Magnetic Resonance Imaging-Determined Tumor Contact Area to predict Pathological Extra Prostatic Extension in Clinical T2 Prostate Cancer.

Magnetic Resonance Imaging-Determined Tumor Contact Area to predict Pathological Extra Prostatic Extension in Clinical T2 Prostate Cancer. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Magnetic Resonance Imaging-Determined Tumor Contact Area to predict Pathological Extra Prostatic Extension in Clinical T2 Prostate Cancer. Masashi Tsujimoto, Yuta Inoue, Hideto Taga, Yumiko Saito, Masatomo Kaneko, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5149841/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives : To assess the valuability of MRI-determined tumor contact area as a predictive factor of pathological extraprostatic extension in cT2N0M0 prostate cancer. Methods : Seventy-two cT2N0M0 prostate cancer patients were retrospectively analyzed who received multiparametric MRI followed by robot-assisted laparoscopic prostatectomy as a primary treatment between February 2014 and April 2021. Patients were excluded whose index lesion did not match between MRI and pathological specimen. MRI-determined tumor contact area was approximated as an ellipse shape, and calculated by two different formula: MRI-TCA1 was calculated using both tumor contact length in axial plane and longer tumor contact length in sagittal or coronal plane. MRI-TCA2 was calculated using tumor contact length in axial plane and tumor thickness in volume data. Results : Sixteen patients were pathologically extraprostatic extension positive. Age, initial PSA, preoperative T classification, Gleason score and resection margin status were no significance between extraprostatic extension positive and negative. MRI-determined tumor contact length, MRI-TCA1 and MRI-TCA2 were significantly greater in extraprostatic extension positive than in negative (p<0.0001, p<0.0001 and p=0.0026, respectively). Conclusions : MRI-determined tumor contact area was clinically available parameter to predict extraprostatic extension in cT2N0M0 prostate cancer. Tumor contact area Tumor contact length Extraprostatic extension Prostate cancer Magnetic resonance imaging Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction EPE for prostate cancer is defined as a presence of cancer cells beyond the prostate gland margin. EPE is related to positive surgical margin for cancer, 1 and is a risk factor for biological recurrence after RP in prostate cancer. 2 Macroscopic EPE could be typically diagnosed by abnormal signs of prostate capsule in MRI; however, microscopic EPE is difficult to be identified based on the issue in relation between resolution of MRI image and size (some micrometer) of cancer cell. We previously reported that ultrasonography- or MRI-determined TCL (defined as the amount of cancer in contact with the prostate capsule) predict the possibility of microscopic EPE. 3 , 4 It will be beneficial to reliably assess microscopic EPE for cT2 patients diagnosed by mpMRI. Since the risk of EPE could be correlated with how much cancer nodule in conctact with prostate margin, it might be better achieved by measure of two-dimensional ‘area’ in contact with prostate capsule than only by measure of single-dimensional ‘length’ in contact with prostate capsule. In previous reports, contact surface area of prostate cancer on mpMRI, calculated with 3D-conversion software, could be better predicting factor of EPE + . 5,6 We investigated the valuability of MRI-determined TCA, measured only in two-dimensional axial plane and calculated from simpler measurement methods, no special processing or no 3D conversion software required, as a clinically applicable EPE + predicting factor (Fig. 1 ). Methods Multiparametric MRI was performed using a 3-Tesla magnetic field strength and a pelvic phased-array coil MR system (MAGNETOM Skyra, Siemens, Erlangen, Germany). T1-weighted, T2-weighted, diffusion-weighted and dynamic gadolinium contrast-enhanced imaging sequences, including the calculation of apparent diffusion coefficient maps, were acquired. We reviewed cT2N0M0 prostate cancer patients who underwent robot assisted laparoscopic prostatectomy between February 2014 and April 2021 in our institution. All the patients had at least one MRI-visible, biopsy-proven tumor (index tumor) which was diagnosed organ-confined (cT2). On the basis of PI-RADs version 2.1, 7 there are four features to indicate EPE: (i) capsular irregularity or bulging; (ii) invasion or asymmetry of the neurovascular bundles; (iii) “filling in” of the retroprostatic angle and (iv) TCL > 10mm in axial plane. We defined cT3a as a tumor which had two or more features among the four features of (i)-(iv). Based on this criteria, we extracted patients whose pathological index tumor was associated with MRI-based index lesion, and 72 patients were eligible. Medical charts were retrospectively reviewed to obtain the data analyzed in this study. This study was approved by the institutional review board of Kyoto Prefectural University of Medicine (ERB-C-1146-2 and ERB-C-1078-2) and conformed to the provisions of the Declaration of Helsinki. Written informed consent was obtained from all patients. We found out each person’s age, preoperative PSA, Gleason score, preoperative T classification, preoperative MRI findings and pathological specimen. MRI-TCL, MRI-TCA and MRI tumor area were calculated using Osirix MD (Pixmeo SARL, Bernex, Switzerland). Pathological-TCL and pathological tumor area were calculated using ImageJ®ฎ (National Institutes of Health, USA). Axial scans of T2-weighted images were used to measure MRI-TCL. MRI-TCL was defined as the maximum length of the contour of index lesion which contact with the prostatic capsule. Extracted prostate specimens were processed according to the modified Stanford protocol by step-section analysis. 