Accurate Use of Prostate-Specific Antigen in Determining Risk of Prostate Cancer

Article Outline

• Abstract
• Development of PSA
• No Lower Limit
• Factors Affecting PSA Values
  • Age and Race/Ethnicity
  • Medications
  • Infectious and Inflammatory Processes
  • Hyperplastic State
  • Body Mass Index
  • Laboratory Variations
• Risk Factors for Prostate Cancer
  • Established Factors
  • Environmental Factors
  • Medications/Vitamins/Supplements
  • Diet
• Screening for Prostate Cancer
• Monitoring PSA Levels
• Implications for Practice
• Acknowledgments
• References
• Copyright

Abstract 

Measuring the level of prostate-specific antigen (PSA) in serum is used as a screening tool for prostate cancer. As more research results on improving the specificity and sensitivity of PSA testing become available, primary care providers will be provided with other methods to indicate when a urology referral is needed. The belief that the normal range is 0 to 4 ng/mL has not been supported by research. Multiple factors such as age, medication, and inflammatory processes can affect PSA level. Risk factors increase the patient's probability of developing prostate cancer. With no standard screening recommendations for prostate cancer, the provider has a greater responsibility to interpret results properly. Implications for practice are discussed.

Keywords:  Prostate , prostate cancer , PSA , screening

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Prostate-specific antigen (PSA) is a protein expressed by the prostate in both benign and neoplastic states.¹ Measuring the level of prostate-specific antigen (PSA) in serum is used as a screening tool for prostate cancer, and levels are often checked on men over 50 years old as part of blood work obtained during an annual physical examination. A persistent misconception is that the normal serum PSA level lies in the 0 to 4 ng/mL range. This range was originally based on older data that has not been shown to relate to the true risk of cancer. In actuality, there is not a normal range for PSA level. Recent research has shown that there is no PSA level that implies a 0% chance of prostate cancer.²

The ability to predict a man's risk of prostate cancer based on PSA level depends on multiple factors, including but not limited to: age, race, family history, result of digital rectal exam (DRE), prostate size, current medication, and result of a previous biopsy (if performed).³ Understanding the current interpretation of PSA levels allows providers to better care for clients by providing a referral to a urologist at the appropriate time. For example, a PSA level of 3.2 ng/mL in a 78-year-old male with an enlarged prostate may be acceptable—but this same level in a 50 year old whose father died of prostate cancer could be very significant.

This article will describe the history of PSA, the interpretation of PSA value, the factors that influence its result, and the value PSA carries in determining the risk of developing prostate cancer. Follow-up of varying PSA values over time and how to determine when a rise in the level becomes significant will also be discussed.

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Development of PSA 

We know that PSA is a protein produced by the epithelium of the prostate and periurethral glands. It is secreted into the semen via prostatic ducts and aids in liquefying the ejaculate.¹, ⁴

In the 1960s, scientists worked in the field of immunology to discover antigens specific to various human organs. While research was being conducted to find an antigen in the semen related to fertility, there was also interest in finding a biological marker in semen that could be used in forensics to assist in cases of rape.⁵ The human prostate antigen was discovered in the late 1960s, but not as it is known today.

Throughout the 1970s, researchers continued to explore, purify, and name the antigen. Late in that decade, several scientists claimed to have discovered the antigen we use at present. In 1984, a patent was granted for the discovery and identification of PSA.¹, ⁵

In 1987, Stamey et al performed one of the first large studies to determine if PSA was an adequate tumor marker.⁵ They found that as the pathologically assigned grade of the prostate cancer increased, so did the level of PSA that was obtained prior to biopsy and/or surgery. They also discovered that PSA became undetectable after prostatectomy. This suggested that PSA was a better tumor marker than the then currently employed prostatic acid phosphatase (PAP) analysis. But because both PSA and PAP were still found to be elevated in benign disease, neither was considered to be specific to prostate cancer.⁵

