Prostate Cancer Screening


Introduction

Prostate cancer is the most frequently diagnosed cancer in 112 countries and the leading cause of cancer death in 48 countries.[1] It is the fifth leading cause of male cancer-related deaths worldwide, with more than 1.4 million newly diagnosed cases and 375,304 deaths reported annually.[2] 

According to the American Cancer Society, prostate cancer is the second leading cause of male cancer-related mortality in the United States (US), with 288,300 new cases and 34,700 deaths estimated in 2023.[3] In addition, data from the National Cancer Institute reveals that the average American man has a 13% risk of being diagnosed with prostate cancer over their lifetime (the incidence increasing with age) and a 2.5% overall risk (1 out of every 41) of dying from it. The Centers for Disease Control and Prevention (CDC) predicts that for every 100 American men, 13 will be diagnosed with prostate cancer, and between 2 and 3 will die from the disease.

The incidence of prostate cancer in Black men is 70% higher than in White males. The lifetime risk of dying from prostate cancer varies in different ethnic groups, with Black men living in the US having the highest risk at 4.2%. American Indians and Alaskan Natives have a reported prostate cancer incidence of less than half that of Black men, but their death rate is slightly less.

According to the National Cancer Institute, the median age of death due to prostate cancer is 80 years, with 75% of prostate cancer-specific mortalities occurring in those older than 75. The average age at the time of diagnosis is 66 years. The US states with the highest prostate cancer mortality rates are Montana, Mississippi, and Vermont.

Prostate cancer is the most frequently diagnosed cancer in men (excluding skin cancer), which understandably raises concerns about the need for prostate cancer screening. However, most prostate cancers are slow-growing and may never become clinically evident. Data suggests that most men die of other causes before their prostate cancer becomes advanced or clinically significant. Definitive treatment is expensive and carries significant morbidity, thus making routine screening somewhat controversial.[4]

Shared decision-making is strongly recommended before starting or discontinuing prostate cancer screening.[5][6][7] According to the 2016 American Urological Association (AUA) study on the Implementation of Shared Decision Making in Urology, it should include the following features:[6] 

  • Both the physician and patient should be involved in the decision-making process.
  • Information should be freely shared between the physician and the patient.
  • Consensus should be built through the free expression of preferences.
  • The physician and patient should agree on implementing the selected plan.

Issues of Concern

Prostate-Specific Antigen

Prostate-specific antigen (PSA) is a glycoprotein enzyme secreted by the prostatic secretory epithelium and seminal vesicles and is the most abundant protein in seminal plasma.[8] The function of PSA is to chemically shorten and break up large proteins found in the semen into smaller molecules over time. This results in decreased seminal viscosity, which facilitates sperm motility and ultimately improves fertility.[8]

A small amount of PSA normally diffuses into the bloodstream. In cases of trauma, prostatic disease, malignancy, or any condition that disrupts prostatic microarchitecture, PSA diffuses into the extracellular space at an elevated rate. The lymphatic system drains extracellular PSA, causing it to enter the bloodstream and raise the serum level.[8] The amount of PSA produced per malignant prostatic cell is less than that of normal or benign hyperplastic prostatic cells. Leakage of PSA from cancer cells increases, resulting in higher plasma levels.[8] PSA levels increase in malignant and benign prostatic conditions such as benign prostatic hyperplasia, prostatic inflammation or infection (prostatitis), and during perineal trauma, as well as during or after ejaculation and sexual activity.[8]

Elevated PSA levels have long been associated with prostatic malignancy and are the key initial element in screening, although high PSA titers are not specific to prostate cancer.[9] An elevated PSA level is a sensitive but nonspecific marker for malignancy, so most men with an elevated PSA level will not have prostate cancer. Conversely, a normal PSA value does not rule out prostate cancer. Screening based solely on PSA level has demonstrated fewer prostate cancer-specific deaths and a reduction in the incidence of metastatic disease in randomized trials.[10][11]