8 Index lesion in the pathological specimen was defined as the lesion which had the highest Gleason score or the largest tumor lesion. Pathological-TCL was also defined as the maximum length of the contour of index lesion which contact with the prostatic capsule. MRI tumor volume, pathological tumor volume and pathological TCA were calculated as below: MRI tumor volume (cm 3 ) = Area (mm 2 ) x slice thickness (3mm) x (number of slice + 1) x 6/π x 1/1000 Pathological tumor volume (cm 3 ) = Area (mm 2 ) x slice thickness (estimated 3mm) x (number of slice + 1) x 6/π x 1/1000 Pathological-TCA (mm 2 ) = TCL (mm) /2 x slice thickness (estimated 3mm) x (number of slice + 1)/2 x π MRI-TCA was calculated by two different ways. MRI-TCA1 was calculated using the formula for area of an ellipse. MRI-TCA2 was calculated using the same way as pathological-TCA (Fig. 2 ): MRI-TCA1 (mm 2 ) = TCL (mm) /2 x (coronal or sagittal TCL: longer one) /2 x π MRI-TCA2 (mm 2 ) = TCL (mm) /2 x slice thickness (3mm) x (number of slice + 1) /2 x π All analyses were conducted with JMP pro version 16.0.0 (SAS Institute, Cary, NC, USA) and p < 0.05 was considered significant. Ordinal variable and nominal variable were statistically analyzed using Peason’s Chi-squared test. Continuous variable was statistically analyzed using Mann-Whitney U test. ROC curves were used to assess the power to predict EPE+. Results Sixteen patients had pathologically EPE + and 56 patients had EPE-. A median age was 69 (range 52–77) for EPE + and 67 years old (range 53–77) for EPE-, respectively (p = 0.49). A median PSA was 7.43 ng/ml (range 4.56–21.20) for EPE + and 7.17 ng/ml (range 2.69–29.20) for EPE-, respectively (p = 0.46) (Fig. S1). With respect to Gleason score and index tumor location (regarding left or right lobe, peripheral or transitional zone), there was no significant difference between EPE + and EPE-. PI-RADs score was significantly higher on EPE + significantly (Table). A median area of index tumor in MRI was 114.85 mm 2 (range 53.23–551.0) for EPE + and 63.545 mm 2 (range 18.072–218.50) for EPE-, respectively (p = 0.0065). A median volume of index tumor in MRI was 1.854 cm 3 (range 0.926–25.256) for EPE + and 1.459 cm 3 (range 0.231–7.511) for EPE-, respectively (p = 0.0213). A median area of index tumor in pathological specimen was 144.912 mm 2 (range 63.942-515.638) for EPE + and 81.555 mm 2 (range 6.944-280.682) for EPE-, respectively (p = 0.0097). A median volume of index tumor in pathological specimen was 6.368 cm 3 (range 1.206–18.306) for EPE + and 2.305 cm 3 (range 0.080-10.583) for EPE-, respectively (p = 0.0037) (Fig. S2). Compared with EPE- patients, EPE + patients had significantly greater MRI-TCL (p = 0.0000438) and MRI-TCA (both MRI-TCA1 and MRI-TCA2, p = 0.0000430 and p = 0.0026, respectively). Pathological-TCL and TCA were also significantly greater in EPE + patients than those in EPE- patients (p = 0.000000579 and p = 0.000000148, respectively) (Fig. 3). ROC curves were drawn to assess the ability to predict EPE. AUC of pathological-TCA (0.933, %95 CI 0.850–0.972) was higher than that of pathological-TCL (0.912, %95 CI 0.819–0.959), but not significant (p = 0.367). Compared with pathological-TCL and pathological-TCA, MRI-TCL (0.835, %95 CI 0.712–0.912) and MRI-TCA (TCA1: 0.837, %95 CI 0.717–0.912; TCA2: 0.748, %95 CI 0.607–0.851) had comparable diagnostic accuracy, respectively (Fig. 4). When we set the threshold of MRI-TCL as 13.0mm, the sensitivity and specificity to predict EPE were 0.938 and 0.661, respectively. When we set the threshold of MRI-TCA1 as 120.174mm 2 , the sensitivity and specificity to predict EPE were 0.875 and 0.732, respectively. When we set the threshold of MRI-TCA2 as 96.133mm 2 , the sensitivity and specificity to predict EPE were 0.875 and 0.589, respectively. Spearman’s rank correlation coefficient between MRI- and pathological-TCL was 0.568 (p = 0.000000192). Spearman’s rank correlation coefficient between MRI-TCA1 and pathological-TCA, or between MRI-TCA2 and pathological-TCA were 0.561 (p = 0.000000289) and 0.520 (p = 0.00000283), respectively (Fig. S3). Discussion With prostate-MRI, which likely visualizes clinically significant cancer, this study demonstrated that both MRI-TCL and MRI-TCA were significant predictive parameter for pathologic EPE for patients with cT2 prostate cancer. Apparent EPE + patients have a greater risk for positive surgical margin than EPE- patients. It will be clinically beneficial if we could predict more accurate EPE+, for current MRI-based diagnosed cT2 patients, in a reliable quantitative measure. In our study, MRI-TCL was significantly longer in EPE + patients than EPE- patients. The optimal threshold of MRI-TCL to predict EPE + was 13.0mm, which was mostly consistent with the threshold in PI-RADs version 2.1 in relation with EPE+. 7 In our study, EPE + cases tended to have larger index tumor volume and higher PIRADs score. Related to that, Dordaneh et al. reported previously index tumor volume on MRI was found to be an independent predictor of EPE+ (p = 0.01). 9 And Kim et al. reported PIRADs score is potentially useful for predicting EPE+ (p = 0.017). 10 Also several previous reports have supported potential utility of these predicting factors. 11 – 14 Our results of index tumor volume and PIRADs score were mostly consisted with these reports. Most importantly, both MRI-TCL and MRI-TCA had fair diagnostic accuracy to predict EPE. MRI-TCL and MRI-TCA had significant correlation with pathological-TCL and pathological-TCA, respectively. TCA, which was calculated in this study, achieve statistically equivalent performance to predict EPE to TCL both in MRI and pathological specimen, but not superior to TCL, contrary to our hypothesis. These results might be only due to calculation formula of MRI-TCA applied in this study but also current resolution of MRI as well as relatively thick slice-thickness. Caglic et al. reported that 3D-converted tumor contact surface, calculated by using 3D-conversion software, had better predictive value than axial TCL (p = 0.01). 5 Veerman et al. also reported 3D-reconstructed contact surface area on mpMRI could predict pathological EPE + of RP patients (p < 0.001). 6 Though these method have good predictive value for EPE detection, these could not be adapted in other MRI devices. The calculation formula (TCA2, estimated by thickness) of MRI-TCA applied in this study, which applied only axial plane, slice number and slice thickness, was clinically easy and highly versatile without the reported 3D-conversion software and image processing. Ukimura et al. reported that TCL, defined as the amount of prostate cancer in contact with the prostatic capsule, correlated better with microscopic EPE than with cancer volume on regression analysis of 189 RP specimens (chi-square 89 vs 63). 