The United States Food and Drug Administration (FDA) initially approved the PSA test in 1986 for use in following up on patients already diagnosed with prostate cancer. In 1994, it was approved as a screening tool.¹, ⁶ In 1998, the Free PSA test was approved to help determine the risk of prostate cancer in men with a PSA value that fell in the 4 to 10 ng/mL range.⁴

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No Lower Limit 

For years, the normal range of PSA level was regarded to be 0 to 4 ng/mL. It was assumed that there was a negligible risk of finding prostate cancer if the PSA level was lower than 4 ng/mL, and prostate biopsies were rarely recommended for a man whose PSA level was within this range.¹, ³

The Prostate Cancer Prevention Trial (PCPT) was a 7-year trial that enrolled 18,882 men and concluded in 2003. Its purpose was to determine if men who took finasteride had a decreased prevalence of prostate cancer as opposed to those who took a placebo. The study found, among many other things, that there is no PSA level that indicates a 0% chance of finding prostate cancer in a biopsy.² This statement was based on the 2950 men, 62 to 91 years old, whose PSA level never rose above 4 ng/mL during the study. Of these 2950 participants, 15.2% (n = 449) were found to have prostate cancer, and more than half of those were a high-grade cancer (Gleason score 7 or greater). In addition, 6.6% of men with a PSA level of 0.5 ng/mL or lower were diagnosed with prostate cancer.² Taking many factors into consideration, the researchers divided PSA values into 7 strata. A PSA level of 0.6 to 1.0 ng/mL gives a man a 10.1% risk of developing prostate cancer, while a level greater than 10.0 ng/mL yields a 58.2% risk of developing prostate cancer² (Table 1).

Table 1. Risk of Detecting Prostate Cancer on Prostate Biopsy²

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Factors Affecting PSA Values 

PSA level is organ specific; it is not prostate cancer-specific and it is not static. The amount of PSA that is detected in the blood on a day-to-day basis can come from normal prostate tissue, or tissue affected by cancerous or benign hyperplastic growth. The amount of PSA in the serum will vary over time for a specific individual, and various types of prostate tissue will emit varying degrees of PSA for different individuals.⁷, ⁸ This variability can be rapid or gradual. Sandhu reviewed several studies that have documented variations of PSA levels and DREs.⁷ The point was made that an isolated finding of elevated PSA level or an abnormal DRE should not be the sole piece of information used to subject a man to a prostate biopsy. Factors other than prostate cancer can influence PSA level and include age, race/ethnicity, medications, prostate gland inflammation, benign enlargement of the prostate gland, lab variability, and body mass index.⁷, ⁸, ⁹, ¹⁰, ¹¹, ¹², ¹³, ¹⁴, ¹⁵, ¹⁶, ¹⁷, ¹⁸ Each of these factors is discussed below.

Age and Race/Ethnicity 

It is widely accepted that as a man ages, his PSA level will naturally increase.⁹ This increase in value is attributed to the growth of the prostate with time. In 1997, Richardson and Oesterling reviewed multiple studies and determined age-specific reference ranges for serum PSA in men of different races.⁹ Men were grouped into 4 decades. Acceptable ranges were determined to be lower for Asians and African Americans than for Caucasians. Asians are known to have a smaller-size prostate, which would contribute to the lower PSA value, while African Americans have a higher prevalence of prostate cancer occurring at an earlier age, with a higher death rate⁹ (Table 2).

Table 2. Age-Specific Reference Ranges for PSA Levels⁹

Medications 

Finasteride is a 5 alpha-reductase inhibitor. It works in the prostate by blocking the conversion of testosterone to dihydrotestosterone. This blocking of dihydrotestosterone formation leads to decreases in prostate volume, which in turn leads to a lower level of PSA in the serum. In the PCPT, men who took finasteride had a 50% decrease in serum PSA level after 1 year of treatment. Therefore, if a patient was taking a 5 alpha-reductase inhibitor such as finasteride (Proscar) or dutasteride (Avodart) for even 1 year, his PSA level would need to be adjusted by multiplying the current value by 2.¹⁰ As the study continued, the decrease continued, but not at the same dramatic rate. By year 4 of the study, the authors determined that a man taking finasteride for the full 4 years should have his PSA level multiplied by 2.3 before comparing it with standard references ranges.¹⁰

