Prostate Cancer Risk Inflation as a Consequence of Image-targeted Biopsy of the Prostate: A Computer Simulation Study

Abstract

BackgroundProstate biopsy parameters are commonly used to attribute cancer risk. A targeted approach to lesions found on imaging may have an impact on the risk attribution given to a man.ObjectiveTo evaluate whether, based on computer simulation, targeting of lesions during biopsy results in reclassification of cancer risk when compared with transrectal ultrasound (TRUS) guided biopsy.Design, setting, and participantsA total of 107 reconstructed three-dimensional models of whole-mount radical prostatectomy specimens were used for computer simulations. Systematic 12-core TRUS biopsy was compared with transperineal targeted biopsies using between one and five cores. All biopsy strategies incorporated operator and needle deflection error. A target was defined as any lesion ≥0.2 ml. A false-positive magnetic resonance imaging identification rate of 34% was applied.Outcome measurements and statistical analysisSensitivity was calculated for the detection of all cancer and clinically significant disease. Cases were designated as high risk based on achieving ≥6 mm cancer length and/or ≥50% positive cores. Statistical significance (p values) was calculated using both a paired Kolmogorov-Smirnov test and the t test.Results and limitationsWhen applying a widely used biopsy criteria to designate risk, 12-core TRUS biopsy classified only 24% (20 of 85) of clinically significant cases as high risk, compared with 74% (63 of 85) of cases using 4 targeted cores. The targeted strategy reported a significantly higher proportion of positive cores (44% vs 11%; p < 0.0001) and a significantly greater mean maximum cancer core length (7.8 mm vs 4.3 mm; p < 0.0001) when compared with 12-core TRUS biopsy. Computer simulations may not reflect the sources of errors encountered in clinical practice. To mitigate this we incorporated all known major sources of error to maximise clinical relevance.ConclusionsImage-targeted biopsy results in an increase in risk attribution if traditional criteria, based on cancer core length and the proportion of positive cores, are applied. Targeted biopsy strategies will require new risk stratification models that account for the increased likelihood of sampling the tumour.

Can multiparametric magnetic resonance imaging predict upgrading of transrectal ultrasound biopsy results at more definitive histology?11Mohamed Abd-Alazeez receives funding from the Egyptian government. Mark Emberton and Hashim U. Ahmed receive funding from USHIFU and Advanced Medical Diagnostics for clinical trials. Mark Emberton is a paid consultant for Steba Biotech, USHIFU and Sanofi-Aventis. Mark Emberton has received research support by GSK for a study evaluating the role of MRI in men with prostate

“…If the confirmatory biopsy includes "targeted" cores based on MRI findings (as is usually the case) then the sampling density will be higher in areas with MRI lesions. Purely as a function of sampling density (and not necessarily because of the MRI findings), these areas are therefore more likely to show upgrades; the effect is to artifactually increase the power of MRI to predict upgrading [17]. To minimize this problem, a high sampling density in areas both with and without MRI lesions is necessary and was achieved in our study by the use of systematic transperineal template mapping biopsy.…”

Performance of biopsy factors in predicting unfavorable disease in patients eligible for active surveillance according to the PRIAS criteria

“…18,19 The targeted biopsy strategies, in fact, demonstrated a higher disease burden, expressed by the increase of maximum cancer core length and the proportion of positive cores. 20 It should be taken into account, therefore, that these new methods are not too easy to be performed in daily practice and that further studies should be conducted before approving them. Second, all subjects of our study underwent transperineal prostate biopsy.…”

Re: Morgan R. Pokorny, Maarten de Rooij, Earl Duncan, et al. Prospective Study of Diagnostic Accuracy Comparing Prostate Cancer Detection by Transrectal Ultrasound–Guided Biopsy Versus Magnetic Resonance (MR) Imaging with Subsequent MR-guided Biopsy in Men Without Previous Prostate Biopsies. Eur Urol 2014;66:22–9

“…No evidence shows that in-bore biopsies achieve better. Indeed, many lesions that are 0.5 ml in volume, the common threshold for clinical significance, are 7 mm, so either in-bore or registration/fusion should be sufficient [6,4].…”

“…The stipulation that more than one core be positive on MR-guided biopsy and more than two cores be positive on TRUS-guided biopsy points to a study that is considerably biased to inherently show higher clinical validity for the new test, MR-guided biopsies. The problem is that MR-guided biopsies lead to oversampling of an area that is more likely to harbour disease; therefore, these biopsies are likely to have a greater number of positive cores [4].…”