3 However, since interpreting TRUS images is highly operator dependent with limitation to visualize the prostate cancer lesion as well as poor correlation between TRUS-visualized lesion and pathological cancer lesion, clinical use of TRUS determined TCL has been limited. Our study shows first demonstrated that using not TRUS but MRI with simple calculation formula, MRI-TCA has significant correlation with pathological-TCA, which had significantly correlated with pathological EPE as well as to clinically predict pathological EPE. Importantly, there were significant correlation between MRI-TCL and pathological-TCL, as well as between MRI-TCA1 and pathological-TCA, and MRI-TCA2 and pathological-TCA. Then, MRI-determined TCL as well as TCA can be clinically available to predict EPE before treatment. We found that when using MRI-TCA1 method, the best threshold of TCA to predict EPE was 120.174 mm 2 , whose sensitivity and specificity to predict EPE were 0.875 and 0.732, respectively. Our study has several limitations; including its retrospective nature. Although TCL as well as TCA is a quantitative measure to predict the probability of EPE, underestimation or overestimation can occur. Especially, since TCA is not a single measure like TCL but calculated by two measures (such as axial TCL plus other), TCA might have more variability among the interpreter. Such underestimation or overestimation would be minimized when MRI technology, including resolution or slice thickness, would advance in future. Finally, any suspicious clinically significant cancer on MRI should be proved to be cancer histologically by targeted biopsy, before the purpose to predict EPE by its measure. In conclusion, both MRI-TCL and MRI-TCA are clinically available predictive quantitative parameter for pathological EPE. MRI-TCA could become more useful accurate way to predict EPE when mpMRI would advance to have ability of thinner slices or higher resolution. Abbreviations AUC: The area under the curve EPE: Extraprostatic extension EPE-: Extraprostatic extension negative EPE+: Extraprostatic extension positive mpMRI: multiparametric magnetic resonance imaging MRI: Magnetic resonance imaging PIRADs: Prostate Imaging-Reporting and Data System PSA: prostate specific antigen TCA: tumor contact area TCL: tumor contact length TRUS: transrectal ultrasound ROC: Receiver Operating Characteristic RP: radical prostatectomy Declarations Conflict of interest statement The authors have no conflicts of interest to report. Approval of the research protocol by an Institutional Reviewer Board Yes (authorization number: ERB-C-1146-2 and ERB-C-1078-2). Informed Consent Yes. Written informed consent was obtained from all patients. Registry and the Registration No. of the study Not applicable. Animal Studies Not applicable. Author Contribution M.T. and Y.I. wrote the main manuscript text and prepared figures. Data curation was done by M.T. and Y.I. All authors reviewed the manuscript.M.T. and Y.I. contributed equally to this article. References Tollefson MK, Karnes RJ, Rangel LJ et al. The impact of clinical stage on prostate cancer survival following radical prostatectomy. J. Urol. 2013; 189: 1707-12. Godoy G, Tareen BU, Lepor H. Site of positive surgical margins influences biochemicalrecurrence after radical prostatectomy. BJU. Int. 2009; 104: 1610-1614. Ukimura O, Troncoso P, Ramirez EI et al. Prostate cancer staging: correlation between ultrasounddetermined tumor contact length and pathologically confirmedextraprostatic extension. J. Urol. 1998; 159: 1251-1259. Baco E, Rud E, Vlatkovic L et al. Predictive value of magnetic resonance imaging determined tumorcontact length for extracapsular extension of prostate cancer. J. Urol. 2015; 193: 466-472. Caglic I, Povalej Brzan P, et al. Defining the incremental value of 3D T2-weighted imaging in the assessment of prostate cancer extracapsular extension. Eur. Radiol. 2019; 29: 5488-97. Veerman H, Hoeks CMA, Sluijter JH, et al. 3D-reconstructed contact surface area and tumour volume on magnetic resonance imaging improve the prediction of extraprostatic extension of prostate cancer. J. Digit. Imaging. 2023; 36: 486-496 Turkbey B, Rosenkrantz AB, Haider MA, et al. Prostate Imaging Reporting and Data System Version 2.1: 2019 Update of Prostate Imaging Reporting and Data System Version 2. Eur. Urol. 2019; 76: 340–351. Stamey TA, Freiha FS, McNeal JE et al. Localized prostate cancer. Relationship of tumor volume to clinical significance for treatment of prostate cancer. Cancer. 1993; 71: 933-8. Dordaneh S, Abhinav S, Amit LJ, et al. Index tumor volume on MRI as a predictor of clinical and pathologic outcomes following radical prostatectomy. International Urology and Nephrology. 2019; 51:1349–1355 Kim SH, Cho SH, Kim WH, et al. Predictors of extraprostatic extension in patients with prostate cancer. J. Clin. Med. 2023; 12: 5321. Sun C, Chatterjee A, Yousuf A, et al. Comparison of T2-Weighted imaging, DWI, and dynamic contrast-enhanced MRI for calculation of prostate cancer index lesion volume: correlation with whole-mount pathology. Am J Roentgenol. 2019; 212: 351–356. Rud E, Diep L, Baco E, et al. A prospective study evaluating indirect MRI-signs for the prediction of extraprostatic disease in patients with prostate cancer: tumor volume, tumor contact length and tumor apparent diffusion coefficient. World J. Urol. 2018; 36: 629-637 Lim C, Flood TA, Hakim SW, et al. Evaluation of apparent diffusion coefficient and MR volumetry as independent associative factors for extraprostatic extension (EPE) in prostatic carcinoma. J. Magn. Reson. Imaging. 2016; 43: 726-736. Abreu-Gomez J, Walker D, Alotaibi T, et al. Effect of observation size and apparent diffusion coefficient (ADC) value in PI-RADS v2.1 assessment category 4 and 5 observations compared to adverse pathological outcomes. Eur. Radiol. 2020; 30: 4251-4261. Table Table is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table.xlsx Table. The comparison between EPE- and EPE+ patients in Gleason score, tumor location and PI-RADs score. Supplementarymaterial.docx Supporting information Figure S1 Comparison between EPE- and EPE+ patients in age and initial PSA using Mann-Whitney U test. Figure S2 Comparison between EPE- and EPE+ patients in MRI tumor area, MRI tumor volume, pathological tumor area and pathological tumor volume using Mann-Whitney U test. Figure S3 Spearman’s rank correlation coefficient between MRI-TCL and pathological-TCL, MRI-TCA1 and pathological-TCA, and MRI-TCA2 and pathological-TCA. