Prostate specific antigen

  • [Contemporary markers and histological features of prostate cancer].

    Increasing prostate cancer incidence rates highlight the importance of more timely diagnosis with the ultimate aim of reducing cancer-specific mortality, while maintaining patients quality of life. Until recently, digital rectal examination and prostate-specific antigen have been used for diagnosis of prostate cancer.

    Published March 7, 2017
  • [Prognostic significance of prostate-specific antigen in defining indications for initial prostate biopsy].

    Currently, prostate biopsy remains the main method used to diagnose prostate cancer (PCa). The indication for the procedure is an elevated level of the serum level of the total prostate-specific antigen (PSA).

    Published August 3, 2018
  • A comparative study on the efficacies of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist in neoadjuvant androgen deprivation therapy combined with transperineal prostate brachytherapy for localized prostate cancer.

    Neoadjuvant androgen deprivation therapy (ADT) has been suggested to confer several clinical benefits in patients with prostate cancer (PCa) undergoing transperineal prostate brachytherapy (TPPB). Unlike gonadotropin-releasing hormone (GnRH) receptor agonists, a GnRH antagonist such as degarelix can achieve castrate levels of testosterone without testosterone flare.

    Published September 6, 2016
  • A randomized study of intra-operative autologous retropubic urethral sling on urinary control after robotic-assisted radical prostatectomy.

    We evaluated whether placement of a retropubic urethral sling fashioned from autologous vas deferens during robotic-assisted radical prostatectomy (RARP) improved recovery of continence.

    In a phase-2, single-blinded trial, age-stratified patients were randomized to undergo RARP by multiple surgeons with or without sling placement.

    Published October 10, 2016
  • Ability of community-based prostate cancer screening to target an appropriate and underserved population.

    Screening is not universally beneficial due to over- and under-diagnosis, and false positives that beget additional testing and associated adverse events and expense. We examined data from all men who participated in a mass community prostate cancer screening between May 2009 and September 2010.

    Published August 31, 2015
  • Actual Contribution of Free to Total PSA Ratio in Prostate Diseases Differentiation.

    To determine significance and sensitivity of the Free to Total prostate specific antigen (PSA) ratio (%fPSA) in diagnosis of prostate cancer and to correlate its sensitivity and specificity with diagnosis.

    Published October 14, 2016
  • Age-specific Serum Prostate Specific Antigen Ranges Among Apparently Healthy Nigerian Men Without Clinical Evidence of Prostate Cancer.

    INTRODUCTION - Serum prostate specific antigen (PSA) levels increase with age and varies among different races and communities. The study was aimed at defining the age-specific reference ranges of serum PSA in our environment.

    Published March 30, 2016
  • Annual Report to the Nation on the Status of Cancer, part II: Recent changes in prostate cancer trends and disease characteristics.

    Temporal trends in prostate cancer incidence and death rates have been attributed to changing patterns of screening and improved treatment (mortality only), among other factors. This study evaluated contemporary national-level trends and their relations with prostate-specific antigen (PSA) testing prevalence and explored trends in incidence according to disease characteristics with stage-specific, delay-adjusted rates.

    Published June 4, 2018
  • Application of transrectal ultrasound-guided repeat needle biopsy in the diagnosis of prostate cancer in Chinese population: A retrospective study.

    Transrectal ultrasound-guided repeat needle biopsy (TUGRNB) is widely used for diagnosis of prostate cancer (PCa). However, significance of TUGRNB in Chinese population was rarely reported. A retrospective study was conducted to evaluate the significance of TUGRNB applied in prediction of PCa in Chinese population.

    Published December 7, 2016
  • Are prostate biopsies necessary for all patients 75years and older?

    To develop nomograms predicting prostate cancer (PCa) and high-grade PCa (HGPCa) in the elderly population.

    We reviewed the data of patients aged 75years and older who underwent first-time prostate biopsy and multiparametric magnetic resonance imaging (mpMRI).

    Published September 26, 2017
  • Baseline prostate atrophy is associated with reduced risk of prostate cancer in men undergoing repeat prostate biopsy.

    INTRODUCTION - We evaluated whether presence and severity of baseline prostate atrophy among men with initial negative biopsy for prostate cancer (PCa) was associated the risk of subsequent PCa detection in a clinical trial with scheduled study-mandated biopsies.

