CANCER SCREENING IN PATIENTS WITH END STAGE KIDNEY DISEASE

Overall prevalence of malignancy has been reported to be higher in end-stage kidney disease (ESKD) patients than that reported in general population.

Cancer screening in patients with end-stage kidney disease

 

CANCER INCIDENCE 

The overall prevalence of malignancy has been reported to be higher in end-stage kidney disease (ESKD) patients than that reported in general population.

One cancer registry reported that cancer has been diagnosed in 25,000 of 830,000 dialysis patients between 1980 and 1994 with an overall cancer incidence approached 1.18. The following findings have been observed:

Surprisingly, the highest incidence of malignancy was in dialysis patients of < 35 y., with a lowered incidence with the increase in age. Types of the reported cancer are similar to those observed in transplant patients, but different from controls. However, dialysis patients were more amenable to develop bladder malignancy, kidney, liver, thyroid, tongue, and cervix cancer in addition to multiple myeloma and non-Hodgkin lymphoma. Other types of solid tumors were not more prevalent in dialysis patients.

Risk factors 

A variety of predisposing factors may contribute to a higher incidence of certain tumors in dialysis cohort:

1]    Acquired renal cysts may increase the risk of renal cell carcinoma development.

2]    Chronic analgesic drugs abuse may predispose to the evolution of bladder ureter and kidney pelvis transitional cell carcinoma, and also to renal cell carcinoma.

3]    Prolonged administration of oral cyclophosphamide is considered a risk factor for cancer bladder development.

4]    Hepatitis B or C viral infection is an important predisposing factor for liver malignancy evolution.

5]    Human papilloma viral infection may induce tongue and cervical malignancies. The depressed immune system integrity among chronic dialysis community may trigger the liability to develop malignancy.

 

PROGNOSIS 

Of note, the increased risk of certain tumors, cancer is a relatively rare cause of mortality in dialysis cohort. For example, the USRDS (United States Renal Data Survey) 2007 annual report observed that malignancy was responsible for about 7 deaths per 1000 risky patient years for period prevalent patients at 2003-2005. On the other hand, cardiac arrest has induced about thirty-eight deaths per 1000 risky patient years at the same period.

Death incidence due to malignancy, however, may also vary with age and other comorbid diseases. The death rates for those of dialysis vintage of > 3 years is higher than that in patients undergoing dialysis for < 3 years (9 vs 6.5 deaths per 1000 patient y. at risk, resp.). Moreover, the prevalence of malignancy among hemodialysis patients is more common than that in peritoneal dialysis cohort; almost 3 times higher in dialysis patients with age > 65 as compared to younger patients; and it is lower in diabetics, probably due to elevated mortality rates related to cardiovascular deaths and other comorbidities.

 

CANCER SCREENING

 

The benefits of cancer screening for early detection of malignancy in dialysis patients should be weighed against the expected cost of screening of large numbers of patients with low survival rate that is related to death from non-malignant etiology.  

A given example of cost-effectiveness comparing cancer screening in dialysis patients to that in general population and analyzed screening benefits of many screening tools like mammography, flexible sigmoidoscopy, and serum PSA (prostate-specific antigen) level. Each one of these tests was supposed to have 100 % sensitivity/specificity, and, if detected, cancer ws supposed to be currently managed with complete cure. This postulation was biased the analysis generally in favor of cancer screening. They got the following results:

1]    Cost per unit survival benefit offered by cancer screening was 1.6 to 19.3 times higher among dialysis patients in comparison to general population.

2]    The overall benefit of life expectancy in dialysis patients through these screening techniques has been calculated to be 5 days or lesser. Similar survival benefits may be offered by decreasing the baseline MR (mortality rate) by 0.02 % in dialysis patients.

Hence, authors of these studies have one conclusion: traditional cancer screening routinely in dialysis patients did not offer any efficient background in the financial point of view. Similarly, were the findings of a Canadian study evaluating the efficacy of breast as well as cervical malignancy screening in women maintained on regular dialysis.

Nevertheless, concluding that routine cancer screening not to be instituted among dialysis patients may be tempered considering patients of variable age, different comorbidity, varying risk factors for certain cancer, and with racial differences. Survival enhancement, for example, among dialyzed African Americans should be considered when evaluating cancer screening programs. One analysis with variable databases, and a life expectancy calculator, proposed that the potential days of life that could be "saved" during screening dialysis patients for malignancy varied according to the individual criteria. Considering breast cancer, as an example, 41-291 potential days may be saved by cancer screening of a 50-y.-old black lady, whilst only 1-16 days could be saved with a 60-y old white female with diabetes.

 

Colorectal cancer

Ther are many tests currently available for colorectal malignancy screening. Screening specificity for cancer colon among dialysis patients may differ from that in the general population as this cohort of patients may show a higher incidence of non-malignant gastrointestinal comorbidities. Stool guaiac test positivity, as an example, may show a higher frequency in dialysis cohort owing to the increased incidence of gastritis, gastrointestinal telangiectasias, and other disorders related to gastrointestinal bleeding. One study reported an incidence of guaiac stools positivity that was 3 times greater in dialysis patients with no symptoms as compared to the non-dialysis controls (15 vs 5 %).

However, the finding of a positive stool guaiac test in a clinically silent dialysis patient may allow the early diagnosis of colorectal cancer. Screening for colorectal malignancy should be currently individualized as it may be beneficial in a particular patient. An accepted approach, despite not well-studied in dialysis patients, is the annual survey via stool guaiac testing, followed by colonoscopy in positive cases.  However, as in other cancer screening programs in dialysis patients, it is better to relate this screening based on the patient's own risk factors and his expected longevity.

