Prediction of Prostate Cancer Risk: The Role of Prostate Volume and Digital Rectal Examination in the ERSPC Risk Calculators

Erasmus University Medical Centre, Department of Urology, Rotterdam, The Netherlands.
European Urology (Impact Factor: 13.94). 11/2011; 61(3):577-83. DOI: 10.1016/j.eururo.2011.11.012
Source: PubMed

ABSTRACT The European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculators (RCs) are validated tools for prostate cancer (PCa) risk assessment and include prostate volume (PV) data from transrectal ultrasound (TRUS).
Develop and validate an RC based on digital rectal examination (DRE) that circumvents the need for TRUS but still includes information on PV.
For development of the DRE-based RC, we studied the original ERSPC Rotterdam RC population including 3624 men (885 PCa cases) and 2896 men (547 PCa cases) detected at first and repeat screening 4 yr later, respectively. A validation cohort consisted of 322 men, screened in 2010-2011 as participants in ERSPC Rotterdam.
Data on TRUS-assessed PV in the development cohorts were re-coded into three categories (25, 40, and 60 cm3) to assess the loss of information by categorization of volume information. New RCs including PSA, DRE, and PV categories (DRE-based RC) were developed for men with and without a previous negative biopsy to predict overall and clinically significant PCa (high-grade [HG] PCa) defined as T stage>T2b and/or Gleason score≥7. Predictive accuracy was quantified by the area under the receiver operating curve. We compared performance with the Prostate Cancer Prevention Trial (PCPT) RC in the validation study.
Areas under the curve (AUC) of prostate-specific antigen (PSA) alone, PSA and DRE, the DRE-based RC, and the original ERSPC RC to predict PCa at initial biopsy were 0.69, 0.73, 0.77, and 0.79, respectively. The corresponding AUCs for predicting HG PCa were higher (0.74, 0.82, 0.85, and 0.86). Similar results were seen in men previously biopsied and in the validation cohort. The DRE-based RC outperformed the PCPT RC (AUC 0.69 vs 0.59; p=0.0001) and a model based on PSA and DRE only (AUC 0.69 vs 0.63; p=0.0075) in the relatively small validation cohort. Further validation is required.
An RC should contain volume estimates based either on TRUS or DRE. Replacing TRUS measurements by DRE estimates may enhance implementation in the daily practice of urologists and general practitioners.