    Published August 5, 2015
  • Biochemical progression-free survival in localized prostate cancer patients treated with definitive external beam radiotherapy.

    Prostate cancer is now the third most frequent noncutaneous malignancy in Iranian men and the fifth most common cancer worldwide. Measurement of total serum prostate specific antigens (PSAs) has been one of the strongest predictors of biochemical progression and overall survival in determining the efficacy of definitive external beam radiation therapy in patients with localized prostate cancer.

    Published November 1, 2015
  • Biological variation estimates for prostate specific antigen from the European Biological Variation Study; consequences for diagnosis and monitoring of prostate cancer.

    Prostate-specific antigen (PSA) is central in the diagnosis of prostate cancer. However, high-quality biological variation (BV) estimates for PSA are scarce. Here BV estimates from the European Biological Variation Study (EuBIVAS) for total (tPSA), free (fPSA), conjugated PSA (cPSA), and percent free PSA (%fPSA) are provided.

    Published August 8, 2018
  • Body mass index in relation to serum prostate-specific antigen levels and prostate cancer risk.

    High Body mass index (BMI) has been directly associated with risk of aggressive or fatal prostate cancer. One possible explanation may be an effect of BMI on serum levels of prostate-specific antigen (PSA).

    Published March 3, 2016
  • Characterization of Differences Between Prostate Cancer Patients Presenting with De Novo Versus Primary Progressive Metastatic Disease.

    Men who present with metastatic disease can have de novo or primary progressive disease. We characterized and compared the outcomes between these 2 groups.

    A retrospective cross-sectional analysis from a single institution of de novo versus primary progressive metastatic patients during a 2-year consecutive period was undertaken.

    Published September 22, 2017
  • Chronic baseline prostate inflammation is associated with lower tumor volume in men with prostate cancer on repeat biopsy: Results from the REDUCE study.

    Background: To evaluate whether baseline acute and chronic prostate inflammation among men with initial negative biopsy for prostate cancer (PC) is associated with PC volume at the 2-year repeat prostate biopsy in a clinical trial with systematic biopsies.

    Published July 19, 2015
  • Chronic Prostate Inflammation is Associated with Severity and Progression of Benign Prostatic Hyperplasia, Lower Urinary Tract Symptoms and Risk of Acute Urinary Retention.

    and Objectives: We evaluated associations between histological prostate inflammation and development and progression of BPH/LUTS in men randomized to placebo in the REDUCE study over a 4-year period.

    Published July 11, 2016
  • Clinical impact of prostate specific antigen (PSA) inter-assay variability on management of prostate cancer.

    To evaluate the inter-assay variability of six commercially available prostate specific antigen (PSA) assays, its clinical impact in prostate cancer (PCa) and comparison of automated versus manual assays.

    Published November 4, 2015
  • Clinical Importance of Histopathological Inflammation in Patients with Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: A Prospective Study of 222 Patients.

    To investigate the relationship between the severity of histopathological prostatic inflammation with lower urinary tract symptoms and prostate specific antigen (PSA) levels.

    We prospectively included 222 consecutive patients eligible for transurethral resection of the prostate in a non-academic referral center by a single surgeon.

    Published September 15, 2017
  • Comparative Study of Blood-Based Biomarkers, α2,3-Sialic Acid PSA and PHI, for High-Risk Prostate Cancer Detection.

    Prostate Specific Antigen (PSA) is the most commonly used serum marker for prostate cancer (PCa), although it is not specific and sensitive enough to allow the differential diagnosis of the more aggressive tumors.

    Published April 25, 2017
  • Design-corrected variation by centre in mortality reduction in the ERSPC randomised prostate cancer screening trial.

    To calculate design-corrected estimates of the effect of screening on prostate cancer mortality by centre in the European Randomised Study of Screening for Prostate Cancer (ERSPC).

    The ERSPC has shown a 21% reduction in prostate cancer mortality in men invited to screening with follow-up truncated at 13 years.

    Published August 16, 2016
  • Development of an electrochemical immunosensor based on gold nanoparticles incorporated chitosan biopolymer nanocomposite film for the detection of prostate cancer using PSA as biomarker.

    In this study, we have developed an electrochemical immunosensor for the detection of prostate-specific antigen (PSA) based on gold nanoparticles (AuNPs) and a chitosan (CHI) nanocomposite film coated on a screen printed electrode (SPE).

