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.