European urology oncology最新文献

{"title":"Association of Tumor-informed Circulating Tumor DNA Detectability Before and After Radical Cystectomy with Disease-free Survival in Patients with Bladder Cancer.","authors":"John P Sfakianos, Arnab Basu, George Laliotis, Shivaram Cumarasamy, Jordan M Rich, Ajitha Kommalapati, Michael Glover, Tamara Mahmood, Neeraja Tillu, Christopher J Hoimes, Grayce Selig, Revathi Kollipara, Tyler F Stewart, Samuel Rivero-Hinojosa, Punashi Dutta, Mark Calhoun, Shruti Sharma, Meenakshi Malhotra, Adam C ElNaggar, Minetta C Liu, James E Ferguson, Marcio Diniz, Reza Mehrazin, Peter Wiklund, Alan Tan, Sumit Shah, Matthew D Galsky","doi":"10.1016/j.euo.2024.07.001","DOIUrl":"https://doi.org/10.1016/j.euo.2024.07.001","url":null,"abstract":"<p><strong>Background and objective: </strong>Despite curative-intent radical cystectomy (RC), patients with muscle-invasive bladder cancer (MIBC) are at high risk of recurrence. Biomarkers are urgently needed to refine prognostication and selection of appropriate perioperative systemic therapies. Our aim was to evaluate the prognostic and predictive value of tumor-informed circulating tumor DNA (ctDNA) results in a multicenter cohort of patients with bladder cancer who underwent RC.</p><p><strong>Methods: </strong>We performed a retrospective analysis of real-world data for a commercial ctDNA test (Signatera; Natera, Austin, TX, USA) performed in 167 patients (852 plasma samples) before RC and during molecular residual disease (MRD; adjuvant decision) and surveillance windows. We assessed the correlation between recurrence and ctDNA status before and after RC using Cox regression analysis.</p><p><strong>Results and limitations: </strong>During study-defined postoperative MRD and surveillance windows, detectable ctDNA was associated with shorter disease-free survival (DFS) when compared to undetectable ctDNA (MRD: hazard ratio 6.93; p < 0.001; surveillance: hazard ratio 23.02; p < 0.001). Of note, patients with undetectable ctDNA did not appear to benefit from adjuvant therapy (p = 0.34). Detectable ctDNA in the pre-RC (p = 0.045), MRD (p = 0.002), and surveillance (p < 0.001) windows was the only risk factor independently associated with shorter DFS. Limitations include the retrospective and nonrandomized nature of the study.</p><p><strong>Conclusions: </strong>ctDNA testing in patients with bladder cancer undergoing RC was prognostic and potentially predictive. Identification of patients at high risk of recurrence may aid in patient counseling and decision-making.</p><p><strong>Patient summary: </strong>We found that outcomes for patients with muscle-invasive bladder cancer are strongly linked to detection of tumor DNA in blood samples. The results show the value of tumor-informed testing for tumor DNA in blood for decisions on the best treatment for each individual patient.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626519","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":"Clinical Characteristics, Management, and Outcomes of Patients with Renal Medullary Carcinoma: A Single-center Retrospective Analysis of 135 Patients.","authors":"Justin M Lebenthal, Panayiotis D Kontoyiannis, Andrew W Hahn, Zita D Lim, Priya Rao, Jessica P Cheng, Beei Chan, Najat C Daw, Rahul A Sheth, Jose A Karam, Chad Tang, Nizar M Tannir, Pavlos Msaouel","doi":"10.1016/j.euo.2024.07.002","DOIUrl":"https://doi.org/10.1016/j.euo.2024.07.002","url":null,"abstract":"<p><strong>Background and objective: </strong>SMARCB1-deficient renal medullary carcinoma (RMC) is a rare kidney cancer associated with sickle cell hemoglobinopathies with poor outcomes described only in case reports and small series. We report disease and management characteristics as well as contemporary survival outcomes in a large cohort of patients with RMC.</p><p><strong>Methods: </strong>Data were extracted retrospectively from all patients with RMC treated at MD Anderson Cancer Center between January 2003 and December 2023. Multivariable Cox regression was used to estimate overall survival (OS) by diagnosis period.