Low-grade Prostate Cancer Research Articles

MP11-19 IT'S ALL IN THE NAME: DOES NOMENCLATURE FOR INDOLENT PROSTATE CANCER IMPACT MANAGEMENT AND ANXIETY?

You have accessJournal of UrologyProstate Cancer: Staging (MP11)1 Sep 2021MP11-19 IT'S ALL IN THE NAME: DOES NOMENCLATURE FOR INDOLENT PROSTATE CANCER IMPACT MANAGEMENT AND ANXIETY? Anuj S. Desai, Matthew T. Hudnall, Kyle P. Tsai, Adam B. Weiner, Amanda X. Vo, Oliver S. Ko, Stephen Jan, Edward M. Schaeffer, and Shilajit D. Kundu Anuj S. DesaiAnuj S. Desai More articles by this author , Matthew T. HudnallMatthew T. Hudnall More articles by this author , Kyle P. TsaiKyle P. Tsai More articles by this author , Adam B. WeinerAdam B. Weiner More articles by this author , Amanda X. VoAmanda X. Vo More articles by this author , Oliver S. KoOliver S. Ko More articles by this author , Stephen JanStephen Jan More articles by this author , Edward M. SchaefferEdward M. Schaeffer More articles by this author , and Shilajit D. KunduShilajit D. Kundu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001984.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Despite consensus guidelines, many men with low-grade prostate cancer are not managed with active surveillance. Patient perception of the nomenclature used to describe low-grade prostate cancers may partly explain this discrepancy. METHODS: A randomized online survey was administered to men without a history of prostate cancer, presenting a hypothetical clinical scenario where the man is given a new diagnosis of low-grade prostate cancer. Using three terms for low-grade prostate cancer, “Gleason 6 out of 10 prostate cancer”, “Grade group 1 out of 5 prostate cancer”, or “Indolent lesion of epithelial origin,” we tested whether diagnosis nomenclature was associated with management preference and diagnosis-related anxiety immediately following the diagnosis and after receiving disease-specific education. Ratings were made on a 1-to-100 scale and adjusted for participant characteristics through multivariable linear regression. RESULTS: Of the 718 participants, 648 were White (90.2%) and the mean age was 61 (standard deviation 11) years. Most participants were college educated and approximately half had annual incomes >$75,000. There were no differences in baseline characteristics between groups. Compared to “Gleason 6 out of 10 prostate cancer,” the term “Grade Group 1 out of 5 prostate cancer” was associated with lower preference for immediate treatment versus active surveillance (b=–9.3, 95% CI [–14.4 to –4.2], p<0.001) and lower diagnosis-related anxiety (b=-8.3, 95% CI [-12.8 to -3.8], p<0.001) at time of initial diagnosis. Differences decreased as participants received more disease-specific education. “Indolent lesion of epithelial origin,” a suggested alternative term for indolent tumors, was not associated with differences in anxiety or preference for active surveillance. CONCLUSIONS: Within a hypothetical clinical scenario, nomenclature for low-grade prostate cancer affects initial perception of the disease and may alter subsequent decision-making, including preference for active surveillance. Disease-specific education reduces the differential impact of nomenclature use, reaffirming the importance of comprehensive counseling between the clinician and patient. Source of Funding: SPORE prostate cancer P50 CA180995 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e186-e187 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anuj S. Desai More articles by this author Matthew T. Hudnall More articles by this author Kyle P. Tsai More articles by this author Adam B. Weiner More articles by this author Amanda X. Vo More articles by this author Oliver S. Ko More articles by this author Stephen Jan More articles by this author Edward M. Schaeffer More articles by this author Shilajit D. Kundu More articles by this author Expand All Advertisement Loading ...

MP32-11 NATURAL HISTORY, AND IMPACT OF SURGERY AND RADIATION ON SURVIVAL OUTCOMES OF MEN DIAGNOSED WITH LOW GRADE PROSTATE CANCER AT ≤55 YEARS OF AGE - A 25-YEAR FOLLOW UP OF &gt;60,000 MEN

INTRODUCTION AND OBJECTIVE:Low grade prostate cancer (LGPC) has low mortality rates at 10 years. However, it is unclear if the response is sustained for more than 25 years of follow up. We compared...

MP32-13 PATTERNS OF MORTALITY AFTER PROSTATE CANCER: A SEER-BASED ANALYSIS

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History II (MP32)1 Sep 2021MP32-13 PATTERNS OF MORTALITY AFTER PROSTATE CANCER: A SEER-BASED ANALYSIS Roderick Clark, Vasily Giannakeas, and Steven Narod Roderick ClarkRoderick Clark More articles by this author , Vasily GiannakeasVasily Giannakeas More articles by this author , and Steven NarodSteven Narod More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002036.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Low-grade prostate cancer is widely considered to be an indolent disease, based on excellent short-term survival rates. To obtain an accurate representation of prostate cancer mortality it is important to follow patients for sufficient time to capture most prostate cancer-related deaths. The objective of our study was to analyze prostate cancer mortality rates up to 25 years from diagnosis using a large population-based cohort of unselected prostate cancer patients. METHODS: We conducted a population-based, cohort study using data from the Surveillance, Epidemiology and End-Results (SEER) program. We identified 116,796 prostate cancer cases diagnosed between 1992-1997 and followed them until 2017. Our primary outcome was prostate cancer-specific survival. We calculated annual prostate cancer mortality rates and actuarial survival rates using by age of diagnosis, tumour grade and race. RESULTS: The annual prostate cancer mortality rate was 1.5%. The rate was higher than this for older men (2.1%) and for men with cancer of Gleason Score 7 and above (3.1%). There were 21,896 deaths from prostate cancer (23% of all deaths). The majority of deaths (55.6%) occurred in men with low-grade disease. Among men with high-grade cancers, most deaths (54.3%) occurred in the first five years. Among men with low-grade cancers, most deaths (70.1%) occurred after five years. CONCLUSIONS: In this large cohort study, the annual prostate-specific mortality for men with low- grade disease increased with time since diagnosis. The majority of deaths from prostate cancer in the US occur in men with low-grade disease. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e570-e570 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Roderick Clark More articles by this author Vasily Giannakeas More articles by this author Steven Narod More articles by this author Expand All Advertisement Loading ...