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5149841","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":421445770,"identity":"babd5c3d-663e-4fa2-9f3d-d395bbd771cc","order_by":0,"name":"Masashi Tsujimoto","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBUlEQVRIiWNgGAWjYJACgwQgwc8DZifARZlxKeeBapGQ7GFgbCBaCwhIGJxB04IT2POfMSh4mGNTZ3zm8PEHHxjS8gwOcCcw/KhhYDfHZYtEjoFB4rY0CbOzbYmNMxhyig0O8G5g7DnGwGzZgEsLD0jLYQmz8zyGzTwMFYkb7r/dwMDbwMBscACHFqDDwFqM+2FaQLb8xaeFIQeixYC3B6QlB6yFGa8tN9IKQH6RnHHmWOLMGQZpxZJALYdljkng9At7/+Fthj+32fDz9yQf+PChIjmP7wDvxodvamyScYUYELAZINgGkIgBOkki2QC7chBgfoDMS4Ax7PBoGQWjYBSMgpEFANMWVlOG8ms0AAAAAElFTkSuQmCC","orcid":"","institution":"Department of Urology, Kyoto Prefectural University of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Masashi","middleName":"","lastName":"Tsujimoto","suffix":""},{"id":421445771,"identity":"eeb32c89-f539-44d8-b313-aa22db0a7db7","order_by":1,"name":"Yuta Inoue","email":"","orcid":"","institution":"Department of Urology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuta","middleName":"","lastName":"Inoue","suffix":""},{"id":421445772,"identity":"4a3dd9d4-47f9-4983-aa91-7dd44383675f","order_by":2,"name":"Hideto Taga","email":"","orcid":"","institution":"Department of Urology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hideto","middleName":"","lastName":"Taga","suffix":""},{"id":421445773,"identity":"2a1665be-9900-4e98-ab22-0942d18e5bb3","order_by":3,"name":"Yumiko Saito","email":"","orcid":"","institution":"Department of Urology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yumiko","middleName":"","lastName":"Saito","suffix":""},{"id":421445774,"identity":"1607d9e9-7b9e-4b76-8fff-b4652b1a0265","order_by":4,"name":"Masatomo Kaneko","email":"","orcid":"","institution":"Department of Urology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Masatomo","middleName":"","lastName":"Kaneko","suffix":""},{"id":421445775,"identity":"2ea4395c-7eb2-4a1d-a5a6-926768652cd6","order_by":5,"name":"Masatsugu Miyashita","email":"","orcid":"","institution":"Department of Urology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Masatsugu","middleName":"","lastName":"Miyashita","suffix":""},{"id":421445776,"identity":"300eb6c1-4f4c-4d72-be96-0a03e428f17b","order_by":6,"name":"Takeshi Yamada","email":"","orcid":"","institution":"Department of Urology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Takeshi","middleName":"","lastName":"Yamada","suffix":""},{"id":421445777,"identity":"7272808b-f2ad-431a-9dc1-26fae378eae5","order_by":7,"name":"Yasuhiro Yamada","email":"","orcid":"","institution":"Department of Urology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yasuhiro","middleName":"","lastName":"Yamada","suffix":""},{"id":421445778,"identity":"eff0dff3-a6a9-4c97-98a3-557ea981498d","order_by":8,"name":"Takashi Ueda","email":"","orcid":"","institution":"Department of Urology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Takashi","middleName":"","lastName":"Ueda","suffix":""},{"id":421445779,"identity":"635b756e-39c8-4650-bb39-7b629e67e59c","order_by":9,"name":"Atsuko Fujihara","email":"","orcid":"","institution":"Department of Urology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Atsuko","middleName":"","lastName":"Fujihara","suffix":""},{"id":421445780,"identity":"c4437c9f-df1a-4365-ab96-21428db38526","order_by":10,"name":"Takumi Shiraishi","email":"","orcid":"","institution":"Department of Urology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Takumi","middleName":"","lastName":"Shiraishi","suffix":""},{"id":421445781,"identity":"e4e1cd2e-dab2-4072-8f5d-4189c4d9198c","order_by":11,"name":"Masayoshi Okumi","email":"","orcid":"","institution":"Department of Urology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Masayoshi","middleName":"","lastName":"Okumi","suffix":""},{"id":421445782,"identity":"9e158bfa-aebe-426d-8407-9aac2c78c12c","order_by":12,"name":"Fumiya Hongo","email":"","orcid":"","institution":"Department of Urology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Fumiya","middleName":"","lastName":"Hongo","suffix":""},{"id":421445783,"identity":"eec806af-318b-4f93-ac1b-6c69fc8b032a","order_by":13,"name":"Eiichi Konishi","email":"","orcid":"","institution":"Department of Clinical Pathology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Eiichi","middleName":"","lastName":"Konishi","suffix":""},{"id":421445784,"identity":"9b67150d-4781-4a7d-8ba6-dd3b47439c75","order_by":14,"name":"Kaori Yamada","email":"","orcid":"","institution":"Department of Radiology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kaori","middleName":"","lastName":"Yamada","suffix":""},{"id":421445785,"identity":"0cb4dfba-f83d-4639-b531-4abab2bec399","order_by":15,"name":"Kei Yamada","email":"","orcid":"","institution":"Department of Radiology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kei","middleName":"","lastName":"Yamada","suffix":""},{"id":421445786,"identity":"9bfe6d1a-49cf-497a-ae6b-8259712e2b9a","order_by":16,"name":"Osamu Ukimura","email":"","orcid":"","institution":"Department of Urology, Kyoto Prefectural University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Osamu","middleName":"","lastName":"Ukimura","suffix":""}],"badges":[],"createdAt":"2024-09-25 07:38:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5149841/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5149841/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":77444615,"identity":"4fb2f343-cf08-4f1d-aaec-45b5187fe9f3","added_by":"auto","created_at":"2025-02-28 16:51:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1450590,"visible":true,"origin":"","legend":"\u003cp\u003eTCL and TCA. TCL is defined as the maximum length of the contour of index lesion which contact with the prostatic capsule. In our study, MRI-TCL was measured in axial plane. TCA is the area where tumor contact with prostate capsule.\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5149841/v1/a9ac056b7778166d609ead59.png"},{"id":77445452,"identity":"342a0cc5-837c-40d9-a2a1-b0d50e9385c3","added_by":"auto","created_at":"2025-02-28 16:59:02","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2470620,"visible":true,"origin":"","legend":"\u003cp\u003eAn example of MRI-TCL, MRI-TCA1, MRI-TCA2, pathological-TCL and pathological-TCA.\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5149841/v1/2253f2ddcefa18b1eec36b83.png"},{"id":77444617,"identity":"12e5795b-8bab-4a8a-950b-ec3e94942993","added_by":"auto","created_at":"2025-02-28 16:51:01","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1880059,"visible":true,"origin":"","legend":"\u003cp\u003eComparison between EPE- and EPE+ patients in MRI-TCL, MRI-TCA1, MRI-TCA2, pathological TCL and pathological TCA.