Michael S Hofman, Veeru Kasivisvanathan, Emma Link, James Buteau, Matthew J Roberts, Roslyn J Francis, Colin Tang, Ian Vela, Paul Thomas, Natalie Rutherford, Jarad M Martin, Mark Frydenberg, Ramdave Shakher, Lih-Ming Wong, Kim Taubman, Sze Ting Lee, Edward Hsiao, Paul Roach, Michelle Nottage, Ian Kirkwood, Dickon Hayne, Amir Iravani, Scott Williams, Jonathan O'Brien, Nathan Lawrentschuk, Declan G Murphy
{"title":"Baseline Nodal Status on <sup>68</sup>Ga-PSMA-11 Positron Emission Tomography/Computed Tomography in Men with Intermediate- to High-risk Prostate Cancer Is Prognostic for Treatment Failure: Follow-up of the proPSMA Trial.","authors":"Michael S Hofman, Veeru Kasivisvanathan, Emma Link, James Buteau, Matthew J Roberts, Roslyn J Francis, Colin Tang, Ian Vela, Paul Thomas, Natalie Rutherford, Jarad M Martin, Mark Frydenberg, Ramdave Shakher, Lih-Ming Wong, Kim Taubman, Sze Ting Lee, Edward Hsiao, Paul Roach, Michelle Nottage, Ian Kirkwood, Dickon Hayne, Amir Iravani, Scott Williams, Jonathan O'Brien, Nathan Lawrentschuk, Declan G Murphy","doi":"10.1016/j.euo.2024.11.006","DOIUrl":"https://doi.org/10.1016/j.euo.2024.11.006","url":null,"abstract":"<p><strong>Background and objective: </strong>There is uncertainty regarding the clinical significance of <sup>68</sup>Ga-PSMA-11 positron emission tomography (PET) computed tomography (CT) findings in men with prostate cancer. In this prespecified objective of the proPSMA study, we report the prognostic value of PET-defined nodal involvement.</p><p><strong>Methods: </strong>Men with intermediate- to high-risk prostate cancer (grade group 3-5, prostate-specific antigen [PSA] ≥20 ng/ml, or clinical stage ≥T3) underwent <sup>68</sup>Ga-PSMA-11 PET-CT or CT and bone scanning as first- or second-line imaging. Patients without distant metastatic disease (miM0) in either arm were stratified by prostate-specific membrane antigen (PSMA) PET-CT negative (miN0) or positive (miN1) regional nodal status and followed for up to 54 mo. Treatment failure was defined as biochemical failure, commencement of salvage therapy, or development of distant metastatic disease. Freedom from treatment failure (FFTF) was plotted on Kaplan-Meier curves for patients with miN0 and miN1 cancer based on PET-CT and CT/bone scan classification. Cox proportional hazards were used to derive a hazard ratio (HR) for FFTF.</p><p><strong>Key findings and limitations: </strong>A total of 302 patients were randomised at ten sites. Of them, 294 underwent a PSMA PET-CT. In all, 251 patients with miM0 disease were included in this analysis. Patients were treated with curative-intent surgery or radiotherapy ± androgen deprivation. FFTF was greater in the PSMA PET-CT miN0M0 group than in the miN1M0 group (HR 2.1 [95% confidence interval {CI} 1.2-3.7], p = 0.01). CT/bone scan-defined N0M0 versus N1M0 was not prognostic for FFTF (HR 0.6, 95% CI 0.1-2.4, p = 0.45). In a multivariate analysis, PSMA PET-CT miN1M0 versus miN0M0 remained prognostic after adjusting for PSA, Gleason grade group, and age (HR 2.0, 95% CI 1.10-3.64, p = 0.007).</p><p><strong>Conclusions and clinical implications: </strong>PSMA PET-CT regional nodal staging at baseline is prognostic for medium-term oncological outcomes, identifying patients at a higher risk of treatment failure.</p><p><strong>Patient summary: </strong>Men with prostate cancer who have cancer in their nearby lymph nodes observed on a prostate-specific membrane antigen positron emission tomography scan have poorer outcomes than men who have no nearby lymph node involvement.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matteo Santoni, Thomas Büttner, Pasquale Rescigno, Ondrej Fiala, Nicolò Cavasin, Umberto Basso, Tarek Taha, Francesco Massari, Zin W Myint, Luigi Formisano, Luca Galli, Sarah Scagliarini, Marc R Matrana, Gaetano Facchini, Aristotelis Bamias, Carlo Messina, Francesca Zacchi, Ray Kopp Manneh, Giandomenico Roviello, Daniele Santini, Alexandr Poprach, Jiri Navratil, Michal Uher, Fabio Calabrò, Erin Pierce, Rossana Berardi, Gaetano Aurilio, Roubini Zakopoulou, Alessandro Rizzo, Jawaher Ansari, Mimma Rizzo, Renato Bisonni, Veronica Mollica, Lorena Incorvaia, Gianpaolo Spinelli, Xue Yan Jiang, Robert Adam Chandler, Francesco Grillone, Franco Morelli, Sebastiano Buti, Fernando C Maluf, Fernando Sabino Marques Monteiro, Nicola Battelli, Camillo Porta, Orazio Caffo, Andrey Soares