MP26-10 CORRELATION OF WHOLE-MOUNT HISTOLOGY WITH FALSE POSITIVES PROSTATE IMAGING REPORTING AND DATA SYSTEMS VERSION 2 CATEGORY 4 AND 5 LESIONS

You have accessJournal of UrologyProstate Cancer: Detection & Screening II (MP26)1 Sep 2021MP26-10 CORRELATION OF WHOLE-MOUNT HISTOLOGY WITH FALSE POSITIVES PROSTATE IMAGING REPORTING AND DATA SYSTEMS VERSION 2 CATEGORY 4 AND 5 LESIONS Yu Xi Terence Law, Edwin Jonathan Aslim, Stephanie Man Chung Fook-Chong, Henry Sun Sien Ho, John Shyi Peng Yuen, Weber Kam On Lau, Lui Shiong Lee, Christopher Wai Sam Cheng, Nye Thane Ngo, Yan Mee Law, and Kae Jack Tay Yu Xi Terence LawYu Xi Terence Law More articles by this author , Edwin Jonathan AslimEdwin Jonathan Aslim More articles by this author , Stephanie Man Chung Fook-ChongStephanie Man Chung Fook-Chong More articles by this author , Henry Sun Sien HoHenry Sun Sien Ho More articles by this author , John Shyi Peng YuenJohn Shyi Peng Yuen More articles by this author , Weber Kam On LauWeber Kam On Lau More articles by this author , Lui Shiong LeeLui Shiong Lee More articles by this author , Christopher Wai Sam ChengChristopher Wai Sam Cheng More articles by this author , Nye Thane NgoNye Thane Ngo More articles by this author , Yan Mee LawYan Mee Law More articles by this author , and Kae Jack TayKae Jack Tay More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002023.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To describe the radiological, clinical and histological features associated with Prostate Imaging Reporting and Date Systems version2 (PIRADsv2) category 4 and 5 lesions that were found to be benign on whole-mount histology. METHODS: We identified men with organ confined prostate cancer who had multiparametric MRI of the prostate performed before primary radical prostatectomy. The MRI images were retrospectively reassessed to identify and grade suspicious lesions. Those of PIRADSv2 categories 4 and 5 were correlated with wholemount histology, classifying the lesions as benign, high grade (Gleason score (GS) 4-5) or low grade (GS 3) prostate cancer. Multivariate logistic regression was used to identify clinical or radiological factors associated with benign histology. RESULTS: There were 128 PIRADSv2 4/5 lesions detected on MRI in 64 patients. On histology, 22.7% (29/128) were benign, 18.0% (23/128) were low-grade (G3) cancer and 59.3% (76/128) were high-grade (GS 4/5) cancer. In 72 PIRADSv2 4 lesions, 20 lesions (28%) are benign, while in 56 PIRADSv2 5 lesions, 9 lesions (16%) are benign. Factors associated with benign pathology at multivariate analysis were lower prostate specific antigen density (PSAD) (Odds ratio (OR) 0.04; p=0.025), smaller volume of MRI lesions (OR 0.93; p=0.041) and posterior location (OR 3.13; p=0.017). The benign histological findings included benign prostate hyperplasia, inflammation (acute, chronic and granulomatous), atrophic glands and high grade prostatic intraepithelial neoplasia. CONCLUSIONS: There is a significant degree of false positive rates with multiparametric MRI for prostate in its current form. Further refinement in techniques, perhaps incorporating certain predictive factors, may improve the diagnostic accuracy for prostate cancer detection. Source of Funding: N.A. © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e466-e466 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yu Xi Terence Law More articles by this author Edwin Jonathan Aslim More articles by this author Stephanie Man Chung Fook-Chong More articles by this author Henry Sun Sien Ho More articles by this author John Shyi Peng Yuen More articles by this author Weber Kam On Lau More articles by this author Lui Shiong Lee More articles by this author Christopher Wai Sam Cheng More articles by this author Nye Thane Ngo More articles by this author Yan Mee Law More articles by this author Kae Jack Tay More articles by this author Expand All Advertisement Loading ...