    Published March 5, 2018
  • Development of glycan specific lectin based immunoassay for detection of Prostate Specific Antigen.

    We describe an analytical approach for the detection and verification of glycosylation patterns of prostate specific antigen (PSA), a key biomarker currently used for understanding the onset and prognosis of prostate cancer.

    Published February 11, 2016
  • Diagnostic Performance of %[-2]proPSA and Prostate Health Index for Prostate Cancer: Prospective, Multi-institutional Study.

    We evaluated the clinical performance of [-2]proPSA (p2PSA) and its derivatives in predicting the presence and aggressiveness of prostate cancer (PCa) in Korean men.

    A total of 246 men with total prostate-specific antigen (tPSA) ≥ 3.

    Published March 9, 2018
  • Diffusion-weighted MRI treatment monitoring of primary hypofractionated proton and carbon ion prostate cancer irradiation using raster scan technique.

    To investigate parametric changes in the apparent diffusion coefficient (ADC) at multiple timepoints during and after completion of primary proton and carbon ion irradiation of prostate cancer (PCa) as compared with normal-appearing prostate parenchyma.

    Published February 5, 2017
  • Discordant prostate specific antigen test results despite WHO assay standardization.

    Total PSA (tPSA) and free PSA (fPSA) are the most commonly used biomarkers for early detection of prostate cancer. Despite standardization efforts, many available PSA assays may still produce discordant results.

    Published May 22, 2018
  • Elevated insulin and reduced insulin like growth factor binding protein-3/prostate specific antigen ratio with increase in prostate size in Benign Prostatic Hyperplasia.

    Insulin and insulin like growth factor-1 (IGF-1) have growth promoting effects, while insulin like growth factor binding protein-3 (IGFBP-3) has growth inhibitory effects. The present study was designed to assess the concentrations of insulin, IGF-1, IGFBP-3 and their association with prostate size in patients with BPH.

    Published March 18, 2017
  • Elevated prostate specific antigen and reduced 10-year survival among a cohort of Danish men consecutively referred from primary care to an urological department during 2005-2006.

    It remains unclear whether total prostate specific antigen (tPSA) or complex PSA (cPSA) has the best diagnostic performance. Additionally, the utility of percentage free PSA (%fPSA) is still debated.

    Published October 26, 2016
  • Evaluation of pT0 prostate cancer in radical prostatectomy patients.

    To evaluate the incidence, predictors and oncologic outcomes of pT0 prostate cancer (PCa).

    Retrospective analysis of 20,222 men undergoing RP for PCa at Mayo Clinic from 1987 to 2012. Disease recurrence was defined as follow-up prostate-specific antigen (PSA) >0.

    Published September 1, 2015
  • Improvement in Therapeutic Efficacy and Reduction in Cellular Toxicity: Introduction of a Novel Anti-PSMA-Conjugated Hybrid Antiandrogen Nanoparticle.

    Second generation antiandrogens have improved overall survival for men with metastatic castrate resistant prostate cancer; however, the antiandrogens result in suppression of androgen receptor (AR) activity in all tissues resulting in dose limiting toxicity.

    Published April 13, 2018
  • Incidence of metastasis and prostate-specific antigen levels at diagnosis in Gleason 3+4 versus 4+3 prostate cancer.

    The aim is to assess for a difference in the incidence of metastasis (IM) and prostate-specific antigen (PSA) levels at diagnosis in patients with Gleason score (GS) 3+4 versus 4+3 prostate cancer using a large veterans affairs database.

    Published May 11, 2018
  • Inverse Association of Prostatic Chronic Inflammation among Prostate Cancer Tumor Grade Groups: Retrospective Study of 738 Consecutive Cases Elected to a First Random Biopsy Set.

    The study aimed to evaluate associations of prostatic chronic inflammation (PCI) with prostate cancer (PCA) grade groups by the International Society of Urological Pathology (ISUP).

    The study evaluated retrospectively 738 cases.

    Published April 24, 2018
  • Long Term PSA Stability and Predictive Factors of Failure after Permanent Seed Prostate Brachytherapy.

    Defining biochemical failure as nadir+2 may overestimate cure after radiotherapy. We assess long term PSA stability after low dose rate prostate brachytherapy and predictors of biochemical failure when the PSA is slowly rising below the nadir + 2 ng/ml threshold.

