Prostate Specific Antigen (PSA) Testing AHS - G2008

Description of Procedure or Service

Prostate-specific antigen (PSA) is a glycoprotein that is produced by both normal and neoplastic prostate tissue. In normal conditions, PSA is produced as a proenzyme in the prostate and secreted into the lumen. The propeptide is removed to activate the proenzyme; from there, it undergoes proteolysis to inactivate it. This inactive form may enter the bloodstream and circulate as “free” PSA. This process differs in prostate cancer; the basal cells that normally regulate this activation process are missing, which allows the secreted PSA direct access into the bloodstream. This increases the PSA concentration in the serum (Freedland, 2024).

Due to these reasons, PSA is often used in assessment of prostate cancer, such as screening, monitoring, diagnosis, and treatment management.

Terms such as male and female are used when necessary to refer to sex assigned at birth.

Related Policies:

AHS-G2007 Prostate Biopsy Specimen Analysis

AHS-M2166 Gene Expression Profiling and Protein Biomarkers for Prostate Cancer

***Note: This Medical Policy is complex and technical. For questions concerning the technical language and/or specific clinical indications for its use, please consult your physician.

Policy

BCBSNC will provide coverage for prostate specific antigen (PSA) testing when it is determined the medical criteria and guidelines below are met.

Benefits Application

This medical policy relates only to the services or supplies described herein. Please refer to the Member's Benefit Booklet for availability of benefits. Member's benefits may vary according to benefit design; therefore, member benefit language should be reviewed before applying the terms of this medical policy.

When Prostate Specific Antigen (PSA) Testing is covered

1.  Reimbursement is allowed for average-risk individuals 45-75 years of age, screening for prostate cancer with the total prostate-specific antigen (PSA) test.
   1. Individual is of African ancestry. 
   2. Individual has germline mutations that increase risk for prostate cancer.
   3. Individual has a suspicious family history.
2. Reimbursement is allowed for individuals 40-75 years of age, annual screening for prostate cancer with the total (PSA) test when one of the following conditions is met: 
   1. Individual is of African ancestry.
   2. Individual has germline mutations that increase risk for prostate cancer.
   3. Individual has a suspicious family history
3. For individuals over 75 years of age who have little, or no comorbidities (*See Note 1), reimbursement is allowed for screening for prostate cancer with a total PSA test. 
4. For individuals with previous total PSA results, repeat screening for prostate cancer with a total PSA test, reimbursement is allowed with the following frequency: 
   1. For individuals less than 76 years of age, when total PSA is <1 ng/ml and digital rectal exam (DRE) is normal (if done): Repeat screening at 2- 4-year intervals
   2. For individuals less than 76 years of age, when total PSA is 1-3 ng/ml and DRE is normal (if done): Repeat screening at 1- 2-year intervals.
   3. For individuals greater than 75 years of age, when total PSA is <4 ng/ml and DRE is normal (if done) and no other indications for biopsy: Repeat screening in select patients (very healthy individuals with little or no comorbidity) at 1- 4-year intervals.
5. A percent free PSA, or a follow-up in 6-12 months with total PSA reimbursement is allowed when any of the following conditions are met:
   1. For individuals less than 76 years of age with a total PSA >3 ng/ml and/or a very suspicious DRE.
   2. For select individuals greater than 75 years of age (very healthy individuals with little or no comorbidity) with a total PSA >4 ng/ml or a very suspicious DRE.
6. For individuals thought to be at a higher risk despite at least one prior negative prostate biopsy, follow-up testing with percent free PSA, reimbursement is allowed.
7. Total PSA testing, reimbursement is allowed, in any of the following situations:
   1. For initial prostate cancer diagnosis in individuals with signs and symptoms of prostate cancer (see Note 2).
   2. For follow-up of individuals with a current or previous diagnosis of prostate cancer.
   3. For ongoing monitoring of individuals who have undergone tumor resection or prostatectomy.
   4. For monitoring response to prostate cancer therapy.
   5. For detecting disease recurrence.

*NOTE 1: According to the NCCN guidelines, “Testing after 75 years of age should be done only in very healthy men with little or no comorbidity (especially if they have never undergone PSA testing or have a rising PSA) to detect the small number of aggressive cancers that pose a significant risk if left undetected until signs or symptoms develop. Widespread screening in this population would substantially increase rates of over-detection and is not recommended (NCCN, 2023b).” Additionally, the term individuals in this policy apply to individuals who have a prostate or were born with a prostate.

*NOTE 2: According to ACS, 2023b: “Most prostate cancers are found early, through screening. Early prostate cancer usually causes no symptoms. More advanced prostate cancers can sometimes cause symptoms, such as:

• Problems urinating, including a slow or weak urinary stream or the need to urinate more often, especially at night. 
• Blood in the urine or semen
• Trouble getting an erection (erectile dysfunction or ED) 
• Pain in the hips, back (spine), chest (ribs), or other areas from cancer that has spread to bones
• Weakness or numbness in the legs or feet, or even loss of bladder or bowel control from cancer pressing on the spinal cord (ACS, 2023b).

When Prostate Specific Antigen (PSA) Testing is not covered

Reimbursement is not allowed for:

1. Percent free PSA as a first-line screening test for prostate cancer. 
2. Percent free PSA, free-to-total PSA ratio, and/or complexed PSA tests for the routine screening of prostate cancer

Policy Guidelines

Prostate cancer is the most common cancer in American men and the second leading cause of death in men over 65 (Balducci et al., 1997; Tabayoyong & Abouassaly, 2015). According to the CDC (2022a), more than 224,000 prostate cancer cases are reported annually in the United States, leading to more than 31,000 prostate cancer deaths each year. The American Cancer Society estimates over 288,000 new cases and 34,000 deaths of prostate cancer in 2023 (American_Cancer_Society, 2023). Prostate cancer survival is related to many factors, especially the extent of the tumor at the time of diagnosis. The 5-year survival rate between for men with localized or regional prostate cancer is nearly 100%, while the 5-year survival rate for men with distant prostate cancer where the cancer has spread to other parts of the body such as the lungs, liver or bones is 31% (ACS, 2024; Preston, 2023). About one man in nine will be diagnosed with prostate cancer during his lifetime in the United States (American Cancer Society, 2023).

Many cases of prostate cancer do not become clinically evident, as indicated in autopsy studies, where prostate cancer is detected in approximately 30 percent of men aged 55 or older and approximately 60 percent of men by age 80 (Bell et al., 2015). These data suggest that prostate cancer often grows so slowly that most men die of other causes before the disease becomes clinically advanced (Preston, 2023).

