Cancer screening in patients on maintenance dialysis

INTRODUCTION — In general, testing for cancer among patients with kidney failure occurs in four situations:

●In patients with clinical evidence of disease, such as rectal bleeding or a palpable breast mass. This is not screening by definition.

●In asymptomatic patients on maintenance dialysis, to ascertain their suitability for kidney transplantation. (See "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient".)

●In asymptomatic patients with a functioning kidney transplant. Transplant recipients require treatment with immunosuppressive medications, which can increase their risk of cancer. This form of screening is discussed elsewhere. (See "Overview of care of the adult kidney transplant recipient", section on 'Screening' and "Malignancy after solid organ transplantation".)

●In asymptomatic patients on maintenance dialysis, aiming to improve outcomes by identifying disease at an earlier and more treatable stage.

Although cancer screening is widely recommended for the general population, these recommendations are not necessarily applicable to patients with end-stage kidney disease (ESKD) who are receiving maintenance dialysis. Unfortunately, the high mortality among patients on dialysis from causes other than malignancy means that cancer screening is often not appropriate for such patients. This topic will review cancer screening among patients with ESKD who are receiving maintenance dialysis.

CANCER RISK IN PATIENTS ON DIALYSIS

Incidence — The overall incidence of cancer in patients with end-stage kidney disease (ESKD) is reportedly higher than that in the general population [1-8]. A systematic review of 22 cohort studies including 1,443,684 patients on dialysis found a pooled standardized incidence ratio (SIR) for overall cancer of 1.40 (95% CI 1.36-1.45) when compared with the general population [7]. In addition, the following findings were noted:

●The risks of melanoma (SIR 2.83) and cancers of the thyroid (SIR 4.92), tongue (SIR 1.8), kidney (SIR 4.87), bladder (SIR 2.51), cervix (SIR 1.76), penis and scrotum (SIR 1.75), and liver (SIR 1.39) were higher among patients on dialysis than in the general population.

●The risks of cancers of the breast, colorectum, stomach, lung, uterus, and prostate were not significantly different between patients on dialysis and those in the general population.

●The risk of myeloma (SIR 4.15) was higher among patients on dialysis, whereas the risks of leukemia, non-Hodgkin lymphoma, and Hodgkin lymphoma were not significantly different between patients on dialysis and those in the general population.

●For cancers in which an excess risk was observed in patients on dialysis, the magnitude of the excess risk was greatest among females and younger patients.

●The magnitude of the excess risk of cancer associated with dialysis varied substantially between studies. This heterogeneity possibly reflects true differences between countries but could also be due to residual confounding by unmeasured characteristics that affected some studies more than others.

Malignancy is more common among patients on hemodialysis than among those on peritoneal dialysis [1,9], approximately three times more common in older patients (over 65 years old) compared with younger patients, and less common in patients with diabetes, probably due to increased mortality from cardiovascular disease and other causes. Patients with a history of cancer prior to initiating dialysis have a relatively high risk (approximately 14 percent) of cancer recurrence or developing a new malignancy after dialysis initiation [10].

Risk factors — The following factors probably contribute to the higher incidence of some types of cancer in patients on dialysis as compared with the general population:

●Acquired kidney cystic disease increases the risk of renal cell carcinoma [11]. (See "Acquired cystic disease of the kidney in adults".)

●Prolonged analgesic abuse is a risk factor for transitional cell carcinoma of the bladder, ureter, and renal pelvis and for renal cell carcinoma [11]. (See "Urinary tract malignancy and atherosclerotic disease in patients with chronic analgesic abuse" and "Malignancies of the renal pelvis and ureter".)

●Prolonged oral cyclophosphamide use is a risk factor for bladder cancer. (See "General toxicity of cyclophosphamide in rheumatic diseases".)

●Infection with the hepatitis B or C viruses is a predisposing factor for the development of liver cancer. (See "Epidemiology and risk factors for hepatocellular carcinoma".)

It is unknown whether reduced immune function or abnormal cellular repair mechanisms among patients on maintenance dialysis contributes to the increased incidence of malignancy [3,12].

