0521 Prostate Cancer Screening (1)

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0521 Prostate Cancer Screening (1)

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Prostate Cancer Screening - Medical Clinical Policy Bulletins | Aetna

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Prostate Cancer Screening

Number: 0521
Policy *Please see amendment for Pennsylvania Medicaid at the end of this CPB.
I. Aetna considers prostate-specific antigen (PSA) screening a medically necessary preventive service for men 45 years of age and older who are considered average-risk for prostate cancer, and for men 40 years of age and older who are considered at high-risk for prostate cancer. Risk groups include African-American men and men with a family history of prostate cancer. Note: Routine prostate cancer screening for members 75 years of age or older is considered not medically necessary unless life expectancy is greater than or equal to 10 years.
II. When used for routine screening, annual PSA screening is considered medically necessary, but additional PSA tests may be considered medically necessary in men with previously elevated PSAs or signs or symptoms of disease.
III. Aetna considers diagnostic PSA testing medically necessary for men of all ages with signs or symptoms of prostate cancer, and for follow-up of men with prostate

Policy History
Last Review 11/25/2020 Effective: 02/12/2002 Next Review: 06/10/2021 Review History
Additional Information
Clinical Policy Bulletin Notes

Prostate Cancer Screening - Medical Clinical Policy Bulletins | Aetna
IV. Aetna considers annual digital rectal examination (DRE) a medically necessary preventive service.
V. Aetna considers measurement of selenium in the blood or in tissues (such as toenail clippings) experimental and investigational to assess the risk of developing prostate cancer because it has no proven value for this indication.
VI. Aetna considers the following experimental and investigational for prostate cancer screening because they have no proven value for this indication (not an allinclusive list):
▪ Alpha-methylacyl coenzyme A racemase (AMACR) ▪ Analysis of prostatic fluid electrolyte composition
(e.g., citrate, zinc; not an all inclusive list) ▪ Apifiny non-PSA blood test (Armune BioScience) ▪ BRAF mutations ▪ Early prostate cancer antigenE ▪ Endoglin ▪ E twenty-six (ETS) gene fusions ▪ Genetic-based screening ▪ Human glandular kallikrein 2 (hK2) (also known as
kallikrein-related peptidase 2 [KLK2]) ▪ Interleukin-6 ▪ MicroRNAs in prostatic fluid/tissue ▪ Neutrophil gelatinase-associated lipocalin (NGAL) ▪ Prostate cancer gene 3 (PCA3) ▪ TMPRSS2:ERG gene fusion ▪ Transforming growth factor-beta 1.
See also CPB 0001 - Transrectal Ultrasound (../1_99/0001.html) and CPB 0352 - Tumor Markers (../300_399/0352.html).

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Prostate Cancer Screening - Medical Clinical Policy Bulletins | Aetna
Note: Some plans exclude coverage of preventive services. Please check benefit plan descriptions for details. Medically necessary diagnostic PSA testing is covered regardless of whether the member has preventive service benefits.
The decision to perform routine prostate cancer screening with digital rectal examination (DRE) or prostate-specific antigen (PSA) is left to the discretion of the clinician. Patients who request screening should be given objective information about the potential benefits and harms of early detection and treatment.
The American Cancer Society (ACS) recommends PSA screening for all men over age 50 and at age 45 for men at higher risk (e.g., men with a family history of prostate cancer and African-American men). Similar recommendations have been issued by the American Urological Association (AUA) and the American College of Radiology. The ACS, however, acknowledges that currently there is no clinical trial evidence that screening for prostate cancer is associated with a reduction in mortality.
The updated ACS guideline for the early detection of prostate cancer (Wolf et al, 2010) recommends both the PSA blood test and DRE should be offered annually, beginning at age 50, to men who have at least a 10-year life expectancy. Men at highrisk (African-American men and men with a strong family of 1 or more first-degree relatives (father, brothers) diagnosed at an early age) should begin testing at age 45. Men at even higher risk, due to multiple first-degree relatives affected at an early age, could begin testing at age 40. Depending on the results of this initial test, no further testing might be needed until age 45. The ACS states that information should be provided to all men about what is known and what is uncertain