    Published August 29, 2017
  • Long-term prognostic significance of rising PSA levels following radiotherapy for localized prostate cancer - focus on overall survival.

    The aim of this study was to evaluate the long-term prognostic significance of rising PSA levels, particularly focussing on overall survival.

    Two hundred ninety-five patients with localized prostate cancer were either treated with low-dose-rate (LDR) brachytherapy with I-125 seeds as monotherapy (n = 94; 145Gy), high-dose-rate (HDR) brachytherapy with Ir-192 as a boost to external beam RT (n = 66; 50.

    Published June 23, 2017
  • Long-term Results of External Beam Radiotherapy for Prostate Cancer with Prostate-specific Antigen of More Than 50 ng/ml and Without Evidence of Lymph Node or Distant Metastasis.

    To evaluate long-term treatment outcomes of external beam radiotherapy for prostate cancer with a pretreatment prostate-specific antigen (PSA) level of more than 50 ng/ml and without evidence of lymph node or distant metastasis.

    Published April 3, 2018
  • Metformin Has a Positive Therapeutic Effect on Prostate Cancer in Patients With Type 2 Diabetes Mellitus.

    Prostate cancer and type 2 diabetes mellitus (DM2) are both common diseases found in the elderly male population. The diabetic drug, metformin, has been shown to have antineoplastic properties and demonstrated better treatment outcomes when used as adjuvant therapy in patients with breast cancer.

    Published April 20, 2016
  • Methodology to study the three-dimensional spatial distribution of prostate cancer and their dependence on clinical parameters.

    A methodology to study the relationship between clinical variables [e.g., prostate specific antigen (PSA) or Gleason score] and cancer spatial distribution is described.

    Published August 10, 2015
  • Multiparametric Magnetic Resonance Imaging for Active Surveillance of Prostate Cancer.

    Active surveillance has gained popularity as an acceptable management option for men with low-risk prostate cancer. Successful utilization of this strategy can delay or prevent unnecessary interventions - thereby reducing morbidity associated with overtreatment.

    Published October 19, 2017
  • Positive Association between Preoperative Total Testosterone Levels and Risk of Positive Surgical Margins by Prostate Cancer: Results in 476 Consecutive Patients Treated Only by Radical Prostatectomy.

    To evaluate preoperative total testosterone (TT) as a predictor of positive surgical margins (PSM) in prostate cancer (PCA).

    During the period from November 2014 to July 2017, preoperative TT was measured in 476 PCA patients undergoing only radical prostatectomy (RP) and including all risk classes.

    Published July 13, 2018
  • Potential of telmisartan in the treatment of benign prostatic hyperplasia.

    Benign prostatic hyperplasia (BPH) is a common health problem in aging men. This study was carried out to investigate the protective effect of telmisartan on testosterone induced-BPH in rats. Fifty-four male Wistar rats (200 - 250g) were randomly divided into 9 groups (n =6) and orally treated for 28 consecutive days: group 1- vehicle normal, olive oil (10 ml/kg); group 2- BPH model control (10 ml/kg); groups 3-5 - telmisartan (5, 10 or 20 mg/kg, respectively); group 6- pioglitazone (20 mg/kg); group 7- celecoxib (20 mg/kg); group 8- combination of telmisartan (5 mg/kg) and pioglitazone (20 mg/kg); group 9- combination of telmisartan (5 mg/kg) and celecoxib (20 mg/kg).

    Published July 22, 2017
  • Predictors of Time to Metastasis in Castration-Resistant Prostate Cancer.

    To investigate predictors of time to metastasis among men treated with androgen deprivation therapy (ADT) for non-metastatic prostate cancer who developed castration-resistant prostate cancer (CRPC) within the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.

    Published June 20, 2016
  • Preliminary study on ultrasound-guided prostate biopsy specimen scores.

    Prostate cancer (PCa) is the second most frequently diagnosed cancer in males worldwide and resulted in ~258,000 cases of cancer-associated mortality in 2008. The present study visually determined the pathology scores of PCa specimens by taking into account five characteristics, including the hardness, color, plumpness, transparency and uniformity of specimens.