</p><p><strong>Key findings and limitations: </strong>Among 135 patients (median follow-up of 54.9 mo), only nine did not harbor a sickle hemoglobinopathy and were categorized as having renal cell carcinoma, unclassified with medullary phenotype (RCCU-MP). Most patients (78%) presented with metastatic disease, predominantly to the retroperitoneal lymph nodes (81.7%), and hematuria was the most frequent presenting symptom (60%) in RMC associated with sickle hemoglobinopathy. Survival outcomes improved by diagnosis year (adjusted hazard ratio 0.70, 95% confidence interval 0.53-0.92, p = 0.01). RCCU-MP occurred in slightly older patients with median OS of 19.5 mo from diagnosis, did not show a predilection to the right kidney or male predominance, and afflicted mainly Caucasians (89%). The study is limited by its retrospective nature conducted at one center.</p><p><strong>Conclusions and clinical implications: </strong>RMC frequently presents with hematuria and is highly likely to spread to the retroperitoneal lymph nodes. Survival outcomes are improving with contemporary management. RCCU-MP is very rare and may be slightly less aggressive.</p><p><strong>Patient summary: </strong>Renal medullary carcinoma (RMC) is a rare and aggressive subtype of kidney cancer afflicting primarily young men and women of African descent. There exist limited data regarding patient demographics and disease characteristics. We reported our institution's experience in treating patients with RMC. The first symptom most patients with RMC reported was blood in the urine, and the most common places where the cancer spread were the lymph nodes around the kidney. Patients with RMC are living longer with contemporary treatments.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626520","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":"Effect of Radical Prostatectomy on Survival for Men with High-risk Nonmetastatic Prostate Cancer Features Selected According to STAMPEDE Criteria: An EMPaCT Study.","authors":"Daimantas Milonas, Alexander Giesen, Annouschka Laenen, Gaëtan Devos, Alberto Briganti, Paolo Gontero, R Jeffrey Karnes, Piotr Chlosta, Frank Claessens, Gert De Meerleer, Wouter Everaerts, Markus Graefen, Giansilvio Marchioro, Rafael Sanchez-Salas, Bertrand Tombal, Henk Van Der Poel, Hendrik Van Poppel, Martin Spahn, Steven Joniau","doi":"10.1016/j.euo.2024.05.016","DOIUrl":"https://doi.org/10.1016/j.euo.2024.05.016","url":null,"abstract":"<p><strong>Background and objective: </strong>A meta-analysis of two randomized STAMPEDE platform trials revealed that 3 yr of abiraterone acetate in addition to androgen deprivation therapy and radiation therapy significantly improved metastasis-free and overall survival (OS) in high-risk nonmetastatic prostate cancer (PCa) and should be considered a new standard of care. The aim of our study was to assess long-term cancer-specific survival (CSS) and OS for surgically treated patients with newly diagnosed nonmetastatic node-negative PCa meeting the STAMPEDE criteria for high risk.</p><p><strong>Methods: </strong>This was a retrospective, multicenter cohort study of patients with European Association of Urology (EAU) high-risk PCa who underwent radical prostatectomy and extended pelvic lymph node dissection. CSS was assessed using cumulative incidence curves and the Kaplan-Meier method was used to evaluate OS. We used a Fine and Gray model to evaluate the prognostic value of STAMPEDE high-risk factors (SHRFs) for CSS, and a Cox proportional-hazards model to assess the association of SHRFs with OS.</p><p><strong>Key findings and limitations: </strong>A total of 2994 patients with EAU high-risk PCa were divided into groups with 0, 1, 2, or 3 SHRFs. The 10-yr survival estimates for patients with 0-1 versus 2-3 SHRFs were 95% versus 82% for CSS and 81% versus 64% for OS (both p < 0.0001). In comparison to patients with 0 SHRFs, hazard ratios were 1.2 (p = 0.5), 3.9 (p < 0.0001), and 5.5 (p < 0.0001) for CSS, and 1.1 (p = 0.4), 2.2 (p < 0.0001), and 2.5 (p = 0.0004) for OS for patients with 1, 2, and 3 SHRFs, respectively.</p><p><strong>Conclusions and clinical implications: </strong>Our results confirm that the STAMPEDE high-risk criteria identify a subgroup of patients with highly aggressive PCa features and adverse long-term oncological outcomes. This population is likely to benefit most from aggressive multimodal treatment. Nevertheless, we have shown for the first time that surgery remains a viable treatment option for patients with STAMPEDE high-risk PCa.