Infectious and Inflammatory Processes 

PSA level elevation and fluctuation exists with prostatitis, and these changes vary depending on the category of the inflammatory process.⁷ The pathology report of prostate biopsies that are negative for prostate cancer will often be positive for prostatitis or inflammatory changes.¹¹

Prostatitis is classified into 4 categories. Prostatitis symptoms range from acute lower urinary tract symptoms and fever to chronic pelvic floor pain. When acute or chronic bacterial prostatitis is treated with appropriate antibiotic therapy, the symptoms resolve and PSA level returns to within an acceptable age-specific range. Non-bacterial or asymptomatic chronic prostatitis is more difficult to treat, and indiscriminate use of antibiotics for the purpose of lowering PSA level is not appropriate.⁷ For a primary care nurse practitioner (NP), this is a case for referral to a urologist for further evaluation to determine the significance of the reported PSA value.

Studies have also shown an increase in PSA level in men with signs and symptoms of urinary tract infection (UTI) and a positive bacterial culture. These studies demonstrated that most of these men had a median PSA level increase of 14.1 ng/mL during the acute phase of an infection, which remained elevated for some time, taking up to 6 months to return to baseline levels.¹², ¹³

Therefore, if a patient has symptoms of a UTI, such as dysuria, increased frequency of urination, or hematuria, determining his PSA level should be delayed for at least 3 to 6 months. Taking a careful history and other laboratory testing, such as a urine culture, would be prudent, along with treatment with antibiotics, as required.

Hyperplastic State 

Benign prostatic hyperplasia (BPH) is a benign growth of the centrally located tissue in the periurethral portion of the prostate. BPH becomes prevalent as men age,¹⁰ and the increased amount of this benign prostatic tissue will cause an increase in PSA value.¹, ⁵ Further laboratory tests used to help differentiate potentially benign versus malignant tissue will be discussed in another section of this paper.

Body Mass Index 

The concept that increased body mass index (BMI) may be associated with lower PSA level has been studied. Several large-scale studies have found an inverse relationship between BMI and PSA levels, reporting a 5% to 21% decrease in PSA value in men with BMI > 30 compared to men with normal BMI.¹⁴, ¹⁵, ¹⁶ This decrease in PSA level is primarily thought to be due to hemodilution. Plasma volume increases with increasing BMI, leading to a dilution of the existing PSA level.¹⁴, ¹⁶ A smaller-scale study did not find a statistically significant relationship between BMI and PSA level.¹⁷

The noted decrease in PSA in relation to increased BMI is not in a direct linear pattern; therefore, it would not be appropriate to make a simple statement to correlate the 2 values.¹⁶ There is no current recommendation by any major cancer screening organizations as to adjusting PSA level based on BMI.

Laboratory Variations 

A study of 2304 men comparing PSA levels using 2 different but common laboratory assays (Hybritec Access and Centaur) found that the Hybritec Access delivered consistently higher readings, 23% higher than with the Centaur system. This study showed that the type of assay used could potentially include or exclude patients from having prostate biopsies.¹⁸ This could be important when comparing a patient's PSA levels if blood was drawn at different laboratories, which could be using different techniques to analyze the specimen.

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Risk Factors for Prostate Cancer 

Established risk factors for prostate cancer include advancing age, African American race, and positive family history of prostate cancer.¹⁹, ²⁰, ²¹, ²² The literature is abundant with factors that may influence or change a man's risk for prostate cancer. Some of the more commonly discussed factors include environmental exposure; vitamins, supplements, and medications; and diet.