Most prostate cancers use androgen-dependent signaling for development and progression (Fisher et al., 2015). As the number of targeted therapy agents increase, it is crucial to determine which patients will benefit from these interventions. Understanding the molecular pathology will allow clinicians to provide better patient management. Recent studies have led to the classification of prostate cancer into different subtypes, yet the utility of this in the clinical setting is to be determined (Rodrigues, et al., 2014).

Prostate-specific antigen (PSA), a glycoprotein produced by prostate epithelial cells, is the most widely accepted biomarker for prostate cancer screening. Levels of this protein can be identified via a simple blood test; many doctors consider abnormal PSA levels to be above 4.0 ng/mL, although there is no official standardized normal or abnormal PSA level (NCI, 2022). Further, PSA levels tend to increase with age, suggesting that age-specific PSA reference ranges may be important for clinical use (NCI, 2022).

In serum, PSA can be identified in three forms. The main form is PSA bound by alpha-1 antichymotrypsin and accounts for approximately 75% of total PSA; PSA bound to alpha-2 macroglobulin has also been identified but cannot be detected by commercial immunoassays and represents less than 0.1% of PSA (Prcic, et al., 2016). Coban et al. (2016) reported that, while total PSA levels are an important prognostic factor for predicting prostate volumes, free PSA levels had a higher predictive value.

Analytical Validity

PSA was originally introduced as a tumor marker to detect cancer recurrence or disease progression following treatment (Brawley et al., 2018. It has been widely adopted for early detection of prostate cancer screening; however, its clinical utility in screening is controversial, and guidelines for PSA screening are conflicting. Non-optimal screening and treatment practices, including excessive screening among older men with lower life expectancy or comorbidities and overtreatment of men with low-risk tumors, have contributed to treatment-related harm and a lower quality of life (Fleshner et al., 2017). Evidence is currently lacking to show that PSA screening actually saves lives; instead, it may only cause overdiagnosis and lead to complications in the treatment of indolent diseases (Ilic et al., 2018).

PSA is not a cancer specific marker, thereby causing many false results that conflict with other screening methods, such as the digital rectal examination (DRE) (Saini, 2016). For example, PSA may be elevated due to conditions including benign prostatic hyperplasia (BPH) or prostatitis. This is particularly important as BPH is common among men over 50, the most common age group in which prostate cancer is observed. For example, a study performed by Stimac et al. (2014) found PSA levels to be unusual despite testing negative for cancer. The authors concluded that subclinical inflammation had a major influence on free PSA levels only if the total levels was <10 ng/mL, and further note that clinical and acute inflammation produce a different profile of PSA release compared to a subclinical inflammation. Overall, the authors state that the molecular cause of the inflammation’s changes to PSA forms are still unknown (Stimac et al., 2014). Furthermore, serum PSA is directly tied to the size of the prostate, which increases with age. Older men may see an increased concentration of PSA despite being completely healthy (Freedland, 2024; Stimac et al., 2014). Other factors such as medication can affect PSA levels as well. Common medications such as statins, NSAIDs, acetaminophen, 5-alpha-reductase inhibitors, and thiazides were all found to reduce PSA levels by varying degrees (Chang, et al., 2010; Hamilton, et al., 2008; Singer, et al., 2008; Wang, et al., 1997). 

Clinical Validity and Utility

The utility of PSA-based screening is also in question. A randomized clinical trial focusing on men undergoing a single PSA-based screening (n = 189386) compared to controls not undergoing a PSA-based screening (n = 219439) found no difference in cancer mortality after a median follow-up of 10 years. The mortality rate in 1000-person years was 0.30 in the intervention group compared to 0.31 in the control group, or one extra death per 100,000 patients. Although prostate cancer was diagnosed more often in the intervention group (4.3% compared to 3.6% in the control group), the mortality rate was almost identical between both groups (Martin et al., 2018).

A systematic review and meta-analysis of 341,342 patients evaluated the overall effectiveness of prostate cancer screening. Results from this study showed that while PSA screening did lead to an increase in the identification of prostate cancer cases at all stages, it did not necessarily reduce the amount of overall or disease specific mortality rates (Ilic et al., 2018). This highlights the uncertainty regarding the effectiveness of prostate cancer screening. The authors also noted that “PSA screening is associated with considerable biopsy-related and cancer treatment-related complications” (Ilic et al., 2018).

In May of 2012, the USPSTF released a grade D recommendation against PSA prostate cancer screening (Ahlering et al., 2019). In 2018, the recommendation was switched to a grade C recommendation, now suggesting that men ages 55 to 69 could be screened for prostate cancer if first counseled about the benefits and harms of screening (USPSTF, 2018). Nonetheless, when the grade D recommendation was first released, many researchers were worried that an increase in late-stage prostate cancer cases would be identified, leading to greater rates of prostate cancer-specific mortality. To assess this risk, data from a total of 19,602 patients from nine high volume referral centers in the United States was collected and analyzed during the time that the USPSTF grade D recommendation was in effect. The researchers found that “All centers experienced consistent decreases of low-grade disease and absolute increases in intermediate and high-risk cancer. For any given age and PSA, propensity matching demonstrates more aggressive disease in the postrecommendation era” (Ahlering et al., 2019).

Osses, et al., (2019) assessed the results of 1,134 men screened for prostate cancer in a 19 year follow up study; at the start of the study, all men were between the ages of 55 and 74. Unfortunately, 63% of the cohort was deceased by the 19-year follow-up period for various reasons. Still, the researchers noted that results suggested “a more substantial reduction in metastatic disease and cancer-specific mortality in favor of prostate cancer screening than previously reported (Osses et al., 2019).” However, more research needs to be completed with a larger sample size to confirm this conclusion.

Magnani et al. (2021) performed a cost analysis on “first-line prostate cancer management” using real-world data. A total of 3433 patients were included, and outcomes such as active surveillance (AS), surgery, and radiation were considered. Surgery was found to be the most common option, with 54.6% of the cohort compared to 22.3% for radiation and 23% for AS. Over a period of 2 years following diagnosis, AS was found to be the cheapest option at $2.97/day (d), with surgery costing $5.67/d and radiation costing $9.34/d, for “favorable” disease. For “unfavorable” disease, surgery cost $7.17/d and radiation cost $16.34/d. Over a period of 5 years following diagnosis, AS was found to be cheaper than surgery, by an amount of $2.71/d to $2.87 for surgery and $4.36 for favorable disease. For unfavorable disease, surgery remained cheaper than radiation, by an amount of $4.15/d to $10.32/d. The authors did remark that this information came from a single health care system and were based on benchmark Medicare estimates rather than actual payment exchanges (Magnani et al., 2021).

