Rationale and Objectives
The study aimed to determine the relationship between T2-weighted magnetic resonance imaging (MRI) signal and histologic sub-patterns in prostate cancer areas with different Gleason grades.
Materials and Methods
MR images of prostates ( n = 25) were obtained prior to radical prostatectomy. These were processed as whole-mount specimens with tumors and the peripheral zone was annotated digitally by two pathologists. Gleason grade 3 was the most prevalent grade and was subdivided into packed, intermediate, and sparse based on gland-to-stroma ratio. Large cribriform, intraductal carcinoma, and small cribriform glands (grade 4 group) were separately annotated but grouped together for statistical analysis. The log MRI signal intensity for each contoured region ( n = 809) was measured, and pairwise comparisons were performed using the open-source software R version 3.0.1.
Results
Packed grade 3 sub-pattern has a significantly lower MRI intensity than the grade 4 group ( P < 0.00001). Sparse grade 3 has a significantly higher MRI intensity than the packed grade 3 sub-pattern ( P < 0.0001). No significant difference in MRI intensity was observed between the Gleason grade 4 group and the sparse sub-pattern grade 3 group ( P = 0.54). In multivariable analysis adjusting for peripheral zone, the P values maintained significance (packed grade 3 group vs grade 4 group, P < 0.001; and sparse grade 3 sub-pattern vs packed grade 3 sub-pattern, P < 0.001).
Conclusions
This study demonstrated that T2-weighted MRI signal is dependent on histologic sub-patterns within Gleason grades 3 and 4 cancers, which may have implications for directed biopsy sampling and patient management.
Introduction
Prostatic adenocarcinoma is the most frequently diagnosed solid organ tumor in men and the second most common cause of male mortality in the western world . Early diagnosis facilitates appropriate management and may improve patient outcome . Transrectal ultrasound guided biopsy is performed to confirm the diagnosis following a serum prostate-specific antigen test and digital rectal examination. This technique randomly samples a small percentage of the prostate and may underestimate the aggressiveness of the disease . As the Gleason score of the biopsy will help dictate management, improved targeting and sampling of tumor foci will help refine individual patient options, specifically by differentiating patients with cancer requiring radical therapy (surgery and external beam radiotherapy) from those who may benefit from newer focal therapies (high intensity focused ultrasound, interstitial brachytherapy, etc), and also help appropriately stratify patients to active surveillance .
T2-weighted (T2W) magnetic resonance imaging (MRI) is an important part of the current multiparametric MRI paradigm but by itself localizes tumors within the prostate with insufficient accuracy . Studies addressing the correlation of MRI findings and histopathologic tumor assessment at radical prostatectomy have been performed , and specifically previous papers have shown that several pathologic characteristics can be determined with MRI-derived parameters, including tumor volume , cell density , intermixed benign tissue , stromal type , percentage area of tissue components , cancer aggressiveness , and histologic architecture .
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Materials and Methods
Subjects
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Table 1
Clinicopathologic Features of 25 Study Participants
Patient Age Biopsy Gleason Score Days Between MRI and Surgery Gland Volume (cc) Preoperative PSA (ng/mL) Prostatectomy Gleason Score T-stage Margins 1 62 3 + 3 9 35.9 5.45 4 + 3 pT2c Negative 2 64 3 + 4 27 31.0 4.3 3 + 4 pT3a Negative 3 59 3 + 4 34 37.1 4.46 3 + 4 pT2c Negative 4 53 3 + 3 7 26.0 3.71 3 + 4 pT2c Negative 5 64 3 + 3 14 39.2 10.26 3 + 4 pT3a Negative 6 56 NA 2 23.1 3.93 3 + 3 pT3a Positive 7 67 3 + 3 15 41.0 5.29 3 + 3 pT2c Negative 8 44 3 + 3 34 23.6 1.25 3 + 3 pT2c Positive 9 58 3 + 3 16 40.2 5.33 3 + 3 pT2c Negative 10 64 3 + 3 8 52.1 6.32 3 + 4 pT3a Negative 11 53 3 + 3 15 34.2 5.15 3 + 4 pT2c Negative 12 62 3 + 4 13 52.5 3.46 3 + 4 pT2c Negative 13 60 3 + 3 2 33.8 4.39 3 + 3 pT3a Negative 14 60 3 + 4 20 29.4 4.81 3 + 4 pT2c Negative 15 63 3 + 4 5 22.9 4.66 3 + 3 pT2c Positive 16 69 3 + 3 1 41.6 4.12 3 + 4 pT2c Negative 17 66 3 + 4 9 61.9 4.3 3 + 4 pT2c Negative 18 70 3 + 4 6 34.4 9.03 3 + 4 pT3b Negative 19 64 3 + 3 9 29.2 7.1 3 + 4 pT3a Negative 20 71 3 + 4 6 29.3 4.22 3 + 4 pT3a Negative 21 59 3 + 3 9 47.5 4.41 3 + 4 pT2c Negative 22 58 3 + 3 34 42.5 18.76 3 + 3 pT2c Positive 23 63 3 + 3 15 46.4 4.71 3 + 3 pT2c Negative 24 56 3 + 3 15 28.8 4.57 3 + 4 pT2c Positive 25 67 3 + 4 20 48.4 11.23 3 + 4 pT2c Negative
MRI, magnetic resonance imaging; PSA, prostate-specific antigen.