{"title":"Apalutamide in Metastatic Castration-sensitive Prostate Cancer: Results from the Multicenter Real-world ARON-3 Study.","authors":"Matteo Santoni, Thomas Büttner, Pasquale Rescigno, Ondrej Fiala, Nicolò Cavasin, Umberto Basso, Tarek Taha, Francesco Massari, Zin W Myint, Luigi Formisano, Luca Galli, Sarah Scagliarini, Marc R Matrana, Gaetano Facchini, Aristotelis Bamias, Carlo Messina, Francesca Zacchi, Ray Kopp Manneh, Giandomenico Roviello, Daniele Santini, Alexandr Poprach, Jiri Navratil, Michal Uher, Fabio Calabrò, Erin Pierce, Rossana Berardi, Gaetano Aurilio, Roubini Zakopoulou, Alessandro Rizzo, Jawaher Ansari, Mimma Rizzo, Renato Bisonni, Veronica Mollica, Lorena Incorvaia, Gianpaolo Spinelli, Xue Yan Jiang, Robert Adam Chandler, Francesco Grillone, Franco Morelli, Sebastiano Buti, Fernando C Maluf, Fernando Sabino Marques Monteiro, Nicola Battelli, Camillo Porta, Orazio Caffo, Andrey Soares","doi":"10.1016/j.euo.2024.11.005","DOIUrl":"https://doi.org/10.1016/j.euo.2024.11.005","url":null,"abstract":"<p><strong>Background and objective: </strong>Apalutamide (APA) is a treatment for metastatic castration-sensitive prostate cancer (mCSPC). In the ARON-3 study we investigated real-world experiences with APA treatment for mCSPC.</p><p><strong>Methods: </strong>We retrospectively assessed real-world clinical outcomes for patients with mCSPC treated with APA in the ARON-3 study. Overall survival (OS) was calculated from APA initiation to death from any cause. PSA<sub>90</sub> was defined as a prostate-specific antigen decline of ≥90% from baseline, and PSA<sub>0.2</sub> as achievement of a PSA level ≤0.2 ng/ml. Data for adverse events were retrospectively collected from electronic and paper charts and categorized according to Common Terminology Criteria for Adverse Events v5.0.</p><p><strong>Key findings and limitations: </strong>We included 531 patients with mCSPC treated with APA. High-volume disease was reported for 214 patients (40%), and 56 (11%) had visceral metastases. Median OS was not reached. PSA<sub>90</sub> was experienced by 461 patients (87%) and PSA<sub>0.2</sub> by 368 (69%). Median OS was significantly longer for patients with PSA<sub>90</sub> or PSA<sub>0.2</sub> than for subjects without these responses (p < 0.001). The incidence of grade 3-4 fatigue was higher among elderly patients (≥80 yr) than among younger patients (19% vs 5%), but the incidence of other adverse events was comparable between the age groups.</p><p><strong>Conclusions and clinical implications: </strong>APA is an effective and tolerable treatment for mCSPC in the real-world setting.</p><p><strong>Patient summary: </strong>The ARON-3 project collects data for patients with prostate cancer treated in multiple centers worldwide to assess outcomes in the real-world setting. We analyzed data for patients with metastatic hormone-sensitive prostate cancer receiving apalutamide. Our results show that apalutamide is a safe and effective drug in the real-world setting as well as in clinical trials.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Timo F W Soeterik, Joris G Heetman, Rick Hermsen, Lieke Wever, Jules Lavalaye, Maarten Vinken, Clinton D Bahler, Courtney Yong, Mark Tann, Claudia Kesch, Robert Seifert, Tugce Telli, Peter Ka-Fung Chiu, Kwan Kit Wu, Fabio Zattoni, Laura Evangelista, Sara Bettella, Francesco Ceci, Antonio Barone, Marcin Miszczyk, Akihiro Matsukawa, Pawel Rajwa, Giancarlo Marra, Alberto Briganti, Francesco Montorsi, Matthijs J Scheltema, Jean-Paul A van Basten, Harm H E van Melick, Roderick C N van den Bergh, Giorgio Gandaglia