    Published October 2, 2017
  • Prophylactic Robotic-assisted Laparoscopic Radical Prostatectomy for Preoperative Suspicion of Prostate Cancer: Experience with 55 Cases: Beyond the Abstract

    Prophylactic surgery is considered acceptable for pre-malignant lesions and high level of risk of developing cancer of the colon and breast, especially in patients with family history [1-3].
    Published October 13, 2016
  • Prostate Cancer Diagnosis

    Signs and symptoms. Prostate cancer rarely demonstrates early symptoms. A nodule may be noticed on a digital rectal exam as tumor volume increases. Symptoms suggest locally advanced or metastatic disease.  With advanced disease, hematuria, obstructive symptoms and bone pain from metastases can be present.  It is less common to diagnosis advanced disease due to sceening with prostate specific antigen (PSA) and digital rectal exams (DRE).  A histological diagnosis is frequently made using prostate needle biospy with transurethral ultrasound guidance.  DRE and PSA are complementary tests and it is recommended that they are used in combination in assessing prostate cancer risk.   

    • Prostate Specific Antigen [PSA] Improves the postive predictive value of DRE for prostate cancer.
      • Biochemical characteristics.
        • PSA is a 240 amino acid single chain glycoprotein that has a molecular weight of 34 kd. It is coded on chromosome 19 (6 Kb: 4 introns, 5 exons), is homologous to members of the kallikrein gene superfamily, and is designated human kallikrein3 (hK3). It behaves as a serine protease.
      • Physiology.
        • PSA liquefies the seminal coagulum that is formed after ejaculation.
        • A substrate produced in the seminal vesicles has been identified. PSA has chymotrypsinand trypsin-like activity. Its half-life is 2.2 to 3.2 days.
      • Marker Properties
        • The generally used monoclonal assay (2 murine MAbs for two specific epitopes) suggest a normal serum value of 4.0 ng/mL. Serum values are not generally altered by DRE, but can be affected by urologic instrumentation, ejaculation, and prostate biopsy. 
        • Benign conditions that can raise PSA levels include prostatitis, prostate infarction, and benign prostatic hypertrophy.
        • The interpretation of PSA values should always include age, presence of urinary tract infection, recent diagnositc procedures, any prstate directed treatments.  
      • Cancer detection (see screening)
      • Treatment surveillance. Serum levels monitored after surgery and external beam radiation therapy. Surgical failure clearly defined by PSA level >0.4 ng/ml. Radiation failure currently defined by 3 successive rises in PSA over time. Several biases built into this definition.
    • Transrectal Ultrasound. Primarily used for appropriate needle placement during biopsy. Classic finding of hypoechoic lesion has a 30% chance of being prostate cancer
    • Prostate needle biopsy. Spring loaded gun obtains 10-13 cores of tissue from the gland under ultrasound guidance. Parameters such a percent positive cores can provide predictive information on treatment outcome. Procedure is well tolerated. Major side effect is hematospermia
    • Bone Scan. In patients with a PSA <10.0ng/ml the chance of a positive scan is approximately 1:1000. May be used as a baseline study. 30-50 of bone mass must be replaced for it to be positive. Plain fim correlates or CT/MRI are use to resolve questionable findings
    • CT and body coil MRI have no proven contemporary role in the staging of prostate cancer. Endorectal coil may provide additional staging resolution in patients with PSA values between 10 and 20 who have >50% of biopsy cores positive for cancer.
    • Bilateral pelvic lymph node dissection. Provides staging information in patients with high grade/stage disease with elevated serum PSA. Generally part of radical prostatectomy. Given stage shift in disease, frozen section less often employed in most cases. Can be performed laparoscopically as a separate procedure.
    • Multimodal staging. Multiple clinical factors can be analyzed for contribution prediction of pathologic stage or clinical outcome. Multivariable analysis, continuous nomograms, and neural networks can be employed.  For more on staging