</p><p><strong>Patient summary: </strong>Prostate cancer that meets the high-risk definitions from the STAMPEDE trial is an aggressive type of cancer. Our results for long-term cancer control outcomes indicate that surgery is a viable option for the subgroup of patients with this type of prostate cancer.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141598911","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":"The Role of Baseline Prostate-specific Antigen Value Prior to Age 60 in Predicting Lethal Prostate Cancer: Analysis of a Contemporary North American Cohort.","authors":"Marco Finati, Matthew Davis, Alex Stephens, Giuseppe Chiarelli, Giuseppe Ottone Cirulli, Chase Morrison, Rafe Affas, Akshay Sood, Nicolò Buffi, Giovanni Lughezzani, Alberto Briganti, Francesco Montorsi, Giuseppe Carrieri, Craig Rogers, Andrew Julian Vickers, Firas Abdollah","doi":"10.1016/j.euo.2024.06.014","DOIUrl":"https://doi.org/10.1016/j.euo.2024.06.014","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Studies evaluating the role of baseline midlife prostate-specific antigen (PSA) as a predictor of development and progression of prostate cancer relied predominately on cohorts from the pre-PSA screening introduction era. The aim of our study was to examine the role of baseline PSA prior to the age of 60 yr as a predictor of developing lethal prostate cancer using a contemporary North American cohort.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Our cohort included all men aged 40-59 yr who received their first PSA through our health system between the years 1995 and 2019. Patients were divided into four categories based on age: 40-44, 45-49, 50-54, and 55-59 yr. Baseline PSA was the predictor of interest. Lethal disease was defined as death from prostate cancer or development of metastatic disease either at diagnosis or during follow-up. Cancer-specific mortality and overall mortality were obtained by linking our database to the Michigan Vital Records registry. Competing-risk regression was used to evaluate the association between PSA and lethal prostate cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key findings and limitations: &lt;/strong&gt;A total of 129067 men met the inclusion criteria during the study period. The median follow-up for patients free from cancer was 7.4 yr. For men aged 40-44, 45-49, 50-54, and 55-59 yr, the estimated rates of lethal prostate cancer at 20 yr were 0.02%, 0.14%, 0.33%, and 0.51% in men with PSA &lt;median, and 0.79%, 0.16%, 2.5%, and 5.4% in men with PSA ≥90th percentile, respectively. For the same age category, the estimated rates of any prostate cancer at 20 yr were, respectively, 1.6%, 2.9%, 3.9%, and 5.8% in men with PSA &lt;median, and 25%, 28%, 38%, and 39% in men with PSA ≥90th percentile. On a multivariable analysis, men with PSA ≥90th percentile had a hazard ratio of 7.48 (95% confidence interval [CI]: 6.20-9.03) for lethal disease, when compared with those with PSA &lt;median. On the multivariable analysis, men with PSA ≥90th percentile had a hazard ratio of 20.47-fold (95% CI: 18.58-22.55) for prostate cancer incidence, when compared with those with PSA &lt;median at first. Limitations included shorter median follow-up than prior literature.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and clinical implications: &lt;/strong&gt;Baseline PSA is a very strong predictor of the subsequent risk of developing lethal prostate cancer in a large contemporary diverse North American cohort, which was exposed to opportunistic PSA screening. The association was far larger than that found for polygenic risk scores, confirming that baseline PSA prior to the age of 60 yr is the most effective tool for adjusting subsequent screening. Compared with studies of unscreened cohorts, there was a smaller difference in discrimination between incident and lethal disease, reflecting the influence of screening.