Medical Policy: 02.04.25
Original Effective Date: October 2009
Reviewed: June 2018
Revised: June 2018
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This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths in American men. In 2018, it is estimated that 164,660 men will be diagnosed with prostate cancer and 29,430 will die of this disease. During the same period, nearly 20 million men in the United States will be confronted with important decisions regarding early detection for prostate cancer. Men born in the United States have about 1 chance in 7 of eventually being diagnosed with this malignancy and about 1 chance in 39 of eventually dying of it. (NCCN 2018)
The primary goal of prostate cancer screening is to reduce deaths due to prostate cancer, therefore, increasing length of life. An additional important outcome would be a reduction in the development of symptomatic metastatic disease. Screening asymptomatic geno typical men for prostate cancer has become a widespread practice in the United States. Test procedures used for prostate cancer screening include digital rectal examination (DRE) and serum prostate specific antigen (PSA).
Many experts continue to recommend DRE for screening, as some clinically significant prostate cancer may potentially be missed using serum PSA cut-point alone. Studies have consistently shown that prostate cancer cases detected through PSA testing are more often confined to the prostate than those detected solely by DRE. Currently, 81% of prostate cancers are pathologically organ-confined at time of diagnosis.
The value of DRE as a stand-alone test for prostate detection is limited, even though DRE picks up some cases of advanced cancer that would otherwise be missed. DRE is recommended to be used as a complementary test with serum PSA in asymptomatic geno typical men who had a risk/benefit discussion and decided to pursue screening for prostate cancer. Those individuals with a very suspicious DRE should be considered for biopsy referral regardless of PSA results, because it may identify high-grade cancers in such situations. DRE should be considered in all geno typical men with an abnormal serum PSA to aid in decisions regarding biopsy.
Although PSA was originally introduced as a tumor marker to detect cancer recurrence or disease progression following treatment, it became widely adopted for cancer screening. PSA is a glycoprotein produced by the prostate epithelial cells. PSA levels may be elevated in geno typical men with prostate cancer because PSA production is increased and because tissue barriers between the prostate gland lumen and the capillary are disrupted, releasing more PSA into the serum. Elevations of serum PSA may also be associated with other prostatic diseases including benign prostatic hypertrophy (BPH) which is a major clinical problem with PSA screening. It is recommended that the interpretation of PSA values should always take into account age, the presence of urinary tract infection or prostate disease, recent diagnostic procedures and prostate directed treatments.
Prostate cancer screening has been a controversial issue. There is evidence that PSA based screening leads to substantial overdiagnosis of prostate tumors and there is a high incidence for physicians and patients to elect to treat most cases of screen detected cancer, given the current inability to distinguish tumors that will remain indolent from those destined to be lethal. Thus, many geno typical men are being subjected to the harms of treatment of prostate cancer that will never become symptomatic. Even for geno typical men whose screen-detected cancer would otherwise have been later identified without screening, most experience the same outcome and are, therefore, subjected to the harms of treatment for much longer period. There is convincing evidence that PSA based screening for prostate cancer results in considerable overtreatment and its associated harms.
Prostate cancer risk calculators have been developed to estimate an individual’s risk for prostate cancer from multiple factors. Common calculators are the Sunnybrook, ERSPC, and PCPT based risk calculators. These online tools combine clinical variables including but not limited to age, family history, race, DRE and PSA, to estimate both the risk for biopsy detectable prostate cancer and the risk for biopsy detectable high grade prostate cancer. Such information potentially allows for more informed decision-making. However, such calculators have not been assessed in RCTs, and cut-points of risk associated with reductions in prostate cancer mortality remain unknown. Such calculators have as much value in determining who might not need biopsy as in identifying those at higher risk. The use of risk calculators alone to determine whether a biopsy is indicated is not recommended.
Even though some guidelines (i.e. USPSTF) discourage the use of screening tests for which the benefits do not outweigh the harms in the target population, they do recognize the common use of PSA screening in practice today and that some physicians will continue to offer it. The decision to initiate or continue PSA screening should reflect an understanding of the possible benefits and harms and respect the patient’s preferences. Physicians should not offer or order PSA screening unless they are prepared to engage in shared decision making that enables an informed choice by the patient. Similarly, patients requesting PSA screening should be provided with the opportunity to make informed choices to be screened that reflect their values about specific benefits and harms.