Due to potential sampling issues and possible undergrading on biopsy, the option of radical prostatectomy was made available to men with biopsy Gleason score 6 prostate cancer.
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MRI
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Table 2
T2W Protocol Parameters
Sequence Clinical T2W High-resolution T2W Ex Vivo T1W Ex Vivo T2W Protocol Fast spin echo (FSE) 3D fast spin echo (3D FSE) 3D spoiled gradient echo 3D fast spin echo (3D FSE) Repetition time (ms) 3800–12,800 2000 6.4–6.5 2000 Echo time (ms) 155–165 144–177 2.3–2.8 146–170 Bandwidth (kHz) 31.25 125 31.25 62.5–125 Number of excitations 2 0.5–2 8–16 3–8 Field of view (cm) 14 14 14 14 Slice thickness (mm) 2.2 1.4 0.4–0.6 0.4–0.6 Slice spacing (mm) 2.2 0.7 0.2–0.3 0.2–0.3 Matrix 320 × 192 320 × 192 256 × 192 320 × 192 Number of slices 29–46 84–144 204–312 204–312 Flip angle (°) 90 90 15 90
3D, three-dimensional; T1W, T1-weighted; T2W, T2-weighted.
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Histology
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Annotations
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Coregistration
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on a total of 1482 control point pairs across 25 patient image pairs), the rigid coregistration of the in vivo images (0.7 ± 0.1 mm, measured using identified pairs of homologous landmarks across three patient images), and the histology reconstruction (0.7 ± 0.4 mm, previously quantified ).
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Statistics
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Results
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Table 3
Pairwise Comparisons of Annotations, n = 809 Contours
Average Difference in MRI Intensity, Log Scale 95% CI_P_ value Overall <0.0001 LC/IDC/SC versus intermediate grade 3 0.17 0.06 to 0.28 2.8 × 10 −3 Packed grade 3 versus intermediate grade 3 −0.16 −0.28 to −0.04 0.011 Sparse grade 3 versus intermediate grade 3 0.13 0.04 to 0.23 7.1 × 10 −3 Packed grade 3 versus LC/IDC/SC −0.33 −0.47 to −0.19 2.5 × 10 −6 Sparse grade 3 versus LC/IDC/SC −0.04 −0.16 to 0.09 0.54 Sparse grade 3 versus packed grade 3 0.29 0.15 to 0.43 3.4 × 10 −5
CI, confidence interval; IDC, intraductal carcinoma; LC, large cribriform; MRI, magnetic resonance imaging; SC, small cribriform.
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Table 4
Pairwise Comparisons of Annotations by Subgroup, n = 809 Contours
Average Difference in MRI Intensity, Log Scale 95% CI_P_ value PZ contours, n = 554 0.26 LC/IDC/SC versus intermediate grade 3 0.08 −0.04 to 0.19 0.21 Packed grade 3 versus intermediate grade 3 −0.09 −0.24 to 0.07 0.27 Sparse grade 3 versus intermediate grade 3 0.03 −0.07 to 0.14 0.52 Packed grade 3 versus LC/IDC/SC −0.16 −0.33 to 0.005 0.058 Sparse grade 3 versus LC/IDC/SC −0.04 −0.18 to 0.09 0.55 Sparse grade 3 versus packed grade 3 0.12 −0.05 to 0.29 0.16 Non-PZ contours, n = 255 LC/IDC/SC versus intermediate grade 3 0.15 −0.03 to 0.34 0.10 Packed grade 3 versus intermediate grade 3 −0.17 −0.33 to 0.001 0.051 Sparse grade 3 versus intermediate grade 3 0.05 −0.07 to 0.18 0.40 Packed grade 3 versus LC/IDC/SC −0.32 −0.53 to −0.11 0.0031 Sparse grade 3 versus LC/IDC/SC −0.10 −0.29 to 0.09 0.31 Sparse grade 3 versus packed grade 3 0.22 0.03 to 0.41 0.021
CI, confidence interval; IDC, intraductal carcinoma; LC, large cribriform; MRI, magnetic resonance imaging; PZ, peripheral zone; SC, small cribriform.
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Table 5
Pairwise Comparisons of Annotations, Adjusted for Peripheral Zone, n = 809 Contours
Average Difference in MRI Intensity, Log Scale 95% CI_P_ value Annotation <0.0001 LC/IDC/SC versus intermediate grade 3 0.12 0.02 to 0.22 0.023 Packed grade 3 versus intermediate grade 3 −0.13 −0.24 to −0.01 0.032 Sparse grade 3 versus intermediate grade 3 0.11 0.03 to 0.20 0.011 Packed grade 3 versus LC/IDC/SC −0.25 −0.38 to −0.11 0.00019 Sparse grade 3 versus LC/IDC/SC −0.0063 −0.12 to 0.11 0.92 Sparse grade 3 versus packed grade 3 0.24 0.11 to 0.37 0.00026 Peripheral zone 0.36 0.29 to 0.43 <0.0001
CI, confidence interval; IDC, intraductal carcinoma; LC, large cribriform; MRI, magnetic resonance imaging; SC, small cribriform.
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Discussion
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Conclusions
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Supplementary Data
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Appendix S1
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