 

 

Prostate cancer 

A debate has been currently ongoing in regard to the early discovery of cancer prostate through PSA (serum prostate-specific antigen) laboratory evaluation in general population. The application of PSA as a screening test may be beneficial in the early detection of malignancy as compared to the dependence on clinical examination or symptomatology, however, the survival benefit of early intervention still uncertain. A higher percentage of prostate malignancy among dialysis patients has been observed. Serum PSA concentration has been shown to be not affected by kidney failure, consequently, some physicians recommend serial serum PSA evaluation. However, recent evidence postulated that screening dialysis patients for prostate malignancy via serum PSA testing is not cost-effective. Exceptions to this role may include:

i.        A pretransplant preparation, that should include serum PSA evaluation and digital per-rectum examination.  

ii.        Young male evaluation, where the benefit of screening should be evaluated similarly as that performed in general population.

In addition, serial serum PSA may be utilized to evaluate the response to therapeutic interventions and the magnitude of tumor burden in dialysis patients with cancer prostate. The SEER study evaluated incident malignancies in dialysis patients in 1992-1999 observed that cancer prostate has been recognized at a later stage of the disease course as compared to general population. This study also recommends that limitation of the PSA screening to those dialysis patients of greater life expectancy of 10 years or more.

 

 

Cervical cancer 

The reported incidence of cancer cervix among dialyzed patients is approaching 2.5-4 times higher than that in the general population. A given explanation to this high risk could be attributed primarily to the increased prevalence of the human papilloma virus (HPV) in this cohort of patients. The identification of HPV as a causal factor for cervical cancer evolution has led to the advent of HPV DNA testing as an adjunctive to Papanicolaou (Pap) smear as a screen technique for cervical cancer, and, consequently, for developing the vaccine that protects against the HPV infection that is responsible for 70 % of cervical cancers and 90 % of the genital warts. Considering that other HPV strains may also induce cancer cervix; cytological screening is still mandated.

Current recommendations denote that HPV vaccine is advised for girls of 9-26 years and is mostly beneficial if administrated prior to onset of sexual maturity. However, this recommendation has not been applied to the patients with chronic kidney disease and kidney transplant recipients, so the exact benefits of this vaccine is not completely established in this cohort.

Moreover, the recommendation for cancer cervix screening and HPV vaccination in females with end stage kidney failure is primarily depending on the presence of risk factors, transplant plan, and the patient’s expected longevity. Screening protocols should consider the following:

1]    The pap smear screening should be instituted at the 21^st year of age.

2]    HPV DNA laboratory testing and HPV vaccination should be considered, particularly in organ transplant recipients.

3]    Pap testing for candidates on transplant waiting list and in those with clear risk factors and prolonged expected survival based according to demographic mapping and co-morbid diseases that impact survival in dialysis patients.

 

Breast cancer 

A general recommendation given by North American centres that screening for breast cancer should be screened via mammography testing either accompanied or not by clinical examination of the breast for every female of 50 years or older. However, there is debate about the best recommendation for females at the age of forties, a deep discussion with the patient explaining benefits/danger should be instituted. On the other hand, such a screening is not amenable for all females on dialysis considering the shortened survival in this group of patients. Moreover, vascular calcification may impede breast imaging in dialyzed ladies. Prevalence of breast cancer seems to be not more common in dialysis patients.

 

 

 

Similar to other malignancies in dialysis patients, the least cost-efficacious can be observed with white race and diabetic cases and patients of more than 65 years old considering their lowered predicted survival. A recommended mammography and breast examination every year for females of more than 40 years old who have been enrolled on transplant waiting list seems to be reasonably accepted considering both better survival and exposure to more risk factors. Considering the recent debate about screening of breast cancer in ladies below 50 years, kidney transplant centre may follow different strategies.

 

 

 

Renal cell cancer

An observed increased risk of renal cell carcinoma has been reported with dialysis patients who developed an acquired renal cystic disease with a particular recommendation for cancer screening among these patients.

 

 

Tumor markers

In view of the glycoprotein nature of the tumor markers with its high molecular weight, they cannot be removed through dialysis treatment. Consequently, markers that normally eliminated by the kidney e.g. carcinoembryonic antigen (CEA) that may result in high false positive levels in dialyzed patients, so, we cannot consider its results in cancer screening. Significance of other tumor markers in dialysis patients still uncertain. However, certain markers may show significant specifity e.g. serum alpha-fetoprotein (AFP) and PSA that may permit the engagement of these markers in evaluation of the response to therapy and tumor follow up. Liver cell carcinoma, testicular germ cell and prostatic cancer are the best example in this concept.

 As mentioned above, significance of the carbohydrate antigens (CA 19-9, CA 50 and CA 125) as crucial tumor markers in dialysis patients still unclear. Many clinicians have considered the high false positive levels of these markers, CA 50 and CA 19-9 in particular, other physicians still considering these markers are of useful value. For example, Serum levels of CA 125 are used in management of ladies with cancer ovary. However, this marker is of less significant indication of tumor burden in ladies on peritoneal dialysis, as its serum level may be triggered due to nonspecific inflammation or due to peritoneal irritation. Moreover, a sudden decline in the effluent CA 125 levels may denote significant inflammation (peritonitis) or occurrence of sclerotic changes. Waiting for more information in this concept, questioning the role of carbohydrate-based markers in patients with kidney failure would be reasonable.

https://www.wjgnet.com/2220-3230/full/v10/i2/29.ht 10.5500/ wjt.v10.i2.29

 N.B. This Blogger is created to declare the possibility of cancer development and screening in HDX patients.