Baniak et al. (2020) compared the clinicopathologic and molecular characteristics of prostate cancer in 90 younger men (45 years or younger) to 200 men of typical screening age (60-65 years). The authors found that younger men tended to have lower PSA values, but a higher frequency of family history of prostate cancer. No significant differences were found in staging or pathological characteristics of core biopsy specimens between the two groups. The younger cohort was also found to have a higher frequency of “grade group 1 disease” at radical prostatectomy. Finally, no statistically significant differences were found regarding prostatic adenocarcinoma prostate specific recurrence/progression or death between the two cohorts (Baniak et al., 2020).

Guidelines and Recommendations

The American Association of Family Physicians (AAFP)

The AAFP recommends against use of PSA-based testing for prostate cancer screening. For men between 55 to 69 years of age who are considering prostate cancer screening, the physician should discuss the risks and benefits and engage in shared decision making before undergoing the screening process. In addition, the AAFP recommends against prostate cancer screening in men older than 70 (AAFP, 2018b). They clarify that for men aged 55 to 69 “The decision to be screened for prostate cancer should be an individual one (Grade: C)”, not to screen for prostate cancer in men aged 70 years and older (Grade: D). However, they also note that “Older age, African American race, and family history of prostate cancer are the most important risk factors for prostate cancer. The workup they describe involve starting with a test to measure PSA in the blood, and then positive results may be followed up with a transrectal ultrasound-guided core-needle biopsy of the prostate to diagnose prostate cancer (AAFP, 2018c).

The American Academy of Family Physicians (AAFP and Choosing Wisely®)

In collaboration with Choosing Wisely, the American Academy of Family Physicians has elaborated on some of their prostate cancer guidelines. There they recommend against routine screening for prostate cancer using a prostate-specific antigen (PSA) test or digital rectal exam, but “For men who desire PSA screening, it should only be performed after engaging in shared decision making.” Though screening may prevent mortality, “whether this potentially small benefit in mortality outweighs the potential harms is dependent on the values and preferences of individual men. Therefore, for men who express a desire for prostate cancer screening, it should only be performed following a discussion of the potential benefits and harms. Routine screening for prostate cancer should not be done. PSA-based prostate cancer screening should not be performed in men over 70 years of age” (AAFP, 2018a).

The United States Preventive Services Task Force (USPSTF)

The USPSTF issued additional draft guidelines which recommend that clinicians inform men aged 55 to 69 years about the potential benefits and harms of PSA–based screening for prostate cancer, noting that the decision to be screened should be up to the patient. The USPSTF also states that screening offers a small potential benefit of reducing the chance of dying of prostate cancer. However, they note many men will be harmed due to false positives and its side effects such as overdiagnosis or other complications such as impotence. The USPSTF recommends discussion with a clinician before deciding to screen, ultimately giving this screening a “C” recommendation. Furthermore, the USPSTF recommends against PSA-based screening for prostate cancer in men over 70 (USPSTF, 2018). The CDC cites the USPSTF recommendation (CDC, 2022b). 

Memorial Sloan Kettering Cancer Center (MSK)

The Memorial Sloan Kettering Cancer Center issued screening guidelines on prostate cancer based on the individual’s age. Their guidelines are for men who are expected to live at least ten years. “Men ages 45 to 49 should have a baseline PSA test. If the PSA level is 3 ng / mL or higher, men should talk with their doctor about having a biopsy of the prostate. If the PSA level is between 1 and 3 ng / mL, men should see their doctor for another PSA test every two to four years. If the PSA level is less than 1 ng / mL, men should see their doctor for another PSA test between the ages of 51 and 55. Men ages 50 to 59 should have their PSA level checked. If the PSA level is 3 ng / mL or higher, men should talk with their doctor about having a biopsy of the prostate. If the PSA level is between 1 and 3 ng / mL, men should see their doctor for another PSA test every two to four years. If the PSA level is less than 1 ng / mL, men should see their doctor for another PSA test at age 60. Men ages 60 to 70 should have their PSA level checked. If the PSA level is 3 ng / mL or higher, men should talk with their doctor about having a biopsy of the prostate. If the PSA level is between 1 and 3 ng / mL, men should see their doctor for another PSA test every two to four years. If the PSA level is less than 1 ng / mL, no further screening is recommended. Men ages 71 to 75 should talk with their doctor about whether to have a PSA test. This decision should be based on past PSA levels and the health of the man. Prostate cancer screening is not recommended for men ages 76 or older. A high PSA level does not generally mean that a man should have a prostate biopsy” (Memorial Sloan Kettering Cancer Center, 2022).

The National Comprehensive Cancer Network (NCCN)

The NCCN also recommends that patients make informed decisions regarding enrollment in an early detection program. Factors such as personal history, previous testing, family history, and race should be considered for determination if an early detection protocol is implemented. The guidelines stated that most panel members favored informed testing starting at 45. The panel supports screening in men until 75, and then continuing screening only in very healthy patients with little or no comorbidity to detect the life threatening and aggressive cancers. However, widespread screening in this age group is not recommended as it would increase rates of over-detection (NCCN, 2023b). The NCCN also relayed their concern about “the problems of overtreatment related to the increased frequency of diagnosis of prostate cancer from widespread use of PSA for early detection of screening” (NCCN, 2023a).

For initial testing, the NCCN recommends that “baseline PSA testing should be offered to healthy, wellinformed men aged 45 to 75 years based on the results of RCTs” (NCCN, 2023b). They also recommend screening starting at 40 years for certain higher risk populations, such as those with “African ancestry,” “suspicious family history,” and germline mutations that increase risk of prostate cancer. Further, baseline testing may be ordered along with a DRE, and any elevated levels should be double checked with repeat testing (NCCN, 2023b).

The NCCN considers three categories for “early evaluation detection,” men of average risk (45-75 years), men of increased risk (such as men with “African ancestry”, “suspicious family history” and “germline mutations that increase the risk of prostate cancer” [such as BRCA]), and men above 75 years. 