Confirmation of an elevated PSA level requires 2 separate abnormal serum PSA levels, obtained 8 weeks apart.[6][12][13] This is because 25% to 40% of men with an initial elevated serum PSA level will demonstrate normal levels on a subsequent recheck and can be spared the expense, discomfort, and inconvenience of unnecessary additional investigations.[13][14] Since a digital rectal exam (DRE) can transiently increase PSA levels, 3 days should pass after a DRE before drawing blood for PSA level testing.[15]

The Choosing Wisely American Urological Association (AUA) Initiative and current AUA guidelines for the early detection of prostate cancer do not recommend empiric antibiotics as the initial treatment for an elevated PSA.[6][16][17][18] However, several studies demonstrate the effectiveness of such empiric therapy in lowering PSA levels in patients with prostatitis, so many experts continue to utilize it selectively.[19][20][21][22][23] Given the controversy, it would seem reasonable to consider empiric antibiotic therapy, at least for patients with elevated PSA levels and signs or symptoms of prostatitis or a history of prostatitis, using a prostate-specific agent (sulfamethoxazole-trimethoprim, doxycycline, or a fluoroquinolone) for 4 to 8 weeks.

Despite its significant lack of specificity, PSA remains the single most widely utilized and recommended screening test for the early detection of prostate cancer.[6] The normal value of PSA is generally considered to be less than or equal to 4 ng/mL. However, serum PSA levels increase with age, and PSA levels rise faster in older men. Various age-specific ranges have been defined to reduce the detection of less advanced tumors in older men and increase the detection of significant but potentially curable tumors in the younger age group.[6][24][25][26] These age-specific normal value PSA ranges are as follows:

  • 40 to 49 years: 0 to 2.5 ng/mL
  • 50 to 59 years: 0 to 3.5 ng/mL
  • 60 to 69 years: 0 to 4.5 ng/mL 
  • 70 to 79 years: 0 to 6.5 ng/mL

Apart from age, studies have shown that certain medications also lower the value of PSA levels. Among these are statins, thiazide diuretics, NSAIDs, and especially 5-alpha-reductase inhibitors.

Typically, after 6 months of use, 5-alpha-reductase inhibitors will lower PSA levels by 50%, with the long-term effect being the stabilization or decline in PSA values.[27][28][29][30] Any rise in PSA levels while a patient uses these medications should raise the suspicion of possible prostate cancer.[30][31][32] For patients on 5-alpha-reductase inhibitors for 6 months or longer, the values should be doubled to compensate for the expected PSA-lowering effect of the medication when making comparisons.[33] Patients should be screened for prostate cancer before starting these medications. See the StatPearls companion topic 5-Alpha-Reductase Inhibitors.[33]

Lower-risk patients include individuals not of African descent, who do not have a family history of prostate cancer, who are aged 40 years with an initial PSA <1 ng/mL, and those with a PSA less than  2 ng/mL at age 60 years. While many guidelines still recommend yearly screenings, the AUA guidelines now advise a screening interval of every 2 to 4 years in low-risk individuals between ages 50 and 69.[6][10][34][35][36][37]

With less frequent testing in low-risk individuals, the number of patients needed to screen to prevent 1 death from prostate cancer at 15 years was 23, and the number needed to diagnose was only 6.3, which indicates a significant overall benefit to screening.[36]

Once started, screenings should generally continue until the patient decides to discontinue screening after a shared decision-making discussion, his reasonable life expectancy is less than 10 years, or the patient is older than 75 with a PSA of less than 3 ng/mL.[6][38] At least one long-term study suggests that stopping screening at age 70 may be too soon and that screenings should be continued or offered until age 75.[37] Shared decision-making is critically important in the aged 70 to 80 years group in deciding when to stop PSA screening, and patients in good health who wish to continue screenings should be accommodated.[6][39][40][41]

High-risk Individuals 

High-risk individuals include patients of African descent, those with a close family member with prostate cancer (especially if diagnosed before age 60, had metastatic disease, or died from it), individuals with a strong family history of malignancies (Lynch syndrome, breast, and ovarian cancers), men with known associated germline mutations (BRCA1, BRCA2, ATM, CHEK2, etc), and Vietnam war veterans with known Agent Orange exposure.[6][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] All these conditions have been associated with an increased risk for prostate cancer. For such high-risk individuals, screenings should start earlier, as early as age 40 years, and be conducted annually until or unless a significant cancer is discovered, the patient changes his mind about screening, or he develops medical comorbidities that limit his reasonable life expectancy to less than 10 years.

