Sensitivity of Prostate Cancer Foci using 1.5 T Multiparametric Magnetic Resonance Imaging

Background: The detection of prostate cancer (CaP) has increasingly being carried out by multiparametric magnetic resonance imaging (mpMRI). Despite many previous studies, the sensitivity for clinically signicant CaP (csCaP) was high, information on mpMRI false-negative lesions is limited. Therefore, the aim of this study was to evaluate the use and limitations of mpMRI in CaP. Methods: A total of 228 CaP foci in 100 patients who underwent 1.5 T mpMRI and radical prostatectomy between December 2015 and June 2017 were retrospectively analyzed. The sensitivities of CaP foci, csCaP, and index tumors (ITs) were measured. Clinically signicant CaP was dened into two categories based on the Gleason score (GS): csCaP/GS ≥ 3 + 4 (GS ≥ 3 + 4 or diameter >10 mm) and csCaP/GS ≥ 4 + 3 (GS ≥ 4 + 3 or diameter >10 mm). In addition, the characteristics of false-negative lesions were identied. The Prostate Imaging Reporting and Data System version 2 was used to determine an mpMRI positive lesion, dened as a lesion having a score of ≥ 3. Results: The sensitivity of all legions, csCaP/GS ≥ 3 + 4, csCaP/GS ≥ 4 + 3, and ITs were 61.4%, 75.8%, 83.0%, and 91%, respectively. There were 91 lesions that were mpMRI false, 40% of which were csCaP/GS ≥ 3 + 4. There were three lesions with a GS of ≥ 8 and ≥ 10 mm in the false-negative results. Conclusions: mpMRI can highly detect ITs and csCaP/GS ≥ 4 + 3; however, a few large and high-GS CaPs constitute undetectable lesions in 1.5 T mpMRI. but large lesions with a high GS were fully detectable[4]. The intensity of the applied magnetic eld may be reason for the missing cases with high-grade and large lesions in our study. In a study by Ulrich et al., the correlation between 1.5 and 3 T within the same patients was reported. This study revealed that comparable objective image quality is revealed by 1.5 T MRI in T2WI but is inferior to 3 T in DWI. The conclusions of the study indicated feasible diagnostic performance even in 1.5 T MRI[24]. However, the inferiority of 1.5 T MRI in DWI might lead to the misdiagnoses in this study.


Background
Prostate cancer (CaP) is the second most prevalent cancer and fth common cause of cancer death among men worldwide [1].
Currently, CaP is diagnosed using prostate-speci c antigen level, digital rectal examination, and transrectal ultrasound-guided systemic biopsy as a standard care. However, overdiagnosis of insigni cant CaP and misdiagnosis of clinically signi cant cancer (csCaP) can result from these strategies.
Therefore, we aimed to analyze the sensitivities of 1.5 T mpMRI without endorectal coil using radical prostatectomy (RP) specimens. In particular, we examined the details of false-negative lesions.

Patients
Men who underwent RP in Yamagata University Hospital between December 2015 and June 2017 were included in this study.
Patients who received androgen deprivation therapy and transurethral resection of prostate before surgery were excluded. mpMRI All patients underwent 1.5 T mpMRI without endorectal coil before prostate biopsy. The orientation of the DWI and DCE MRI was the same as for the T2WI. Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) was used to evaluate the images obtained and were scored as follows: 1, clinically signi cant disease highly unlikely to be present; 2, clinically signi cant cancer unlikely to be present; 3, the presence of clinically signi cant cancer is equivocal; 4, clinically signi cant cancer likely to be present; Page 3/14 and 5, clinically signi cant cancer highly likely to be present [17]. Basically, an mpMRI positive lesion was de ned as a lesion with a score of ≥3 in the PI-RADS v2.

Pathological analysis
Whole prostate specimens were xed in 10% buffered formaldehyde for 48 h, after which the specimens were sectioned perpendicular to the urethra in 4-6-mm serial axial slices and embedded into para n (FFPE block). A 5-μm-thick FFPE section was mounted on glass slides and stained with hematoxylin and eosin.
Each major cancer foci was evaluated for Gleason score (GS), largest size (mm), extra-prostatic extension (EPE), and surgical margin (SM). For each patient, up to three foci were always evaluated, but beyond that, minimal lesions were excluded.
IT was de ned as a lesion having a maximum foci or a high GS within 5 mm of the maximum, which is considered to re ect mainly the prognosis [18,19]. Prostate cancer was categorized into two groups: csCaP/GS ≥3 + 4 (GS ≥3 + 4 or diameter >10 mm) and csCaP/GS ≥4 + 3 (GS ≥4 + 3 or diameter >10 mm).