MP33-08 GUT MICROBIOTA PROFILE ASSOCIATED WITH HIGH-GRADE PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology I (MP33)1 Sep 2021MP33-08 GUT MICROBIOTA PROFILE ASSOCIATED WITH HIGH-GRADE PROSTATE CANCER Kazutoshi Fujita, Makoto Matsushita, Daisuke Motooka, Koji Hatano, Shota Fukae, Norihiko Kawamura, Eisuke Tomiyama, Yujiro Hayashi, Eri Banno, Tetsuya Takao, Shingo Takada, Shinichi Yachida, Takafumi Minami, Masahiro Nozawa, Kazuhiro Yoshimura, Hirotsugu Uemura, Shota Nakamura, and Norio Nonomura Kazutoshi FujitaKazutoshi Fujita More articles by this author , Makoto MatsushitaMakoto Matsushita More articles by this author , Daisuke MotookaDaisuke Motooka More articles by this author , Koji HatanoKoji Hatano More articles by this author , Shota FukaeShota Fukae More articles by this author , Norihiko KawamuraNorihiko Kawamura More articles by this author , Eisuke TomiyamaEisuke Tomiyama More articles by this author , Yujiro HayashiYujiro Hayashi More articles by this author , Eri BannoEri Banno More articles by this author , Tetsuya TakaoTetsuya Takao More articles by this author , Shingo TakadaShingo Takada More articles by this author , Shinichi YachidaShinichi Yachida More articles by this author , Takafumi MinamiTakafumi Minami More articles by this author , Masahiro NozawaMasahiro Nozawa More articles by this author , Kazuhiro YoshimuraKazuhiro Yoshimura More articles by this author , Hirotsugu UemuraHirotsugu Uemura More articles by this author , Shota NakamuraShota Nakamura More articles by this author , and Norio NonomuraNorio Nonomura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002042.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The gut microbiota is involved in a variety of diseases that affect the entire body. Diet and body size influence the gut microbiota and are important risk factors for prostate cancer (PCa). However, the association between the gut microbiota and PCa is not well understood. To clarify this association, we analysed the gut microbiota profiles of men with high-grade PCa. METHODS: We collected rectal swab samples of 189 Japanese men who were suspected of PCa based on screening such as MRI or prostate specific antigen (PSA) tests and underwent prostate biopsies from December 2018 to March 2020 at the Osaka University Hospital, Osaka Police Hospital and Osaka General Medical Center. All hospitals are located in Osaka, Japan. RESULTS: One hundred fifty-two Japanese men undergoing prostate biopsies were included in the study and divided into two cohorts: discovery cohort (114 subjects, 72 with cancer and 42 without cancer) and external test cohort (38 subjects, 24 with cancer and 14 without cancer). The gut microbiota in the discovery cohort was compared between two groups, a high-grade PCa group (men with Gleason score 7 or higher PCa) and a negative+low-grade PCa group (men with negative biopsy or Gleason score 6 PCa) using 16S rRNA gene sequencing. Alpha diversity and beta diversity did not differ significantly between the two groups. Using the linear discriminant analysis (LDA) effect size (LEfSe) method, the relative abundance of Rikenellaceae, Alistipes, and Lachnospira were shown to be significantly increased in patients with high-grade PCa (LDA score>2.5). Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) showed a significant increase in five metabolic pathways: multiple amino acid metabolisms, phenylalanine, tryptophan, tyrosine, and histidine (LDA score>2.0). In the receiver operating characteristic (ROC) curve analysis, the index calculated from the amount of 18 bacterial genera, including Lachnospira, which were selected by least absolute shrinkage and selection operator (LASSO) regression, detected high-grade PCa in the discovery cohort with higher accuracy than the prostate-specific antigen (PSA) test (area under the curve (AUC)=0.85 vs. 0.74). Validation of the index in the test cohort showed similar results (AUC = 0.81 vs. 0.67). CONCLUSIONS: The results demonstrate an association between a gut microbiota composed of 18 genera and the presence of high-grade PCa in Japanese men. This gut microbiota profile could be a novel useful marker for the detection of high-grade PCa with greater accuracy than the PSA test. Source of Funding: The Japanese Urological Association, Yakult Bio-Science Foundation © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e609-e609 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazutoshi Fujita More articles by this author Makoto Matsushita More articles by this author Daisuke Motooka More articles by this author Koji Hatano More articles by this author Shota Fukae More articles by this author Norihiko Kawamura More articles by this author Eisuke Tomiyama More articles by this author Yujiro Hayashi More articles by this author Eri Banno More articles by this author Tetsuya Takao More articles by this author Shingo Takada More articles by this author Shinichi Yachida More articles by this author Takafumi Minami More articles by this author Masahiro Nozawa More articles by this author Kazuhiro Yoshimura More articles by this author Hirotsugu Uemura More articles by this author Shota Nakamura More articles by this author Norio Nonomura More articles by this author Expand All Advertisement Loading ...

Observational Study of the Association between Air Cadmium Exposure and Prostate Cancer Aggressiveness at Diagnosis among a Nationwide Retrospective Cohort of 230,540 Patients in the United States

Although studies have investigated cadmium and prostate cancer (PC) incidence and mortality, the role of cadmium in PC progression might be more clinically relevant. In this observational study, we assessed the association between air cadmium exposure and PC aggressiveness, with PC stage defined as metastatic or localized and Gleason grade defined as high (Gleason score ≥ 8) or low (Gleason score ≤ 6) among PC patients from the 2010–2014 US Surveillance, Epidemiology, and End Results database. The 2005 and 2011 National Air Toxics Assessment provided county-level air cadmium concentrations. Results were presented as odds ratios (OR) with 95% confidence intervals (CI) and were calculated using random intercept mixed effects logistic regression, comparing the 80th to 20th percentile of exposure. We adjusted for age, sociodemographic status, smoking prevalence, and overall air quality at the county level, and stratified by race, age, and degree of urbanization. The cohort consisted of 230,540 cases from 493 counties. Strong associations were observed in nonmetropolitan, urban areas: (OR 1.26, CI 1.14–1.39) for metastatic vs. localized and (OR 1.41, CI 1.27–1.57) for high- vs. low-grade PC where 40 million Americans reside. This study may be hypothesis-generating to inform future studies and public health measures.