Digital Rectal Examinations

Digital rectal examinations (DREs) have long been used to aid prostate cancer screenings, but the DRE has low sensitivity and specificity when used alone. A DRE evaluates the prostate gland's consistency, size, symmetry, tenderness, and texture. An abnormal DRE would likely reveal nodularity, induration, tissue consistency change, or prostatic asymmetry, possibly suggesting a malignancy. It may also detect unrelated pathologies, such as hemorrhoids and rectal cancer. A DRE alone, particularly in a primary care setting, has a sensitivity and specificity for prostate cancer of less than 60%, which could be attributed to clinician inexperience and insufficient training. DREs alone are not recommended to screen for prostate cancer without PSA testing.[57] The DRE has shown some benefit in evaluating patients with elevated PSA levels and is therefore only recommended in men with a PSA level of 2 ng/mL or higher.[6]

Free and Total PSA 

Free and Total PSA can help stratify the relative risk of prostate cancer. If the total PSA is <10 ng/mL, a low free PSA percentage can suggest a higher cancer risk. The higher the percentage of free PSA in the serum, the lower the estimated cancer risk. This varies by age, but in general, the cancer risk will be over 50% if the free PSA percentage is <10%, while the risk of malignancy will be <10% if the free PSA percentage is >25%.[58][59]

Since a second confirmatory PSA level must be completed for patients with an initial elevated PSA level, it is suggested that this second laboratory study take advantage of the opportunity to perform a free and total PSA assay if not previously done. 

Disadvantages of Prostate-Specific Antigen Screenings

Overall survival is unchanged for at least the first 10 years after the initial diagnosis of prostate cancer for the vast majority of patients.[60][61] Between 70% to 75% of patients who undergo biopsies show no sign of cancer. As most biopsies are negative and only tend to cause increased patient anxiety, discomfort, higher medical costs, and possible complications (prostatitis, urinary tract infections, and bleeding), they can be considered unnecessary.

Patients who have low-risk disease may ultimately be overtreated. Screenings tend to find lower-risk, slower-growing cancers and miss the more aggressive, faster-growing malignancies, which are more dangerous. A finding of low-risk, low-grade prostate cancer will not affect survival, can cause considerable patient anxiety, and can easily lead to overtreatment with side effects and complications that could have been avoided.

Those countries that do not perform extensive PSA testing but generally have sound healthcare systems have noted similar reductions in prostate cancer-specific death rates compared to the US, which conducts extensive PSA screenings. However, several large-scale studies have shown little or no survival benefit to screenings.

Most patients with elevated PSA levels do not have cancer. Patients with prostatitis or benign prostatic hyperplasia tend to have elevated PSA levels, and their prostate cancer evaluations will ultimately be unnecessary.

In one study, PSA testing prevented 1 prostate cancer-related mortality for every 1,000 men screened over 10 years.[62] Another study demonstrated that PSA screenings might help prevent 3 metastatic prostate cancer cases for every 1,000 men tested.[1]

Several recent screening trials showed no significant change in overall mortality resulting from PSA testing.[63] For example, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening trial and the initial results of the large European Randomized Study of Screening for Prostate Cancer (ERSPC) study showed little or no benefit from large-scale prostate cancer screening. They formed the basis for the 2012 USPSTF recommendations against routine PSA testing.[64][65]

The large-scale European PIVOT trial (Prostate Cancer Intervention Versus Observation Trial) and several others showed little to no benefit from early definitive prostate cancer treatment.[66][67]

Advantages of PSA Screenings

Prostate cancer remains the second leading cause of cancer death in men, and worldwide incidence is increasing. Stopping PSA screenings will not reduce prostate cancer mortality or morbidity, and it remains a sensitive and inexpensive test. However, it also remains a nonspecific test for prostate cancer.

