Characterising Indeterminate Lesions (Likert 3/5) in the Peripheral Zone of the Prostate on Multi-parametric MRI
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

1. 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. Contemp Clin Trials. Jan 2014;37(1):69-83.

2. Barzell WE, Melamed MR. Appropriate patient selection in the focal treatment of prostate cancer: the role of transperineal 3-dimensional pathologic mapping of the prostate--a 4-year experience. Urology. Dec 2007;70(6 Suppl):27-35.

3. Barzell WE, Melamed MR, Cathcart P, Moore CM, Ahmed HU, Emberton M. Identifying candidates for active surveillance: an evaluation of the repeat biopsy strategy for men with favorable risk prostate cancer. J Urol. Sep 2012;188(3):762-767.

4. Eggener SE, Badani K, Barocas DA, et al. Gleason 6 Prostate Cancer: Translating Biology Into Population Health. J Urol. Apr 4 2015.

5. Peng Y, Shen D, Liao S, et al. MRI-based prostate volume-adjusted prostate-specific antigen in the diagnosis of prostate cancer. J Magn Reson Imaging. May 2015.

6. European Society of Uro-Radiologists. PI-RADS v2. 2015; http://www.esur.org/fileadmin/content/user_upload/PIRADS_v2_20141223.pdf, 2015.

Figures

Figure 1. Flow-diagram representing the cohort of patients for this study.

Figure 2. Box-and-whisker diagram illustrating the higher PSA density of patients with significant cancer (red plot: median PSA density = 0.189 ng.cc/ml) than those with non-significant cancer (green plot: median PSA density = 0.134 ng.cc/ml) at a statistically significant difference (p=0.0040).

Figure 3. Bar chart representing the proportion of clinically significant cancer (in blue) among prostate mpMRI which were either upscored to PIRADS 4 (8/25, 32%), downscored to PIRADS 2 (10/41, 24%) or scored PIRADS 3 (0/5, 0%).

Figure 4. This table summarises the results of qualitative mpMRI descriptors used for characterizing Likert 3/5 prostate lesions. None of the diffuse discontinuous signal changes were associated with significant cancer.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
2503