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Available from: Monique J Roobol, Sep 27, 2015
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    • "Also transrectal ultrasound measurement of prostate volume is prone to be affected by interexaminer variability. Meanwhile, a recent study demonstrated that a new ERSPC risk calculator incorporating prostate volume based upon DRE provided comparable predictive accuracy in predicting significant prostate cancer with transrectal ultrasound-based risk calculator (AUC 0.85 versus 0.86) [71]. Such replacement of transrectal ultrasound measurements with DRE estimates may well enhance the implementation of PSAD as well as prostate volume into risk stratification in clinical setting. "
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    ABSTRACT: The introduction of testing for prostate-specific antigen (PSA), a member of the fifteen-gene family of kallikrein-related peptidases and also known as kallikrein-related peptidase 3 (KLK3), in blood has revolutionized both the detection and management of prostate cancer. Given the similarities between PSA and other KLK gene family members along with limitations of PSA as a biomarker for prostate cancer mainly in reference to diagnostic specificity, the potential roles of other members of this gene family as well as PSA derivatives and isoforms in the management of prostate cancer have been studied extensively. Of these, approaches to measure distinct molecular forms of PSA (free, intact, complexed PSA, and pro-PSA) combined with kallikrein-related peptidase 2 (KLK2), also known as hK2, have been considered holding particular promise in enhancing the diagnosis of prostate cancer. Recently, an integrated approach of applying a panel of four kallikrein markers has been demonstrated to enhance accuracy in predicting the risk of prostate cancer at biopsy. This review presents an overview of kallikreins, starting with the past and current status of PSA, summarizing published data on the evaluations of various KLKs as biomarkers in the diagnosis, prognostication, and monitoring of prostate cancer.
    04/2014; 2014:526341. DOI:10.1155/2014/526341
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    • "The rationale behind this somewhat conservative definition is to avoid misclassification of aggressive PCa do to undersampling on the biopsy, as our results are based on sextant biopsies. Data from our group showed that in men with a screen-detected clinically staged T2a/2b PCa and a biopsy Gleason score <7, the percentage of extracapsular extension (ie, pT3) was approximately 15%, whereas in men with a clinically staged T2c PCa and a biopsy Gleason score <7, this percentage was 26% [13] "
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    ABSTRACT: BACKGROUND: Inconclusive test results often occur after prostate-specific antigen (PSA)-based screening for prostate cancer (PCa), leading to uncertainty on whether, how, and when to repeat testing. OBJECTIVE: To develop and validate a prediction tool for the risk of PCa 4 yr after an initially negative screen. DESIGN, SETTING, AND PARTICIPANTS: We analyzed data from 15 791 screen-negative men aged 55-70 yr at the initial screening round of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Follow-up and repeat screening at 4 yr showed either no PCa, low-risk PCa, or potentially high-risk PCa (defined as clinical stage >T2b and/or biopsy Gleason score ≥7 and/or PSA ≥10.0 ng/ml). A multinomial logistic regression analysis included initial screening data on age, PSA, digital rectal examination (DRE), family history, prostate volume, and having had a previous negative biopsy. The 4-yr risk predictions were validated with additional follow-up data up to 8 yr after initial screening. RESULTS AND LIMITATIONS: Positive family history and, especially, PSA level predicted PCa, whereas a previous negative biopsy or a large prostate volume reduced the likelihood of future PCa. The risk of having PCa 4 yr after an initially negative screen was 3.6% (interquartile range: 1.0-4.7%). Additional 8-yr follow-up data confirmed these predictions. Although data were based on sextant biopsies and a strict protocol-based biopsy indication, we suggest that men with a low predicted 4-yr risk (eg, ≤1.0%) could be rescreened at longer intervals or not at all, depending on competing risks, while men with an elevated 4-yr risk (eg, ≥5%) might benefit from immediate retesting. These findings need to be validated externally. CONCLUSIONS: This 4-yr future risk calculator, based on age, PSA, DRE, family history, prostate volume, and previous biopsy status, may be a promising tool for reducing uncertainty, unnecessary testing, and overdiagnosis of PCa.
    European Urology 07/2012; 63(4). DOI:10.1016/j.eururo.2012.07.029 · 13.94 Impact Factor
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    • "The ERSPC DRE-based volume calculators were developed on a cohort of 3,624 men who had never before had a biopsy (DREvol-RC3) and a cohort of men (N = 2,896) previously screened/biopsied (DREvol-RC4/5) [11]. The model based on PSA and DRE outcome only was developed on similar cohorts resulting in a model suitable for men previously unscreened (PSADRE-model) and men previously screened and/or biopsied (PSADRE-model, see “Appendix” for formulas). "
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    ABSTRACT: To compare the predictive performance and potential clinical usefulness of risk calculators of the European Randomized Study of Screening for Prostate Cancer (ERSPC RC) with and without information on prostate volume. We studied 6 cohorts (5 European and 1 US) with a total of 15,300 men, all biopsied and with pre-biopsy TRUS measurements of prostate volume. Volume was categorized into 3 categories (25, 40, and 60 cc), to reflect use of digital rectal examination (DRE) for volume assessment. Risks of prostate cancer were calculated according to a ERSPC DRE-based RC (including PSA, DRE, prior biopsy, and prostate volume) and a PSA + DRE model (including PSA, DRE, and prior biopsy). Missing data on prostate volume were completed by single imputation. Risk predictions were evaluated with respect to calibration (graphically), discrimination (AUC curve), and clinical usefulness (net benefit, graphically assessed in decision curves). The AUCs of the ERSPC DRE-based RC ranged from 0.61 to 0.77 and were substantially larger than the AUCs of a model based on only PSA + DRE (ranging from 0.56 to 0.72) in each of the 6 cohorts. The ERSPC DRE-based RC provided net benefit over performing a prostate biopsy on the basis of PSA and DRE outcome in five of the six cohorts. Identifying men at increased risk for having a biopsy detectable prostate cancer should consider multiple factors, including an estimate of prostate volume.
    World Journal of Urology 12/2011; 30(2):149-55. DOI:10.1007/s00345-011-0804-y · 2.67 Impact Factor
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