Simple SummaryEfforts are ongoing to improve the diagnosis of prostate cancer. Novel blood and tissue-based biomarkers, advanced imaging modalities and image-guided biopsy techniques have further improved cancer detection rates. However, approximately 30–40% of cancers are still missed. Analysis of radical prostatectomy specimens is the only gold standard method for confirming the presence or absence of cancers. In this article, we aim to study those cancers that are missed by standard biopsy techniques and advanced imaging modalities, the so-called ‘Stealth’ prostate cancers. We focus on the lobe of the prostate where cancer is not detected on standard biopsy or by preoperative magnetic resonance imaging (MRI). This article helps to explain the significant false negative rates for current diagnostic modalities for prostate cancer. This will help future research to develop new strategies to improve the detection of these ‘stealth’ tumors.AbstractBackground: The aim of this study was to determine the false negative rates of prebiopsy magnetic resonance imaging (MRI) and MRI–ultrasound (US) 12-core systematic prostate biopsy (PBx) by analyzing radical prostatectomy specimens. Methods: This retrospective study included 3600 prostate cancer (PCa) patients who underwent robot-assisted laparoscopic radical prostatectomy. Based on comparison of lobe-specific data on final pathology with preoperative biopsy and imaging data, the study population was subdivided into group I—contralateral (CL) benign PBx (n= 983), group II—CL and/or bilateral (BL) non-suspicious mpMRI (n= 2223) and group III—CL benign PBx + non-suspicious mpMRI (n= 688). This population was studied for the presence of PCa, clinically significant PCa (csPCa), extracapsular extension (ECE) (pathological stage pT3), positive frozen section and final positive surgical margin (PSM) in the CL lobe. Descriptive statistics were performed. Results: In subgroups I, II and III, PCa was respectively detected in 21.5%, 37.7% and 19.5% of cases, and csPCa in 11.3%, 16.3% and 10.3% of cases. CL pT3 disease was seen in 4.5%, 4% and 5.5%, and CL surgical margins and/or frozen section analysis were positive in 6%, 7% and 5% of cases in subgroups I, II and III, respectively. Conclusions: There are still significant rates of false negatives in the standard care diagnostics of PCa. Further strategies are required to improve the accuracy of diagnosis and determination of tumor location.