The 2012 USPSTF report recommended the elimination of routine PSA screenings.[68] This caused a significant drop in overall prostate cancer diagnosis but increased the incidence of higher-stage disease, especially in higher-risk populations.[69] The previous steady decline in prostate cancer-specific mortality rate flattened and rose after the 2012 USPSTF report.[70] This held across all age groups, races, and ethnicities in all regions of the country.[70]

The USPSTF report disregarded many positive aspects of prostate cancer screening, overly exaggerated many negatives, ignored many studies favorable to PSA testing, overlooked many statistical errors, brushed aside many procedural flaws, and was badly flawed overall, which resulted in the recommendation against PSA testing being retracted just 6 years later.[1][71] This was also prompted by the growing acceptance of active surveillance in low-risk prostate cancers and a reexamination of the PLCO and ERSPC data.[72]

The Surveillance, Epidemiology, and End Results (SEER) program data showed a significant overall increase in metastatic prostate cancer detection starting after the USPSTF recommendations were released in 2012.[73] The long-term results from the ERSPC study showed that PSA screening significantly reduced prostate cancer mortality.[10]

Most studies that suggested a lack of any survival benefit to PSA screenings have been shown to have significant statistical mistakes, included computational errors, used contaminated data, utilized poor methodology, or demonstrated a clear selection bias.[71] However, numerous correctly done studies comparing PSA-screened with unscreened populations followed for at least 10 years consistently show a clear 50% cancer-specific survival advantage in the screened groups.[71]

Since PSA testing became widely available in the United States (US) in 1992, prostate cancer-specific mortality has decreased by over 50%.[74] Other countries that do not extensively use PSA testing reported a significantly smaller decrease in prostate cancer-specific mortality over the same period, typically at half the rate of the US. For example, PSA testing is minimal in Sweden, which has a modern health system but enjoys a prostate cancer-specific death rate more than double that of the US.[75]

Long-term Scandinavian studies prove the value of definitive curative therapy for prostate cancer, although this may not be appreciated for 10 years or more.[76] If all PSA screenings were suspended in the US, the National Institutes of Health has estimated that after 10 years, an additional 25,000 to 30,000 men would die annually from prostate cancer that would otherwise have been cured.

Currently, only 9% of all new prostate cancer cases involve advanced disease compared to 32% before the introduction of PSA testing, a 72% reduction. In addition, there has been an 80% reduction, from 21% to 4%, in the rate of initial detection of metastatic prostate cancer since the introduction of PSA testing. There is no other reasonable explanation for this benefit other than PSA screening.

The optimal use of risk stratification bioassays in lower-risk patients and MRI scans in higher-risk individuals can eliminate unnecessary biopsies while improving the retrieval rate of clinically significant diseases. Overtreatment of prostate cancer has been significantly reduced due to the advent of active surveillance, MRI testing, MRI-transrectal ultrasound fusion biopsies, and now genomic testing. Many new diagnostic aids and treatment options now have lower costs, minimal side effects, and improved outcomes. Without reasonable PSA screenings, these new minimally invasive therapies are useless as the disease presentation would otherwise be too far advanced.

Professional Society Guidelines and Expert Recommendations for Prostate Cancer Screening

There are many different recommendations regarding when and whom to screen for prostate cancer; these measures all incorporate serum PSA testing as the primary initial screening tool. The primary focus of all of these recommendations should be shared decision-making to help the patient make an informed decision regarding whether or not to undergo screening after a careful review of the benefits and potential risks, as well as to take into consideration their values, age, general health, comorbidities, and preferences in this process.