Established Factors 

A man's risk of prostate cancer notably increases at age 50. An average 45-year-old man has a 1 in 2500 chance of being diagnosed with prostate cancer. This risk increases to 1 in 476 at age 50 and 1 in 13 at age 70.²⁰ Men of African American race are diagnosed with prostate cancer more frequently and with a higher stage of the disease at the time of diagnosis. They are also more likely to die of the disease.⁹, ¹⁹ A positive family history of prostate cancer in a first-degree relative (eg, father, brother, or son) also increases the relative risk of being diagnosed with the disease. This risk increases as the age that the relative was diagnosed decreases. For example, if the father of a patient was diagnosed with prostate cancer at 70, the patient's risk is increased fourfold over the general population, but if his father was 50 at diagnosis, then his relative risk increases sevenfold.²¹

Environmental Factors 

Loeb and Schaeffer recently reviewed the literature regarding potential risk factors and prevention methods for prostate cancer.²² Environmental factors found to increase the risk for prostate cancer included Agent Orange and various chemicals used in the farming industry. Because of the many chemical exposures encountered by farmers, the precise causative agents are not identified, but it is known that men in this occupation have a higher risk of developing prostate cancer. A reduced risk for prostate cancer has been linked to higher lifetime exposure to sun in several large studies. This decreased risk is thought to be related to vitamin D levels in the body, obtained from sun exposure.²²

Medications/Vitamins/Supplements 

Finasteride was shown to reduce the risk of prostate cancer in some men in the PCPT; however, initially, researchers found an increase in the risk of higher grade tumors in those who did develop cancer.¹⁰, ²² Further analyses showed this to actually be an improvement in the detection of the cancer due to finasteride's effect on the prostate and not a true increase in disease.²³, ²⁴

Supplementation with selenium, a trace element, and vitamin E, an antioxidant, were thought to reduce prostate cancer risk, but a recent, large, randomized study did not show a benefit from either supplement to reduce this risk.²² There is contradicting evidence regarding other dietary supplements and herbal products. While moderate use of products such as a multivitamin is beneficial, megadoses have been found to increase the risk of aggressive prostate cancer. Herbal supplements are not regulated by the FDA; therefore, safety and consistency of these products cannot be assured and the effect of these products on prostate cancer risk is not known.²²

Diet 

Loeb and Schaeffer also reviewed studies regarding dietary habits. Increased consumption of lycopene, predominantly from cooked tomato products, has been associated with a 10% to 20% reduction in prostate cancer risk. Some data have suggested that consuming greater than 5 servings per week of cruciferous vegetables may lower the risk of developing prostate cancer, but no specific recommendations regarding level of consumption and effect on prostate cancer risk have been established. An inverse relationship between consumption of fish and prostate cancer risk has been demonstrated. This is thought to be linked to protective factors of omega-3 fatty acids. There are no statistically significant data that link increased consumption of fats, red meat, and dairy to increased risk of prostate cancer.²²

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Screening for Prostate Cancer 

Prostate cancer screening is currently performed with a DRE and a serum PSA level. The posterior portion of the prostate is examined for areas of firmness or asymmetry. Both of these tests, PSA and DRE, are nonspecific to prostate cancer. They cannot determine if cancer exists; only if further testing may be warranted. Abnormalities in PSA levels or DRE are possible indications for prostate biopsy, and any abnormalities should be confirmed with either repeat testing or referral to a urologist. Prostate cancer is diagnosed by examining pathology samples obtained via transrectal ultrasound and biopsy of the prostate.¹, ⁴

There are no standard recommendations for prostate cancer screening. The United States Preventive Services Task Force concluded that current evidence is insufficient to recommend screening men younger than 75 years old, and recommends against screening for those 75 and older.²⁵ However, in the author's experience, there has been relatively little acceptance of this cutoff in the urology community.