Statistical analyses
Differences were compared using the Welch t test and the Fisher test, and the free statistical software package R version 3.5.2 (https://cran.r-project.org) was used to perform all statistical analyses.

Sensitivity of pT3
Lesions that were upgraded to pT3 are shown in Table 6. Only four (11.8%) cases of 13 pT3 were diagnosed as cT3 by mpMRI. On the other hand, all pT3 were diagnosed as cT3 by mpMRI.

Discussion
The overall results of this study are similar to those of previous studies. The sensitivity of all lesions with a PI-RADS score of ≥ 3 was 61.4% in this study and 31-62% in previous studies that used RP specimens (Table 3) [6,10,15,20]. The low sensitivity of all lesions re ects the low sensitivity of small and low-GS lesions. However, even in GS ≥ 8, mpMRI misdiagnosed one-third of the lesions with diameters of ≤ 10 mm. In lesions with GS 3 + 4 and diameter ≤ 10 mm, the sensitivity was only 31.6%, which caused the low sensitivity of csCaP/GS ≥ 3 + 4 (77.7%) ( Table 3). Detection rates for csCaP/GS ≥ 3 + 4 (67-75%) in previous studies were similar.
It has been suggested in recent reports that lesions associated with cancer progression and metastasis could be the largest lesions in prostate or highest GS within 5 mm of maximum, called IT [18] [19]. Focal therapy for limited CaP is rationally based on IT hypothesis. Multiparametric MRI, which might be considered a suitable tool for IT detection, has a high detection rate for IT (91% in this study and 80-91% in the previous studies). Nevertheless, the approximately 10% rate of misdiagnosis needs our attention (Table 3).
Tumors undetected in mpMRI are often characterized as small and multifocal [23]. Ninety-one (39.9%) lesions in this study were mpMRI negative, 67 (73.6%) of which were insigni cant cancers (GS ≤ 3 + 4 and ≤ 10 mm) ( Table 4). In case of IT, most undiagnosed lesions were multifocal cancers. However, it was surprising that two cases had an IT with ≥ 20 mm and GS 4 + 5. A previous study using mainly 3 T mpMRI mentioned that mpMRI negative lesions could be high GS, but large lesions with a high GS were fully detectable [4]. The intensity of the applied magnetic eld may be reason for the missing cases with high-grade and large lesions in our study. In a study by Ulrich et al., the correlation between 1.5 and 3 T within the same patients was reported. This study revealed that comparable objective image quality is revealed by 1.5 T MRI in T2WI but is inferior to 3 T in DWI. The conclusions of the study indicated feasible diagnostic performance even in 1.5 T MRI [24]. However, the inferiority of 1.5 T MRI in DWI might lead to the misdiagnoses in this study.
Positive SM is an important factor that re ects the postoperative outcome [25] [26]. Postoperative functional outcomes, including continence and erectile function, are improved by neurovascular bundle preservation techniques [27] [28], which potentially increase positive SM when neurovascular bundle is preserved on the EPE positive side. Although mpMRI is mainly used to predict EPE before surgery, previous reports have mentioned that the sensitivity of EPE is not enough. A meta-analysis showed a sensitivity of 57% and a speci city of 91% for microscopic EPE [29]. The sensitivity and speci city in this study were only 11.8% and 100%, respectively (Table 6). Positive mpMRI lesions had more positive EPE and SM than mpMRI negative lesions (Table 3).
Several limitations of this study should be mentioned. First, this was a retrospective study. Second, the PI-RADS score was estimated by a single physician. Several studies have revealed that there are diagnostic differences across readers [10,30]. Third, there could be differences in characteristics between patients who underwent RP in this study and those who underwent other treatments. Fourth, up to three lesions were always evaluated; however, minimal lesions beyond these three were excluded from this analysis.

Conclusions
Detection of IT and csCaP/GS ≥4 + 3 through mpMRI is high; however, large and high-GS CaPs are sometimes undetected in 1.5 T mpMRI.