• For men aged 45 to 75 years with average risk, the panel recommends repeat testing every 2 to 4 years if PSA is <1 ng/mL. If the PSA level is 1 to 3 ng/mL, frequency of testing should be every 1 to 2 years. If PSA > 3 ng/ml (or if the DRE is “very suspicious”), a biopsy should be considered. 
• The above decision tree also applies to high-risk populations (African ancestry, suspicious or concerning family history, germline mutations that increase the rate of prostate cancer), though the NCCN recommends starting these evaluations at 40 years rather than 45 years of age. The NCCN also writes to “consider” screening these high-risk populations “annually” rather than the less frequent intervals discussed.
• For select patients over 75 years, repeat testing in select patients at 1 – 3-year intervals is recommended if the PSA is <4 ng/ml, the DRE is normal, and there are no other indications for biopsy. In this case, they also state that one should “consider discontinuing screening if clinically appropriate.” 
• However, in select patients over 75 years of age, if the patient has PSA >4 ng/ml and/or a very suspicious DRE, a repeat PSA test, DRE (if not performed during initial risk assessment), and workup for benign disease is indicated. A multiparametric MRI (mpMRI) should be considered. However, it is noted that “a negative MRI does not exclude the possibility of cancer,” and so it is recommended to “consider biomarkers and/or PSA density when deciding whether to avoid a biopsy in an individual with a negative mpMRI result.”
  • If there is high suspicion for clinically significant cancer, image-guided biopsy via transrectal or transperineal approach with MRI targeting or without MRI targeting is indicated, though MRI targeting is preferred.
  • If there is low suspicion for clinically significant cancer, there should be a follow-up in 6-12 months with PSA/DRE (NCCN, 2023b).

The NCCN also comments on several biomarkers’ ability to assess early detection of prostate cancer.  

They note that “Unbound or free PSA (fPSA), expressed as a ratio of tPSA, is a clinically useful molecular form of PSA, with the potential to improve early detection, staging, and monitoring of prostate cancer”, explaining that “Most immunoreactive PSA is bound to the protease inhibitor alpha-1-antichymotrypsin. Other immunoreactive PSA-protease inhibitor complexes, such as alpha-1-antitrypsin and protease C inhibitor, exist at such low serum concentrations that their clinical significance has not been determined” (NCCN, 2023b). Another notable proportion of PSA is complexed with alpha-2-macroglobulin (AMG), though “this PSA-AMG complex cannot be measured by conventional assays because of the shielding (or "caging") of PSA antigenic epitopes by AMG” (NCCN, 2023b). 

Testing for %fPSA is included in the NCCN guidelines as “an option before initial biopsy and for those with a prior negative biopsy” since “The FDA approved the use of %fPSA for the early detection of prostate cancer in individuals aged ≥50 years with a non-suspicious DRE and PSA levels between 4 ng/mL and 10 ng/mL (PSA levels where most secondary testing is done). The multi-institutional study that characterized the clinical utility of this assay showed that a 25% fPSA cutoff detected 95% of prostate cancers while avoiding 20% of unnecessary prostate biopsies” (NCCN, 2023b).

The NCCN also includes recommendations for PSA testing in non-screening situations, such as monitoring. Regarding “patients initially treated with intent to cure”, the NCCN recommends testing serum PSA levels “every 6 to 12 months for the first 5 years and then annually.” The NCCN also notes that for men with “high” risk of recurrence, testing PSA every three months may be preferred. For patients with “castrationnaïve disease on ADT [androgen deprivation therapy], PSA measurement may be done every three to six months based on clinical judgement. Moreover, the NCCN notes that “Local recurrence may result in substantial morbidity and can, in rare cases, occur in the absence of a PSA elevation. Therefore, annual DRE is appropriate to monitor for prostate cancer recurrence and to detect colorectal cancer. Similarly, after RT, the monitoring of serum PSA levels is recommended every six months for the first five years and then annually and a DRE is recommended annually. The clinician may opt to omit the DRE if PSA levels remain undetectable” (NCCN, 2023a).

The American Cancer Society (ACS)

The ACS recommends that physicians provide patients with information on benefits, risks, and uncertainties of the PSA test, and state that screening not be done until such information is received. The ACS recommends that discussions (and screening) begin at age 50 for individuals of average risk, at age 45 for those at increased risk (i.e., African-American men and men who have a first-degree relative (father or brother) diagnosed with prostate cancer at an early age (younger than 65)”, and at age 40 for those at highest risk (those with more than one first degree relative with a history of early-onset prostate cancer (ACS, 2023a). 

After having this discussion, individuals who want to be screened should get the PSA screening. A digital rectal exam (DRE) may also be performed. Because prostate cancer is growing slowly, the ACS does not recommend PSA screening in any individual without symptoms of prostate cancer and with a life expectancy of less than 10 years. However, they also note that overall health and not age alone is important to decide when to pursue screening (ACS, 2023a).

The ACS remarks that overall health and not age alone is important to decide when to pursue screening. Moreover, “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” and further discussions must incorporate patients’ health, values, and preferences (ACS, 2023a).

The National Cancer Institute (NCI)

The NCI has deemed the evidence insufficient to determine whether PSA-based screenings or DREs reduce mortality from prostate cancer. The NCI states that although screening can detect cancer in its earlier stages, it is unclear that earlier detection (and treatment) changes the natural course of the disease. The NCI also states that there is significant harm in screening such as overdiagnosis and complications caused by the screenings (NCI, 2023). Moreover, NCI states there is “solid evidence,” that current treatments such as radical prostatectomy and radiation therapy, result in “permanent side effects in many men” (NCI, 2023).

The American College of Physicians (ACP)

The ACP agrees with the informed decision-making requirement for PSA testing, and states that clinicians should not screen using the PSA test in patients who “do not express a clear preference for screening”. It is also worth mentioning that “it has been suggested that those who are at high risk may benefit from earlier screening beginning at age 45, while even higher risk men (those with two or more first-degree relatives with prostate cancer before the age of 65), should be screened at age 40.” The ACP recommends against screening with PSA for individuals under 50 or over 70, as the primary target is between the ages of 50 and 69. The ACP also cautions that “clinicians should not screen for prostate cancer using the PSA test in average-risk men aged 50 to 69 years who have not had an informed discussion and do not express a clear preference for screening” (Wilt et al., 2015). Asymptomatic men over 75 and those with a life expectancy of less than 10 years should also not be offered screening because screening can introduce substantial harms for questionable benefit (Qaseem, et al., 2013; Wilt et al., 2015).

