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 21st 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.
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