{"title":"The Added Value of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography to Magnetic Resonance Imaging for Local Staging of Prostate Cancer in Patients Undergoing Radical Prostatectomy.","authors":"Timo F W Soeterik, Joris G Heetman, Rick Hermsen, Lieke Wever, Jules Lavalaye, Maarten Vinken, Clinton D Bahler, Courtney Yong, Mark Tann, Claudia Kesch, Robert Seifert, Tugce Telli, Peter Ka-Fung Chiu, Kwan Kit Wu, Fabio Zattoni, Laura Evangelista, Sara Bettella, Francesco Ceci, Antonio Barone, Marcin Miszczyk, Akihiro Matsukawa, Pawel Rajwa, Giancarlo Marra, Alberto Briganti, Francesco Montorsi, Matthijs J Scheltema, Jean-Paul A van Basten, Harm H E van Melick, Roderick C N van den Bergh, Giorgio Gandaglia","doi":"10.1016/j.euo.2024.11.002","DOIUrl":"https://doi.org/10.1016/j.euo.2024.11.002","url":null,"abstract":"<p><strong>Background and objective: </strong>The role of prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET)/computed tomography (CT) in addition to magnetic resonance imaging (MRI) for local staging of prostate cancer (PC) has been poorly addressed so far. Our aim was to assess the diagnostic accuracy of PSMA PET/CT and MRI, alone and combined, for detection of extraprostatic extension (EPE) and seminal vesicle invasion (SVI) in PC.</p><p><strong>Methods: </strong>We conducted a multicenter retrospective study evaluating patients undergoing PSMA PET/CT and MRI before radical prostatectomy. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC) for detection of EPE and SVI were calculated for MRI and PSMA PET/CT alone and combined.</p><p><strong>Key findings and limitations: </strong>We included 550 patients, of whom 2%, had low-risk, 43% had intermediate-risk, and 55% had high-risk PC. Overall, 52% of patients had EPE and 21% had SVI at histopathology. Patient-based comparison of MRI versus PSMA PET/CT for detection of EPE revealed sensitivity of 60% versus 41% (p < 0.001), specificity of 77% versus 83% (p = 0.075), PPV of 75% versus 73% (p = 0.6), NPV of 64% versus 56% (p < 0.001), and AUC of 69% versus 62% (p = 0.01). Combining the modalities increased the sensitivity (73%; p < 0.001) and NPV (69%; p < 0.001) and decreased the specificity (67%; p < 0.001) and PPV (71%; p = 0.01) over MRI alone. Patient-based comparison of MRI versus PSMA PET/CT for detection of SVI revealed sensitivity of 36% versus 44% (p = 0.2), specificity of 96% versus 96% (p > 0.99), PPV of 71% versus 75% (p = 0.6), NPV of 85% versus 87% (p = 0.2), and AUC of 66% versus 70% (p = 0.2). Combining the modalities increased the sensitivity (60%; p < 0.001), NPV (90%; p < 0.001), and AUC (76%; p < 0.001) and decreased the specificity (92%; p < 0.001) over MRI alone. Limitations include the retrospective nature of the study, selection of higher-risk cases for PSMA PET/CT, and lack of central review.</p><p><strong>Conclusions and clinical implications: </strong>PSMA PET/CT has lower sensitivity for EPE detection in comparison to MRI. However, addition of PSMA PET information to MRI improved the sensitivity for EPE and SVI detection. Thus, the two modalities should be combined to guide treatment selection.</p><p><strong>Patient summary: </strong>Combining MRI (magnetic resonance imaging) scans with another type of imaging called PSMA PET/CT (prostate-specific membrane antigen positron emission tomography/computed tomography) for patients with prostate cancer leads to better identification of cancer growth outside the prostate in comparison to MRI alone. This could potentially improve the choice of prostate cancer treatment.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Frailty in Older Adults with Prostate Cancer.","authors":"Neha Pathak, Efthymios Papadopoulos, Vikaash Kumar, Shabbir Alibhai","doi":"10.1016/j.euo.2024.11.007","DOIUrl":"https://doi.org/10.1016/j.euo.2024.11.007","url":null,"abstract":"<p><p>Older adults with all stages of prostate cancer are prone to developing frailty. These patients should have a frailty assessment and be managed by a multidisciplinary team. Lifestyle measures and tailoring of cancer-related treatment to the patient's fitness level can help in mitigating the adverse effects of frailty.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ivo I de Vos, Charlotte Rosenstand, Renée Hogenhout, Roderick C N van den Bergh, Sebastiaan Remmers, Monique J Roobol