\u003c/p\u003e","description":"","filename":"figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5149841/v1/5a1a8790f8486305494908c6.png"},{"id":77444618,"identity":"91ba8851-261a-4caf-b303-be6a28f13b07","added_by":"auto","created_at":"2025-02-28 16:51:01","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1369006,"visible":true,"origin":"","legend":"\u003cp\u003eROC curves were drawn to assess the ability to predict EPE. AUC was drawn to compare between MRI-TCL and MRI-TCA1, MRI-TCL and MRI-TCA2, and pathological-TCL and pathological-TCA.\u003c/p\u003e","description":"","filename":"figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-5149841/v1/23c64b809b4e6a89504bc1e8.png"},{"id":77445783,"identity":"51b8a240-fe14-44e3-876c-cf26a29bb4da","added_by":"auto","created_at":"2025-02-28 17:07:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7234451,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5149841/v1/b098d7fb-af54-4eef-827f-29a7ce174717.pdf"},{"id":77445451,"identity":"8b415e8b-bd14-4cf6-9721-34733a47e924","added_by":"auto","created_at":"2025-02-28 16:59:01","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":10100,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTable.\u003c/strong\u003e The comparison between EPE- and EPE+ patients in Gleason score, tumor location and PI-RADs score.\u003c/p\u003e","description":"","filename":"Table.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5149841/v1/a8b41b7e14d840e22eb58385.xlsx"},{"id":77444619,"identity":"e1848523-d056-4942-be28-a93a24b93edc","added_by":"auto","created_at":"2025-02-28 16:51:02","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":345210,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupporting information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure S1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eComparison between EPE- and EPE+ patients in age and initial PSA using Mann-Whitney U test.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure S2\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eComparison between EPE- and EPE+ patients in MRI tumor area, MRI tumor volume, pathological tumor area and pathological tumor volume using Mann-Whitney U test.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure S3\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSpearman’s rank correlation coefficient between MRI-TCL and pathological-TCL, MRI-TCA1 and pathological-TCA, and MRI-TCA2 and pathological-TCA.\u003c/p\u003e","description":"","filename":"Supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-5149841/v1/d63ed00bb902e03bcec154d6.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Magnetic Resonance Imaging-Determined Tumor Contact Area to predict Pathological Extra Prostatic Extension in Clinical T2 Prostate Cancer.","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEPE for prostate cancer is defined as a presence of cancer cells beyond the prostate gland margin. EPE is related to positive surgical margin for cancer,\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e and is a risk factor for biological recurrence after RP in prostate cancer.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Macroscopic EPE could be typically diagnosed by abnormal signs of prostate capsule in MRI; however, microscopic EPE is difficult to be identified based on the issue in relation between resolution of MRI image and size (some micrometer) of cancer cell. We previously reported that ultrasonography- or MRI-determined TCL (defined as the amount of cancer in contact with the prostate capsule) predict the possibility of microscopic EPE.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e It will be beneficial to reliably assess microscopic EPE for cT2 patients diagnosed by mpMRI. Since the risk of EPE could be correlated with how much cancer nodule in conctact with prostate margin, it might be better achieved by measure of two-dimensional \u0026lsquo;area\u0026rsquo; in contact with prostate capsule than only by measure of single-dimensional \u0026lsquo;length\u0026rsquo; in contact with prostate capsule. In previous reports, contact surface area of prostate cancer on mpMRI, calculated with 3D-conversion software, could be better predicting factor of EPE\u0026thinsp;+\u0026thinsp;.\u003csup\u003e5,6\u003c/sup\u003e We investigated the valuability of MRI-determined TCA, measured only in two-dimensional axial plane and calculated from simpler measurement methods, no special processing or no 3D conversion software required, as a clinically applicable EPE\u0026thinsp;+\u0026thinsp;predicting factor (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eMultiparametric MRI was performed using a 3-Tesla magnetic field strength and a pelvic phased-array coil MR system (MAGNETOM Skyra, Siemens, Erlangen, Germany). T1-weighted, T2-weighted, diffusion-weighted and dynamic gadolinium contrast-enhanced imaging sequences, including the calculation of apparent diffusion coefficient maps, were acquired.\u003c/p\u003e \u003cp\u003eWe reviewed cT2N0M0 prostate cancer patients who underwent robot assisted laparoscopic prostatectomy between February 2014 and April 2021 in our institution. All the patients had at least one MRI-visible, biopsy-proven tumor (index tumor) which was diagnosed organ-confined (cT2). On the basis of PI-RADs version 2.1,\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e there are four features to indicate EPE: (i) capsular irregularity or bulging; (ii) invasion or asymmetry of the neurovascular bundles; (iii) \u0026ldquo;filling in\u0026rdquo; of the retroprostatic angle and (iv) TCL\u0026thinsp;\u0026gt;\u0026thinsp;10mm in axial plane. We defined cT3a as a tumor which had two or more features among the four features of (i)-(iv). Based on this criteria, we extracted patients whose pathological index tumor was associated with MRI-based index lesion, and 72 patients were eligible. Medical charts were retrospectively reviewed to obtain the data analyzed in this study. This study was approved by the institutional review board of Kyoto Prefectural University of Medicine (ERB-C-1146-2 and ERB-C-1078-2) and conformed to the provisions of the Declaration of Helsinki. Written informed consent was obtained from all patients.