    • Albertson PC, Hanley JA, Gleason DR, Barry MJ: Competing risk analysis of men aged 55 to 74 years at diagnosis managed conservatively for clinically localized prostate cancer. JAMA 280:975-980, 1998.
    • Cooney, K. A., J. D. McCarthy, et al. (1997). "Prostate cancer susceptibility locus on chromosome 1q: a confirmatory study." J Natl Cancer Inst 89(13): 955-9.
    • Devgan, S. A., B. E. Henderson, et al. (1997). "Genetic variation of 3 beta-hydroxysteroid dehydrogenase type II in three racial/ethnic groups: implications for prostate cancer risk." Prostate 33(1): 9-12.
    • Greenlee, R. T., T. Murray, et al. (2000). "Cancer statistics, 2000." CA Cancer J Clin 50(1): 7-33.
    • Jemal, A., T. Murray, et al. (2003). "Cancer statistics, 2003." CA Cancer J Clin 53(1): 5-26.
    • Kalapurakal, J. A., A. N. Jacob, et al. (1999). "Racial differences in prostate cancer related to loss of heterozygosity on chromosome 8p12-23." Int J Radiat Oncol Biol Phys 45(4): 835-40.
    • Makridakis, N., R. K. Ross, et al. (1997). "A prevalent missense substitution that modulates activity of prostatic steroid 5alpha-reductase." Cancer Res 57(6): 1020-2.
    • Makridakis, N. M., R. K. Ross, et al. (1999). "Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA." Lancet 354(9183): 975-8.
    • Naughton et al, 2000. Naughton CK, Miller DC, et al: A prospective randomized trial comparing 6 versus 12 prostate biopsy cores: impact on cancer detection. J Urol  2000; 164(2):388-392.
    • Pettaway, C. A., P. Troncoso, et al. (1998). "Prostate specific antigen and pathological features of prostate cancer in black and white patients: a comparative study based on radical prostatectomy specimens." J Urol 160(2): 437-42.
    • Platz, E. A., M. N. Pollak, et al. (1999). "Racial variation in insulin-like growth factor-1 and binding protein-3 concentrations in middle-aged men." Cancer Epidemiol Biomarkers Prev 8(12): 1107-10.
    • Ross, R. K., L. Bernstein, et al. (1992). "5-alpha-reductase activity and risk of prostate cancer among Japanese and US white and black males." Lancet 339(8798): 887-9.
    • Sakr, W. A., D. J. Grignon, et al. (1995). "Epidemiology of high grade prostatic intraepithelial neoplasia." Pathol Res Pract 191(9): 838-41.
    • Schroder et al, 1998. Schroder FH, van der Maas P, Beemsterboer P, et al: Evaluation of the digital rectal examination as a screening test for prostate cancer. Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. J Natl Cancer Inst  1998; 90(23):1817-1823.
    • Smith, J. R., D. Freije, et al. (1996). "Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search." Science 274(5291): 1371-4.
    • Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Minasian LM, Ford LG, Lippman SM, Crawford ED, Crowley JJ, Coltman CA Jr. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med. 2004 May 27;350(22):2239-46.
    • Tricoli, J. V., D. L. Winter, et al. (1999). "Racial differences in insulin-like growth factor binding protein-3 in men at increased risk of prostate cancer." Urology 54(1): 178-82.
    • Winter, D. L., A. L. Hanlon, et al. (2001). "Plasma levels of IGF-1, IGF-2, and IGFBP-3 in white and African-American men at increased risk of prostate cancer." Urology 58(4): 614-8.
    • Xu, J., D. Meyers, et al. (1998). "Evidence for a prostate cancer susceptibility locus on the X chromosome." Nat Genet 20(2): 175-9.
    Published April 14, 2015
  • Prostate Cancer for the Internist.

    In the United States, approximately 240,000 men are diagnosed annually with prostate cancer. Although effective treatment options are available for clinically localized cancer, the potential burdensome co-morbidities and attendant healthcare costs from over diagnosis and over treatment have escalated the discussion and controversy regarding appropriate screening, diagnosis, and optimal management of prostate cancer.

    Published December 30, 2015
  • Prostate Cancer Screening

    Prostate cancer screening refers to testing for disease in healthy, asymptomatic populations, where diagnosis is the identification of disease among individuals with signs or symptoms. The goal of screening is to improve overall health outcomes by identifying and treating disease at an earlier stage.