The American Urological Association (AUA)

The AUA recommends against use of PSA screening in men under 40, and routine screening for average-risk men between ages 40 to 54 years. The AUA does recommend informed decision making for men ages 55 to 69 years. The AUA recommends against PSA screening in men 70 years of age and older, or in any man with a life expectancy less than 10 – 15 years, although they do acknowledge that some men in excellent health 70 years and older may benefit from screening. The AUA recommends an individualized screening program be developed for individuals less than 55 years old, who are at high risk, such as those with a positive family history and African Americans. The AUA notes that a routine screening interval of two or more years may be preferred, but also notes that screening intervals “can be individualized by a baseline PSA level” (Carter et al., 2013).

The American Urological Association (AUA) and the Society of Urologic Oncology (SUO)

The American Urological Association and the Society of Urologic Oncology collaborated to produce a series of guideline statements. Regarding the use of PSA screening in the early detection of prostate cancer, they expounded that:

• “1. Clinicians should engage in SDM with people for whom prostate cancer screening would be appropriate and proceed based on a person’s values and preferences. (Clinical Principle)” 
• “2. When screening for prostate cancer, clinicians should use PSA as the first screening test. (Strong Recommendation; Evidence Level: Grade A) 
• 3. For people with a newly elevated PSA, clinicians should repeat the PSA prior to a secondary biomarker, imaging, or biopsy. (Expert Opinion)” 
• “4. Clinicians may begin prostate cancer screening and offer a baseline PSA test to people between ages 45 to 50 years. (Conditional Recommendation; Evidence Level: Grade B) 
• “5. Clinicians should offer prostate cancer screening beginning at age 40 to 45 years for people at increased risk of developing prostate cancer based on the following factors: Black ancestry, germline mutations, strong family history of prostate cancer. (Strong Recommendation; Evidence Level: Grade B)” 
• “6. Clinicians should offer regular prostate cancer screening every 2 to 4 years to people aged 50 to 69 years. (Strong Recommendation; Evidence Level: Grade A)”
• “7. Clinicians may personalize the re-screening interval, or decide to discontinue screening, based on patient preference, age, PSA, prostate cancer risk, life expectancy, and general health following SDM. (Conditional Recommendation; Evidence Level: Grade B)” 
• “8. Clinicians may use digital rectal exam (DRE) alongside PSA to establish risk of clinically significant prostate cancer. (Conditional Recommendation; Evidence Level: Grade C)”
• “9. For people undergoing prostate cancer screening, clinicians should not use PSA velocity as the sole indication for a secondary biomarker, imaging, or biopsy. (Strong Recommendation; Evidence Level: Grade B)” 
• “10. Clinicians and patients may use validated risk calculators to inform the SDM process regarding prostate biopsy. (Conditional Recommendation; Evidence Level: Grade B)”
• “11. When the risk of clinically significant prostate cancer is sufficiently low based on available clinical, laboratory, and imaging data, clinicians and patients may forgo near-term prostate biopsy. (Clinical Principle)” (Wei et al., 2023).

The AUA and SUO also partnered to discuss advanced prostate cancer as well, reported below (Lowrance et al., 2021).

Regarding the use of PSA screening for the Biochemical Recurrence without Metastatic Disease after Exhaustion of Local Treatment Options, they proposed that “Clinicians should inform patients with PSA recurrence after exhaustion of local therapy regarding the risk of developing metastatic disease and follow such patients with serial PSA measurements and clinical evaluation. Clinicians may consider radiographic assessments based on overall PSA and PSA kinetics. (Clinical Principle).”

Moreover, PSA screening also plays a role in the prognosis of Metastatic Hormone-Sensitive Prostate Cancer, such that “Clinicians should obtain a baseline PSA and serial PSAs at three- to six-month intervals after initiation of ADT in mHSPC patients and consider periodic conventional imaging. (Clinical Principle).”

In patients with Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC), “clinicians should obtain serial PSA measurements at three- to six-month intervals and calculate a PSADT starting at the time of development of castration-resistance. (Clinical Principle).”

Lastly, in patients with Metastatic Castration-Resistant Prostate Cancer, “clinicians should obtain baseline labs (e.g., PSA, testosterone, LDH, Hgb, alkaline phosphatase level) and review location of metastatic disease (lymph node, bone, visceral), disease-related symptoms, and performance status to inform discussions of prognosis and treatment decision-making. (Clinical Principle).” However, “In mCRPC patients without PSA progression or new symptoms, clinicians should perform imaging at least annually. (Expert Opinion)” (Lowrance et al., 2021).

The European Society for Medical Oncology (ESMO)

The ESMO recommends against population-based screening for prostate cancer because the reduction in mortality does not offset the harms done, such as overdiagnosis and overtreatment. Early PSA testing should only be offered to men > 50 years, men > 45 years with a family history of prostate cancer, African Americans > 45 years, and BRCA1/2 carriers who are > 40 years of age. Prostate cancer screening should not be performed in asymptomatic men with a life expectancy of less than ten years. ESMO also recommends against screening in asymptomatic men over 70 (Parker et al., 2020).

The American Association of Clinical Urologists Inc. (AACU)

The AACU recommends use of tissue-based molecular testing to assess risk stratification in prostate cancer treatment decision making. The AACU states pursing germline testing when appropriate is encouraged and support any further research into these tests AACU (AACU, 2018).

The European Association of Urology (EAU)

In 2021, the EAU released updated guidelines on their position regarding prostate antigen testing, recommending a risk-adapted strategy for the early detection of prostate cancer and reaffirming the joint guidelines in the table above. They noted that an absence of regular and routine widespread PSA testing had led to “opportunistic” testing in several EU member states. In addition, the impact of COVID-19, particularly the redeployment of medical resources to fight COVID-19, as well as a move during COVID-19 to “deprioritise all oncology screening, including PSA testing,” was of strong concern. Their position concluded with the need to reverse current unfavorable trends in order to accurately diagnose advanced stage prostate cancer and save lives (Van Poppel et al., 2021).

The European Association of Urology (EAU), European Association of Nuclear Medicine (EANM), European Society for Radiotherapy and Oncology (ESTRO), European Society of Urogenital Radiology (ESUR), and International Society of Geriatric Oncology (SIOG)

Joint guidelines on prostate cancer screening and early detection from the EAU, EANM, ESTRO, ESUR and SIOG include the table below taken from Mottet et al. (2020).