PATIENTS WHO ARE ACTIVE ON THE TRANSPLANT WAITING LIST — Placement on the waiting list for kidney transplantation should be preceded by investigations to rule out serious comorbidities, including active malignancy. Once patients on dialysis are active on the waiting list, international guidelines recommend routine screening for common cancers (such as colorectal, breast, cervical, and prostate cancer) as per the general population [13]. The rationale for screening in this situation is to maximize the likelihood of a successful outcome following transplantation rather than to reduce the risk of death from cancer per se. Thus, unlike the situation in the general population, a detailed discussion of patient preferences and the benefits and harms of screening is not generally required.

Screening for lung, kidney, and bladder cancer is not advised for all transplant candidates but may be appropriate in selected patients, as discussed elsewhere:

●Lung cancer (see "Screening for lung cancer", section on 'Our approach to counseling for screening')

●Renal cell carcinoma (see "Clinical manifestations, evaluation, and staging of renal cell carcinoma", section on 'Screening' and "Acquired cystic disease of the kidney in adults", section on 'Surveillance')

●Bladder cancer (see "Screening for bladder cancer", section on 'Our approach')

PATIENTS WHO ARE NOT TRANSPLANT CANDIDATES

General approach — For most patients on dialysis who are not candidates for kidney transplantation, there is no role for routine cancer screening given their high mortality from causes other than malignancy [14]. (See 'Rationale against screening' below.)

However, cancer screening as recommended for the general population may be appropriate for selected patients, such as those with longer life expectancy who are not interested in kidney transplantation or who are not transplant candidates because of psychosocial issues rather than medical comorbidities. The potential benefits of screening may also outweigh its potential harms in patients with an unusually high risk of cancer (eg, due to a known genetic predisposition, such as BRCA1 or BRCA2, or a strong family history of cancer). In such patients, we engage in shared decision-making about cancer screening and individualize screening based on factors such as patient preferences, expected lifespan, and cancer risk.

If the decision is made to proceed with cancer screening, screening methods and strategies for the general population may be used, as discussed in separate topic reviews, recognizing that net benefit will likely be lower.

We generally do not screen for acquired cystic disease of the kidney, given that there is no evidence that this practice is beneficial.

Rationale against screening — We advise against routine cancer screening for most patients on dialysis who are not kidney transplant candidates due to their limited life expectancy and high mortality from causes other than cancer. In addition, the unknown efficacy of commonly used screening tests, potential harms resulting from false-positive results and unnecessary investigations, uncertain outcomes with cancer treatment, and lack of cost effectiveness of screening in this patient population all argue against routine screening.

Limited life expectancy — Patients on maintenance dialysis have a high mortality rate from causes other than malignancy and therefore may not be expected to survive long enough to develop the cancer or its consequences. Thus, cancer screening is unlikely to be beneficial for most patients [9,15-17]. (See "Patient survival and maintenance dialysis".)

Risk of death from cancer — Despite the higher risk of developing particular tumors among patients on dialysis, malignancy is a relatively rare cause of death in this patient population. As an example, the United States Renal Data System (USRDS) 2020 annual report found that malignancy was the cause of approximately 3 percent of all deaths among patients on hemodialysis who died in 2018 [18]. By comparison, arrhythmia/cardiac arrest, withdrawal from dialysis, and infection caused 44, 19, and 7 percent of all deaths, respectively.

Efficacy of screening tests — Data evaluating the performance characteristics of cancer screening tests among patients on maintenance dialysis are scarce, and the positive and negative predictive value, sensitivity, and specificity of most cancer screening tests in this patient population are unknown. Certain screening tests may have high false-positive rates in patients on dialysis, which may lead to inappropriate and possibly harmful testing without benefit for the patient. As examples:

●Fecal occult blood testing – The use of fecal occult blood testing for colon cancer screening may result in high false-positive test results among patients on dialysis because they have a higher incidence of nonmalignant gastrointestinal abnormalities than the general population. A positive stool guaiac test, for example, occurs at a higher frequency in patients on dialysis due to an increased incidence of gastritis, gastrointestinal telangiectasias, and other causes of gastrointestinal blood loss. In one series, the incidence of guaiac-positive stools was three times higher in asymptomatic patients on dialysis compared with non-end-stage kidney disease (ESKD) controls (15 versus 5 percent) [19]. Colonoscopy performed in follow-up of abnormal results from fecal occult blood testing appears to be associated with at least a 10-fold higher risk of serious complications in patients on dialysis than in the general population [20].