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Patient summary: &lt;/strong&gt;In this study, we found that a single baseline prostate-specific antigen (PSA) value is strongly predictive of t","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590043","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":"Long-term Renal Function Outcomes After Stereotactic Ablative Body Radiotherapy for Primary Renal Cell Carcinoma Including Patients with a Solitary Kidney: A Report from the International Radiosurgery Oncology Consortium of the Kidney.","authors":"Vivian S Tan, Rohann J M Correa, Andrew Warner, Muhammad Ali, Alexander Muacevic, Lee Ponsky, Rodney J Ellis, Simon S Lo, Hiroshi Onishi, Anand Swaminath, Young Suk Kwon, Scott C Morgan, Fabio L Cury, Bin S Teh, Anand Mahadevan, Irving D Kaplan, William Chu, Raquibul Hannan, Michael Staehler, Nicholas G Zaorsky, Alexander V Louie, Shankar Siva","doi":"10.1016/j.euo.2024.06.012","DOIUrl":"10.1016/j.euo.2024.06.012","url":null,"abstract":"<p><strong>Background and objective: </strong>Renal function preservation is particularly important following nonoperative treatment of localized renal cell carcinoma (RCC) since patients are often older with medical comorbidities. Our objective was to report long-term renal function outcomes after stereotactic ablative radiotherapy (SABR) including patients with a solitary kidney.</p><p><strong>Methods: </strong>Patients with primary RCC treated with SABR with ≥2 yr of follow-up at 12 International Radiosurgery Consortium for Kidney institutions were included. Renal function was measured by estimated glomerular filtration rate (eGFR).</p><p><strong>Key findings and limitations: </strong>In total, 190 patients (56 with a solitary kidney) underwent SABR and were followed for a median of 5.0 yr (interquartile range [IQR]: 3.4-6.8). In patients with a solitary kidney versus bilateral kidneys, pre-SABR eGFR (mean [standard deviation]) was 61.1 (23.2) versus 58.0 (22.3) ml/min (p = 0.32) and the median tumor size was 3.65 cm (IQR: 2.59-4.50 cm) versus 4.00 cm (IQR: 3.00-5.00 cm; p = 0.026). At 5 yr after SABR, eGFR decreased by -14.5 (7.6) and -13.3 (15.9) ml/min (p = 0.67), respectively, and there were similar rates of post-SABR dialysis (3.6% [n = 2/56] vs 3.7% [n = 5/134]). A multivariable analysis demonstrated that increasing tumor size (odds ratio [OR] per 1 cm: 1.57; 95% confidence interval [CI]: 1.14-2.16, p = 0.0055) and baseline eGFR (OR per 10 ml/min: 1.30; 95% CI: 1.02-1.66, p = 0.034) were associated with an eGFR decline of ≥15 ml/min at 1 yr.</p><p><strong>Conclusions and clinical implications: </strong>With long-term follow-up after SABR, kidney function decline remains moderate, with no observed difference between patients with a solitary kidney and bilateral kidneys. Tumor size and baseline eGFR are dominant factors predictive of long-term renal function decline.</p><p><strong>Patient summary: </strong>With long-term follow-up, stereotactic ablative radiotherapy (SABR) yields moderate long-term renal function decline and low dialysis rates even in patients with a solitary kidney. SABR thus represents a promising noninvasive, nephron-sparing option for patients with localized renal cell carcinoma.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579367","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":"Patients' Preferences for Cytoreductive Treatments in Newly Diagnosed Metastatic Prostate Cancer: The IP5-MATTER Study.","authors":"Martin J Connor, Mesfin Genie, Tim Dudderidge, Hangjian Wu, Johanna Sukumar, Mark Beresford, Diletta Bianchini, Chee Goh, Gail Horan, Pasquale Innominato, Vincent Khoo, Natalia Klimowska-Nassar, Sanjeev Madaan, Stephen Mangar, Stuart McCracken, Peter Ostler, Sangeeta Paisey, Angus Robinson, Bhavan Rai, Naveed Sarwar, Narayanan Srihari, Kamal Thippu Jayaprakash, Mohini Varughese, Mathias Winkler, Hashim U Ahmed, Verity Watson","doi":"10.1016/j.euo.2024.06.010","DOIUrl":"https://doi.org/10.1016/j.euo.2024.06.010","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Cytoreductive treatments for patients diagnosed with de novo synchronous metastatic hormone-sensitive prostate cancer (mHSPC) confer incremental survival benefits over systemic therapy, but these may lead to added toxicity and morbidity. Our objective was to determine patients' preferences for, and trade-offs between, additional cytoreductive prostate and metastasis-directed interventions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A prospective multicentre discrete choice experiment trial was conducted at 30 hospitals in the UK between December 3, 2020 and January 25, 2023 (NCT04590976). The individuals were eligible for inclusion if they were diagnosed with