Active Surveillance Strategies for Low-Grade Prostate Cancer: Comparative Benefits and Cost-effectiveness.

Background Active surveillance (AS) is the recommended treatment option for low-risk prostate cancer (PC). Surveillance varies in MRI, frequency of follow-up, and the Prostate Imaging Reporting and Data System (PI-RADS) score that would repeat biopsy. Purpose To compare the effectiveness and cost-effectiveness of AS strategies for low-risk PC with versus without MRI. Materials and Methods This study developed a mathematical model to evaluate the cost-effectiveness of surveillance strategies in a simulation of men with a diagnosis of low-risk PC. The following strategies were compared: watchful waiting, prostate-specific antigen (PSA) and annual biopsy without MRI, and PSA testing and MRI with varied PI-RADS thresholds for biopsy. MRI strategies differed regarding scheduling and use of PI-RADS score of at least 3, or a PI-RADS score of at least 4 to indicate the need for biopsy. Life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were calculated by using microsimulation. Sensitivity analysis was used to assess the impact of varying parameter values on results. Results For the base case of 60-year-old men, all strategies incorporating prostate MRI extended QALYs and life-years compared with watchful waiting and non-MRI strategies. Annual MRI strategies yielded 16.19 QALYs, annual biopsy with no MRI yielded 16.14 QALYs, and watchful waiting yielded 15.94 QALYs. Annual MRI with PI-RADS score of at least 3 or of at least 4 as the biopsy threshold and annual MRI with biopsy even after MRI with negative findings offered similar QALYs and the same unadjusted life expectancy: 23.05 life-years. However, a PI-RADS score of at least 4 yielded 42% fewer lifetime biopsies. With a cost-effectiveness threshold of $100 000 per QALY, annual MRI with biopsy for lesions with PI-RADS scores of 4 or greater was most cost-effective (incremental cost-effectiveness ratio, $67 221 per QALY). Age, treatment type, risk of initial grade misclassification, and quality-of-life impact of procedural complications affected results. Conclusion The use of active surveillance (AS) with biopsy decisions guided by findings from annual MRI reduces the number of biopsies while preserving life expectancy and quality of life. Biopsy in lesions with PI-RADS scores of 4 or greater is likely the most cost-effective AS strategy for men with low-risk prostate cancer who are younger than 70 years. © RSNA, 2021 Online supplemental material is available for this article. An earlier incorrect version appeared online. This article was corrected on July 13, 2021.

Progression on active surveillance for prostate cancer in Black men: a systematic review and meta-analysis.

Several studies evaluated prostate cancer (PCa) outcomes in Black men on active surveillance (AS); most studies contained few Black men and results were conflicting. We performed a systematic review and meta-analyze of race and outcomes on AS. A systematic search was performed for articles of men with Grade Group 1 or 2 (GG1 or GG2) PCa on AS. All studies required race-specific comparative progression data. Progression to treatment, PSA, or biopsy progression were considered and relative risk (RR) estimates of Black men progressing were extracted and pooled using random-effects models. Differences by study-level characteristics were evaluated using subgroup and a cumulative meta-analysis by time. In total, 12 studies were included (3137 Black and 12,206 non-Black men); eight prospective (27%, n = 4210) and four retrospectives (73%, n = 11,133) cohorts. The overall RR of progression for Black men was 1.62 (95%CI, 1.21-2.17), I2 = 64% (95% CI, 32-80%), (χ2 = 30.23; P = 0.001; τ2 = 0.16). Black men with GG1 PCa alone had a higher pooled progression: RR = 1.81 (95% CI, 1.23-2.68). Including only studies with clinical progression (excluding progression to treatment), potentiated results: RR = 1.82 (95%CI, 1.27-2.60). However, a cumulative meta-analysis demonstrated decreasing pooled effect over time, with contemporary studies after 2019 showing a tempered effect (RR: 1.29, 95% CI: 1.20-1.39). Many studies attribute racial disparity in PCa to delayed presentation of disease, however, AS is unique since all AS eligible men have a low grade and stage PCa. Our findings suggest Black men may have an increased risk of progression during AS, but the association is not so strong that Black men should be discouraged from undergoing AS. Indeed, contemporary evidence suggests stricter inclusion, better confirmatory testing or better access to care may temper these findings. Importantly, these results utilize self-reported race, a social construct that has many limitations.

Comparison of Sensitivity and Specificity of Biparametric versus Multiparametric Prostate MRI in the Detection of Prostate Cancer in 431 Men with Elevated Prostate-Specific Antigen Levels.

