Correlation Between mpMRI Staging and Final Surgical Pathology in Prostate Cancer

Purpose: We evaluated the role of multiparametric magnetic resonance imaging (mpMRI) in the diagnosis of prostate cancer and predicting of surgical staging of prostate cancer. Materials and Methods: The study was done in 110 subjects who got mpMRI before radical prostatectomy in our hospital from 2016 to 2019. Preoperative mpMRI findings of 110 were compared to surgical pathology results following radical Prostatectomy. A comparison was made between pathologic staging of prostate cancer and the mpMRI findings. Results: pathologic evaluation confirmed prostate cancer foci (237) were recognized in 110 subjects. Generally, mpMRI sensitivity of 46.4% was found for prostate cancer detection (110/237). Pathological tumor volume was a significant predictor of prostate cancer detection using mpMRI. In 33% of the cases, the pathologic staging is precisely similar to mpMRI and in 43%of the cases, there was a slight difference between the pathologic staging and staging by mpMRI but the cancer was confined to the prostate.in 24% of the cases, there was a significant difference between the pathologic staging and staging by mpMRI. The mpMRI was not able to identify the significant cancer in 24% of the cases. Conclusion: The preoperative mpMRI was useful in detecting prostate cancer and in predicting surgical staging. However, the detection of 24% of clinically significant cancer was missed using mpMRI. As we move toward personalized medicine, use of MRI to biopsy each man's prostate differently rather than based on a pre-defined 12 core seems to be supported in the recent literature.

. Mp-MRI has been used to assess prostate cancer aggressiveness and to identify anteriorly located tumors before and during active surveillance. With the technological advancement of imaging modalities used in prostate cancer assessment, Introduction of the Prostrate Imaging Reporting and Data System (PI-RADS), constitutes a globally accepted standard for the detection, scoring and reporting of suspicious lesions on mpMRI (Weinreb et al., 2016). In two studies, improved detection of clinically significant cancer and a decrease in the identification of indolent cancer were demonstrated with the use of mpMRI in conjunction with PI-RADS and a subsequent targeted biopsy (Borkowetz et al., 2016;Toner et al., 2017). However, as mpMRI with PI-RADS is rapidly being adopted for prostate cancer detection and surveillance, additional efforts to identify the diagnostic accuracy of mpMRI in prostate cancer detection and its ability to predict tumor aggressiveness are warranted to determine if it should play a decisive role in prostate cancer management.
Thus, the essential aims of present study were to evaluate the diagnostic accuracy of mpMRI in the detection of prostate cancer and prediction of pathological staging, and to directly compare the findings on mpMRI with the histological findings from the radical prostatectomy specimen.

Materials and Methods
For this study, we have identified a hundred and ten patients who had experienced mpMRI prior to radical prostatectomy for localized prostate cancer between 2016 and 2019 at our institute. Inclusion criteria were histologically confirmed prostate adenocarcinoma. Finally, 110 patients were selected for inclusion in the study. Data were collected in a database in which patient demographics, clinical results, prostate biopsy results, mpMRI-related information and final histopathological results were documented.
A total of 110 patients underwent mpMRI at the Department of Radiology of our Hospital. In the Department of Radiology, all mpMRI of the prostate is performed on a 3-Tesla MRI system (Siemens Medical Solutions Germany). The mpMRI protocol of the prostate included T2-weighted images in transverse and coronal orientation, T1-weighted images in transverse orientation, diffusion weighted images in transverse orientation, dynamic contrast enhanced imaging in transverse orientation and contrast enhanced T1-weighted images with fat suppression in transverse orientation. The total MRI acquisition time was 30min. Endorectal coil was not used. The mpMRI findings have been scored by using PI-RADS version 2.
The prostate specimens were reviewed by a dedicated uropathologist who was blinded to the mpMRI findings. All prostatic biopsies and radical prostatectomy specimens were investigated at the Pathology unit of our Hospital. The whole prostate was prepared in 3-5mm increments and embedded in paraffin. These sections were cut and stained with haematoxylin and eosin for microscopic examination. Each individual tumor focus in the radical prostatectomy specimen graded according to the Gleason grading system. The highest Gleason score recorded per tumor foci was equated to a corresponding score using the new grading system For example, grade group 1 equated to a Gleason score of 3+3 (the least aggressive), grade group 2 was the equivalent of a Gleason score of 3+4, grade group 3 amounted to a Gleason score of 4+3, grade group 4 equated to a Gleason score of 4+4, 3+5 and 5+3 and a grade group 5 was the equivalent of a Gleason score of 9-10 (the most aggressive).The pathological index tumor was defined as the tumor in the highest-grade group. Based on the calculation of tumor volume, clinically significant cancer was defined as a tumor in grade group 2 with a cancer volume of 0.5 cc. (Weinreb et al., 2016;Wolters et al., 2011;Lee, Ku, Park, Lee, & Ha, 2018).
Data were analysed using SPSS v.23.0. Categorical data are presented as absolute and relative frequencies.
Continuous variables are described using mean values, complemented by median and range values. Linear-by-linear association and the chi-square test were used to compare the rate of tumors detected and missed on mpMRI, according to the pathological features. Spear-man's rank-correlation coefficient was used to determine an association between the PI-RADS score and the pathological features of grade and volume. Cut-off values for pathological tumor volume detected by mpMRI were obtained using the Youden index. A P value <0.05 was taken to indicate statistical significance.