de novo synchronous mHSPC within 4 mo of commencing androgen deprivation therapy and had performance status 0-2. A discrete choice experiment instrument was developed to elicit patients' preferences for cytoreductive prostate radiotherapy, prostatectomy, prostate ablation, and stereotactic ablative body radiotherapy to metastasis. Patients chose their preferred treatment based on seven attributes. An error-component conditional logit model was used to estimate the preferences for and trade-offs between treatment attributes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key findings and limitations: &lt;/strong&gt;A total of 352 patients were enrolled, of whom 303 completed the study. The median age was 70 yr (interquartile range [IQR] 64-76) and prostate-specific antigen was 94 ng/ml (IQR 28-370). Metastatic stages were M1a 10.9% (33/303), M1b 79.9% (242/303), and M1c 7.6% (23/303). Patients preferred treatments with longer survival and progression-free periods. Patients were less likely to favour cytoreductive prostatectomy with systemic therapy (Coef. -0.448; [95% confidence interval {CI} -0.60 to -0.29]; p &lt; 0.001), unless combined with metastasis-directed therapy. Cytoreductive prostate radiotherapy or ablation with systemic therapy, number of hospital visits, use of a \"day-case\" procedure, or addition of stereotactic ablative body radiotherapy did not impact treatment choice. Patients were willing to accept an additional cytoreductive treatment with 10 percentage point increases in the risk of urinary incontinence and fatigue to gain 3.4 mo (95% CI 2.8-4.3) and 2.7 mo (95% CI 2.3-3.1) of overall survival, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and clinical implications: &lt;/strong&gt;Patients are accepting of additional cytoreductive treatments for survival benefit in mHSPC, prioritising preservation of urinary function and avoidance of fatigue.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Patient summary: &lt;/strong&gt;We performed a large study to ascertain how patients diagnosed with advanced (metastatic) prostate cancer at their first diagnosis made decisions regarding additional available treatments for their prostate and cancer deposits (metastases). Treatments would not provide cure but may reduce cancer burden (cytoreduction), prolong life, and extend time without cancer progression. We reported that most patients were w","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554499","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":"Use of Decipher Prostate Biopsy Test in Patients with Favorable-risk Disease Undergoing Conservative Management or Radical Prostatectomy in the Surveillance, Epidemiology, and End Results Registry.","authors":"Alec Zhu, James A Proudfoot, Elai Davicioni, Ashley E Ross, Valentina I Petkov, Sarah Bonds, Nicki Schussler, Nicholas G Zaorsky, Angela Y Jia, Daniel E Spratt, Edward M Schaeffer, Yang Liu, Mary O Strasser, Jim C Hu","doi":"10.1016/j.euo.2024.06.007","DOIUrl":"https://doi.org/10.1016/j.euo.2024.06.007","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;The extent of prostate cancer found on biopsy, as well as prostate cancer grade and genomic tests, can affect clinical decision-making. The impact of these factors on the initial management approach and subsequent patient outcomes for men with favorable-grade prostate cancer has not yet been determined on a population level. Our objective was to explore the association of Decipher 22-gene genomic classifier (GC) biopsy testing on the initial use of conservative management versus radical prostatectomy (RP) and to determine the independent effect of GC scores on RP pathologic outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 87 140 patients diagnosed with grade group 1 and 2 prostate cancer between 2016 and 2018 from the Surveillance, Epidemiology, and End Results registry data were linked to GC testing results (2576 tested and 84 564 untested with a GC). The primary endpoints of interest were receipt of conservative management or RP, pathologic upgrading (pathologic grade group 3-5), upstaging (pathologic ≥T3b), and adverse pathologic features (pathologic upgrading, upstaging, or lymph node invasion). Multivariable logistic regressions quantified the association of variables with outcomes of interest.