{"title":"Reducing Overtreatment of Prostate Cancer Patients: Revisiting the European Association of Urology Pretreatment Risk Group Classification Using Long-term Follow-up Data from the European Randomized Study of Screening for Prostate Cancer Rotterdam.","authors":"Ivo I de Vos, Charlotte Rosenstand, Renée Hogenhout, Roderick C N van den Bergh, Sebastiaan Remmers, Monique J Roobol","doi":"10.1016/j.euo.2024.11.004","DOIUrl":"https://doi.org/10.1016/j.euo.2024.11.004","url":null,"abstract":"<p><strong>Background and objective: </strong>Tailored treatment for prostate cancer (PCa) requires accurate risk stratification. This study examines the effectiveness of the European Association of Urology (EAU) classification in predicting long-term PCa-specific mortality (PCSM) and assesses whether an alternative system can improve the identification of patients with low-risk disease.</p><p><strong>Methods: </strong>This study included two cohorts of patients with localized PCa: one with screen-detected PCa (n = 1563; S-cohort) and the other with clinically detected PCa (n = 755; C-cohort), all from a population-based, randomized screening study, who underwent primary radical prostatectomy or radiation monotherapy. Patients were stratified according to the traditional EAU risk classification and an alternative risk classification where low-risk disease is adjusted according to contemporary active surveillance (AS) eligibility criteria. The 15-yr time-dependent area under the curve (AUC) and the cumulative incidence of PCSM at 15 yr after diagnosis were assessed for each risk classification and cohort.</p><p><strong>Key findings and limitations: </strong>With a median follow-up of 20 yr in the S-cohort and 12 yr in the C-cohort, the EAU classification demonstrated 15-yr AUCs of 0.76 (95% confidence interval [CI]: 0.71-0.80) and 0.72 (95% CI: 0.65-0.79), respectively, for predicting PCSM. The alternative classification showed a 15-yr AUC of 0.74 (95% CI: 0.69-0.79) in the S-cohort and 0.75 (95% CI: 0.68-0.81) in the C-cohort. The alternative classification identified 45% more men having a low risk in the S-cohort and 83% more in the C-cohort than the EAU classification, with no statistically significant increase in the 15-yr PCSM incidence (S-cohort subhazard ratio: 1.33 [95% CI: 0.66-2.68]; C-cohort subhazard ratio: 0.99 [95% CI: 0.29-3.38]).</p><p><strong>Conclusions and clinical implications: </strong>The EAU classification predicts PCSM accurately, but an alternative classification, adjusted for AS eligibility, identifies substantially more men as having a low risk. This could enhance AS acceptance and utilization in clinical practice, reducing overtreatment.</p><p><strong>Patient summary: </strong>This study shows that while a commonly used pretreatment risk classification for prostate cancer predict disease prognosis accurately, an alternative system based on active surveillance eligibility criteria identifies many more men as having a low risk. Adopting this classification could enhance the acceptance and use of active surveillance, reducing unnecessary treatments.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Arthur Peyrottes, Charles Dariane, Michael Baboudjian, Eric Barret, Laurent Brureau, Gaelle Fiard, Gaelle Fromont, Romain Mathieu, Jonathan Olivier, Raphaëlle Renard-Penna, Guilhem Roubaud, Morgan Rouprêt, Paul Sargos, Stéphane Supiot, Alexandre de la Taille, Léa Turpin, François Desgrandchamps, Guillaume Ploussard, Alexandra Masson-Lecomte