The American Urological Association (AUA) has released its Prostate-Specific Antigen Best Practice Statement: 2009 Update. It recommends that discussion regarding prostate cancer screening be individualized for each patient and that the discussion include risks and benefits of testing and the consequences of the test results. The AUA discourages screening in men with less than a 10-year life expectancy. They do recommend a baseline PSA level be obtained at age 40 to identify men at high risk. A higher risk of prostate cancer is found in men in their 40s if the PSA level is above the accepted median range of 0.6 to 0.7 ng/mL. Future screening intervals can then be based on this baseline PSA level and other risk factors.²⁶

The American Cancer Society recommends offering annual screening for men at 50 who have at least a 10-year life expectancy. Screening should start at 45 for African Americans and possibly at age 40 if multiple first-degree relatives have been diagnosed.²⁷ The National Cancer Institute does not offer a current recommendation because there is no standard screening test or schedule.¹⁹ The Centers for Disease Control and Prevention recommends that the patient discuss the issue with his provider and make a personal decision to be screened based on that information.²⁰

Thompson et al²³ developed a prostate cancer risk calculator using data obtained from the PCPT and using variables to estimate risk of prostate cancer. The calculator takes into account the following patient information: age, race, recent PSA level, any family history of prostate cancer, DRE result, and whether there has been a previous negative-result prostate biopsy. The PCPT risk calculator is available at the following link http://deb.uthscsa.edu/URORiskCalc/Pages/uroriskcalc.jsp.³, ²³ This calculator has not performed well in one clinical study, and research is ongoing to create a better version.²⁸

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Monitoring PSA Levels 

Serial PSA levels will change over time due to the various factors discussed earlier. There are several ways to follow a patient's PSA level. Researchers continue to further analyze the PSA test in hope of improving its use as a screening tool.⁸

PSA is a serine protease that exists in the blood in 2 different forms. PSA that is bound to one of several different types of protein is known as “complexed” PSA (cPSA), and is the most abundant form of PSA in the serum. PSA that is not bound to a protein is known as “free” PSA (fPSA).⁴ The value reported when a PSA test is ordered is a “total” PSA (tPSA). The tPSA is a combination of the fPSA and one form of the protein-bound antigens attached to antichymotrypsin. It does not include all of the bound PSA, although what is left is a negligible percentage.⁸

An fPSA level determination can be ordered as a laboratory test. The fPSA is more abundant in the serum of men who have a normal prostate or only benign growth than in men with prostate cancer.¹, ⁴ Malignant tissue causes a change in the PSA that produces a greater percentage of cPSA to be present in the serum of a man with prostate cancer.⁴ Free PSA is used to help make a determination as to whether the elevation in the serum PSA value is likely to be from a benign or malignant growth of the prostate. A landmark study in 1998 by Catalona et al reported that in men whose serum PSA level was between 4 and 10 ng/mL, an fPSA of greater than 25% only resulted in an 8% risk of prostate cancer. However, an fPSA of less than 10% demonstrated a 56% risk of prostate cancer.²⁹

PSA velocity (PSAV) is the rate of change in PSA level per year. The recommended minimum amount of time to monitor PSA values prior to determining the velocity is 18 months, in which at least 3 PSA readings have been obtained. Instead of choosing to biopsy the prostate of a man who has a specific value of PSA, it is recommended to utilize the rate of change of the PSA level to help guide that decision. Carter et al reported that men with a PSA level of 4 to 10 ng/mL who had a PSAV of 0.75 ng/mL were at a significant risk for prostate cancer.³⁰ Other studies suggest a lower velocity of 0.4 ng/mL if the patient is younger or has a baseline PSA level below 4 ng/mL.²⁶ Take, for an example, a patient who has an original PSA level of 1.0 ng/mL, 1 year later a level of 1.42 ng/mL, and at year 3, a level of 1.93 ng/mL. The PSAV is calculated by taking the change divided by time between the first 2 points, adding it to the change divided by time for the next 2 points, then dividing all by 2. Our example would be (0.42/1 year) + (0.51/1 year)/2 = 0.465 ng/mL/year. This would warrant a referral to a urologist even though the level 1.93 ng/mL is still within the old standard “normal range.”

PSA-doubling time (PSADT) is the amount of time required to double the PSA value. This is expressed in units of time such as months or years. This type of trending is useful in patients who have undergone curative intervention for prostate cancer and have shown recurrence of disease, and can help determine which patients may be candidates for additional treatment.³⁰

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Implications for Practice 

The following are suggestions that an advanced practice nurse (APN) should consider implementing into the care plan when managing males as they enter the 4th decade of life:

In summary, PSA level, while a valuable tumor marker, is not an absolute value for diagnosis of prostate cancer. New research is ongoing regarding the sensitivity and specificity of PSA testing in an effort to improve the clinical utility of the PSA level. While no number is a guarantee that cancer is not present, there are multiple pieces of information that can be utilized to help determine what level is of concern. Many factors need to be considered when determining if a given PSA level is acceptable for an individual patient.

