Validation of a diagnostic transition zone prostate cancer model trained in a 1.5T MRI scanner on an independent cohort of patients scanned on a 3T MRI scaner.
Nikolaos Dikaios1, Ed William Johnston1, Hashim Ahmed2, Lucy, Simmons3, Alex Freeman4, Clare Allen5, David Atkinson1, and Shonit Punwani1

1Centre of Medical Imaging, UCL, London, United Kingdom, 2Department:Research Department of Urology, UCL, London, United Kingdom, 3Div of Surgery & Interventional Sci, UCL, London, United Kingdom, 4Histopathology, UCL, London, United Kingdom, 5Radiology, UCL, London, United Kingdom

Synopsis

Diagnostic models for classifying prostate cancer within the transition zone based on multi-parametric magnetic resonance imaging (mp-MRI) have been proposed to improve radiologist’s performance. Such diagnostic models are trained on mp-MRI data acquired at 1.5T or 3T MRI scanners, but to the best of our knowledge no-one has yet examined whether these magnet specific models are interchangeable. This work applied a previously published diagnostic model trained on mp-MRI data acquired at a 1.5T scanner, on an independent cohort of patients with mp-MRI data acquired at a 3T and found that the performance of the model doesn’t drop significantly.

Purpose

Multi-parametric MRI (mp-MRI) facilitates identification of transition zone (TZ) cancers, yet its overall diagnostic accuracy is likely lower in this part of the prostate compared with the peripheral zone. Prior studies [1] have built a TZ diagnostic model based on quantitative mp-MRI parameters for three different cancer definitions and validated it on a temporal cohort of patients, scanned at the same 1.5T Siemens MR scanner at a different time period. In this study we validate the diagnostic ability of this model on a truly independent cohort of patients scanned on a 3T Philips MR scanner.

Multi-parametric magnetic resonance imaging

The previously reported Logistic Regression (LR) model was derived from 1.5T (Avanto, Siemens, Erlangen, Germany) mp-MRI studies [1]. All patients within the new independent cohort underwent a 3T (Achieva, Philips Medical Systems, Best, Netherlands) mp-MRI. All images were acquired with a pelvic-phased array coil; 0.2 mg/kg (maximum 20 mg) of spasmolytic (Buscopan; Boehringer Ingelheim, Ingelheim, Germany) was administered intravenously to reduce peristalsis. The mp-MRI included axial and coronal small field of view T2-weighted imaging; and was supplemented by axial diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE) imaging as reported in the PICTURE dataset [2].

Patient Cohort

All men within the PICTURE study underwent a mp-MRI followed by full template mapping biopsy of the prostate. For this study, the PICTURE database was retrospectively searched for (i) a cohort of men with histologically confirmed transition zone prostate cancer; (ii) a cohort of men negative for transition zone prostate cancer. Sixty-five men (mean age 64 years, range 48–83) with a mean PSA of 8.68 ng/ml (range 0.5–32.4 ng/ml) and mean prostate gland volume of 37.7 ml (range 3–90 ml) comprised the full independent cohort. Cancer was classified by three definitions of significance: (i) anycancer; (ii) definition-1 (≥Gleason 4+3 or ≥6mm cancer core length (CCL)) [high risk-significant]; and (iii) definition-2 (≥Gleason 3+4 or ≥4mm CCL) cancer [intermediate-high risk-significant]. Previous work1 has showed that the three mp-MRI variables that best classified TZ PCa are the Apparent Diffusion Coefficient (ADC), normalized T2 signal intensity and Maximum Enhancements (ME), and trained a LR model based on these parameters for each cancer definition. These LR models are now validated on the PICTURE independent cohort using receiver operating characteristic (ROC) analysis for each cancer definition.

Results

In the PICTURE independent validation patient cohort, 31/65 patients were positive for any-cancer, of these 19/31 for definition-2 cancer, and of these 14/19 for definition-1 cancer. 34/65 patients had a negative biopsy of the transition zone. Applying the previously derived LR model [1] to the PICTURE dataset, the ROC area under curve (ROC-AUC) for prediction of patients with any-cancer, definition-2 and definition-1 cancer model was 0.69 (95% CI 0.56–0.82), 0.66 (95% CI 0.53–0.79) and 0.63 (95% CI 0.50–0.77). To achieve >90% sensitivity on the PICTURE independent cohort, the specificities of the models were 32% (thre=0.65; any-cancer), 52% (thre=0.96; definition-2), and 45% (thre=0.35; definition-1), where thre is the probability threshold.

Compare with previously reported data

Figures 1 and 2 compare the performance of the LR model on the PICTURE independent cohort of patients scanned on a 3T scanner with the previously published performance1 on a temporal validation cohort scanned on a 1.5T scanner. The ROC-AUC performance on the temporal validation cohort for any-cancer, definition-2 and definition-1 cancer model was 0.76 (95% CI 0.66–0.87), 0.67 (95% CI 0.55–0.79) and 0.70 (95% CI 0.55–0.85). To achieve >90% sensitivity on the temporal validation cohort, the LR model had specificities of 25% (thre=0.52; any-cancer), 30% (thre=0.27; definition-2), and 33% (thre=0.27; definition-1). The specificities achieved on the temporal validation cohort for high sensitivities are lower than the respective specificities for the PICTURE independent cohort for all cancer definitions.

Conclusions

Clinically it will be more important not to miss patients with significant cancer. A high sensitivity is required to achieve this. We demonstrate that overall performance of TZ specific mp-MRI LR model based on a 1.5T MR scanner can be applied on an independent cohort of patients scanned at a 3T MR scanner. Furthermore, at a high sensitivity (>90%) the models provide a moderate specificity (approx. 50%) for significant cancer (definition-2).

Acknowledgements

This work was undertaken at the Comprehensive Biomedical Centre, University College Hospital London, which received a proportion of the funding from the National Institute for Health Research (NIHR) Biomedical Research Centre and was supported by the CRUK/EPSRC KCL/UCL comprehensive cancer imaging centre.

References

[1] Dikaios N, Alkalbani J, Sidhu HS, et al. Logistic regression model for diagnosis of transition zone prostate cancer on multi-parametric MRI.Eur Radiol. 2015;25(2):523-32

[2] Simmons LA, Ahmed HU, Moore CM, et al. The PICTURE study -- prostate imaging (multi-parametric MRI and Prostate HistoScanning™) compared to transperineal ultrasound guided biopsy for significant prostate cancer risk evaluation.M.Contemp Clin Trials. 2014;37(1):69-83.

Figures

Receiver operating characteristic curves for temporal and independent validation of LR models to classify the presence of definition-2 cancer (≥4 mm with ≥ Gleason 3+4).

Receiver operating characteristic curves for temporal and independent validation of LR models to classify the presence of definition-1 cancer (≥6 mm with ≥ Gleason 4+3).



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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