{"title":"Anatomic Factors Associated with Complications After Radical Prostatectomy: A Systematic Review and Meta-analysis.","authors":"Arthur Peyrottes, Charles Dariane, Michael Baboudjian, Eric Barret, Laurent Brureau, Gaelle Fiard, Gaelle Fromont, Romain Mathieu, Jonathan Olivier, Raphaëlle Renard-Penna, Guilhem Roubaud, Morgan Rouprêt, Paul Sargos, Stéphane Supiot, Alexandre de la Taille, Léa Turpin, François Desgrandchamps, Guillaume Ploussard, Alexandra Masson-Lecomte","doi":"10.1016/j.euo.2024.10.018","DOIUrl":"https://doi.org/10.1016/j.euo.2024.10.018","url":null,"abstract":"<p><strong>Background and objective: </strong>The role of anatomical factors in predicting outcomes after radical prostatectomy (RP) remains unclear. This review aims to evaluate the impact of various anatomical factors on the perioperative outcomes of patients undergoing RP for localized prostate cancer (PCa).</p><p><strong>Methods: </strong>A comprehensive literature search was conducted through January 2024 using the PubMed/Medline, Embase, and Web of Science databases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed to identify eligible studies. Data were extracted and pooled for a meta-analysis, with outcomes including operative time, blood loss, transfusion rates, overall complications, and positive surgical margins (PSMs). Heterogeneity was assessed using Cochrane Q test, and subgroup analyses were conducted to explore the influence of surgical approach.</p><p><strong>Key findings and limitations: </strong>A total of 91 studies met our inclusion criteria. Among the anatomical factors, prostate volume (PV), prostate weight, and median lobe (ML) were suitable for the meta-analysis. Larger prostates were associated with increased operative time, blood loss, and complication rates, but with fewer PSMs (all p < 0.05). ML presence was not associated with a higher risk of complications. Heterogeneity was high across studies (Cochrane Q tests <0.05), reflecting inconsistent definitions and methods. In subgroup analyses, the open approach was associated with a longer operative time than robotic surgery for large prostates (p = 0.03) and a lower PSM rate (p < 0.001).</p><p><strong>Conclusions and clinical implications: </strong>Anatomical factors, particularly PV, play a significant role in RP outcomes. Larger prostates are associated with higher complication rates but fewer PSMs. Further research with standardized outcome measures is necessary to clarify these relationships and guide clinical decision-making.</p><p><strong>Patient summary: </strong>In this study, we examined how a patient's individual anatomy might affect the results of prostate surgery for cancer. We found that larger prostates tend to lead to longer surgeries and increased blood loss, but these also have a lower risk of leaving cancer cells behind. These findings could help doctors in better planning surgeries and improving patient outcomes.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrea Discacciati, Ahmad Abbadi, Mark S Clements, Magnus Annerstedt, Stefan Carlsson, Henrik Grönberg, Fredrik Jäderling, Martin Eklund, Tobias Nordström
{"title":"Repeat Prostate Cancer Screening using Blood-based Risk Prediction or Prostate-specific Antigen in the Era of Magnetic Resonance Imaging-guided Biopsies : A Secondary Analysis of the STHLM3-MRI Randomized Clinical Trial.","authors":"Andrea Discacciati, Ahmad Abbadi, Mark S Clements, Magnus Annerstedt, Stefan Carlsson, Henrik Grönberg, Fredrik Jäderling, Martin Eklund, Tobias Nordström","doi":"10.1016/j.euo.2024.10.016","DOIUrl":"https://doi.org/10.1016/j.euo.2024.10.016","url":null,"abstract":"<p><strong>Background and objective: </strong>The use of blood-based risk prediction tools has been proposed to improve prostate cancer screening, but data on repeated screening are lacking. Our aim was to compare outcomes using the blood tests prostate-specific antigen (PSA) and Stockholm3 for repeat prostate cancer screening.