The American Academy of Family Physicians

  • Routine PSA screening is not recommended.
  • Men aged 55 to 69 years considering periodic PSA testing should engage in collaborative decision-making regarding the risks and benefits of screening.
  • Screening for prostate cancer in men aged greater than 70 years is not recommended.[77]

The American Cancer Society

  • Asymptomatic men with less than a 10-year life expectancy must receive information about risks, benefits, and uncertainties associated with prostate cancer screening before making an informed decision. 
  • Moderate-risk men should receive this information beginning at the age of 50 years. 
  • Men at high risk (eg, Black men or those with a family history of prostate cancer, particularly a first-degree relative diagnosed before age 65) should receive this information before the age of 50 years.[78]

American Urological Association

  • Recommends against PSA screening for men younger than 40 years of age.
  • PSA testing for high-risk patients aged 40 to 45 years may be offered.
  • Screening for men at low to average risk may begin at ages 45 to rs.
  • For men of low to average risk, ages 55 to 69 years, screening may be offered every 2 to 4 years.
  • The rescreening interval may be lengthened or even discontinued for men 75 years or older with a PSA <3 ng/mL.
  • Patients with less than a 10-year reasonable life expectancy are not likely to benefit from screening.
  • Shared decision-making regarding screening is critical in men between 70 and 80 years who are otherwise in good health.
  • The typical man in the US with average health reaches his statistical 10-year life expectancy at age 77.[6]

The Canadian Task Force on Preventive Health Car

  • Recommends against PSA-based screening for prostate cancer.[79]

The European Association of Urology

  • Patients considering PSA testing should have a life expectancy of at least 10 to 15 years and be counseled on the potential risks and benefits.
  • Patients at low risk can be safely screened every 2 years. Low risk is defined as having an adverse family history, a PSA <1 ng/mL at 40 years, or <2 ng/mL at age 60.
  • Patients at average risk should consider starting screening at age 50.
  • Men at higher risk (African descent, family history of prostate cancer) should start screening at age 45.
  • Men with known BRCA2 mutations should start screening starting at age 40.[80]

The United States Preventive Services Task Force [1]

  • In men aged 55 to 69 years, the US Preventive Services Task Force (USPSTF) states that the decision to undergo periodic PSA screening should be an individual one after a thorough upfront discussion between the physician and patient regarding the risks, benefits, and limitations of such screening incorporating the patient's values and preferences.
  • Recommends against routine PSA screening in men aged 70 and older. This is because the potential survival benefits from treatment are statistically minimal, and they do not outweigh the significant adverse effects and health issues that the average man in this age group may experience due to treatment. 

Which Guideline to Follow

With no consensus guideline, each healthcare provider must decide which protocol to follow.[60] Remember that guidelines are suggestions, not rules or laws. Factors and issues to be considered include:

  • It is recommended and good practice to have a meaningful, frank, and well-documented discussion of the pros and cons of PSA screenings with every male patient within the recommended age group of 45 to 75 years.
  • Performing screenings in patients unlikely to accept therapy, even if a significant treatable cancer is found, is unreasonable.
  • Performing screenings in men older than 75 years or with a reasonable life expectancy of fewer than 10 years based on age or comorbidities is unreasonable as they are not likely to demonstrate any benefit.
  • For patients who request a PSA test after a comprehensive review of the risks and benefits, it is usually preferable to perform the testing even if the indications are questionable or outside of guidelines.
  • It typically takes a small, localized, moderately aggressive (Gleason score of 4), untreated prostate cancer at least 10 years to become symptomatic, possibly metastatic, and potentially clinically harmful to the patient. 
  • According to the Social Security Administration, the typical 70-year-old American man with reasonable health enjoys an average life expectancy of 14 years and 3 months. 
  • At age 75, the average male life expectancy is about 11 years. The average male life expectancy in the US does not reach 10 years until age 77 years.
  • Prostate cancer is relatively rare in individuals younger than 50 years, and it only accounts for about 1% to 3% of all such malignancies; however, it tends to be quite aggressive when it occurs in this younger age group.[81]

Careful consideration of these various issues, topics, and published guidelines suggests that it may be reasonable to recommend PSA screening for informed, selected individuals with general good health between the ages of 45 and 75. In addition, it is appropriate to encourage even earlier screenings (at ages 40-45 years) in high-risk patients. High-risk individuals would include, but not be limited to, men of African descent or ethnicity, those with a family history of prostate cancer, men with a family history of multiple cancers or Lynch syndrome, veterans with Agent Orange exposure, and patients with a known high-risk genomic mutation such as BRCA1 or BRCA2. These issues are best addressed and most closely aligned with the latest guidelines from the AUA.[6]