(1) Background: the study of dynamic contrast enhancement (DCE) has a limited role in the detection of prostate cancer (PCa), and there is a growing interest in performing unenhanced biparametric prostate-MRI (bpMRI) instead of the conventional multiparametric-MRI (mpMRI). In this study, we aimed to retrospectively compare the performance of the mpMRI, which includes DCE study, and the unenhanced bpMRI, composed of only T2-weighted imaging and diffusion-weighted imaging (DWI), in PCa detection in men with elevated prostate-specific-antigen (PSA) levels. (2) Methods: a 1.5 T MRI, with an endorectal-coil, was performed on 431 men (aged 61.5 ± 8.3 years) with a PSA ≥4.0 ng/mL. The bpMRI and mpMRI tests were independently assessed in separate sessions by two readers with 5 (R1) and 3 (R2) years of experience. The histopathology or ≥2 years follow-up served as a reference standard. The sensitivity and specificity were calculated with their 95% CI, and McNemar’s and Cohen’s κ statistics were used. (3) Results: in 195/431 (45%) of histopathologically proven PCa cases, 62/195 (32%) were high-grade PCa (GS ≥ 7b) and 133/195 (68%) were low-grade PCa (GS ≤ 7a). The PCa could be excluded by histopathology in 58/431 (14%) and by follow-up in 178/431 (41%) of patients. For bpMRI, the sensitivity was 164/195 (84%, 95% CI: 79–89%) for R1 and 156/195 (80%, 95% CI: 74–86%) for R2; while specificity was 182/236 (77%, 95% CI: 72–82%) for R1 and 175/236 (74%, 95% CI: 68–80%) for R2. For mpMRI, sensitivity was 168/195 (86%, 95% CI: 81–91%) for R1 and 160/195 (82%, 95% CI: 77–87%) for R2; while specificity was 184/236 (78%, 95% CI: 73–83%) for R1 and 177/236 (75%, 95% CI: 69–81%) for R2. Interobserver agreement was substantial for both bpMRI (κ = 0.802) and mpMRI (κ = 0.787). (4) Conclusions: the diagnostic performance of bpMRI and mpMRI were similar, and no high-grade PCa was missed with bpMRI.

Abstract 2362: Long non-coding RNA NORAD interaction with miR-346 impacts DNA damage response and anti-tumor immunity in prostate cancer

Abstract NORAD (NOn-Coding RNA Activated by DNA Damage) is a highly-abundant, evolutionarily-conserved lncRNA. It maintains mitosis, DNA damage repair (DDR), and chromosomal integrity through PUM1/2 sequestration (PUM1/2 activity increases turnover of DDR factors), and through formation of a TOPO2-containing complex critical for genome integrity. We show that NORAD activity is regulated by microRNA-346 (miR-346), which disrupts NORAD:PUM2, interaction, leading to PUM2 destabilization and derepression of PUM1/2 DDR targets in prostate cancer (PCa) cells. RNA-seq reveals widespread miR-346 dysregulation of DNA damage, DNA replication and cell cycle transcripts. A novel method for high resolution, amplification-free genome-wide mapping of double strand DNA breaks (DSBs) (INDUCE-seq) reveals miR-346 induces DSBs specifically at transcription start sites characterized by phospho-PolII/CTCF/ZFX binding - a phenomenon not previously described for any microRNA. Mechanistically, DSBs result from miR-346 activation of transcription, R-loop formation and replicative catastrophe. This results in rapid dose-dependent induction of DNA damage, leading to checkpoint activation and cytosolic DNA accumulation, rescuable by NORAD. This cytosolic DNA activates cytokine-inducing cGAS-STING/RIG-1 innate immune pathways. Indeed, RNA-seq analysis reveals the top NORAD-enriched pathway as interferon signaling, while cytokine arrays reveal secretion of pro-Treg, MDSC and TAM factors by NORAD-overexpressing cells. NORAD inversely correlates with tumor immune response in gene expression data sets, and expression-based immune infiltration scoring predicts increased M2 macrophages, and reduced NK, CD8+ve, Th1 and cytotoxic T cells in NORAD-high vs NORAD-low PCa, indicating an ‘immune-cold' microenvironment. Excitingly, NORAD silencing results in several thousand-fold increase in mature miR-346 without affecting pri-miR levels, supporting NORAD's ability to drive target-directed microRNA decay (TDMD) of miR-346 as a critical novel genome protection mechanism. However, miR-346-induced DNA damage is in part NORAD-independent, since miR-346 induces DSBs within 1h, and in contrast to most miRs is predominantly chromatin-bound (NORAD is cytoplasmic). Critically, miR-346 sensitizes PCa cells to DNA-damaging chemotherapy and PARP inhibition. MiR-346 expression is associated with improved PCa survival, and reduced in high vs low Gleason grade PCa. Notably, NORAD strongly correlates with DDR signatures in early-stage, but not advanced metastatic PCa. Despite its DDR-promoting activity, and in contrast to miR-346, it is associated with worse survival across multiple patient cohorts. In conclusion, these data demonstrate that the NORAD:miR-346 interaction determines DNA damage response and innate immune pathway activity to regulate tumor immune response in PCa. Citation Format: Claire Fletcher, Lin Deng, Folake Orafidiya, Wei Yuan, Ines Figueiredo, Bora Gurel, Damien Leach, Fadi Issa, Antje Neeb, Denisa Bogdan, Felix Dobbs, Yiannis Philippou, Emma A. Murphy, Shuang G. Zhao, Joanna Hester, Richard J. Bryant, Simon H. Reed, Karen E. Knudsen, Ian G. Mills, Johann de Bono, Charlotte L. Bevan. Long non-coding RNA NORAD interaction with miR-346 impacts DNA damage response and anti-tumor immunity in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2362.

Gleason skor 6 prostat kanserinin ekstraprostatik yayılımı: tek merkez deneyimi

Objective: For Gleason Score (GS) 3+3:6 prostate cancer (PC) cases, recent guidelines recommend clinical follow-up instead of radical treatment due to complications. One of the most important disadvantages of clinical follow-up is that low-grade PC may include local aggressive behavior. Hence, our aim here was to investigate the incidence of extraprostatic extension (EPE), a local aggressive behavior, in GS6 PC cases. Material and Methods: We examined 119 materials diagnosed with prostatic adenocarcinoma (GS 3+3:6) with no tertiary pattern and that were sent to our department as radical prostatectomy materials between January 2010 – May 2019. We investigated how many of the materials had EPE. Results: We observed EPE in 16 (13.45%) of our cases. 5 of the cases had vesicula seminalis invasion (pT3b) and 11 had EPE and/or bladder neck invasion (pT3a) without vesicula seminalis invasion. Conclusion: Among our patients diagnosed with GS-6 PC, we observed EPE (pT3) in 13.45% and vesicula seminalis invasion (pT3b) in 4.2%, which suggests that the possibility of EPE is not uncommon in GS-6 PC. Based on these findings, we argue that patients with GS-6 PC under clinical follow-up should be followed more carefully for EPE. Keywords: prostate cancer; gleason score; extraprostatic extension

It's all in the name: Does nomenclature for indolent prostate cancer impact management and anxiety?