</p><p><strong>Methods: </strong>In the population-based screening-by-invitation STHLM3-MRI trial, men aged 50-74 yr were invited to participate in screening. At 2-3 yr after the initial round, men with PSA ≥1.5 ng/ml at trial inclusion who were randomized to magnetic resonance imaging (MRI)-enhanced screening and were not diagnosed with prostate cancer after the initial round were invited for repeat screening involving analysis of PSA and Stockholm3. Biparametric 1.5-T MRI was performed in cases with PSA ≥3 ng/ml or Stockholm3 ≥0.11. Men with Prostate Imaging0Reporting and Data System ≥3 lesions were referred for targeted plus systematic biopsies. The primary outcome was Gleason ≥7 cancer. Secondary outcomes included the number of MRI scans and biopsy procedures, and detection of Gleason 6 and Gleason ≥4 + 3 cancer. Outcomes were compared using the relative positive fractions (RPF).</p><p><strong>Key findings and limitations: </strong>Of 7609 men from the initial screening round, 2078 were eligible for repeat screening and 1500 (72%) participated. For detection of Gleason ≥7 prostate cancer, the area under the receiver operating characteristic curve was 0.765 (95% confidence interval [CI] 0.725-0.805) for Stockholm3 and 0.651 (95% CI 0.601-0.701) for PSA. Stockholm3 ≥0.15 was associated with 41% fewer MRI scans in comparison to PSA ≥3 ng/ml (RPF 0.59, 95%CI 0.54-0.64), while the detection of GS ≥4 + 3 cancers was similar (RPF 1.00, 95% CI 0.78-1.29). Stockholm3 ≥0.15 detected fewer Gleason ≥7 (RPF 0.75, 95% CI 0.59-0.95) and Gleason 6 (RPF 0.73, 95% CI 0.46-1.16) cancers. Stockholm3 ≥0.11 was associated with no decrease in the number of MRI scans, but an increase of the number of cancer cases detected. Limitations include the lack of long-term outcomes.</p><p><strong>Conclusions and clinical implications: </strong>Use of the Stockholm3 test for repeated prostate cancer screening could reduce the need for MRI while maintaining detection rates for high-risk cancer.</p><p><strong>Patient summary: </strong>In this study, we invited men to a second round of prostate cancer screening. We found that use of a new blood test called Stockholm3 can make screening programs more efficient by using fewer resources while still detecting aggressive cancers.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Raag Agrawal, Sarah Al-Hiyari, Rupert Hugh-White, Robert Hromas, Yash Patel, Elizabeth A Williamson, Mohammed F E Mootor, Alfredo Gonzalez, Jianmin Fu, Roni Haas, Madison Jordan, Brian L Wickes, Ghouse Mohammed, Mao Tian, Molly J Doris, Christian Jobin, Kevin M Wernke, Yu Pan, Takafumi N Yamaguchi, Seth B Herzon, Paul C Boutros, Michael A Liss
{"title":"Colibactin Exerts Androgen-dependent and -independent Effects on Prostate Cancer.","authors":"Raag Agrawal, Sarah Al-Hiyari, Rupert Hugh-White, Robert Hromas, Yash Patel, Elizabeth A Williamson, Mohammed F E Mootor, Alfredo Gonzalez, Jianmin Fu, Roni Haas, Madison Jordan, Brian L Wickes, Ghouse Mohammed, Mao Tian, Molly J Doris, Christian Jobin, Kevin M Wernke, Yu Pan, Takafumi N Yamaguchi, Seth B Herzon, Paul C Boutros, Michael A Liss","doi":"10.1016/j.euo.2024.10.015","DOIUrl":"https://doi.org/10.1016/j.euo.2024.10.015","url":null,"abstract":"<p><strong>Background and objective: </strong>The etiology of prostate cancer (PC) is multifactorial and poorly understood. It has been suggested that colibactin-producing Escherichia coli positive for the pathogenicity island pks (pks<sup>+</sup>) initiate cancers via induction of genomic instability. In PC, androgens promote oncogenic translocations. Our aim was to investigate the association of pks<sup>+</sup>E. coli with PC diagnosis and molecular architecture, and its relationship with androgens.</p><p><strong>Methods: </strong>We quantified the association of pks<sup>+</sup>E. coli with PC diagnosis in a volunteer-sampled 235-person cohort from two institutional practices (UT San Antonio). We then used colibactin 742 and DNA/RNA sequencing to evaluate the effects of colibactin 742, dihydrotestosterone (DHT), and their combination in vitro.