\u003c/p\u003e \u003cp\u003eWe found out each person\u0026rsquo;s age, preoperative PSA, Gleason score, preoperative T classification, preoperative MRI findings and pathological specimen. MRI-TCL, MRI-TCA and MRI tumor area were calculated using Osirix MD (Pixmeo SARL, Bernex, Switzerland). Pathological-TCL and pathological tumor area were calculated using ImageJ\u0026reg;ฎ (National Institutes of Health, USA). Axial scans of T2-weighted images were used to measure MRI-TCL. MRI-TCL was defined as the maximum length of the contour of index lesion which contact with the prostatic capsule.\u003c/p\u003e \u003cp\u003eExtracted prostate specimens were processed according to the modified Stanford protocol by step-section analysis.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Index lesion in the pathological specimen was defined as the lesion which had the highest Gleason score or the largest tumor lesion. Pathological-TCL was also defined as the maximum length of the contour of index lesion which contact with the prostatic capsule. MRI tumor volume, pathological tumor volume and pathological TCA were calculated as below:\u003c/p\u003e \u003cp\u003eMRI tumor volume (cm\u003csup\u003e3\u003c/sup\u003e)\u0026thinsp;=\u0026thinsp;Area (mm\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e) x slice thickness (3mm) x (number of slice\u0026thinsp;+\u0026thinsp;1) x 6/π x 1/1000\u003c/p\u003e \u003cp\u003ePathological tumor volume (cm\u003csup\u003e3\u003c/sup\u003e)\u0026thinsp;=\u0026thinsp;Area (mm\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e) x slice thickness (estimated 3mm) x (number of slice\u0026thinsp;+\u0026thinsp;1) x 6/π x 1/1000\u003c/p\u003e \u003cp\u003ePathological-TCA (mm\u003csup\u003e2\u003c/sup\u003e)\u0026thinsp;=\u0026thinsp;TCL (mm) /2 x slice thickness (estimated 3mm) x (number of slice\u0026thinsp;+\u0026thinsp;1)/2 x π\u003c/p\u003e \u003cp\u003eMRI-TCA was calculated by two different ways. MRI-TCA1 was calculated using the formula for area of an ellipse. MRI-TCA2 was calculated using the same way as pathological-TCA (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e):\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMRI-TCA1 (mm\u003csup\u003e2\u003c/sup\u003e)\u0026thinsp;=\u0026thinsp;TCL (mm) /2 x (coronal or sagittal TCL: longer one) /2 x π\u003c/p\u003e \u003cp\u003eMRI-TCA2 (mm\u003csup\u003e2\u003c/sup\u003e)\u0026thinsp;=\u0026thinsp;TCL (mm) /2 x slice thickness (3mm) x (number of slice\u0026thinsp;+\u0026thinsp;1) /2 x π\u003c/p\u003e \u003cp\u003eAll analyses were conducted with JMP pro version 16.0.0 (SAS Institute, Cary, NC, USA) and p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant. Ordinal variable and nominal variable were statistically analyzed using Peason\u0026rsquo;s Chi-squared test. Continuous variable was statistically analyzed using Mann-Whitney U test. ROC curves were used to assess the power to predict EPE+.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eSixteen patients had pathologically EPE + and 56 patients had EPE-. A median age was 69 (range 52–77) for EPE + and 67 years old (range 53–77) for EPE-, respectively (p = 0.49). A median PSA was 7.43 ng/ml (range 4.56–21.20) for EPE + and 7.17 ng/ml (range 2.69–29.20) for EPE-, respectively (p = 0.46) (Fig. S1). With respect to Gleason score and index tumor location (regarding left or right lobe, peripheral or transitional zone), there was no significant difference between EPE + and EPE-. PI-RADs score was significantly higher on EPE + significantly (Table). A median area of index tumor in MRI was 114.85 mm\u003csup\u003e2\u003c/sup\u003e (range 53.23–551.0) for EPE + and 63.545 mm\u003csup\u003e2\u003c/sup\u003e (range 18.072–218.50) for EPE-, respectively (p = 0.0065). A median volume of index tumor in MRI was 1.854 cm\u003csup\u003e3\u003c/sup\u003e (range 0.926–25.256) for EPE + and 1.459 cm\u003csup\u003e3\u003c/sup\u003e (range 0.231–7.511) for EPE-, respectively (p = 0.0213). A median area of index tumor in pathological specimen was 144.912 mm\u003csup\u003e2\u003c/sup\u003e (range 63.942-515.638) for EPE + and 81.555 mm\u003csup\u003e2\u003c/sup\u003e (range 6.944-280.682) for EPE-, respectively (p = 0.0097). A median volume of index tumor in pathological specimen was 6.368 cm\u003csup\u003e3\u003c/sup\u003e (range 1.206–18.306) for EPE + and 2.305 cm\u003csup\u003e3\u003c/sup\u003e (range 0.080-10.583) for EPE-, respectively (p = 0.0037) (Fig. S2).\u003c/p\u003e\n\u003cp\u003eCompared with EPE- patients, EPE + patients had significantly greater MRI-TCL (p = 0.0000438) and MRI-TCA (both MRI-TCA1 and MRI-TCA2, p = 0.0000430 and p = 0.0026, respectively). Pathological-TCL and TCA were also significantly greater in EPE + patients than those in EPE- patients (p = 0.000000579 and p = 0.000000148, respectively) (Fig.\u0026nbsp;3).\u003c/p\u003e\n\u003cp\u003eROC curves were drawn to assess the ability to predict EPE. AUC of pathological-TCA (0.933, %95 CI 0.850–0.972) was higher than that of pathological-TCL (0.912, %95 CI 0.819–0.959), but not significant (p = 0.367). Compared with pathological-TCL and pathological-TCA, MRI-TCL (0.835, %95 CI 0.712–0.912) and MRI-TCA (TCA1: 0.837, %95 CI 0.717–0.912; TCA2: 0.748, %95 CI 0.607–0.851) had comparable diagnostic accuracy, respectively (Fig.\u0026nbsp;4). When we set the threshold of MRI-TCL as 13.0mm, the sensitivity and specificity to predict EPE were 0.938 and 0.661, respectively. When we set the threshold of MRI-TCA1 as 120.174mm\u003csup\u003e2\u003c/sup\u003e, the sensitivity and specificity to predict EPE were 0.875 and 0.732, respectively. When we set the threshold of MRI-TCA2 as 96.133mm\u003csup\u003e2\u003c/sup\u003e, the sensitivity and specificity to predict EPE were 0.875 and 0.589, respectively.\u003c/p\u003e\n\u003cp\u003eSpearman’s rank correlation coefficient between MRI- and pathological-TCL was 0.568 (p = 0.000000192). Spearman’s rank correlation coefficient between MRI-TCA1 and pathological-TCA, or between MRI-TCA2 and pathological-TCA were 0.561 (p = 0.000000289) and 0.520 (p = 0.00000283), respectively (Fig. S3).