●Mammography – Vascular calcification, which is common among patients on maintenance dialysis, may complicate the interpretation of screening mammograms for breast cancer and potentially increase the risk of false-positive tests [21].

●Tumor markers – Most tumor markers are glycoproteins with relatively high molecular weights (3400 to 5000 kD), and they are ineffectively removed by dialysis [22]. Thus, markers that depend upon kidney elimination or metabolism (such as carcinoembryonic antigen [CEA]) yield high false-positive rates in dialysis and are of little value in the screening or management of patients with cancer [22-24].

Outcomes of cancer treatment — Data examining outcomes among patients on dialysis who receive cancer therapy are limited, and it is unclear if treatment results in outcomes that are comparable to those of patients who are not on dialysis.

Patients on maintenance dialysis who receive surgical treatment for certain cancers may have worse outcomes than those not receiving dialysis. As an example, in a retrospective study of 42,403 patients with colorectal cancer undergoing surgical tumor resection, of whom 265 (0.6 percent) were receiving dialysis, patients undergoing dialysis had higher risks of postoperative mortality, reintubation, prolonged ventilatory support, sepsis, deep surgical site infection, pneumonia, and septic shock [25]. Similarly, a study of six patients on hemodialysis undergoing pulmonary resection for non-small cell lung cancer found a high rate of postoperative complications (two patients with atrial fibrillation and two with hyperkalemia) [26].

Cost effectiveness of screening — Cancer screening is not cost effective in the maintenance dialysis population. As an example, one analysis compared cancer screening in patients with ESKD with screening in the general population and examined the screening benefits of mammography, Papanicolaou tests, flexible sigmoidoscopy, and serum prostate-specific antigen (PSA) levels [27]. Each test was assumed to have 100 percent sensitivity and specificity, and if detected, cancer was assumed to be instantly treated and cured. These assumptions biased the study in favor of cancer screening in general. The following results were reported:

●The costs per unit of survival benefit conferred by cancer screening were 1.6 to 19.3 times greater among patients with ESKD compared with the general population.

●The net gain of life expectancy in patients with ESKD via these screening programs was calculated to be five days or less. Similar survival gains could be obtained by reducing the baseline ESKD mortality rate by 0.02 percent.

The authors concluded that routine cancer screening in the ESKD population did not represent an efficient allocation of financial resources [27]. Similar findings were reported in studies evaluating the efficacy of breast and cervical cancer screening of Canadian females undergoing maintenance dialysis [28] and the cost-effectiveness of breast cancer screening among Australian females undergoing maintenance dialysis [29].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dialysis".)

SUMMARY AND RECOMMENDATIONS

●Cancer risk – The overall incidence of cancer in patients with end-stage kidney disease (ESKD) is reportedly higher than that in the general population. Malignancy is more common among patients on hemodialysis than among those on peritoneal dialysis, approximately three times more common in patients aged >65 years compared with younger patients, and less common in patients with diabetes. (See 'Incidence' above.)

●Approach to screening – Although cancer screening is widely recommended for the general population, these recommendations are not necessarily applicable to patients with ESKD receiving maintenance dialysis. Our approach is as follows:

•Patients active on the transplant waiting list – Patients on dialysis who are active on the waiting list for kidney transplantation should receive routine screening for common cancers (such as colorectal, breast, lung, and prostate cancer) as per the general population. The rationale for screening in this situation is to maximize the likelihood of a successful outcome following transplantation rather than to reduce the risk of death from cancer per se. (See 'Patients who are active on the transplant waiting list' above.)

•Patients who are not transplant candidates – For most patients on dialysis who are not candidates for kidney transplantation, there is no role for routine cancer screening given their high mortality from causes other than malignancy. However, cancer screening may be appropriate for selected patients, such as those with longer life expectancy who are not interested in kidney transplantation or who are not transplant candidates because of psychosocial issues rather than medical comorbidities. The potential benefits of screening may also outweigh its potential harms in patients with an unusually high risk of cancer. In such patients, we engage in shared decision-making about cancer screening and individualize screening based upon factors such as patient preferences, expected lifespan, and cancer risk. (See 'Patients who are not transplant candidates' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledges Jean Holley, MD, FACP, who contributed to an earlier version of this topic review.