Prostate CancerProstate Cancer Detection in the “Grey Area” of Prostate-Specific Antigen Below 10 ng/ml: Head-to-Head Comparison of the Updated PCPT Calculator and Chun’s Nomogram, Two Risk Estimators Incorporating Prostate Cancer Antigen 3
Introduction
Nomograms and risk calculators have shown better accuracy than prostate-specific antigen (PSA) in predicting prostate cancer (PCa) on biopsy [1]. The use of prostate cancer antigen 3 (PCA3) testing in clinical practice still remains to be established; its indications and cut-off values have not so far been agreed on. Its clinical usefulness may be greater in the so-called grey area of PSA values or in the setting of repeat biopsy (R-biopsy). It has also been suggested that the PCA3 test should be incorporated into diagnostic models that include multiple variables [2].
To our knowledge, only two multivariable risk estimators that include PCA3 have been published. The Prostate Cancer Prevention Trial (PCPT) calculator was updated to include PCA3 in risk calculation [3], and Chun et al have recently published a nomogram that includes a PCA3 score to estimate risk of cancer on biopsy [4]. The former is available online [5] and comprises six other variables beside PCA3: race, age, PSA, family history, digital rectal examination (DRE), and prior biopsy. The latter was built as a nomogram that includes PCA3 together with five other variables: age, PSA, DRE, prior biopsy, and prostate volume. Both have been externally validated in European cohorts [3], [6]. In this study, a head-to-head comparison of these two models is performed in a clinical scenario of patients in the grey area of PSA (ie, ≤10 ng/ml) referred to biopsy.
Section snippets
Study design
This was a prospective, multicentre Italian study. Men referred for prostate biopsy because of abnormal PSA and/or suspicious DRE were enrolled in three Italian centres (I.N.T. “G. Pascale” Foundation, Napoli; Magna Graecia University, Catanzaro; Second University of Naples, Napoli) between October 2008 and October 2009. The respective independent ethics committees approved the study protocol, and informed consent was obtained. Men with a PSA level >10 ng/ml, who received medical therapy in the
Results
Two hundred eighteen patients were enrolled and submitted to prostate biopsy. Their characteristics are shown in Table 1. Prostate biopsy was positive for cancer in 73 patients (33.5%); 27 high-grade cancers (Gleason ≥7) were diagnosed.
Total PSA and PCA3 scores were significantly higher on positive biopsy patients. In contrast, fPSA% was significantly lower in cancer patients. Increasing PCA3 scores (according to previously published cut-offs) were accompanied by increasing rates of positive
Discussion
To more accurately predict an individual’s risk of harbouring PCa at biopsy, statistical and computational models were developed, mostly because PSA and PSA-related measurements were shown to be limited in this task. Schröder and Kattan performed a systematic review of 36 predictive models, including 14 direct comparisons between model and PSA accuracies (AUC-ROC), showing a benefit from nomograms or artificial neural networks over PSA varying between 2% and 26% [1].
Recently, Cavadas et al
Conclusions
Both Chun’s nomogram and the PCPT calculator, by incorporating PCA3 into their multivariable predictive models, can assist in the decision to biopsy by assigning an individual risk of harbouring PCa, specifically in the PSA levels <10 ng/ml, where dilemmas are most frequent.
References (18)
- et al.
The comparability of models for predicting the risk of a positive prostate biopsy with prostate-specific antigen alone: a systematic review
Eur Urol
(2008) - et al.
Urinary prostate cancer 3 test: toward the age of reason?
Urology
(2010) - et al.
Predicting prostate cancer risk through incorporation of prostate cancer gene 3
J Urol
(2008) - et al.
Prostate cancer gene 3 (PCA3): development and internal validation of a novel biopsy nomogram
Eur Urol
(2009) - et al.
External validation of urinary PCA3-based nomograms to individually predict prostate biopsy outcome
Eur Urol
(2010) - et al.
Prostate Cancer Prevention Trial and European Randomized Study of Screening for Prostate Cancer risk calculators: a performance comparison in a contemporary screened cohort
Eur Urol
(2010) - et al.
Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy
Eur Urol
(2008) - et al.
PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy
Urology
(2007) - et al.
PCA3 urine mRNA testing for prostate carcinoma: patterns of use by community urologists and assay performance in reference laboratory setting
Urology
(2009)
Cited by (69)
Biomolecule-functionalized nanoformulations for prostate cancer theranostics
2023, Journal of Advanced ResearchDiagnostic Performance of the Prostate Cancer Antigen 3 Test in Prostate Cancer: Systematic Review and Meta-analysis
2020, Clinical Genitourinary CancerWhat risk of prostate cancer led urologist to recommend prostate biopsies?
2015, Progres en UrologieImpact of Early Diagnosis of Prostate Cancer on Survival Outcomes
2015, European Urology FocusThe Role of Biomarkers and Genetics in the Diagnosis of Prostate Cancer
2015, European Urology FocusCitation Excerpt :This is especially important in deciding the need for rebiopsy in patients with a prior negative biopsy. Perhaps the most well-known transcriptome-based marker is prostate cancer antigen 3 (PCA3), a noncoding RNA transcribed from chromosome 9 [20–24]. With the development of urinary assays for the detection of RNA transcripts, PCA3, often in conjunction with TMPRSS2:ERG fusion messenger RNA (mRNA) [9,25], is increasingly being used to guide the decision for repeat biopsy in men with elevated PSA and prior negative biopsies.
- 1
These authors contributed equally to this article.