    • There is strong evidence that prostate cancer screening reduces the rates of advanced disease, but it remains controversial.  
    • The prostate-cancer mortality in the European Randomized Study of Screening for Prostate Cancer was recently updated with 2 additional years of follow-up.  Analyses after 2 additional years of follow-up confirmed previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality.
    • The role for true prostate cancer screening is not proven. Absolute proof of screening is a decrease in the death rate of that cancer due to screening activity. Stage shift in prostate cancer and decrease in death rate statistics indirectly suggest a positive effect of PSA in disease detection. Prospective trials are continuing.
    • The American Cancer Society, American Radiological Association, and American Urological Association recommends early detection with an annual DRE and PSA beginning at age 50 for all men with a life expectancy greater than 10 years and age 45 for men of African American race and age 40 for men with a family history of prostate cancer. Those men with a serum PSA equal or greater to 0.6 ng/ml (the median PSA for that age group) should undergo yearly screening, whereas those with a value less than 0.6 ng/ml may have another interval PSA at age 45. The same rule applies at age 45. The American Cancer Society recommends that men thinking about prostate cancer screening should make informed decisions based on available information, discussion with their doctor, and their own views on the benefits and side effects of screening and treatment.
    • Digital Rectal Exam. More cancer is detected with the use of DRE and PSA than with either exam alone. With high penetrance of PSA use in younger patients however, abnormal DRE exams are much less common.
    • PSA. In general 5-8 percent of a screening population will have an abnormal DRE. A value between 4-10 ng/ml has a 15-30% chance of being positive. Values above 10 are associated with a positive biopsy in greater than two thirds of cases. PSA has a sensitivity of 80% and a specificity of 35-50%. False positive findings are common. The optimal upper limit of normal for PSA is controversial. Recent studies suggest that using a PSA cutoff of 2.5 ng/ml for men younger than 60 years may be more appropriate. A subset analysis of data from the Prostate Cancer Prevention Trial from men with serum PSA levels less than 4.0 ng/ml (2950 men) showed a prostate cancer incidence of 15.2%, with 15% of these being of Gleason score 7 or greater. The prostate cancer prevalence was 6.6% among men with a PSA level of =0.5 ng/ml, 10.1% among those with values of 0.6 to 1.0 ng/ml, 17.0% among those with values of 1.1 to 2.0 ng/ml, 23.9% among those with values of 2.1 to 3.0 ng/ml, and 26.9% among those with values of 3.1 to 4.0 ng/ml. These data suggest that using absolute values for triggering a biopsy may not be as important as assessing PSA velocity.
    • Free and complexed PSA. PSA may be found free in serum or bound to alpha -1-antichymotrypsin and alpha-2 macroglobin. Higher fraction of free PSA noted in benign disease. If percent free PSA is >25% the probability of a positive biopsy drops from 15-30 percent to 5-7%. Generally used in consideration for repeat biopsies. As a single test for screening, cPSA may improve specificity over total PSA and comparable specificity to free-to-total PSA for prostate cancer detection, and may reduce the number of unnecessary prostate biopsies in the 2.6-4.0 ng/mL tPSA range.
    • Precursor PSA (pPSA). PSA is secreted from the prostate luminal epithelial cells as pPSA, an inactive proenzyme containing a 7-amino acid pro-leader peptide and 237 amino acids of mature PSA. The pro-leader peptide is removed extracellularly to produce active, mature PSA. Since no pPSA forms have been found in seminal plasma, pPSA has been identified as a serum marker with greater cancer specificity. Using 1091 retrospective serum specimens of patients with a total PSA between 2 and 4 ng/ml, Catalona and colleagues recently showed that using a cutoff of pro- to free-PSA (percent pro-PSA) of 1.8% for recommending prostate biopsy detected 90% of cancers, including 16 of 16 extracapsular tumors and 28 of 29 tumors with a pathology Gleason score of 7 or greater, while avoiding 19% of unnecessary biopsies
      • PSA velocity. Several studies suggest that if the serum PSA increases greater than 0.75 g/mL per year the potential for prostate cancer is greater. Unfortunately, since PSA variability can be as high as 23.5 percent per reading, three separate readings 6 months apart are necessary to establish a true trend. In addition, no added benefit has been demonstrated in patients with a PSA level between 4 and 10 ng/mL. A recent study by D'Amico et al published in the New England Journal of Medicine suggested that an annual PSA velocity of 2 ng/ml or greater was independently associated with prostate cancer mortality after radical prostatectomy. Potentially this may serve as a marker for identifying patients who may be considered for novel neoadjuvant strategies before undergoing surgery.
      • Age adjusted PSA. Concept of raising PSA threshold in older patients and lowering it in younger patients. Data suggests normal PSA of 2.5 may be more appropriate in men under the age of 60. Many suggest lowering value for young men and maintaining 4.0 for older patients to minimize "miss rate" in this population
    • Screening bias. Length time bias consists of detecting a case at an earlier time in its history and suggesting a longer survival period from treatment, which is actually just a longer period of observation. Lead-time bias consists in part of selecting cases from a disease population with good survival traits and thus suggesting an apparent survival benefit that does not exist.
    • Beneficence. Does disease detection provide a benefit, or do side effects of therapy or the anxiety of false negative tests outweigh the benefit?
    • Screening costs. Can be significant, yet most estimates based on extremely high compliance rates. Elevated PSA detects clinically significant tumors and does not over detect microscopic pathological disease.