</p><p><strong>Key findings and limitations: </strong>Colibactin exposure was positively associated with PC diagnosis (p = 0.04) in our clinical cohort, and significantly increased replication fork stalling and fusions in vitro (p < 0.01). Combined in vitro exposure to colibactin 742 and DHT induced more somatic mutations of all types than exposure to either alone. The combination also elicited kataegis, with a higher density of somatic point mutations. Laboratory analyses were conducted using a single cell line, which limited our ability to fully recapitulate the complexity of PC etiology.</p><p><strong>Conclusions and clinical implications: </strong>Our findings are consistent with synergistic induction of genome instability and kataegis by colibactin 742 and DHT in cell culture. Colibactin-producing pks<sup>+</sup> E. coli may plausibly contribute to PC etiology.</p><p><strong>Patient summary: </strong>We investigated whether a bacterial toxin that is linked to colon cancer can also cause prostate cancer. Our results support this idea by showing a link between the toxin and prostate cancer diagnosis in a large patient population. We also found that this toxin causes genetic dysfunction in prostate cancer cells when combined with testosterone.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Praful Ravi, Caiwei Zhong, Wanling Xie, Emma Kelly, Bridget Whelpley, Katelyn Kuczmarski, Himisha Beltran, Kerry L Kilbridge, Martin T King, Bradley A McGregor, Alicia K Morgans, Mark Pomerantz, Mary-Ellen Taplin, Alok K Tewari, Srinivas R Viswanathan, Xiao X Wei, Mai Anh Huynh, Atish D Choudhury
{"title":"Combined Fixed-duration Systemic Treatment and Metastasis-directed Radiotherapy for Oligometastatic Hormone-sensitive Prostate Cancer.","authors":"Praful Ravi, Caiwei Zhong, Wanling Xie, Emma Kelly, Bridget Whelpley, Katelyn Kuczmarski, Himisha Beltran, Kerry L Kilbridge, Martin T King, Bradley A McGregor, Alicia K Morgans, Mark Pomerantz, Mary-Ellen Taplin, Alok K Tewari, Srinivas R Viswanathan, Xiao X Wei, Mai Anh Huynh, Atish D Choudhury","doi":"10.1016/j.euo.2024.10.014","DOIUrl":"https://doi.org/10.1016/j.euo.2024.10.014","url":null,"abstract":"<p><strong>Background and objective: </strong>It is unclear whether \"total therapy\" (androgen deprivation therapy [ADT] with or without an androgen receptor pathway inhibitor [ARPI], metastasis-directed therapy, and local therapy to the prostate if de novo) may lead to long-term durable remission in oligometastatic hormone-sensitive prostate cancer (omHSPC). This study aims to evaluate the outcomes after the completion of total therapy in patients with omHSPC.</p><p><strong>Methods: </strong>A retrospective single-institution cohort of consecutive patients with omHSPC identified on conventional or molecular imaging treated with total therapy was assembled. All patients had prostate-specific antigen ≤0.1 ng/ml at the completion of systemic therapy. Kaplan-Meier and Cox regression models were used to evaluate the key outcomes of interest: clinical progression-free survival (cPFS), eugonadal progression-free survival (PFS), and time to restart of ADT (TTrADT).</p><p><strong>Key findings and limitations: </strong>Eighty-nine patients were included, of whom 23 were with de novo omHSPC; the median number of metastases was 1, and detection of disease by molecular imaging was performed in 43 patients (48%). Forty-nine patients (55%) received ADT + ARPI doublet and 40 (45%) received ADT alone. At a median follow-up of 37 mo, there were 46 cPFS events; 3-yr cPFS rate was 45% (95% confidence interval 33-56) and the median eugonadal PFS was 12 mo. The median TTrADT was 47 mo, and 60% had not restarted ADT at 3 yr. Duration of systemic therapy ≥12 mo was the only significant predictor of better outcomes.