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Acknowledgments 

The author wishes to thank both J. Stephen Jones, MD, FACS, chairman of the department of urology at the Cleveland Clinic Health System Glickman Urological Institute and professor of surgery (urology) at the Cleveland Clinic Lerner College of Medicine at CWRU, for his willingness to review this manuscript and offer content expertise; and Jackie Owens, PhD(c), RN, CNS, doctoral candidate at Kent State University, for her assistance in the manuscript development.

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References 

1. Loeb S , Han M , Catalona WJ . Prostate-specific antigen and prostate cancer screening . In:  Jones JS editors. Prostate biopsy: indications, techniques and complications . Totowa, NJ: Humana Press; 2008;p. 14–24
   • View In Article
2. Thompson IM , Pauler DK , Goodman PJ , et al.   Prevalence of prostate cancer among men with a prostate-specific antigen level greater than or equal to 4.0 ng per milliliter . N Engl J Med . 2004;350(22):2239
   • View In Article
   • CrossRef
3. Thompson IM , Ankerst DP . Prostate-specific antigen in the early detection of prostate cancer . CMAJ JAMC . 2007;176(13):1853–1858
   • View In Article
4. Nielsen ME , Partin AW . The role of complexed prostate-specific antigen in prostate cancer screening . In:  Jones JS editors. Prostate biopsy: indications, techniques, and complications . Totowa, NJ: Humana Press Inc; 2008;
   • View In Article
5. Rao AR , Motiwala HG , Karim OMA . The discovery of prostate-specific antigen . BJU Int . 2008;101(1):5–10
   • View In Article
   • CrossRef
6. Federal Food and Drug Administration  . FDA Approves Test for Prostate Cancer . Available at: http://www.scienceblog.com/community/older/archives/M/1/fda0245.htm Accessed October 25, 2009
   • View In Article
7. Sandhu JS . Management of elevated prostate-specific antigen in men with nonbacterial chronic prostatitis . Curr Urol Rep . 2009;10:302–306
   • View In Article
   • CrossRef
8. Canto EI , Slawin KM . Newly recognized forms of prostate-specific antigen and emerging molecular markers . In:  Jones JS editors. Prostate biopsy: indications, techniques, and complications . Totowa, NJ: Humana Press; 2008;p. 40–56
   • View In Article
9. Richardson TD , Oesterling JE . Age-specific reference ranges for serum prostate-specific antigen . Urol Clin North Am . 1997;24(2):339–351
   • View In Article
   • Full Text
   • Full-Text PDF (959 KB)
   • CrossRef
10. Etzioni RD , Howlander N , Sahw PA , et al.   Long-term effects of finasteride on prostate specific antigen levels: results from the prostate cancer prevention trial . J Urol . 2005;174:877–881
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (135 KB)
    • CrossRef
11. Potts J . Prospective identification of National Institutes of Health category IV prostatitis in men with elevated prostate specific antigen . J Urol . 2000;164(5):1550–1553
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (84 KB)
    • CrossRef
12. Ulleryd P , Zackrisson B , Aus G , Bergdahl S , Hugosson J , Sandberg T . Prostatic involvement in men with febrile urinary tract infection as measured by serum prostate-specific antigen and transrectal ultrasonography . BJU Int . 1999;84(4):470–474
    • View In Article
    • MEDLINE
    • CrossRef
13. Zackrisson B , Ulleryd P , Aus G , Lilja H , Sandberg T , Hugosson J . Evolution of free, complexed, and total serum prostate-specific antigen and their ratios during 1 year of follow-up of men with febrile urinary tract infection . Urology . 2003;62(6):287; 281
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (92 KB)
    • CrossRef
14. Bañez LL , Hamilton RJ , Partin AW , et al.   Obesity-related plasma hemodilution and PSA concentration among men with prostate cancer . JAMA . 2007;298(19):2275–2280