Serum total PSA was the only PSA based test available in early detection programs for prostate cancer. Since then, several PSA derivatives have been developed and proposed to improve the performance of the PSA measurement, thus possibly increasing specificity and decreasing unnecessary biopsies. These PSA derivatives include:
In 2018, de Koning et. al. reported on the efficacy of prostate-specific antigen screening and the impact of the key components in the European Randomized Study for Prostate Cancer (ERSPC) and the U.S. Prostate, Lung, Colorectal and Ovarian (PLCO) trials. The European Randomized Study of Screening for Prostate Cancer (ERSPC) demonstrated that prostate-specific antigen (PSA) screening significantly reduced prostate cancer mortality (rate ratio, 0.79; 95% confidence interval, 0.69-0.91). The U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) trial indicated no such reduction but had a wide 95% CI (rate ratio for prostate cancer mortality, 1.09; 95% CI, 0.87-1.36). Standard meta-analyses are unable to account for key differences between the trials that can impact the estimated effects of screening and the trials' point estimates. The authors calibrated 2 microsimulation models to individual-level incidence and mortality data from 238,936 men participating in the ERSPC and PLCO trials. A cure parameter for the underlying efficacy of screening was estimated by the models separately for each trial. The authors changed step-by-step major known differences in trial settings, including enrollment and attendance patterns, screening intervals, PSA thresholds, biopsy receipt, control arm contamination, and primary treatment, to reflect a more ideal protocol situation and differences between the trials. Using the cure parameter estimated for the ERSPC, the models projected 19% to 21% and 6% to 8%, respectively, prostate cancer mortality reductions in the ERSPC and PLCO settings. Using this cure parameter, the models projected a reduction of 37% to 43% under annual screening with 100% attendance and biopsy compliance and no contamination. The cure parameter estimated for the PLCO trial was 0. The authors concluded, the observed cancer mortality reduction in screening trials appears to be highly sensitive to trial protocol and practice settings. Accounting for these differences, the efficacy of PSA screening in the PLCO setting is not necessarily inconsistent with ERSPC results.
Professional Society guidelines recognize the common use of PSA screening in practice today and understand that some geno typical men will continue to request screening and some physicians will continue to offer it. The decision to initiate or continue PSA screening should reflect an explicit understanding of the possible benefits and harms and respect patients’ preferences. Physicians should not offer or order PSA screening unless they are prepared to engage in shared decision making that enables an informed choice by patients. Similarly, patients requesting PSA screening should be provided with the opportunity to make informed choices to be screened that reflect their values about specific benefits and harms. The primary goal of PSA based screening is to find men from whom treatment would reduce morbidity and mortality.
In 2012, the American Society of Clinical Oncology (ASCO) issued a provisional clinical opinion regarding screening for prostate cancer with prostate specific antigen testing, which included the following:
In one randomized trial, PSA testing in men who would not otherwise have been screened resulted in reduced death rates from prostate cancer, but it is uncertain whether the size of the effect was worth the harms associated with screening and subsequent unnecessary treatment. Although there are limitations to the existing data, there is evidence to suggest that men with longer life expectancy may benefit from PSA testing. Adverse events associated with prostate biopsy are low for the majority of men; however, several population-based studies have shown increasing rates of infectious complications after prostate biopsy, which is a concern.
On the basis of identified evidence and the expert opinion of the panel:
*Calculation of life expectancy is based on a variety of individual factors and circumstances. A number of life expectancy calculators. ASCO does not endorse any one calculator over another.
In 2013, the American Urological Association (AUA) published guidelines for the early detection of prostate cancer:
The Panel recommends against PSA screening men under age 40 years. (Recommendation; Evidence Strength Grade C). In this age group there is a low prevalence of clinically detectable prostate cancer, no evidence demonstrating benefit of screening and likely the same harms of screening as in other age groups.
The Panel does not recommend routine screening in me between ages 40 to 54 years at average risk. (Recommendation; Evidence Strength Grade C). For men younger than age 55 years at higher risk (e.g. positive family history or African American race), decisions regarding prostate cancer screening should be individualized.
For men ages 55 to 69 years the Panel recognizes that the decision to undergo PSA screening involves weighing the benefits of prostate cancer mortality in 1 man for every 1,000 men screened over a decade against the known potential harms associated with screening and treatment. For this reason, the Panel strongly recommends shared decision making for men age 55 to 69 years that are considering PSA screening, and proceeding based on a man’s values and preferences. (Standard; Evidence Strength Grade B). The greatest benefit of screening appears to be in men ages 55 to 69 years.
To reduce the harms of screening, a routine screening interval of two years or more may be preferred over annual screening in those men who have participated in shared decision making and decided on screening. As compared to annual screening, it is expected that screening intervals of two years preserve the majority of the benefits and reduce overdiagnosis and false positives. (Option; Evidence Strength Grade C). Additionally, intervals for rescreening can be individualized by a baseline PSA level.
The Panel does not recommend routine PSA screening in men age 70+ years or any man with less than a 10 to 15 year life expectancy. (Recommendation; Evidence Strength Grade C).
Some men age 70+ years who are in excellent health may benefit from prostate cancer screening.
The panel concluded that PSA based screening should not be performed in the absence of shared decision making. Thus, they recommend against organized screening in settings where shared decision making is not part of routine practice (e.g., including but not limited to health fairs, health system promotions, community organizations).