Despite consensus guidelines, many men with low-grade prostate cancer are not managed with active surveillance. Patient perception of the nomenclature used to describe low-grade prostate cancers may partly explain this discrepancy. A randomized online survey was administered to men without a history of prostate cancer, presenting a hypothetical clinical scenario in which they are given a new diagnosis of low-grade prostate cancer. The authors determined whether diagnosis nomenclature was associated with management preference and diagnosis-related anxiety using ratings given on a scale from 1 to 100, adjusting for participant characteristics through multivariable linear regression. The survey was completed by 718 men. Compared with Gleason 6 out of 10 prostate cancer, the term grade group 1 out of 5 prostate cancer was associated with lower preference for immediate treatment versus active surveillance (β = -9.3; 95% CI, -14.4, -4.2; P < .001), lower diagnosis-related anxiety (β = -8.3; 95% CI, -12.8, -3.8; P < .001), and lower perceived disease severity (β = -12.3; 95% CI, -16.5, -8.1; P < .001) at the time of initial diagnosis. Differences decreased as participants received more disease-specific education. Indolent lesion of epithelial origin, a suggested alternative term for indolent tumors, was not associated with differences in anxiety or preference for active surveillance. Within a hypothetical clinical scenario, nomenclature for low-grade prostate cancer affects initial perception of the disease and may alter subsequent decision making, including preference for active surveillance. Disease-specific education reduces the differential impact of nomenclature use, reaffirming the importance of comprehensive counseling and clear communication between the clinician and patient.

Active surveillance for prostate cancer.

Many men diagnosed with localized prostate cancer can postpone definitive treatment without raising their risk of metastasis or death from disease. Active surveillance (AS) is a method of monitoring select men, with the option of switching to active treatment upon signs of progression, thereby avoiding the well-known side-effects of surgery and radiotherapy. This review analyzes the data from long-running AS cohorts to determine the safety and efficacy of AS. We conducted a narrative review of recently published data, including 14 articles from 13 AS cohorts. The cohorts used varying inclusion criteria, with reported differences in clinical T stage and Gleason Score (Grade Group), among other features. Some studies (n=5) limited their cohorts to low-risk patients, while others (n=8) also included intermediate-risk patients. The heterogeneity of the cohorts produced mixed results, with the risk of prostate cancer metastasis ranging from 0.1–1.0% at 10 years and the risk of prostate cancer mortality ranging from 0–1.9% at 10 years. However, the majority of studies reported risks of less than 0.5% at 10 years for both metastasis and death. For most cohorts, half of men remained untreated for 5–10 years, with estimates ranging from 37% receiving active treatment in the Toronto cohort to 73% in the Prostate Cancer Research International AS (PRIAS) study. Current data do not support the use of negative magnetic resonance imaging (MRI) to avoid scheduled biopsy. Taken together, the data collected from these AS cohorts suggests that AS is a safe approach for men with low-grade prostate cancer and some men with intermediate risk disease. AS should be more broadly implemented for eligible patients to avoid the decreases in quality of life from undergoing active treatment. Studies expanding the inclusion criteria and further defining a subset of men with favorable intermediate-risk prostate cancer who might safely benefit from AS are needed to assess the long-term outcomes of using AS in intermediate-risk groups.

Utility of PSA Density in Predicting Upgraded Gleason Score in Men on Active Surveillance With Negative MRI

ObjectivesTo determine whether PSA density (PSAD), can sub-stratify risk of biopsy upgrade among men on active surveillance (AS) with normal baseline MRI. MethodsWe identified a cohort of patients with low and favorable intermediate-risk prostate cancer on AS at two large academic centers from February 2013 - December 2017. Analysis was restricted to patients with GG1 cancer on initial biopsy and a negative baseline or surveillance mpMRI, defined by the absence of PI-RADS 2 or greater lesions. We assessed ability of PSA, prostate volume and PSAD to predict upgrading on confirmatory biopsy. ResultsWe identified 98 patients on AS with negative baseline or surveillance mpMRI. Median PSA at diagnosis was 5.8 ng/mL and median PSAD was 0.08 ng/mL/mL. Fourteen men (14.3%) experienced Gleason upgrade at confirmatory biopsy. Patients who were upgraded had higher PSA (7.9 vs 5.4 ng/mL, P = .04), PSAD (0.20 vs 0.07 ng/mL/mL, P < .001), and lower prostate volumes (42.5 vs 65.8 mL, P = .01). On multivariate analysis, PSAD was associated with pathologic upgrade (OR 2.23 per 0.1-increase, P = .007). A PSAD cutoff at 0.08 generated a NPV of 98% for detection of pathologic upgrade. ConclusionPSAD reliably discriminated the risk of Gleason upgrade at confirmatory biopsy among men with low-grade prostate cancer with negative MRI. PSAD could be clinically implemented to reduce the intensity of surveillance for a subset of patients.