Additional guidelines for the risk-assessment of asymptomatic men from (Mottet et al., 2020) state:

The guideline also notes the presence of newer biological markers, such as “TMPRSS2-ERG fusion, PCA3, or kallikreins as incorporated in the Phi or 4Kscore tests” but despite promising early results, the guideline considers these markers to have “too limited data to implement these markers into routine screening programmes” (Mottet et al., 2020).

State and Federal Regulations, as applicable

The FDA has approved several screening tests for prostate cancer beginning with a PSA immunoassay in 1986 (FDA, 2023).

On June 14, 2012, the FDA approved the Access® Hybritech® p2PSA assay created by Beckman Coulter, Inc. From the FDA website: “The Access® Hybritech® p2PSA assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of [-2] proPSA antigen, an isoform of free PSA, in human serum using the Access Immunoassay Systems. Access@ Hybritech® p2PSA is intended to be used in combination with Access® Hybritech® (total) PSA and Access@ Hybritech@ free PSA to calculate the Beckman Coulter Prostate Health Index (phi), an In Vitro Diagnostic Multivariate Index Assay (IVDMIA)” (FDA, 2012).

Many labs have developed specific tests that they must validate and perform in house. These laboratorydeveloped tests (LDTs) are regulated by the Centers for Medicare and Medicaid (CMS) as high-complexity tests under the Clinical Laboratory Improvement Amendments of 1988 (CLIA ’88). As an LDT, the U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. 

Billing/Coding/Physician Documentation Information

This policy may apply to the following codes. Inclusion of a code in this section does not guarantee that it will be reimbursed. For further information on reimbursement guidelines, please see Administrative Policies on the Blue Cross Blue Shield of North Carolina web site at www.bcbsnc.com. They are listed in the Category Search on the Medical Policy search page.

Applicable service codes: 84152, 84153, 84154, G0103

BCBSNC may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included. 

Scientific Background and Reference Sources

For Policy Titled: Prostate Cancer Screening

AACU. (2018). Retrieved from https://aacuweb.org/docs/position-statements/ps_genomic-testingin-prostate-cancer.aspx

AAFP. (2018a), Choosing Wisely® Prostate Cancer Screening. https://www.aafp.org/familyphysician/patient-care/clinical-recommendations/all-clinical-recommendations/cw-prostatecancer.html

AAFP. (2018b). Counseling Patients About Prostate Cancer Screening. Am Fam Physician, 98(8), 478-483. https://www.aafp.org/afp/2018/1015/p478.html 

AAFP. (2018c). Screening for Prostate Cancer: Recommendation Statement. Am Fam Physician, 98(8), Online. https://www.aafp.org/pubs/afp/issues/2018/1015/od1.html

ACS. (2023a, November 22, 2023). American Cancer Society Recommendations for Prostate Cancer Early Detection. https://www.cancer.org/cancer/types/prostate-cancer/detection-diagnosisstaging/acs-recommendations.html

ACS. (2023b, November 22, 2023). Signs and Symptoms of Prostate Cancer. https://www.cancer.org/cancer/prostate-cancer/detection-diagnosis-staging/signs-symptoms.html

ACS. (2024, January 17, 2024). Survival Rates for Prostate Cancer. https://www.cancer.org/cancer/prostate-cancer/detection-diagnosis-staging/survival-rates.html

Ahlering, T., Huynh, L. M., Kaler, K. S., Williams, S., Osann, K., Joseph, J., . . . Hu, J. C. (2019). Unintended consequences of decreased PSA-based prostate cancer screening. World J Urol, 37(3), 489-496. https:doi.org/10.1007/s00345-018-2407-3

American_Cancer_Society. (2023). Key Statistics for Prostate Cancer. https://www.cancer.org/cancer/prostate-cancer/about/keystatistics.html#:~:text=The%20American%20Cancer%20Society's%20estimates,33%2C330%20de aths%20from%20prostate%20cancer

Balducci, L., Pow-Sang, J., Friedland, J., & Diaz, J. I. (1997). Prostate cancer. Clin Geriatr Med, 13(2), 283-306. https://pubmed.ncbi.nln.nih.gov/9115452/

Baniak, N., Sholl, L. M., Mata, D. A., D'Amico, A. V., Hirsch, M. S., & Acosta, A. M. (2020). Clinicopathologic and Molecular Characteristics of Prostate Cancer Diagnosed in Young Men Aged up to 45 Years. Histopathology. https://doi.org/10.1111/his.14315

Bell, K. J., Del Mar, C., Wright, G., Dickinson, J., & Glasziou, P. (2015). Prevalence of incidental prostate cancer: A systematic review of autopsy studies. Int J Cancer, 137(7), 1749-1757. https://doi.org/10.1002/ijc.29538

Brawley, S., Mohan, R., & Nein, C. (2018). Localized Prostate Cancer: Treatment Options. American Family Physician, 97(12), 798-805. https://www.aafp.org/pubs/afp/issues/2018/0615/p798.html

Carter, H. B., Albertsen, P. C., Barry, M. J., Etzioni, R., Freedland, S. J., Greene, K. L., . . . Zietman, A. L. (2013). Early detection of prostate cancer: AUA Guideline. J Urol, 190(2), 419- 426. https://doi.org/10.1016/j.juro.2013.04.119

CDC. (2022a). Leading Cancer Cases and Deaths, Male, 2019. Retrieved from https://gis.cdc.gov/Cancer/USCS/DataViz.html 

CDC. (2022b). Should I Get Screened for Prostate Cancer? Retrieved 12/30/2020 https://www.cdc.gov/cancer/prostate/basic_info/get-screened.html

Chang, S. L., Harshman, L. C., & Presti, J. C., Jr. (2010). Impact of common medications on serum total prostate-specific antigen levels: analysis of the National Health and Nutrition Examination Survey. J Clin Oncol, 28(25), 3951-3957. https://doi.org/10.1200/jco.2009.27.9406

Coban, S., Doluoglu, O. G., Keles, I., Demirci, H., Turkoglu, A. R., Guzelsoy, M., . . . Demirbas, M. (2016). Age and total and free prostate-specific antigen levels for predicting prostate volume in patients with benign prostatic hyperplasia. Aging Male, 19(2), 124-127. doi:10.3109/13685538.2015.1131260