The Role of Other Adjunctive Screening Tests

PSA density

PSA density is the calculated value of the total PSA in ng/mL divided by the prostate volume in mL. The volume of the prostate can be determined objectively by MRI or ultrasound. The formula for calculating prostatic volume is prostate width × length × height × 0.52. A value of greater than 0.15 is considered suspicious for prostatic cancer.[82][83][84][85] However, PSA velocity (the change in PSA values over time) is not considered a good or reliable indicator of possible malignancy.[6][86][87][88][89] 

Transrectal ultrasound

Transrectal ultrasound can be used to measure the volume of the prostate and is helpful when performing prostatic biopsies. Unfortunately, it cannot reliably differentiate malignant prostatic tissue from benign and, therefore, cannot be used alone for diagnosis.[60]

MRI of the prostate can reliably locate many high-risk or suspicious areas in the prostate for targeted (fusion) biopsies. Still, they may also miss 25% to 35% of the clinically significant malignancies.[90] An MRI is expensive and time-consuming, so it is not considered a screening test. A positive MRI does not guarantee cancer; a negative study cannot rule it out. While helpful, a prostatic MRI is not definitive or absolute and should not be used to indicate whether or not a biopsy should be done.[91][92] It is most useful once a decision has been made to perform a biopsy, during the initial screening of high-risk patients, or if a repeat biopsy is needed and an MRI has not been performed.[91] It may optionally be used in low and moderate-risk patients with elevated PSA levels.[91]

Prostatic MRIs

Prostatic MRIs may be useful after the decision has been made to perform a biopsy by highlighting suspicious nodules inside the gland for an MRI-guided fusion biopsy, examining the seminal vesicles and prostatic capsule for possible involvement or malignant extension, and visualizing surrounding structures for possible metastases or other abnormalities.[60] MRI-guided fusion biopsies should be performed for Prostate Imaging Reporting and Data System (PI-RADS) category 3 and higher lesions when possible.[91] At least 2 samples should be taken from each suspicious lesion, but obtaining more than 3 cores is discouraged.[91][93]

Bioassay Risk Stratification Testing 

Bioassay risk stratification testing may also help determine the need for a prostatic biopsy in low-risk patients with moderately elevated PSA levels (<10 ng/mL). These blood or urine tests (My Prostate Score, the Prostate Health Index, 4K score, prostate cancer antigen 3, IsoPSA, SelectMDx, and EPI Exosome testing) are primarily designed to identify patients with a low risk of significant cancer, so they can safely avoid biopsies.[6][91][94][95][96][97][98][99][100][101] They have an excellent negative predictive value of >90%, which means if the test is negative, there is high confidence that the patient has no clinically significant prostate cancer.[101] They are instrumental in helping determine the need for performing a biopsy or even an MRI in low- to medium-risk patients and in various borderline situations.[91][101][102] They are also useful in patients undergoing active surveillance, although their exact role remains unclear.[101]

Bioassay risk stratification tests are designed to have a negative predictive value of 90% or more. If the test is negative, a biopsy can be safely avoided in low-risk individuals.[6][101] A risk stratification bioassay can also help make the final determination in selected cases of PI-RADS 3 (borderline) findings on a prostatic MRI or a higher-risk patient with negative imaging who wishes to avoid a biopsy.[101][103] Shared decision-making discussions with the patient are critically important in such situations. 