</p><p><strong>Conclusions and clinical implications: </strong>Of the patients receiving total therapy for omHSPC, 45% remained progression free at 3 yr after completing therapy, hinting at the potential for long-term remission and possible cure with this strategy in a subset of patients with omHSPC. Prospective trials evaluating this approach are needed.</p><p><strong>Patient summary: </strong>In this report, we looked at outcomes in men who had received a fixed duration of hormonal therapy along with radiotherapy to metastatic sites (and prostate radiotherapy or surgery in those with newly diagnosed disease) for oligometastatic prostate cancer. We found that nearly half of the patients had no evidence of cancer recurrence at 3 yr after completing therapy, and 60% had not resumed any therapy at this time point.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sébastien Molière, Dimitri Hamzaoui, Guillaume Ploussard, Romain Mathieu, Gaelle Fiard, Michael Baboudjian, Benjamin Granger, Morgan Roupret, Hervé Delingette, Raphaele Renard-Penna
{"title":"A Systematic Review of the Diagnostic Accuracy of Deep Learning Models for the Automatic Detection, Localization, and Characterization of Clinically Significant Prostate Cancer on Magnetic Resonance Imaging.","authors":"Sébastien Molière, Dimitri Hamzaoui, Guillaume Ploussard, Romain Mathieu, Gaelle Fiard, Michael Baboudjian, Benjamin Granger, Morgan Roupret, Hervé Delingette, Raphaele Renard-Penna","doi":"10.1016/j.euo.2024.11.001","DOIUrl":"https://doi.org/10.1016/j.euo.2024.11.001","url":null,"abstract":"<p><strong>Background and objective: </strong>Magnetic resonance imaging (MRI) plays a critical role in prostate cancer diagnosis, but is limited by variability in interpretation and diagnostic accuracy. This systematic review evaluates the current state of deep learning (DL) models in enhancing the automatic detection, localization, and characterization of clinically significant prostate cancer (csPCa) on MRI.</p><p><strong>Methods: </strong>A systematic search was conducted across Medline/PubMed, Embase, Web of Science, and ScienceDirect for studies published between January 2020 and September 2023. Studies were included if these presented and validated fully automated DL models for csPCa detection on MRI, with pathology confirmation. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and the Checklist for Artificial Intelligence in Medical Imaging.</p><p><strong>Key findings and limitations: </strong>Twenty-five studies met the inclusion criteria, showing promising results in detecting and characterizing csPCa. However, significant heterogeneity in study designs, validation strategies, and datasets complicates direct comparisons. Only one-third of studies performed external validation, highlighting a critical gap in generalizability. The reliance on internal validation limits a broader application of these findings, and the lack of standardized methodologies hinders the integration of DL models into clinical practice.</p><p><strong>Conclusions and clinical implications: </strong>DL models demonstrate significant potential in improving prostate cancer diagnostics on MRI. However, challenges in validation, generalizability, and clinical implementation must be addressed. Future research should focus on standardizing methodologies, ensuring external validation and conducting prospective clinical trials to facilitate the adoption of artificial intelligence (AI) in routine clinical settings. These findings support the cautious integration of AI into clinical practice, with further studies needed to confirm their efficacy in diverse clinical environments.</p><p><strong>Patient summary: </strong>In this study, we reviewed how artificial intelligence (AI) models can help doctors better detect and understand aggressive prostate cancer using magnetic resonance imaging scans. We found that while these AI tools show promise, these tools need more testing and validation in different hospitals before these can be used widely in patient care.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}