FDA. (2012). ACCESS HYBRITECH P2PSA ON THE ACCESS IMMUNOASSAY SYSTEMS. Summary of Safety and Effectiveness Data (SSED). Retrieved from https://www.accessdata.fda.gov/cdrh_docs/pdf9/P090026B.pdf

FDA. (2023). TANDEM-R PSA IMMUNORADIOMETRIC ASSAY. https://www.accessdata.fda.gov/scripts/cdrh/devicesatfda/index.cfm?db=pma&id=319006

Fisher, K. W., Montironi, R., Lopez Beltran, A., Moch, H., Wang, L., Scarpelli, M., . . . Cheng, L. (2015). Molecular foundations for personalized therapy in prostate cancer. Curr Drug Targets, 16(2), 103-114. https://doi.org/10.2174/1389450115666141229154500

Fleshner, K., Carlsson, S. V., & Roobol, M. J. (2017). The effect of the USPSTF PSA screening recommendation on prostate cancer incidence patterns in the USA. Nat Rev Urol, 14(1), 26-37. https://doi.org/10.1038/nrurol.2016.251

Freedland, S. (2024, January 23, 2024). Measurement of prostate-specific antigen. Wolters Kluwer. Retrieved 1/19/21 from https://www.uptodate.com/contents/measurement-of-prostatespecificantigen?search=prostate%20specific%20antigen&source=search_result&selectedTitle=1~130&usa ge_type=default&display_rank=1

Hamilton, R. J., Goldberg, K. C., Platz, E. A., & Freedland, S. J. (2008). The influence of statin medications on prostate-specific antigen levels. J Natl Cancer Inst, 100(21), 1511-1518. https://doi.org/10.1093/jnci/djn362

Ilic, D., Djulbegovic, M., Jung, J. H., Hwang, E. C., Zhou, Q., Cleves, A., . . . Dahm, P. (2018). Prostate cancer screening with prostate-specific antigen (PSA) test: a systematic review and metaanalysis. Bmj, 362, k3519. https://doi.org/10.1136/bmj.k3519 

Lowrance, W. T., Breau, R. H., Chou, R., Chapin, B. F., Crispino, T., Dreicer, R., Jarrard, D. F., Kibel, A. S., Morgan, T. M., Morgans, A. K., Oh, W. K., Resnick, M. J., Zietman, A. L., & Cookson, M. S. (2021). Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART I. J Urol, 205(1), 14-21. https://doi.org/10.1097/ju.0000000000001375

Magnani, C. J., Bievre, N., Baker, L. C., Brooks, J. D., Blayney, D. W., & Hernandez-Boussard, T. (2021). Real-world Evidence to Estimate Prostate Cancer Costs for First-line Treatment or Active Surveillance. Eur Urol Open Sci, 23, 20-29. https://doi.org/10.1016/j.euros.2020.11.004

Martin, R. M., Donovan, J. L., Turner, E. L., Metcalfe, C., Young, G. J., Walsh, E. I., . . . Hamdy, F. C. (2018). Effect of a Low-Intensity PSA-Based Screening Intervention on Prostate Cancer Mortality: The CAP Randomized Clinical Trial. Jama, 319(9), 883-895. https://doi.org/10.1001/jama.2018.0154

Memorial Sloan Kettering Cancer Center. (2022). Prostate Cancer Screening Guidelines. https://www.mskcc.org/cancer-care/types/prostate/screening/screening-guidelines-prostate

Mottet, N., Bellmunt, J., Bolla, M., Briers, E., Cumberbatch, M. G., De Santis, M., . . . Cornford, P. (2020). EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer—2020 Update. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol, 71(4), 618-629. https://doi.org/10.1016/j.eururo.2016.08.003

NCCN. (2023a). NCCN Clinical Practice Guidelines in Oncology; Prostate Cancer Version 4.2023-September 7,2023. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf

NCCN. (2023b, January 2, 2024). Prostate Cancer Early Detection. Version 1.2024. Retrieved 2/9/2023 from https://www.nccn.org/professionals/physician_gls/pdf/prostate_detection.pdf

NCI. (2022, March 11, 2022). Prostate-Specific Antigen (PSA) Test. https://www.cancer.gov/types/prostate/psa-fact-sheet

NCI. (2023, October 26, 2023). Prostate Cancer Screening (PDQ®)–Health Professional Version. https://www.cancer.gov/types/prostate/hp/prostate-screening-pdq#_1

Osses, D. F., Remmers, S., Schroder, F. H., van der Kwast, T., & Roobol, M. J. (2019). Results of Prostate Cancer Screening in a Unique Cohort at 19yr of Follow-up. Eur Urol, 75(3), 374-377. https://doi.org/10.1016/j.eururo.2018.10.053

Parker, C., on behalf of the, E. G. C., Gillessen, S., on behalf of the, E. G. C., Heidenreich, A., on behalf of the, E. G. C., . . . on behalf of the, E. G. C. (2020). Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. https://www.annalsofoncology.org/action/showPdf?pii=S0923-7534%2820%2939898-7

Prcic, A., Begic, E., & Hiros, M. (2016). Actual Contribution of Free to Total PSA Ratio in Prostate Diseases Differentiation. Med Arch, 70(4), 288-292. https://pubmed.ncbi.nlm.nih.gov/27703291/

Preston, M. A. (2023, December 5, 2023). Screening for prostate cancer. https://www.uptodate.com/contents/screening-for-prostate-cancer?source=see_link#H30

Qaseem, A., Barry, M. J., Denberg, T. D., Owens, D. K., & Shekelle, P. (2013). Screening for prostate cancer: a guidance statement from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med, 158(10), 761-769. https://doi.org/10.7326/0003-4819-158- 10-201305210-00633

Rodrigues, D. N., Butler, L. M., Estelles, D. L., & de Bono, J. S. (2014). Molecular pathology and prostate cancer therapeutics: from biology to bedside. J Pathol, 232(2), 178-184. https://doi.org/10.1002/path.4272 Saini, S. (2016). PSA and beyond: alternative prostate cancer biomarkers. Cell Oncol (Dordr), 39(2), 97-106. https://doi.org/10.1007/s13402-016-0268-6

Singer, E. A., Palapattu, G. S., & van Wijngaarden, E. (2008). Prostate-specific antigen levels in relation to consumption of nonsteroidal anti-inflammatory drugs and acetaminophen: results from the 2001-2002 National Health and Nutrition Examination Survey. Cancer, 113(8), 2053-2057. https://doi.org/10.1002/cncr.23806