    • View In Article
    • CrossRef
15. Werny DM , Thompson T , Saraiya M , et al.   Obesity is negatively associated with prostate-specific antigen in U.S. men, 2001-2004 . Cancer Epidemiol Biomarkers Prev . 2007;16(1):70–76
    • View In Article
    • MEDLINE
    • CrossRef
16. Rundle A , Neugut AI . Obesity and screening PSA levels among men undergoing an annual physical exam . Prostate . 2008;68:373–380
    • View In Article
    • CrossRef
17. Hutterer G , Perrotte P , Gallina A , et al.   Body mass index does not predict prostate-specific antigen or percent free prostate-specific antigen in men undergoing prostate cancer screening . Eur J Cancer . 2007;43(7):1180–1187
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (584 KB)
    • CrossRef
18. Link RE , Shariate SF , Nguyen CV , et al.   Variation in prostate specific antigen results from 2 different assay platforms: clinical impact on 2,304 patients undergoing prostate cancer screening . Clin Urol . 2004;171(6, Part 1):2234–2238
    • View In Article
19. National Institutes of Health  , National Cancer Institute  . Prostate Cancer Screening . Available at: http://www.cancer.gov/cancertopics/pdq/screening/prostate/patient/ Accessed October 25, 2009.
    • View In Article
20. Center for Disease Control  . Prostate Cancer Screening; A Decision Guide . Available at: http://www.cdc.gov/cancer/Prostate/publications/decisionguide/ Accessed October 25, 2009.
    • View In Article
21. Presti JC , Kane CJ , Shinohara K , Carroll PR . Neoplasms of the Prostate Gland . In:  Tanagho EA ,  McAninch JW editor. Smith's general urology . 17th ed.. New York: McGraw Hill; 2008; (ch. 22).
    • View In Article
22. Loeb S , Schaeffer EM . Risk factors, prevention and early detection of prostate cancer . Prim Care . 2009;36(3):603–621
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (187 KB)
    • CrossRef
23. Brawley OW , Ankerst DP , Thompson IM . Screening for prostate cancer . CA Cancer J Clin . 2009;59:264–273
    • View In Article
    • CrossRef
24. Klotz L , Drachenberg D , Fradet Y , et al.   Gleason grading controversies: what the chemoprevention trials have taught us . CUAJ . 2009;3(3 Suppl 2):S115–S120
    • View In Article
25. U.S. Preventive Services Task Force  . Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement . Available at: http://www.ahrq.gov/clinic/uspstf08/prostate/prostaters.htm Accessed October 25, 2009.
    • View In Article
26. Prostate-Specific Antigen Best Practice Statement: 2009 Update. American Urological Association . Available at: http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines/main-reports/psa09.pdf 2009; Accessed October 25, 2009.
    • View In Article
27. American Cancer Society  . American Cancer Society Guidelines for the Early Detection of Cancer . Available at: http://www.cancer.org/docroot/PED/content/PED_2_3X_ACS_Cancer_Detection_Guidelines_36.asp?sitearea=PED Accessed October 25, 2009.
    • View In Article
28. Nguyen CT , Yu C , Moussa A , Kettan MW , Jones JS . Performance of prostate cancer prevention trial risk calculator in a contemporary cohort screened for prostate cancer and diagnosed by extended prostate biopsy . J Urol . 2010;183:529–533
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (294 KB)
    • CrossRef
29. Catalona WJ , Partin AW , Slawin KM , et al.   Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease . JAMA . 1998;279:1542–1547
    • View In Article
    • MEDLINE
    • CrossRef
30. Carter HB . The role of prostate specific antigen velocity in the diagnosis and management of prostate cancer . In:  Jones JS editors. Prostate biopsy: indications, techniques, and complications . Totowa, NJ: Humana Press; 2008;p. 57–66
    • View In Article