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Prostate Cancer Screening - Medical Clinical Policy Bulletins | Aetna
about the benefits and limitations of early detection and treatment of prostate cancer so that they can make an informed decision about testing. Men who ask their doctor to make the decision on their behalf should be tested. The ACS states that discouraging testing is inappropriate. Furthermore, not offering testing is also inappropriate.
In a review on prostate cancer screening, Ilic and colleagues (2011) concluded that prostate cancer screening did not significantly decrease all-cause or prostate cancer-specific mortality in a combined meta-analysis of 5 randomized controlled trials. Any benefits from prostate cancer screening may take greater than 10 years to accrue; therefore, men who have a life expectancy of less than 10 to 15 years should be informed that screening for prostate cancer is not beneficial and has harms.
The American Urological Association (AUA, 2013) recommends against PSA screening in men under age 40 years (Grade C) and does not recommend routine screening in men between ages 40 to 54 years at average risk (Grade C). AUA state that the greatest benefit of screening appears to be in men ages 55 to 69 years. "For men younger than age 55 years at higher risk, decisions regarding prostate cancer screening should be individualized. Those at higher risk may include men of African American race; and those with a family history of metastatic or lethal adenocarcinomas (e.g., prostate, male and female breast cancer, ovarian, pancreatic) spanning multiple generations, affecting multiple first-degree relatives, and that developed at younger ages."
The National Comprehensive Cancer Network (NCCN, v.2.2018) recommends baseline screening beginning at age 45. "African-American men and men with a family history of prostate cancer represent high-risk groups. However, the panel believes that current data are insufficient to definitively inform the best strategy for prostate cancer screening in these populations, and also notes that a baseline PSA value is a

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Prostate Cancer Screening - Medical Clinical Policy Bulletins | Aetna
stronger predictive factor than a positive family history or race. Overall, the panel believes that it is reasonable for AfricanAmerican men and those with a strong family history to begin discussing PSA screening with their providers earlier than those without such risk factors and to consider screening at annual rather than less frequent screening intervals." Panelists uniformly agreed that PSA testing should only be offered to men with a 10 or more year life expectancy. The panel supports screening in men until age 75. The panel recommends that PSA testing to be considered only in very healthy patients older than 75 years (category 2B); however, the panel uniformly discourage PSA testing in men unlikely to benefit from prostate cancer diagnosis based on age and/or comorbidity. The panel recommends that frequency of testing be 2 to 4 years for men aged 45 to 75 years with serum PSA values below 1 ng/mL, and at 1 to 2 year intervals for men with PSA of 1 to 3 ng/mL.
Most professional societies do not recommend routine screening for prostate cancer with DRE or serum tumor markers (e.g., PSA). These include the American Academy of Family Physicians, the U.S. Preventive Services Task Force (USPSTF), the Institute for Clinical Systems Improvement, the Canadian Task Force on the Periodic Health Examination, the American College of Preventive Medicine, the U.S. Office of Technology Assessment, the American Society for Internal Medicine and American College of Physicians, the National Cancer Institute, the Centers for Disease Control and Prevention, and the technology assessment agencies of Canada, England, Sweden, and Australia.
The USPSTF (2018) recommends individualized decisionmaking about prostate cancer screening for men aged 55 to 69, thus providing a grade C recommendation for prostate cancer screening for men in that age group. The USPSTF systematically reviewed evidence on prostate-specific antigen (PSA)-based prostate cancer screening, treatments for localized prostate cancer, and prebiopsy risk

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Prostate Cancer Screening - Medical Clinical Policy Bulletins | Aetna
calculators, concluding that although screening offers a small potential benefit of reducing chance of death from prostate cancer in some men, many men will experience potential harms of screening (i.e., false-positives results that require additional testing and possible prostate biopsy, overdiagnosis, overtreatment, and treatment complications such as erectile dysfunction and urinary difficulties). In regard to age and the effectiveness of PSA-based screening and prostate cancer mortality, outcomes from randomized clinical trials showed that randomization to screening was not associated with statistically significant reductions in prostate cancer mortality among men aged 65 to 74 years at baseline in the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial (RR, 1.02 [95% CI, 0.77-1.37]) or among men aged 70 to 74 years at baseline in the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial (RR, 1.17 [95% CI, 0.82-1.66]). The systematic review revealed that across all studies, relatively few men older than 70 years were enrolled, and there is limited evidence about the differential benefits or harms of screening for men at higher risk. The USPSTF concluded that the evidence is limited on the benefit of screening among men older than 70 years, thus, providing a grade D recommendation against PSA-based screening for prostate cancer in men 70 years and older. The USPSTF further concluded that the evidence was insufficient to make a specific recommendation regarding screening discussions for higherrisk groups: African-American men and those with a family history of prostate cancer.
The American Academy of Family Physicians (AAFP, 2018) makes the recommendation against routine screening (i.e., PSA test or DRE) for prostate cancer. For men who desire PSA screening, it should only be performed after engaging in shared decision making. Furthermore, PSA-based prostate cancer screening should not be performed in men over 70 years of age.