Stimac, G., Spajic, B., Reljic, A., Katusic, J., Popovic, A., Grubisic, I., & Tomas, D. (2014). Effect of histological inflammation on total and free serum prostate-specific antigen values in patients without clinically detectable prostate cancer. Korean J Urol, 55(8), 527-532. https://doi.org/10.4111/kju.2014.55.8.527

Tabayoyong, W., & Abouassaly, R. (2015). Prostate Cancer Screening and the Associated Controversy. Surg Clin North Am, 95(5), 1023-1039. https://doi.org/10.1016/j.suc.2015.05.001

USPSTF. (2018). Draft Recommendation Statement: Prostate Cancer: Screening - US Preventive Services Task Force. https://www.uspreventiveservicestaskforce.org/Page/Document/draftrecommendation-statement/prostate-cancer-screening1

Van Poppel, H., Roobol, M. J., Chapple, C. R., Catto, J. W. F., N’Dow, J., Sønksen, J., Stenzl, A., & Wirth, M. (2021). Prostate-specific Antigen Testing as Part of a Risk-Adapted Early Detection Strategy for Prostate Cancer: European Association of Urology Position and Recommendations for 2021. European Urology, 80(6), 703-711. https://doi.org/10.1016/j.eururo.2021.07.024

Wang, L. G., Liu, X. M., Kreis, W., & Budman, D. R. (1997). Down-regulation of prostate-specific antigen expression by finasteride through inhibition of complex formation between androgen receptor and steroid receptor-binding consensus in the promoter of the PSA gene in LNCaP cells. Cancer Res, 57(4), 714-719. https://pubmed.ncbi.nlm.nih.gov/9044850/

Wei, J. T., Barocas, D., Carlsson, S., Coakley, F., Eggener, S., Etzioni, R., Fine, S. W., Han, M., Kim, S. K., Kirkby, E., Konety, B. R., Miner, M., Moses, K., Nissenberg, M. G., Pinto, P. A., Salami, S. S., Souter, L., Thompson, I. M., & Lin, D. W. (2023). Early Detection of Prostate Cancer: AUA/SUO Guideline Part I: Prostate Cancer Screening. J Urol, 210(1), 46-53. https://doi.org/10.1097/ju.0000000000003491

Wilt, T. J., Harris, R. P., & Qaseem, A. (2015). Screening for cancer: advice for high-value care from the American College of Physicians. Ann Intern Med, 162(10), 718-725. https://doi.org/10.7326/m14-2326Specialty Matched Consultant Advisory Panel 8/2019 Medical Director review 8/2019

Medical Director review 4/2020

Specialty Matched Consultant Advisory Panel 8/2020

For Policy Titled: Prostate Specific Antigen (PSA) Testing

Medical Director review 4/2021

Specialty Matched Consultant Advisory Panel 8/2021

Medical Director review 4/2023

Medical Director review 4/2024

Policy Implementation/Update Information

For Policy Titled: Prostate Cancer Screening

1/1/2019 New policy developed. BCBSNC will provide coverage for prostate cancer screening when it is determined to be medically necessary and criteria are met. Medical Director review 1/1/2019. Policy noticed 1/1/2019 for effective date 4/1/2019. (lpr)

6/11/19 Reviewed by Avalon 1st Quarter 2019 CAB. Under “When Covered” section: changed “men” to “individuals.” Under “When Not Covered” section: re-ordered and re-worded indications. Updated “gene expression analysis” general terminology to include “use of Prolaris, Oncotype DX, Promark or Decipher tumor-based molecular assays to guide management of prostate cancer as well as urine testing.” Added PLA codes 0005U and 0047U to Billing/Coding section. Medical Director review 5/2019. (lpr)

10/1/19 Reviewed by Avalon 2nd Quarter 2019 CAB. Policy statement revised to read: BCBSNC will provide coverage for prostate cancer screening when it is determined the medical criteria and guidelines noted below are met. Revised Description Section. Wording changed in the When Covered section. “Medically Necessary” changed to “Reimbursement is allowed…” Wording revised in the Not Covered section. “Investigational” changed to read “Reimbursement is not allowed…” Deleted coding grid. Policy Guidelines updated. References added. Policy noticed 10/1/2019 for effective date 12/2/2019. (an)

12/31/19 Specialty Matched Consultant Panel review 8/21/19. No change to policy statement. CPT code 81542 added to Billing/Coding section for effective date 1/1/2020. (lpr)

3/24/2020 CPT codes 81541, 81551 and PLA code 0005U removed from Billing/Coding section. (lpr)

5/12/20 Reviewed by Avalon 1st Quarter 2020 CAB. Medical Director review 4/2020. Added CPT codes 0005U and 81551 to Billing/Coding section. Switched the term “testing” to “screening” in the “When Covered” section. Added ExoDx prostate, Intelliscore, Select MDX, PCA3, KLK3, Confirm MDX, PPCA to “When Not Covered” section. Updated Policy Guidelines and References. (lpr)

9/8/20 Specialty Matched Consultant Advisory Panel review 8/19/2020. No changes to policy statement. (lpr)

For Policy Titled: Prostate Specific Antigen (PSA) Testing

5/18/21 Reviewed by Avalon 1st Quarter 2021 CAB. Medical Director review 4/2021. Under “When Covered” section: revised and updated to include total PSA testing for average risk individuals aged 45-75 with African ancestry, germline mutations that increase risk for prostate cancer, suspicious family history. Updated Description and Policy Guidelines sections as well as References. Revised and updated Billing/Coding section. Policy title changed from: Prostate Cancer Screening to: Prostate Specific Antigen (PSA) Testing. (lpr)

9/7/21 Specialty Matched Consultant Advisory Panel review 8/18/2021. No change to policy statement. (lpr)

5/17/22 Reviewed by Avalon 1st Quarter 2022 CAB. Medical Director review 4/2022. Updated guidelines/recommendations and references. (lpr)

7/18/23 Reviewed by Avalon 1st Quarter 2023 CAB. Medical Director review 4/2023. Deleted related policies section. Updated policy guidelines and references. Re-ordered and edited “when covered” section for clarity. No change to policy statement. (lpr)

5/15/24 Reviewed by Avalon Q1 2024 CAB. Medical Director review 4/2024. Added related policies section. Updated policy guidelines and references. Edit for clarity: removed reference to TRUS guided biopsy and digital rectal exam (DRE) from coverage criteria #5 in “when covered” section, as these are outside of Avalon’s scope. (lpr)