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWith prostate-MRI, which likely visualizes clinically significant cancer, this study demonstrated that both MRI-TCL and MRI-TCA were significant predictive parameter for pathologic EPE for patients with cT2 prostate cancer. Apparent EPE\u0026thinsp;+\u0026thinsp;patients have a greater risk for positive surgical margin than EPE- patients. It will be clinically beneficial if we could predict more accurate EPE+, for current MRI-based diagnosed cT2 patients, in a reliable quantitative measure. In our study, MRI-TCL was significantly longer in EPE\u0026thinsp;+\u0026thinsp;patients than EPE- patients. The optimal threshold of MRI-TCL to predict EPE\u0026thinsp;+\u0026thinsp;was 13.0mm, which was mostly consistent with the threshold in PI-RADs version 2.1 in relation with EPE+. \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn our study, EPE\u0026thinsp;+\u0026thinsp;cases tended to have larger index tumor volume and higher PIRADs score. Related to that, Dordaneh et al. reported previously index tumor volume on MRI was found to be an independent predictor of EPE+ (p\u0026thinsp;=\u0026thinsp;0.01).\u003csup\u003e9\u003c/sup\u003e And Kim et al. reported PIRADs score is potentially useful for predicting EPE+ (p\u0026thinsp;=\u0026thinsp;0.017).\u003csup\u003e10\u003c/sup\u003e Also several previous reports have supported potential utility of these predicting factors.\u003csup\u003e\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Our results of index tumor volume and PIRADs score were mostly consisted with these reports.\u003c/p\u003e \u003cp\u003eMost importantly, both MRI-TCL and MRI-TCA had fair diagnostic accuracy to predict EPE. MRI-TCL and MRI-TCA had significant correlation with pathological-TCL and pathological-TCA, respectively. TCA, which was calculated in this study, achieve statistically equivalent performance to predict EPE to TCL both in MRI and pathological specimen, but not superior to TCL, contrary to our hypothesis. These results might be only due to calculation formula of MRI-TCA applied in this study but also current resolution of MRI as well as relatively thick slice-thickness.\u003c/p\u003e \u003cp\u003eCaglic et al. reported that 3D-converted tumor contact surface, calculated by using 3D-conversion software, had better predictive value than axial TCL (p\u0026thinsp;=\u0026thinsp;0.01).\u003csup\u003e5\u003c/sup\u003e Veerman et al. also reported 3D-reconstructed contact surface area on mpMRI could predict pathological EPE\u0026thinsp;+\u0026thinsp;of RP patients (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003csup\u003e6\u003c/sup\u003e Though these method have good predictive value for EPE detection, these could not be adapted in other MRI devices. The calculation formula (TCA2, estimated by thickness) of MRI-TCA applied in this study, which applied only axial plane, slice number and slice thickness, was clinically easy and highly versatile without the reported 3D-conversion software and image processing.\u003c/p\u003e \u003cp\u003eUkimura et al. reported that TCL, defined as the amount of prostate cancer in contact with the prostatic capsule, correlated better with microscopic EPE than with cancer volume on regression analysis of 189 RP specimens (chi-square 89 vs 63).\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e However, since interpreting TRUS images is highly operator dependent with limitation to visualize the prostate cancer lesion as well as poor correlation between TRUS-visualized lesion and pathological cancer lesion, clinical use of TRUS determined TCL has been limited. Our study shows first demonstrated that using not TRUS but MRI with simple calculation formula, MRI-TCA has significant correlation with pathological-TCA, which had significantly correlated with pathological EPE as well as to clinically predict pathological EPE.\u003c/p\u003e \u003cp\u003eImportantly, there were significant correlation between MRI-TCL and pathological-TCL, as well as between MRI-TCA1 and pathological-TCA, and MRI-TCA2 and pathological-TCA. Then, MRI-determined TCL as well as TCA can be clinically available to predict EPE before treatment. We found that when using MRI-TCA1 method, the best threshold of TCA to predict EPE was 120.174 mm\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, whose sensitivity and specificity to predict EPE were 0.875 and 0.732, respectively.\u003c/p\u003e \u003cp\u003eOur study has several limitations; including its retrospective nature. Although TCL as well as TCA is a quantitative measure to predict the probability of EPE, underestimation or overestimation can occur. Especially, since TCA is not a single measure like TCL but calculated by two measures (such as axial TCL plus other), TCA might have more variability among the interpreter. Such underestimation or overestimation would be minimized when MRI technology, including resolution or slice thickness, would advance in future. Finally, any suspicious clinically significant cancer on MRI should be proved to be cancer histologically by targeted biopsy, before the purpose to predict EPE by its measure.\u003c/p\u003e \u003cp\u003eIn conclusion, both MRI-TCL and MRI-TCA are clinically available predictive quantitative parameter for pathological EPE. MRI-TCA could become more useful accurate way to predict EPE when mpMRI would advance to have ability of thinner slices or higher resolution.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAUC: The area under the curve\u003c/p\u003e\n\u003cp\u003eEPE: Extraprostatic extension\u003c/p\u003e\n\u003cp\u003eEPE-: Extraprostatic extension negative\u003c/p\u003e\n\u003cp\u003eEPE+: Extraprostatic extension positive\u003c/p\u003e\n\u003cp\u003empMRI: multiparametric magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003eMRI: Magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003ePIRADs: Prostate Imaging-Reporting and Data System\u003c/p\u003e\n\u003cp\u003ePSA: prostate specific antigen\u003c/p\u003e\n\u003cp\u003eTCA: tumor contact area\u003c/p\u003e\n\u003cp\u003eTCL: tumor contact length\u003c/p\u003e\n\u003cp\u003eTRUS: transrectal ultrasound\u003c/p\u003e\n\u003cp\u003eROC: Receiver Operating Characteristic\u003c/p\u003e\n\u003cp\u003eRP: radical prostatectomy\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflict of interest statement\u003c/h2\u003e\n\u003cp\u003eThe authors have no conflicts of interest to report.\u003c/p\u003e\n\u003ch2\u003eApproval of the research protocol by an Institutional Reviewer Board\u003c/h2\u003e\n\u003cp\u003eYes (authorization number: ERB-C-1146-2 and ERB-C-1078-2).\u003c/p\u003e\n\u003ch2\u003eInformed Consent\u003c/h2\u003e\n\u003cp\u003eYes. Written informed consent was obtained from all patients.