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Prostate Cancer Screening - Medical Clinical Policy Bulletins | Aetna
An UpToDate review on "Screening for prostate cancer" (Hoffman, 2018) recommend prostate cancer screening beginning at age 40 to 45 years for men at high risk (e.g., black men, men with family history of prostate cancer, particularly in relatives younger than age 65, and men who are known or likely to have the BRCA1 or BRCA2 mutations) and have a life expectancy greater than or equal to 10 years (Grade 2C). For men at "average risk", the authors recommend prostate screening discussions with their healthcare provider starting at the age of 50, and who also have a life expectancy greater than or equal to 10 years. The authors recommend discontinuing the screening after age 69, or earlier when comorbidities limit life expectancy to less than 10 years, or patient decides against screening (Grade 2B). The authors further note that stopping screening at age 65 may be appropriate if the PSA level is less than 1 ng/mL.
If screening is to be performed, the generally accepted approach is to screen with DRE and PSA and to limit screening to men with a life expectancy of greater than 10 years. There is currently insufficient evidence to determine the need and optimal interval for repeat screening or whether PSA thresholds must be adjusted for density, velocity, or age.
Schenk-Braat and Bangma (2006) noted that PSA is currently the most important biochemical marker for the diagnosis of prostate cancer. Because of the limited specificity of PSA, clinically irrelevant tumors and benign abnormalities are also detected that can potentially lead to over-treatment and the associated physical as well as emotional burden for the patient. Furthermore, PSA is used as an indicator of progression or clinical response following prostate cancer therapy, but the prognostic value of this marker is limited. Ongoing research is examining several alternative markers (e.g., osteoprotegerin, human kallikrein 2, and the gene DD3 (PCA3)) that may improve the specificity of current PSA-based diagnostics and the prognostic value of PSA.

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Prostate Cancer Screening - Medical Clinical Policy Bulletins | Aetna
Prostate-specific antigen velocity, the yearly rate of increase of PSA, has not been proven to improve the test characteristics of PSA, Schroder and colleagues (2006) stated that PSAdriven screening has been applied to a large part of the male population in many countries. An elevated PSA in secondary screens may indicate benign enlargement of the prostate rather than prostate cancer. In such cases the yearly rate of increase of PSA (PSA velocity [PSAV]) may improve the test characteristics of PSA. These investigators examined if PSAV predict prostate cancer in pre-screened populations. Data from the European Randomized Study of Screening for Prostate Cancer Rotterdam were used to study the issue. Relative sensitivity, relative specificity, and positive predictive value (PPV) were calculated. Logistic regression analysis was used to compare odds ratios for positive biopsies. The relationship between PSAV and parameters of tumor aggressiveness was investigated. A total of 588 consecutive participants were identified who presented at their first screening with PSA values less than 4.0 and who progressed to PSA values greater than 4.0 ng/ml 4 years later were included in this study. None was biopsied in round-1, all were biopsied in round-2. Relative sensitivity and specificity depend strongly on PSAV cut-offs of 0.25 to 1.0 ng/ml/year. The use of PSAV cut-offs did not improve the PPV of the PSA cut-off of 4.0 ng/ml, nor did any of the PSAV cut-offs improve the odds ratio (OR) for identifying prostate cancer with respect to the cut-off value of 4.0 ng/ml. The rate of aggressive cancers seems to increase with increasing PSAV. The authors concluded that PSAV did not improve the detection characteristics of a PSA cut-off of 4.0 ng/ml in secondary screening after 4 years.
Wolters et al (2009) evaluated the value of PSAV in screening for prostate cancer. Specifically, the role of PSAV in lowering the number of unnecessary biopsies and reducing the detection rate of indolent prostate cancer was evaluated. All men included in the study cohort were subjects in the European Randomized Study of Screening for Prostate