    • Albertson PC, Hanley JA, Gleason DR, Barry MJ: Competing risk analysis of men aged 55 to 74 years at diagnosis managed conservatively for clinically localized prostate cancer. JAMA 280:975-980, 1998.
    • Barry, 2009. Barry MJ: Screening for prostate cancer—the controversy that refuses to die. N Engl J Med  2009; 360(13):1351-1354.
    • Catalona WJ, Bartsch G, Rittenhouse HG, Evans CL, Linton HJ, Horninger W, Klocker H, Mikolajczyk SD.Serum pro-prostate specific antigen preferentially detects aggressive prostate cancers in men with 2 to 4 ng/ml prostate specific antigen. J Urol. 2004 Jun;171(6 Pt 1):2239-44.
    • D'Amico AV, Chen MH, Roehl KA, Catalona WJ. Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Engl J Med. 2004 Jul 8;351(2):125-35.
    • Parsons JK, Brawer MK, Cheli CD, Partin AW, Djavan R.Complexed prostate specific antigen (PSA) reduces unnecessary prostate biopsies in the 2.6-4.0 ng/mL range of total PSA. BJU Int. 2004 Jul;94(1):47-50.
    • Schroder et al, 2012. Schroder FH, Hugosson J, Roobol MJ, ERSPC Investigatorset al:Prostate-cancer mortality at 11 years of follow-up. N Engl J Med 2012 Mar 15;366(11):981-90.
    • Schroder et al, 2009. Schroder FH, Hugosson J, Roobol MJ, et al: Screening and prostate-cancer mortality in a randomized European study. N Engl J Med  2009; 360(13):1320-1328.
    • Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Minasian LM, Ford LG, Lippman SM, Crawford ED, Crowley JJ, Coltman CA Jr. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med. 2004 May 27;350(22):2239-46.
    • van der Cruijsen-Koeter et al, 2006. van der Cruijsen-Koeter IW, Roobol MJ, Wildhagen MF, et al: Tumor characteristics and prognostic factors in two subsequent screening rounds with four-year interval within prostate cancer screening trial, ERSPC Rotterdam. Urology  2006; 68(3):615-620.
    Published April 1, 2012
  • Prostate Cancer Screening and the Associated Controversy.

    Prostate cancer is the most common malignancy diagnosed in men and the second leading cause of cancer death for men in the United States. Widespread use of prostate-specific antigen (PSA) screening led to a decrease in mortality; however, PSA screening may have led to overdiagnosis and overtreatment of clinically insignificant cancers.

    Published September 24, 2015
  • Prostate Cancer Screening in Early Medicaid Expansion States.

    The Affordable Care Act of 2010 included a provision to expand Medicaid by 2014. Six states and jurisdictions elected to expand Medicaid early, before 2012. This provided a natural experiment to test the association between expanded insurance coverage and preventive service utilization, including prostate cancer screening.

    Published August 9, 2017
  • Prostate Health Index (PHI) improves prostate cancer detection at initial biopsy in Taiwanese men with PSA 4-10 ng/mL.

    In this study, we aimed to validate the Prostate Health Index (PHI) for the detection of prostate cancer (PCa). We prospectively enrolled patients aged 50-75 years with a serum prostate specific antigen (PSA) level of 4-10 ng/mL undergoing transrectal biopsy of the prostate between April 2016 and May 2017.

    Published July 31, 2018
  • Prostate specific antigen testing after radical prostatectomy: can we stop at 20 years?

    To examine the clinical features and outcomes associated with delayed biochemical recurrence after radical prostatectomy, specifically amongst men with over 20 years of follow-up.

    16,720 men underwent radical prostatectomy and 2,699 experienced biochemical recurrence.

    Published August 25, 2017

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