\u003c/p\u003e\n\u003ch2\u003eRegistry and the Registration No. of the study\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eAnimal Studies\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eM.T. and Y.I. wrote the main manuscript text and prepared figures. Data curation was done by M.T. and Y.I. All authors reviewed the manuscript.M.T. and Y.I. contributed equally to this article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTollefson MK, Karnes RJ, Rangel LJ et al. The impact of clinical stage on prostate cancer survival following radical prostatectomy. J. Urol. 2013; 189: 1707-12.\u003c/li\u003e\n\u003cli\u003eGodoy G, Tareen BU, Lepor H. Site of positive surgical margins influences biochemicalrecurrence after radical prostatectomy. BJU. Int. 2009; 104: 1610-1614.\u003c/li\u003e\n\u003cli\u003eUkimura O, Troncoso P, Ramirez EI et al. Prostate cancer staging: correlation between ultrasounddetermined tumor contact length and pathologically confirmedextraprostatic extension. J. Urol. 1998; 159: 1251-1259.\u003c/li\u003e\n\u003cli\u003eBaco E, Rud E, Vlatkovic L et al. Predictive value of magnetic resonance imaging determined tumorcontact length for extracapsular extension of prostate cancer. J. Urol. 2015; 193: 466-472.\u003c/li\u003e\n\u003cli\u003eCaglic I, Povalej Brzan P, et al. Defining the incremental value of 3D T2-weighted imaging in the assessment of prostate cancer extracapsular extension. Eur. Radiol. 2019; 29: 5488-97.\u003c/li\u003e\n\u003cli\u003eVeerman H, Hoeks CMA, Sluijter JH, et al. 3D-reconstructed contact surface area and tumour volume on magnetic resonance imaging improve the prediction of extraprostatic extension of prostate cancer. J. Digit. Imaging. 2023; 36: 486-496\u003c/li\u003e\n\u003cli\u003eTurkbey B, Rosenkrantz AB, Haider MA, et al. Prostate Imaging Reporting and Data System Version 2.1: 2019 Update of Prostate Imaging Reporting and Data System Version 2. Eur. Urol. 2019; 76: 340\u0026ndash;351.\u003c/li\u003e\n\u003cli\u003eStamey TA, Freiha FS, McNeal JE et al. Localized prostate cancer. Relationship of tumor volume to clinical significance for treatment of prostate cancer. Cancer. 1993; 71: 933-8.\u003c/li\u003e\n\u003cli\u003eDordaneh S, Abhinav S, Amit LJ, et al. Index tumor volume on MRI as a predictor of clinical and pathologic outcomes following radical prostatectomy. International Urology and Nephrology. 2019; 51:1349\u0026ndash;1355 \u003c/li\u003e\n\u003cli\u003eKim SH, Cho SH, Kim WH, et al. Predictors of extraprostatic extension in patients with prostate cancer. J. Clin. Med. 2023; 12: 5321.\u003c/li\u003e\n\u003cli\u003eSun C, Chatterjee A, Yousuf A, et al. Comparison of T2-Weighted imaging, DWI, and dynamic contrast-enhanced MRI for calculation of prostate cancer index lesion volume: correlation with whole-mount pathology. Am J Roentgenol. 2019; 212: 351\u0026ndash;356.\u003c/li\u003e\n\u003cli\u003eRud E, Diep L, Baco E, et al. A prospective study evaluating indirect MRI-signs for the prediction of extraprostatic disease in patients with prostate cancer: tumor volume, tumor contact length and tumor apparent diffusion coefficient. World J. Urol. 2018; 36: 629-637\u003c/li\u003e\n\u003cli\u003eLim C, Flood TA, Hakim SW, et al. Evaluation of apparent diffusion coefficient and MR volumetry as independent associative factors for extraprostatic extension (EPE) in prostatic carcinoma. J. Magn. Reson. Imaging. 2016; 43: 726-736.\u003c/li\u003e\n\u003cli\u003eAbreu-Gomez J, Walker D, Alotaibi T, et al. Effect of observation size and apparent diffusion coefficient (ADC) value in PI-RADS v2.1 assessment category 4 and 5 observations compared to adverse pathological outcomes. Eur. Radiol. 2020; 30: 4251-4261.\u003c/li\u003e\n\u003c/ol\u003e\n"},{"header":"Table","content":"\u003cp\u003eTable is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Tumor contact area, Tumor contact length, Extraprostatic extension, Prostate cancer, Magnetic resonance imaging","lastPublishedDoi":"10.21203/rs.3.rs-5149841/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5149841/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e: To assess the valuability of MRI-determined tumor contact area as a predictive factor of pathological extraprostatic extension in cT2N0M0 prostate cancer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: Seventy-two cT2N0M0 prostate cancer patients were retrospectively analyzed who received multiparametric MRI followed by robot-assisted laparoscopic prostatectomy as a primary treatment between February 2014 and April 2021. Patients were excluded whose index lesion did not match between MRI and pathological specimen. MRI-determined tumor contact area was approximated as an ellipse shape, and calculated by two different formula: MRI-TCA1 was calculated using both tumor contact length in axial plane and longer tumor contact length in sagittal or coronal plane. MRI-TCA2 was calculated using tumor contact length in axial plane and tumor thickness in volume data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Sixteen patients were pathologically extraprostatic extension positive. Age, initial PSA, preoperative T classification, Gleason score and resection margin status were no significance between extraprostatic extension positive and negative. MRI-determined tumor contact length, MRI-TCA1 and MRI-TCA2 were significantly greater in extraprostatic extension positive than in negative (p\u0026lt;0.0001, p\u0026lt;0.0001 and p=0.0026, respectively).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: MRI-determined tumor contact area was clinically available parameter to predict extraprostatic extension in cT2N0M0 prostate cancer.\u003c/p\u003e","manuscriptTitle":"Magnetic Resonance Imaging-Determined Tumor Contact Area to predict Pathological Extra Prostatic Extension in Clinical T2 Prostate Cancer.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-28 16:50:57","doi":"10.21203/rs.3.rs-5149841/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"26baf431-d2c6-4bf1-b841-8256ec50c98a","owner":[],"postedDate":"February 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-28T16:50:57+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-28 16:50:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5149841","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5149841","identity":"rs-5149841","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}