Bioassay risk stratification testing should only be performed when the results will be used to help make clinical management decisions, generally to stop further investigations and return to routine surveillance if the test is negative.[6][60][91][101] Bioassay testing is unnecessary if a biopsy will be performed regardless of the outcome.[6][60][91][101]

After a negative biopsy, bioassay risk stratification testing or tissue-based biomarkers may be used if the results change follow-up management.[91] They are not recommended in low-risk patients with negative biopsy results.[91]

Bioassay risk stratification testing should be performed first in evaluating elevated PSA levels in lower-risk patients. At the same time, MRI scans are typically preferred as the initial study in higher-risk individuals.[60][104] The optimal use of bioassay risk stratification testing could reduce the number of prostate biopsies performed by about 35% while delaying the detection of clinically significant cancers by only 5% to 10%.[6][60][94][101]

When to Perform a Biopsy

After shared decision-making, a biopsy is usually indicated or justified when the patient has a reasonable life expectancy of at least 10 years and 2 abnormal PSA values. Any of the following, in addition to elevated PSA levels, would further increase the risk of cancer:[60][91]

  • A PSA increase >0.75 ng/mL over 1 year
  • A PSA increase of >25% over 1 year
  • The PSA is >10 ng/mL on 2 separate laboratory evaluations
  • A palpable abnormality on DRE that is suggestive of cancer
  • A known high-risk germline mutation such as BRCA2
  • A family history of prostate cancer, especially at a younger age, metastatic disease, or resulting in mortality
  • A family history of multiple cancers, especially starting at a younger age
  • A family history of Lynch syndrome
  • Patients of African descent or ethnicity

For some older men or those with other comorbidities with a raised PSA level, not pursuing a biopsy may be appropriate when the patient preferences align with a less aggressive approach to further management. A patient who would not accept any treatment even if significant cancer were found is not a suitable candidate for PSA testing or prostate cancer screening, even if they meet the other criteria. 

Patients with PSA levels >50 ng/mL with no signs of infection or history of recent urological instrumentation may omit a biopsy where treatment is urgent or if a biopsy poses a significant risk.[91] High-grade prostate cancer will be found in up to 98.5% of such cases.[105] Shared decision-making should be utilized with patients in these situations.[91] 

Although the widespread availability of PSA screening in 1992 did lead to an increase in the number of prostate cancers detected and a 44% reduction in mortality as suggested by simulation models, calculations indicate that screening does not improve quality-adjusted life years, even if there is an overall reduction in mortality.[106] For prostate cancer screening, there is a high potential for overdiagnosis. Overdiagnosis means screening for a condition that would not have been clinically evident in the patient's lifetime. The prevalence of prostate cancer detection during autopsies of men who died due to other causes is higher than the lifetime incidence of prostate cancer in the population.

It is estimated that 23% to 50% of prostate cancers are overdiagnosed.[107][108][109] Many prostate malignancies detected by screening are likely early-stage, low-grade malignancies. This initial screening can lead to further confirmatory testing and potentially unnecessary treatment. Solely diagnosing cancer, no matter how harmless, can cause patients significant adverse effects from anxiety and cancer-related psychological effects.

It has been argued that overdiagnosis is not a real problem if patients are appropriately counseled, and precautions are taken to avoid treating patients who would not benefit. Approximately 25% of patients will initially have a low-stage, low-grade prostatic malignancy that will progress to a higher stage or grade for which treatment is indicated. Such patients would not have been identified without initial screening and appropriate follow-up examinations.

The lack of consensus on guidelines for prostate cancer screening has led to multiple recommendations from different sources and professional societies, causing greater confusion on the issue. The most comprehensive, reasonable, and reliable guidelines are from the AUA.[6]

High-Grade Prostatic Intraepithelial Neoplasia, Atypical Small Acinar Proliferation, and Atypical Intraductal Proliferation

High-grade prostatic intraepithelial neoplasia is considered a high-risk finding on prostatic biopsy. Previous recommendations included mandatory repeat prostatic biopsies, but newer data suggests about 25% of such patients normalize their pathology over time.[110] Current recommendations are to consider them high-risk and follow them with DREs, serial PSA levels, and MRIs.[91][110] Repeat biopsies should be based on these findings and shared decision-making, not performed routinely or automatically.[91]

Atypical small acinar proliferation and atypical intraductal proliferation are associated with a substantially higher risk of prostate cancer, especially atypical small acinar proliferation.[91][111][112][113][114][115] In these cases, current recommendations suggest that additional testing (serial PSA levels, MRIs, risk-stratification bioassays, tissue-based biomarkers, and early repeat prostate biopsies) should be performed utilizing shared decision-making based on the patient's overall risk assessment, expectations, comorbidities, age, and personal preferences after a thorough review of the risks and benefits.[91]

