Short summary

Prostate cancer is the most common form of cancer amongst men in Denmark with approximately 4.500 new cases each year. Thus, ensuring that the process of diagnosing prostate cancer is safe and efficient is of great importance. Previous research has found multiparametric magnetic resonance imaging (mpMRI) prior to biopsy to be a superior method in detecting clinically significant prostate cancers and reducing the number of false positives compared to the standard method. Interpreting the results

Rationale

Prostate cancer is the most common form of cancer amongst men in Denmark with approximately 4.500 new cases each year [1], and around 8.000 going through the diagnostic procedure [2]. Although prostate cancer has a 5-year survival rate at 87% [1], prostate cancer accounts for the second highest number of cancer related deaths in Denmark [3]. Ensuring that the process of diagnosing prostate cancer is safe and efficient is therefore of utmost importance. Moreover, as there is substantial variation in the severity of prostate cancer - some tumors may remain latent for years, whereas others progress rapidly and ultimately lead to mortality - it is important to be able to identify those cases that are clinically significant [2]. The standard method of diagnosing prostate cancer is digital rectal examination (DRE), serum prostate specific antigen (PSA) and transrectal ultrasound scanning (TRUS) with 10-12 biopsies simultaneously. Due to the advancements in the field of magnetic resonance imaging, the Danish national guidelines from DaProCa now recommend multi parametric magnetic resonance imaging (mpMRI) prior to any biopsy [4]. With mpMRI it is possible to map the affected areas, and thereby reduce the number of biopsies needed from 10-12 to 2-4 [2]. More importantly though, by utilizing mpMRI medical doctors who have undergone extensive training can detect approximately 90% of all clinical significant prostate cancers (i.e., prostate cancer with a Gleason score of 7 or higher, including 3+4 prominent, but not predominant Gleason 4 components, and/or a volume of m ≥ 0,5cc and/or extra prostatic extension). Furthermore, mpMRI has a high predicative negative value. Compared to the standard method, mpMRI therefore significantly reduce the false positive rate, as well as decrease the number of biopsy related complications such as fibrosis, sepsis, and in worst case death [4].

To ensure standardization and consistency in the performance, interpretation and reporting of mpMRI exams the prostate imaging-reporting and data system (PIRADS) has been developed. PIRADS provides a grading system that predicts the malignancy of an affected area within the prostate. The newest version v2.1 was reviewed in 2019. Diffusion weighted imaging (DWI) and its derivative apparent diffusion coefficient (ADC) are key elements when grading mpMRI prostate exams according to PIRADS. DWI reflects the random motion of water which in prostate cancer differs from normal prostate tissue. Most clinically significant cancer has restricted diffusion and the ADC value has been reported to correlate inversely with histological grade [5]. PSA density, as measured by mpMRI, correlates with the probability of clinically significant cancer and is another value information that is reported within the PIRADS system [6].

Since 2020, mpMRI prior to any biopsies has gradually been implemented as the standard method of diagnosing prostate cancer at OUH. However, as the interpretation of prostate mpMRI results are very challenging and prone to human error, it is important to engage in continuous quality assurance. The purpose of this study is therefore to investigate the overall quality of clinical interpretations of prostate mpMRI exams performed at OUH. In order to investigate this we compare Gleason's scores with PIRADS 3-5 grades, ADC values and PSA densities from a sample of adult men who have undergone a prostate mpMRI exam and subsequent biopsy.

4.0 HYPOTHESIS AND SPECIFIC AIM The present study is a retrospective study aimed at investigating the overall quality of clinical interpretations of prostate mpMRI exams by comparing Gleason's scores with PIRADS scores, ADC values and PSA densities from a sample of adult men who have undergone a prostate mpMRI exam at OUH. In particular, we will test the null hypothesis that there is no significant difference between Gleason scores and PIRADS scores obtained from prostate mpMRI exams.

9.0 REFERENCES 1. Gaardsted A.M, Engholm G. Statistik om prostatacancer. [internet]. Cancer.dk; kræftens bekæmpelse [2019 aug. 5; cited 2021 apr. 19]. available at: https://www.cancer.dk/prostatakraeft/statistik-prostatakraeft/ 2. Borre M, Wittendorff H, Bentzen L et. al. Diagnostik af prostatacancer: version 2.0. [internet]. Ducg.dk: DaProCa; [2019 oct. 29; cited 2021 apr. 19]. available at: https://ducg.dk/fileadmin/ingen_mappe_valgt/DaProCa_5.2_Diagnostik_v2.pdf 3. Asp-Poulsen K. Kræft i Danmark 2020. [internet]. Cancer.dk; kræftens bekæmpelse [2020 jun.; cited 2021 apr. 19]. avaliable at: https://www.cancer.dk/dyn/resources/File/file/0/8830/1599042887/kraeft-i-danmark_2020.pdf 4. Løgager V, Grauman O, Asmussen J et. al. MR prostata guideline: Dansk Urologisk Selskabs rekommandation for MR-prostata [internet]. Uroradiologi.dk: Dansk Urologisk Selskab; [2020 apr.; cited 2021 apr. 19]. avaliable at: http://uroradiologi.dk/mr-prostata-guideline/ 5. Chatfiels M, Hicks L, Kaur D et. al. PI-RADS: Prostate Imaging - Reporting and Data System: Version 2.1. [internet]. ACR.org: ESUR, ACE and AdMe Tech Foundation: [2019; cited 2021 apr. 19]. Available https://www.acr.org/-/media/ACR/Files/RADS/Pi-RADS/PIRADS-V2-1.pdf?la=en 6. Verma A, St Onge J, Dhillon K, Chorneyko A. PSA density improves prediction of prostate cancer. Can J Urol. 2014 Jun;21(3):7312-21. PMID: 24978363.

Description of the cohort

5.1 Inclusion criteria All biopsy naive men who are 18 years or older and who have, because of prostate cancer suspicion, undergone a mpMRI exam at OUH will be included in this study. The following data must be available for all patients included: CPR-number, procedure sequence, and Gleason score. Only participants who have no prior history of prostate cancer will be included.

5.2 Exclusion criteria Insufficient quality of imaging, failure to administer iv. contrast when performing the mpMRI, any prior radiotherapy, partial- total prostatectomy or other form of treatment that can give elevated serum PSA.

5.3 Study date range This study will use retrospective data collected from 01.06.2016 to 01.06.2021 and prospective data from 01.06.2021 and forward.

Data and biological material

5.5 Data to be collected The following data will be collected: - CRP-number - Age - PSA and calculated PSA-density - PIRADS 3-5 and the ADC-value - Biopsy results from the group with PIRADS 3-5 on mpMRI, including both MR fusion target biopsies and standard biopsies