The Panel believes that annual PSA screening as a routine should be discouraged for those who choose to be screened, that two year PSA intervals are reasonable approach and will be unlikely to miss a curable prostate cancer in most men, and that for men over 60 with PSA levels below 1.0ng/ml, longer PSA screening intervals (e.g. of four years) could be considered.
In 2016, the American Cancer Society recommends that men make an informed decision with their health care provider about whether to be screened for prostate cancer. The decision should be made after getting information about the uncertainties, risk, and potential benefits of prostate cancer screening. Men should not be screened unless they have received this information. The discussion about screening should take place at:
After this discussion men who want to be screened should be tested with the prostate specific antigen (PSA) blood test. The digital rectal exam (DRE) may also be done as part of screening.
If, after this discussion, a man is unable to decide if testing is right for him, the screening decision can be made by the health care provider, who should take into account the man’s general health preferences and values.
If no prostate cancer is found as a result of screening, the time between future screenings depends on the results of the PSA blood test:
Because prostate cancer often grows slowly, men without symptoms of prostate cancer who do not have a 10-year life expectancy should not be offered testing since they are not likely to benefit. Overall health status, and not age alone, is important when making decisions about screening.
Even after a decision about testing has been made, the discussion about the pros and cons of testing should be repeated as new information about the benefits and risks of testing becomes available. Further discussions are also needed to take into account changes in a man’s health, values, and preferences.
History and physical including:
bAfrican American men have a higher incidence of prostate cancer, increased prostate cancer mortality, and earlier age of diagnosis compared to Caucasian-American men. This is attributable to a greater risk of developing preclinical prostate cancer and a higher likelihood that preclinical tumor will spread. Consequently, it is reasonable for African-American men to begin discussing PSA screening with their providers several years earlier than Caucasian-American men and to consider screening at annual intervals rather than every other year.
Most Panel members favor informed testing beginning at age 45 years. Repeat testing at 1 to 2 year intervals is recommended for men who have a PSA value ≥ 1.0 ng/mL and at 2 to 4 year intervals for men with PSA <1 ng/mL (also see frequency testing below).
The panel concluded that tailoring screening intervals based on PSA levels might maximize survival advantage while decreasing the number of screenings and limiting over-diagnosis. The panel recommends repeat teating every 2 to 4 years if PSA is <1 ng/mL and every 1 to 2 years if PSA 1 to 3 ng/mL in men aged 45 to 75 years. The panel notes that a younger man on the higher end of PSA (e.g. 45 year old man with PSA 0.9 ng/mL) might be screened in 2 years, whereas an older man with a lower PSA might be screened in 4 years. Clinical judgment should be used.
The Panel supports screening in men until age 75. Continuing screening beyond this age should be only with caution in very healthy patients with little to no comorbidity (category 2B for continuing screening beyond age 75 years) to detect the small number of aggressive cancers that post a significant risk if left undetected until signs or symptoms develop. Older men who chose to continue PSA based prostate cancer early detection (category 2B) and how have a PSA < 4 ng/mL, a normal DRE (if done), and no other indications for biopsy can undergo repeat testing at 1 to 4 year intervals, but again only in very select patients. Those with PSA > 4 ng/mL or a very suspicious DRE should be considered for biopsy as indicated in the guidelines.
African-American men and men with a first degree relative with prostate cancer (especially cancer found at a younger age) have a higher risk of developing prostate cancer. In fact, having a first degree relative with prostate cancer diagnosed before theage of 60 increases the likelihood of prostate cancer diagnosis by 2.1 to 2.5 fold. Data, however, suggest that prostate cancer in men with a family history of prostate cancer is not more likely to be aggressive, and cancer specific outcomes are similar between those with and without a family history.
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 inform the best strategy for prostate cancer screening in these populations and also note that baseline PSA value is a stronger predictive factor that a positive family history or race. Overall, the panel believes that it is reasonable for African-American 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. Recent information suggests that screening high risk groups, including those of low socioeconomic status, is of benefit.
In 2018, The USPSTF published updated recommendations regarding prostate cancer screening that states the following:
For men aged 55 to 69 years, the decision to undergo periodic prostate-specific antigen (PSA)–based screening for prostate cancer should be an individual one. Before deciding whether to be screened, men should have an opportunity to discuss the potential benefits and harms of screening with their clinician and to incorporate their values and preferences in the decision.
C Recommendation
The USPSTF recommends against PSA-based screening for prostate cancer in men age 70 years and older.
D Recommendation
Not applicable
See Related Medical Policies
Prostate cancer screening using prostate specific antigen (PSA) may be considered medically necessary for any of the following indications after informed decision with a health care provider:
After the initial PSA is determined, the time interval for repeat testing is dependent upon the PSA value. For those men with a PSA of:
All other screening indications in asymptomatic men are considered not medically necessary.
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