Rapid Diagnosis of Prostate Cancer Disease Progression Using Paper Spray Ionization Mass Spectrometry.

The limitation of prostate specific antigen (PSA) for prostate cancer (PC) diagnosis is well-recognized. The Gleason score (GS) has been the most widely used grading system for prostate tumor differentiation and represents the best-established prognostic indicator for prostate cancer progression. However, a rapid and sensitive noninvasive diagnostic marker that differentiates GS-based prostate cancer disease progression is needed. As PC is becoming a leading cause of cancer related death for men in the U.S. and worldwide, an immediate need exists for an improved, sensitive, noninvasive, and rapid diagnostic test for PC screening. Here, we employed paper spray ionization-mass spectrometry (PSI MS)-based global metabolomics of urine liquid biopsies to distinguish between healthy (negative for any prostate specific health problems) and progressive PC states (low grade PC such as GS6 and high-grade PC such as GS7, GS8, and GS9). For PSI-MS-based direct untargeted metabolic investigation, a raw urine sample was directly pipetted onto a triangular paper substrate, without any additional sample preparation. Multivariate statistical analysis revealed distinct GS-specific metabolic signatures compared to a healthy control. Variable importance in projection from partial least-squares-discriminant analysis showed distinct metabolic patterns that were correlatively elevated with progressive disease and could serve as biomarkers for diagnosis of prostate cancer risk categorization.

Guy\u2019s and St Thomas NHS Foundation active surveillance prostate cancer cohort: a characterisation of a prostate cancer active surveillance database

BackgroundThe routine clinical use of serum prostatic specific antigen (PSA) testing has allowed earlier detection of low-grade prostate cancer (PCa) with more favourable characteristics, leading to increased acceptance of management by active surveillance (AS). AS aims to avoid over treatment in men with low and intermediate-risk PCa and multiple governing bodies have described several AS protocols. This study provides a descriptive profile of the Guy’s and St Thomas NHS Foundation Trust (GSTT) AS cohort as a platform for future research in AS pathways in PCa.MethodsDemographic and baseline characteristics were retrospectively collected in a database for patients at the GSTT AS clinic with prospective collection of follow-up data from 2012. Seven hundred eighty-eight men being monitored at GSTT with histologically confirmed intermediate-risk PCa, at least 1 follow-up appointment and diagnostic characteristics consistent with AS criteria were included in the profile. Descriptive statistics, Kaplan-Meier survival curves and multivariable Cox proportion hazards regression models were used to characterize the cohort.DiscussionA relatively large proportion of the cohort includes men of African/Afro-Caribbean descent (22%). More frequent use of magnetic resonance imaging and trans-perineal biopsies at diagnosis was observed among patients diagnosed after 2012. Those who underwent trans-rectal ultrasound diagnostic biopsy received their first surveillance biopsy 20 months earlier than those who underwent trans-perineal diagnostic biopsy. At 3 years, 76.1% men remained treatment free. Predictors of treatment progression included Gleason score 3 + 4 (Hazard ratio (HR): 2.41, 95% Confidence interval (CI): 1.79–3.26) and more than 2 positive cores taken at biopsy (HR: 2.65, CI: 1.94–3.62). A decreased risk of progressing to treatment was seen among men diagnosed after 2012 (HR: 0.72, CI: 0.53–0.98).ConclusionAn organised biopsy surveillance approach, via two different AS pathways according to the patient’s diagnostic method, can be seen within the GSTT cohort. Risk of patients progressing to treatment has decreased in the period since 2012 compared with the prior period with more than half of the cohort remaining treatment free at 5 years, highlighting that the fundamental aims of AS at GSTT are being met. Thus, this cohort is a good resource to investigate the AS treatment pathway.

Association between male infertility and prostate cancer: a systematic review and meta-analysis.

Male infertility has been shown to be associated with different maladies. The present systematic review and meta-analysis aimed to summarize the available evidence on the association between male infertility or childlessness and prostate cancer. The PubMed, Web of Science, and Scopus databases were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies were deemed eligible if they compared males with known infertility or childlessness to the control group including fertile males with regards to the diagnosis of prostate cancer. Overall, ten studies met our eligibility criteria. Three studies found that infertility was associated with higher risk of prostate cancer, four studies - with a reduced risk of prostate cancer, and three studies found no association. The forest plot revealed that infertility was not associated with prostate cancer (odds ratio [OR]: 1.26, 95% confidence interval [CI] 0.63-2.54; P = 0.5). Infertility was not associated with high (OR: 1.44, 95% CI 0.54-3.83; P = 0.5) or low (OR: 0.99, 95% CI 0.43-2.27; P = 0.9) grade prostate cancer. Infertility or childlessness were not associated with the risk of prostate cancer. The significant heterogeneity between the included studies supports the need for more granular research to guide/fine tune early detection guidelines based on fertility.

