to prevent the potential for doing more harm from immunosuppression in patients with undiagnosed cancer, and to ensure the best use of a scarce resource, the donor organ. In addition, screening may also detect premalignant lesions, allowing for timely intervention. For example, screening for colon cancer may detect adenomas that pose a risk for development into malignancy. Table 1 summarizes the AST recommendations for cancer screening prior to listing a patient for kidney transplantation.[10]

What appears to be lacking is good information on how compliant transplant teams have become with incorporating standard cancer prevention recommendations into the initial evaluation or how regularly patients are screened thereafter while on the transplant waiting list. A 2002 survey by the AST Clinical Practice Guidelines Committee of 287 kidney transplant programs (192 (67%) responded) in the United States to review the policies of kidney transplant programs with respect to the management of wait-listed patients, indicated that 69% reported that they insisted on screening for breast, cervical, and colon cancer, while 11% did not screen for these cancers and 20% deferred the decision to screen to referring nephrologists.[15] Regular prostate-specific antigen testing of older male patients was required by 79% of programs.
Patients With a History of Malignancy

The AST screening recommendations do not apply to patients with a prior history of malignancy. Patients with a prior history must undergo a series of tests to detect tumor recurrence. Table 2 lists the recommended wait times before listing a patient for transplantation who has a history of malignancy. It is important to note that although after the recommended wait times the risk of recurrence is low, tumor recurrence is still possible. Other situations that require investigation in the pretransplant population that are not specifically addressed in the guidelines include the patient with known Von Hippel-Lindau disease and the patient with liver disease. Patients with known Von Hippel-Lindau disease must undergo a battery of screening tests specific for this disease,[16] and patients with liver disease should have a work-up for early detection of hepatic malignancy and may require combined kidney-liver transplantation.[17]