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Prostate Cancer Screening - Medical Clinical Policy Bulletins | Aetna
Cancer (ERSPC), Rotterdam section. During the first and second screening round, a PSA test was performed on 2,217 men, and all underwent a biopsy during the second screening round 4 years later. Prostate specific antigen velocity was calculated and biopsy outcome was classified as benign, possibly indolent prostate cancer, or clinically significant prostate cancer. A total of 441 cases of prostate cancer were detected, 333 were classified as clinically significant and 108 as possibly indolent. The use of PSAV cut-offs reduced the number of biopsies but led to important numbers of missed (indolent and significant) prostate cancer; PSAV was predictive for prostate ancer (OR: 1.28, p < 0.001) and specifically for significant prostate cancer (OR: 1.46, p < 0.001) in uni-variate analyses. However, multi-variate analyses using age, PSA, prostate volume, DRE and transrectal ultrasonography outcome, and previous biopsy (yes/no) showed that PSAV was not an independent predictor of prostate cancer (OR: 1.01, p = 0.91) or significant prostate cancer (OR: 0.87, p = 0.30). The authors concluded that the use of PSAV as a biopsy indicator would miss a large number of clinically significant cases of prostate cancer with increasing PSAV cut-offs. In this study, PSAV was not an independent predictor of a positive biopsy in general or significant prostate cancer on biopsy. Thus, PSAV does not improve the ERSPC screening algorithm.
The role of selenium in cancer prevention has been the subject of recent study and debate. Population studies suggest that people with cancer are more likely to have low selenium levels (measured in the blood or in tissues such as toenail clippings) than healthy matched individuals. However, in most cases it is not clear if low selenium levels are a cause or merely a consequence of disease. Initial evidence from the Nutritional Prevention of Cancer (NPC) trial suggests that selenium supplementation reduces the risk of prostate cancer among men with normal baseline PSA levels and low selenium blood levels. The ongoing Selenium and Vitamin E Cancer Prevention Trial (SELECT) aims to definitively address the role of selenium in prostate cancer prevention. The study, which

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Prostate Cancer Screening - Medical Clinical Policy Bulletins | Aetna
spans from 2001 to 2013, will include 32,400 men. Currently, it is unclear if selenium is beneficial in the treatment of prostate cancer or any type of cancer. Measurement of body selenium (e.g., in serum, toenail clippings) has no proven value in the prevention of prostate cancer.
Costello and Franklin (2009) proposed that changes in prostatic fluid composition could provide accurate and reliable biomarkers for the screening of prostate cancer. Most notable is the consistent and significant decrease in citrate and zinc that is associated with the development and progression of prostate cancer. These researchers provided the clinical and physiological basis and the evidence in support of the utility of prostatic fluid analysis as an effective approach for screening/detection of prostate cancer, especially early stage and "at-risk" subjects. The problem of interference from benign prostatic hypertrophy that hampers PSA testing is eliminated in the potential prostatic fluid biomarkers. The potential development of rapid, simple, direct, accurate clinical tests would provide additional advantageous conditions. The authors stated that further exploration and development of citrate, zinc and other electrolytes as prostatic fluid biomarkers are needed to address this critical prostate cancer issue.
A long-term randomized controlled clinical trial found prostate cancer screening had no effect on mortality (Andriole et al, 2009). From 1993 through 2001, investigators randomly assigned 76,693 men at 10 U.S. study centers to receive either annual screening (38,343 subjects) or usual care as the control (38,350 subjects). Men in the screening group were offered annual PSA testing for 6 years and DRE for 4 years. The subjects and health care providers received the results and decided on the type of follow-up evaluation. Usual care sometimes included screening, as some organizations have recommended. The numbers of all cancers and deaths and causes of death were ascertained. In the screening group, rates of compliance were 85 % for PSA testing and 86 % for DRE. Rates of screening in the control group increased from

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