Clinical Significance

Screening aims to reduce prostate cancer-specific morbidity and mortality by early detection of localized, high-risk cancers that can be successfully treated. Screening has been shown to reduce the chance of dying from prostate cancer in some men.[1]

Studies from randomized controlled trials have suggested that in men aged 55 to 69, PSA-based screening can prevent 1 prostate cancer-related death over 10 years and 3 metastatic prostate cancer cases per 1000 men screened.[1][62] Current results from some screening trials show no reduction in all-cause mortality.[63]

Other studies have refuted these findings. They show persistent reductions of 50% in prostate cancer-specific mortality from PSA-screened groups followed for 10 years or more compared to identical but unscreened populations.[60][116] A 15-year Swedish study comparing a PSA-screened population from the Göteborg trial with a similar unscreened group from the Malmö Preventive Project showed substantial benefit from PSA screenings, with 1 prostate cancer death avoided for every 23 patients screened.[36]

While the controversy continues, virtually all medical professional societies and organizations recommend prostate cancer screening or discussing screenings with men of suitable age and life expectancy. They also recommend shared decision-making with patients at each critical management point in the screening process, including when to start and discontinue PSA testing.

Stopping PSA screening is generally recommended for most patients between ages 70 and 80 but should be highly individualized based on age, general health, medical comorbidities, patient preferences, and shared decision-making discussions.[6][41]

Other Issues

One of the most significant concerns regarding prostate cancer screening is overdiagnosis. Overtreatment of low-grade prostate cancer can decrease the quality of life by adding treatment-associated side effects and psychological harm.[117] Such outcomes are particularly problematic when the malignancy would probably not have caused any clinical harm to the patient. This outcome can be overcome by utilizing bioassays to diminish unnecessary biopsies in low-risk individuals, adopting active surveillance (monitoring) for low-grade prostate cancers, and increasing the PSA testing intervals in low-risk patients.

Active surveillance is one of the management strategies in which a select group of low-grade cancer patients is under close observation and monitoring. They are followed throughout their disease course, with intervention occurring only if their cancer progresses or advances.[118] This approach leads to avoiding treatment-associated adverse effects in most such patients. About 30% of patients on active surveillance experience disease progression and require further treatment; the remainder can safely avoid definitive therapy and its associated complications.[119] This monitoring is only achievable and successful by patient-centered care coordination amongst the interdisciplinary team members and their cumulative efforts.[120]

Enhancing Healthcare Team Outcomes

To enhance prostate cancer screening outcomes, an interprofessional team of specialty-trained nurses, general practitioners, advanced practice providers, urologists, and oncologists must coordinate to deal with challenges regarding prostate cancer screening guidelines and outcomes. Some of these challenges include:

  • Individualizing the evaluation of a single, elevated PSA level
  • Recognizing that a second, separate PSA test is required to confirm a diagnosis of an elevated PSA
  • Resolving the controversy regarding empiric antibiotic therapy
  • Using other tests to complement PSA levels in improving diagnostic and prognostic accuracy
  • Using prostatic MRIs and risk stratification bioassays appropriately
  • Implementing new prostate screening guidelines when they become available
  • Using the new genomic and risk-stratification bioassay tests at crucial decision points of the evaluation where the results will be clinically valuable
  • Resolving conflicting recommendation guidelines
  • Utilizing shared decision-making for the initiation of PSA screening and its discontinuance

Decision aids for patients can be found on the websites of the American Cancer Society, the American Society of Clinical Oncology, and the CDC.

Enhancing outcomes is achievable by being familiar with the new recommendations and information regarding screening for prostate cancer, as well as effective collaboration and communication among the interdisciplinary team members. The interprofessional team can individualize the appropriate evaluation of each patient through shared communication and care coordination. Specialty care nurses must work with the team to coordinate care and aid in educating patients.

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Manisha A. Jain

Author

Stephen W. Leslie

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Amit Sapra

Updated:

10/26/2023 11:51:52 PM

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