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How to improve the equivocal category PI-RADS score 3? Quantitative multiparametric MRI assessment of prostate cancerous and non-cancerous areas using correlative histopathology.
Giovanni Barchetti1, Martina Pecoraro1, Isabella Ceravolo1, Maurizio Del Monte1, Carlo Catalano1, and Valeria Panebianco1

1Department of Radiology, Sapienza University, Policlinico Umberto I, Rome, Italy

Synopsis

To stratify patients with PI-RADSv2 category 3 to define the correct diagnostic work-up (biopsy or follow-up), quantitatively analyzing mpMRI parameters (ADC, k-trans, K-ep and ve). Among 1272 men who underwent mpMRI, we retrospectively enrolled 98 patients treated with radical prostatectomy. Furthermore, we selected 100 negative patients. The 198 mpMRI exams were randomly, blindly reviewed by two radiologists. 95 PI-RADSv2 category 3 were found and quantitatively analyzed. ROC and AUC were determined to identify a cut-off value to define which PI-RADS 3 lesion should be biopsied. Quantitative imaging represents a tool to objectively stratify patients classified as PI-RADSv2 category 3.

Introduction

Multiparametric MRI of the prostate (mpMRI) has become the state-of-the-art technique for staging and characterizing prostate cancer (PCa). Nowadays, European recommendation rely on qualitative analysis of mpMRI images applying PI-RADSv2 scoring system;1,2 however there is a consistent number of patients that fall in the equivocal group of PI-RADSv2 category 3 in which other clinical factors become increasingly important.2 Currently, much of the work is focusing on evaluation of mpMRI parameters’ quantitative analysis that has got the advantage of offering user-independent data, to determine its clinical applications. In light of the background, the aim of the study is to stratify patients with PI-RADSv2 category 3 which might undergo TRUS-MRI targeted biopsy, quantitatively analyzing mpMRI parameters (ADC, k-trans, K-ep and ve).

Methods

Among the 1272 men who underwent mpMRI for PCa suspicion at our centre from January 2015 to September 2017, we retrospectively enrolled 98 patients who were subsequently treated with radical prostatectomy. Furthermore, we selected 100 patients suspected of harboring PCa with at least two negative mpMRI examination (nMRI), the second 8-12 months apart from the first, at least one negative systematic transrectal ultrasound guided prostate biopsy after nMRI, and a minimum follow-up of 60 months. Every exam was performed at 3T mpMRI using the same protocol, which included T2-weighted imaging, diffusion weighted imaging (DWI) with apparent diffusion coefficient (ADC) maps and dynamic contrast-enhanced imaging (DCE). The mpMRI exams of the final population of 198 patients were randomly reviewed in consensus by two radiologists with more than 10 years’ experience in the field. The readers were blinded to both clinical data and histopathology reports, when available. For all patients, a structured report was obtained, and each lesion was described according to PI-RADSv2. A total of 95 PI-RADSv2 category 3 were found and quantitative analysis of these regions was performed. The quantitative evaluation was performed using GenIQ software for measuring pharmacokinetic parameters (k-trans, k-ep and ve) from DCE perfusion study, and READY View (GE Healthcare) for ADC values calculated from DWI sequences.

Results

The median patients age was 62, the median total PSA was 6,32 ng/mL, the median PSA density was 0,12 ng/mL2. Mean ADC value of 79,785 mm2/s (95% CI = 75,427 to 84,143), mean k-trans of 0,273 min-1 (95% CI= 0,229 to 0,316), mean k-ep of 0,532 min-1 (95% CI = 0,462 to 0, 623) and mean ve of 0,71 (95% CI = 0,236 to 0, 317). Receiver operating characteristic analysis and area under curve (AUC) were determined to identify a cut-off value to define which PI-RADS 3 lesion should be biopsied by TRUS-MRI targeted biopsy. Accordingly, we stratified results in two subgroups: group A, patients enter follow-up programs; group B, patients suited to undergo TRUS-MRI targeted biopsy.

Discussion

The major limitation of PI-RADS score system version 2 is how to define the clinical approach to patients classified as PI-RADS category 3. Indeed, for PI-RADS 3 other clinical factors become increasingly important such as PSA density. 2 Nonetheless, few studies in literature have demonstrated how quantitative analysis of mpMRI parameters might give further objective data to standardize the diagnostic work-up of PI-RADS 3 patients. Felker et al 3 reported how the yield of targeted biopsy in PI-RADSv2 category 3 TZ lesions for clinically significant PCa significantly improves to 60% among men with PSA density of 0.15 ng/mL2 or greater and lesion ADC value of less than 1000 mm2/s. Metzger et al 4 reported that among others ADC values, K-trans, and k-ep were significantly different between cancer and noncancer voxels (P , .001), with ADC showing the best accuracy. Hoang Dinh et al 5 described how the model of the 10th percentile of the ADC with time-to-peak (TTP) yielded accurate results in discriminating cancers with a Gleason score of at least 7 among peripheral zone (PZ) lesions. Hauth et al 6 reported how ADC min can differentiate PCa from benign prostate lesions in PZ. Peak enhancement might be able to differentiate low grade from high-grade PCa. We demonstrated that by quantitatively measuring mpMRI parameters of PI-RADS 3 lesion, confirmed by histopathologic correlation, it is possible to differentiate patients’ that should undergo to TRUS-MRI targeted biopsy from those who should enter follow-up programs.

Conclusion

Quantitative analysis of multiparametric MRI parameters might represent a tool to objectively stratify the equivocal group of patients classified as PI-RADSv2 category 3, to define the correct patients’ diagnostic planning (biopsy or follow-up). Hence, to improve prostate cancer detection while decreasing the number of unnecessary biopsies and the number of false negative results.

Acknowledgements

No acknowledgement found.

References

1. Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2017 Apr;71(4):618–29.

2. Barentsz JO, Weinreb JC, Verma S, Thoeny HC, Tempany CM, Shtern F, et al. Synopsis of the PI-RADS v2 Guidelines for Multiparametric Prostate Magnetic Resonance Imaging and Recommendations for Use. Eur Urol. 2016 Jan;69(1):41–9.

3. Felker ER, Raman SS, Margolis DJ, Lu DSK, Shaheen N, Natarajan S, et al. Risk Stratification Among Men With Prostate Imaging Reporting and Data System Version 2 Category 3 Transition Zone Lesions: Is Biopsy Always Necessary? Am J Roentgenol. 2017 Aug 31;1–6.

4. Metzger GJ, Kalavagunta C, Spilseth B, Bolan PJ, Li X, Hutter D, et al. Detection of Prostate Cancer: Quantitative Multiparametric MR Imaging Models Developed Using Registered Correlative Histopathology. Radiology. 2016 Jun;279(3):805–16.

5. Hoang Dinh A, Melodelima C, Souchon R, Lehaire J, Bratan F, Mège-Lechevallier F, et al. Quantitative Analysis of Prostate Multiparametric MR Images for Detection of Aggressive Prostate Cancer in the Peripheral Zone: A Multiple Imager Study. Radiology. 2016 Jul;280(1):117–27.

6. Hauth E, Halbritter D, Jaeger H, Hohmuth H, Beer M. Diagnostic value of semi-quantitative and quantitative analysis of functional parameters in multiparametric MRI of the prostate. Br J Radiol. 2017 Oct;90(1078):20170067.

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)
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