Mrishta Brizmohun Appayya1, Harbir Singh Sidhu2,3, Nikolaos Dikaios2, Edward William Johnston2,3, Lucy Simmons4, Alex Freeman5, Alex Kirkham3, Hashim Uddin Ahmed4, and Shonit Punwani2,3
1Department of Radiology, Erasme Hospital, Universite Libre de Bruxelles, Brussels, Belgium, 2Centre for Medical Imaging, University College of London, London, United Kingdom, 3Department of Radiology, University College London Hospital, London, United Kingdom, 4Division of Surgery and Interventional Science, University College London Hospital, London, United Kingdom, 5Department of Pathology, University College London Hospital, London, United Kingdom
Synopsis
Despite the strong potential of multi-parametric
MRI (mpMRI) in prostate cancer detection, 37% of prostate mp-MRI are Likert-scored
3/5, which are indeterminate for the presence of significant cancer. In this study, we assessed whether quantitative
analysis of PSA, gland volume, volume-adjusted PSA density, PIRADS rescoring of Likert 3/5
lesions and qualitative prostate mpMRI descriptors could better characterise equivocal
prostate lesions within the peripheral. We found that discontinuous signal
changes on qualitative mpMRI were associated with clinically non-significant
cancer; PIRADS rescoring did not appropriately categorise patients with clinically
significant cancer. Conversely, PSA density was the most statistically
significant discriminator (p=0.0040).Purpose
The main aim
of this study is to characterize the indeterminate Likert-scored 3/5 lesions within the peripheral zone (PZ) of
the prostate on mpMRI by (i) quantitative analysis of serum Prostate-Specific
Antigen (PSA), prostate gland volume and PSA density, (ii) the application of
the latest PIRADS scoring system to the Likert-scored 3/5 lesions, and (iii) qualitative
mpMRI morphological descriptors.
Methods
Study population: 330 men enrolled in the PICTURE study 1 underwent mpMRI of the prostate which were
all prospectively scored on a Likert scale by a radiologist (Reader A) with 8
years of experience blinded to histopathological results. Inclusion criteria: Patients with a score of 3/5 within the PZ, on
prostate mpMRI (T2, DWI with b2000 weighted imaging, ADC map and DCE) at 3T
with a pelvic-phased array coil and
in whom twenty-zone trans-perineal template prostate mapping biopsy 2,3 combined to any additional MRI-targeted
index lesion biopsies were performed. This was our standard reference test. The
exclusion criteria are illustrated
in Figure 1. The presence of any Gleason 4 pattern or higher (Gleason ≥7), in
the PZ was considered as clinically significant 4.
PSA
density was calculated by
the quotient of serum PSA over the MRI-calculated whole gland volume 5.
PIRADS
rescoring: A second radiologist
(Reader B), with 4 years of experience retrospectively read and re-scored the
previously reported Likert 3/5 PZ lesions from Reader A, by using the latest
version of PIRADS_v2 6, blinded to histopathology.
Qualitative
mpMRI assessment:
Reader B also qualitatively assessed the
Likert 3/5 scored PZ by using the following morphological criteria: (i) focal –
when it occupied <50% of the slice on which it was best seen, (ii) diffuse
continuous – when it occupied >50% of the gland in an uninterrupted fashion
(iii) diffuse discontinuous – when prostate lesions were interspersed by normal
prostate tissue on >50% of the slice.
Statistics
Mann-Whitney test for unpaired data was used to compare the medians of PSA, gland volume and PSA density between the significant and non-significant cancer group. P-value significance of 0.05 was used. Descriptive statistics were used for PIRADS rescoring and qualitative mpMRI assessment. GraphPad statistical software was used for analysis.
Results
118 of 319 men (37%) had their prostate mpMRI prospectively scored 3/5 (3% [11/319] TZ, 34% [107/319] PZ). Their median age and median PSA were respectively 61 years
(interquartile range, IQR [57-66]) and 7.25 ng/dl (IQR [5.03-10.6]).
76 patients were eligible for quantitative analysis of PSA, gland volume
and PSA density. 21 of them (28%) had clinically significant cancer, 31/76
(41%) harboured low grade (Gleason 3+3) disease and 24/76 (31%) had no cancer. The
median PSA, gland volume and the PSA density of patients with clinically
significant cancer versus non-significant cancer were respectively 7.17/7.20
ng/dl; 42.3/54.5 cc; and 0.134/0.189 ng.cc/ml at a statistical difference of p
=0.9151 for the PSA, p =0.0061 for the gland volume p =0.0040 for the PSA
density as illustrated in
Figure 2.
71 patients were eligible for PIRADS
rescoring of the PZ. 4 of them had distorted DWI and the PIRADS ‘Assessment
without adequate DWI’ was used for scoring.
25 of 71 patients (35%) were up-scored
from Likert score 3 to PIRADS score 4. 17 of 25 (68%) had non-significant
cancer and only 8 (8/25, 32%) had clinically significant prostate cancer. Of
the 8 patients, 3 patients had a maximum cancer core length
(MCCL) of up to 2mm, 3 patients had a MMCL of 4-5 mm and only two had a MCCL of each
9mm and 10mm.
41 of 71 patients (58%) were down-scored to 2 on PIRADS scale. 31/41
(76%) had non-clinically significant cancer while 10/41 (24%) had clinically significant
prostate: one patient had a dominant Gleason 4 pattern (4+3, MCCL 6mm), one
patient had Gleason 3+4 with MCCL of 6mm, five had a MCCL of 4-5mm, and three
patients had a MCCL of 1-3mm.
5 patients of 71 (7%) were scored 3 on PIRADS and none had clinically
significant cancer.
These results are illustrated in Figure 3. Three of the four men with distorted DWI were
upscored to 4 and two of them had clinically significant cancer, MCCL of 4 and
9 mm.
The results for qualitative mpMRI assessment are summarized in Figure 4. None of the diffuse discontinuous signal changes
were associated with significant cancer.
Conclusion
Volume-adjusted PSA density is a key driver to better classify the 3/5
Likert-scored peripheral zone of the prostate on mpMRI to discriminate the
presence of significant cancer. PIRADS rescoring of the Likert 3/5 lesions have
not appropriately distinguished significant prostate cancer from
non-significant ones.
Acknowledgements
This work has been supported by the KCL-UCL Comprehensive Cancer Imaging Centre funding [Cancer Research UK (CR-UK) & Engineering and Physical Sciences Research Council (EPSRC)].The majority of this work was undertaken at University College London Hospital and University College London, which receive a proportion of funding from the NIHR Biomedical Research Centre funding scheme [Department of Health UK].References
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