Results
The demographic characteristics of the study are shown in Table 1. The median age of the 110 men who underwent mpMRI prior to RP was 63 years (50-75 years) and median PSA was 10.7 ng/mL (5.1-30). The median time taken from performing mpMRI to conducting RP was 29 days (7-63 days). Unique pathologically confirmed prostate cancer foci (237)  In addition, higher PI-RADS scores were significantly associated with increased tumor volume (P < 0.001). Pathological index tumor volume was the strongest predictor of tumor detection by mpMRI with PI-RADS (P = 0.03). In 33% of the cases, the pathologic staging is precisely similar to mpMRI and in 43%of the cases, there was a slight difference between the pathologic staging and staging by mpMRI but the cancer was confined to the prostate.in 24% of the cases, there was a significant difference between the pathologic staging and staging by mpMRI. The mpMRI was not able to identify the significant cancer in 24% of the cases.

Discussion
The aim of our study was to determine the accuracy of MRI for predicting pathological staging of prostate cancer. The main role of mpMRI with PI-RADS in prostate cancer diagnosis is to identify clinically significant cancer. Although there is no general consensus on the definition of clinically significant PCa, clinically significant cancer is defined on pathology as grade group 2 with a cancer volume of 0.5 cc (Weinreb et al., 2016;Wolters et al., 2011). In present study, 3T mpMRI with PI-RADS demonstrated overall sensitivity of 46.4% and specificity of 75.5% in detecting clinically significant cancer. These results are consistent with those of previous studies. Jesse et al. reported overall sensitivity and specificity of 47% and 72%, respectively, for the detection of clinically significant cancer,12 and Bratan et al. reported 53-59% overall sensitivity (Bratan et al., 2013). Although the individual sequences are useful, T2WI in combination with two functional sequences has been shown to provide better characterization of tumor in the prostate ([42, 43, and 44). In a diagnostic meta-analysis of seven studies, de Rooij et al. revealed a high overall sensitivity and specificity on accuracy of mp-MRI using T2WI, DWI and DCE MRI. Pooled sensitivity and specificity were 0.74 and 0.88, respectively, with negative predictive value (NPV) ranging from 0.65 to 0.94 (de Rooij, Hamoen, Fütterer, Barentsz, & Rovers, 2014).
Although, theoretically, mpMRI with PI-RADS is known to be able to detect intermediate-to high-grade cancers with volumes 0.5cc (Weinreb et al., 2016). Our data showed that 24% of clinically significant cancer and pathological index tumors were missed using this approach.
Wang et al. reported that a decrease in the degree of intensity in the peripheral zone on T2WI correlated with Gleason grade (Wang, Mazaheri, Zhang, Ishill, Kuroiwa, & Hricak, 2008). Similarly, in the case of DWI, the diffusion of water molecules was more restricted in tightly packed high-grade prostate cancer compared to that in low-grade PCa, which is more loosely packed or more normal prostate-like tissue architecture, thus depicting hyperintense focal lesions on high b-value DWI and hypointense focal lesions on ADC mapping. Elsewhere, an inverse correlation between quantitative ADC mapping values and Gleason grade was demonstrated (Hambrock et al., 2011;Nowak et al., 2016). Although our data and those in previous studies suggest that mpMRI with PI-RADS can be used as a tool to predict prostate cancer aggressiveness, attention should be paid to the fact that 36% of lesions classified as PI-RADS 2 were grade group 2. Borkowetz et al. and Truong et al. reported that most tumors that could not be visualized on mpMRI were found to be cribriform ones, which are currently interpreted as Gleason pattern 4 (Borkowetz et al., 2016;Truong, Hollenberg, Weinberg, Messing, Miyamoto, & Frye, 2017). It was suggested that the more open cellular architecture of cribriform tumors, compared to Gleason pattern 4 or 5 tumors, could lead to misinterpretation of high-grade tumors as normal architecture or low-grade tumors on mpMRI.
The value of using staging and treatment planning for prostate cancer has been demonstrated in contemporary studies on mpMRI in prostate cancer (McClure et al., 2012;Somford et al., 2013). In addition, it was shown in a recent prospective trial that when used with targeted biopsy, mpMRI improved the detection of significant prostate cancer and reduced the need for unnecessary invasive tests (Ahmed et al., 2017).

Conclusion
We evaluated the ability mpMRI with PI-RADS (version 2) to detect prostate cancer and a direct comparison was made with the pathology findings for RP specimens. Sensitivity of 76% was found for both clinically significant cancer detection and the findings for pathological index tumors. A moderate and significant correlation was observed between a high PI-RADS score and a high pathological grade, tumor volume, index tumor status and clinically significant cancer status. Pathological index tumor volume was the strongest predictor of tumor detection. The mpMRI was not able to identify the significant cancer in 24% of the cases. MRI/US-fusion biopsy was associated with a higher detection rate of clinically significant prostate cancer while taking fewer cores, especially in patients with prior negative biopsy. As we move toward personalized medicine, use of MRI to biopsy each man's prostate differently rather than based on a pre-defined 12 core seems to be supported in the recent literature.