Clinical use of the SelectMDx urinary-biomarker test with or without mpMRI in prostate cancer diagnosis: a prospective, multicenter study in biopsy-na\xefve men

BackgroundRisk stratification in men with suspicion of prostate cancer (PCa) requires reliable diagnostic tests, not only to identify high-grade PCa, also to minimize the overdetection of low-grade PCa, and reduction of “unnecessary” prostate MRIs and biopsies. This study aimed to evaluate the SelectMDx test to detect high-grade PCa in biopsy-naïve men. Subsequently, to assess combinations of SelectMDx test and multi-parametric (mp) MRI and its potential impact on patient selection for prostate biopsy.MethodsThis prospective multicenter diagnostic study included 599 biopsy-naïve patients with prostate-specific antigen level ≥3 ng/ml. All patients underwent a SelectMDx test and mpMRI before systematic transrectal ultrasound-guided biopsy (TRUSGB). Patients with a suspicious mpMRI also had an in-bore MR-guided biopsy (MRGB). Histopathologic outcome of TRUSGB and MRGB was used as reference standard. High-grade PCa was defined as ISUP Grade Group (GG) ≥ 2. The primary outcome was the detection rates of low- and high-grade PCa and number of biopsies avoided in four strategies, i.e., (1) SelectMDx test-only, (2) mpMRI-only, (3) SelectMDx test followed by mpMRI when SelectMDx test was positive (conditional strategy), and (4) SelectMDx test and mpMRI in all (joint strategy). A positive SelectMDx test outcome was a risk score of ≥−2.8. Decision curve analysis (DCA) was performed to assess clinical utility.ResultsPrevalence of high-grade PCa was 31% (183/599). Thirty-eight percent (227/599) of patients had negative SelectMDx test in whom biopsy could be avoided. Low-grade PCa was not detected in 35% (48/138) with missing 10% (18/183) high-grade PCa. Yet, mpMRI-only could avoid 49% of biopsies, not detecting 4.9% (9/183) of high-grade PCa. The conditional strategy reduces the number of mpMRIs by 38% (227/599), avoiding biopsy in 60% (357/599) and missing 13% (24/183) high-grade PCa. Low-grade PCa was not detected in 58% (80/138). DCA showed the highest net benefit for the mpMRI-only strategy, followed by the conditional strategy at-risk thresholds >10%.ConclusionsSelectMDx test as a risk stratification tool for biopsy-naïve men avoids unnecessary biopsies in 38%, minimizes low-grade PCa detection, and misses only 10% high-grade PCa. Yet, using mpMRI in all patients had the highest net benefit, avoiding biopsy in 49% and missing 4.9% of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx test positive patients is a good alternative strategy.

Association between vasectomy and risk of prostate cancer: a meta-analysis.

The debate over the association between vasectomy and prostate cancer has been lasted about 40 years and there is no sign of stopping. In the present study, we aimed to evaluate whether vasectomy is associated with prostate cancer based on the most comprehensive and up-to-date evidence available. The PubMed, Cochrane Library, and EMBASE databases were systematically searched inception to March 14, 2021 without year or language restriction. Multivariable adjusted risk ratios (RRs) were used to assess each endpoint. Risk of bias was assessed using the Newcastle-Ottawa scale. A total of 58 studies involving 16,989,237 participants fulfilled inclusion criteria. There was significant association of vasectomy with risk of any prostate cancer (risk ratio, 1.18, 95% CI, 1.07-1.31). Association between vasectomy and advanced prostate cancer (risk ratio, 1.06, 95% CI, 1.01-1.12), low-grade prostate cancer (risk ratio, 1.06, 95% CI, 1.02-1.10), and intermediate-grade prostate cancer (risk ratio, 1.12, 95% CI, 1.03-1.22) were significant. There was no significant association between vasectomy and prostate cancer-specific mortality (risk ratio, 1.01, 95% CI, 0.93-1.10). This study found that vasectomy was associated with the risk of any prostate cancer and advanced prostate cancer. From the current evidence, patients should be fully informed of the risk of prostate cancer before vasectomy.

Radiomics Models Based on Apparent Diffusion Coefficient Maps for the Prediction of High-Grade Prostate Cancer at Radical Prostatectomy: Comparison With Preoperative Biopsy.

It is feasible to use magnetic resonance (MR)-based radiomics to distinguish high-grade from low-grade prostate cancer (PCa), but radiomics model performance based on fully automated segmentation remains unknown. To develop and test radiomics models based on manually or automatically gained masks on apparent diffusion coefficient (ADC) maps to predict high-grade (Gleason score ≥ 4 + 3) PCa at radical prostatectomy (RP). Retrospective. A total of 176 patients (94 high-grade PCa and 82 low-grade PCa) with complete RP, preoperative biopsy, and multiparametric magnetic resonance imaging (mpMRI) were retrospectively recruited and randomly divided into training (N=123) and test (N=53) cohorts. Using a 3.0-T MR scanner, ADC maps were calculated from diffusion-weighted imaging (b values=0, 1400 s/mm2 , echo planar imaging). Two radiologists segmented the whole prostate gland and the most index prostate lesion. Automatic segmentation of the prostate and the lesion were performed. Four radiomics models were constructed using four masks (manual/automatic prostate gland/PCa lesion segmentation). According to the standard reference of the RP histopathologic assessment, the performance of each radiomics models was compared with that of biopsy and Prostate Imaging Reporting and Data System version 2.1 (PI-RADS) assessment. A receiver operating characteristic curve analysis was employed to estimate the area under the curve (AUC) values of the models. The AUCs of the four models, biopsy, and PI-RADS assessment were compared using the DeLong test. The four radiomics models yielded AUCs of 0.710, 0.731, 0.726, and 0.709 in the test cohort, respectively; biopsy and PI-RADS assessment yielded AUCs of 0.793 and 0.680, respectively. No significant differences were found among model, biopsy, and PI-RADS assessment comparisons (P=0.132-0.988). To distinguish high-grade from low-grade PCa, radiomics models based on automatic segmentation on ADC maps exhibit approximately the same diagnostic efficacy as manual segmentation and biopsy, highlighting the possibility of a fully automatic workflow combining automated segmentation with radiomics analysis. 4 TECHNICAL EFFICACY: Stage 2.