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key findings and limitations: &lt;/strong&gt;GC tested patients were more likely to have grade group 2 on biopsy (51% vs 46%, p &lt; 0.001) and lower prostate-specific antigen (6.1 vs 6.3, p = 0.016). Conservative management increased from 37% to 39% and from 22% to 24% during 2016-2018 for the GC tested and untested populations, respectively. GC testing was significantly associated with increased odds of conservative management (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.9-2.4, p &lt; 0.001). The distribution of biopsy GC risk was as follows: 45% low risk, 30% intermediate risk, and 25% high risk. In adjusted analyses, higher GC (per 0.1 increment) scores (OR 1.24, 95% CI 1.17-1.31, p &lt; 0.001) and percent positive cores (1.07, 95% CI 1.02-1.12, p = 0.009) were significantly associated with the receipt of RP. A higher GC score was significantly associated with all adverse outcomes (pathologic upgrading [OR 1.29, 95% CI 1.12-1.49, p &lt; 0.001], upstaging [OR 1.31, 95% CI 1.05-1.62, p = 0.020], and adverse pathology [OR 1.27, 95% CI 1.12-1.45, p &lt; 0.001]). Limitations include observational biases associated with the retrospective study design.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and clinical implications: &lt;/strong&gt;Men who underwent GC testing were more likely to undergo conservative management. GC testing at biopsy is prognostic of adverse pathologic outcomes in a large population-based registry.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Patient summary: &lt;/strong&gt;In this population analysis of men with favorable-risk prostate cancer, those who underwent genomic testing at biopsy were more likely to undergo conservative management. Of men who initially underwent radical prostatectomy, higher genomic risk but not tumor volume was asso","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554500","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":"Intensifying Salvage Therapy in Prostate-specific Antigen Recurrent Prostate Cancer After Radical Prostatectomy with Apalutamide, Salvage Radiation, and Docetaxel: The Phase 2 STARTAR Trial.","authors":"Tian Zhang, Lauren Howard, Bridget F Koontz, Scott T Tagawa, Himanshu Nagar, Rhonda L Bitting, Bart A Frizzell, Luke Nordquist, Julia Rasmussen, Colleen Riggan, Marco Reyes, Catrin Davies, Steven R Gray, Carly R Newman, Escarleth Fernandez, Sundhar Ramalingam, Michael R Harrison, Daniel J George, Yuan Wu, Andrew J Armstrong","doi":"10.1016/j.euo.2024.06.013","DOIUrl":"https://doi.org/10.1016/j.euo.2024.06.013","url":null,"abstract":"<p><strong>Background and objective: </strong>Androgen deprivation therapy (ADT) with salvage radiation therapy (RT) improves survival for patients with prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) for prostate cancer (PC), but many patients suffer further relapse. This study aims to determine the benefit of the combination of ADT, apalutamide, salvage RT, and docetaxel for high-risk PSA recurrent PC.</p><p><strong>Methods: </strong>STARTAR is a multicenter, investigator-initiated phase 2 trial of men with PSA recurrent PC after RP. The key inclusion criteria included M0 by computed tomography/bone scan, Gleason 7 with either T3/positive margin/N1 disease or Gleason 8-10 prostate adenocarcinoma, PSA relapse (0.2-4 ng/ml) <4 yr after RP, and fewer than four positive resected lymph nodes. Patients received ADT with apalutamide for 9 mo, RT starting week 8, and then six cycles of docetaxel. The primary endpoint was 36-mo progression-free survival (PFS) with testosterone recovery and compared against the prior STREAM trial.</p><p><strong>Key findings and limitations: </strong>We enrolled 39 men, including those with Gleason 8-10 (46%), pN1 (23%); the median PSA was 0.58 ng/ml. The median follow-up was 37 mo. All patients achieved undetectable PSA nadir. At 24 and 36 mo, PFS rates were 84% and 71%, respectively, which improved significantly over 3-yr 47% historic PFS and 54% enzalutamide/ADT/RT (STREAM) PFS rates (p = 0.004 and p = 0.039, respectively). Common any-grade adverse events included 98% hot flashes, 88% fatigue, 77% alopecia, 53% rash (10% G3), and 5% febrile neutropenia.</p><p><strong>Conclusions and clinical implications: </strong>In this phase 2 trial of ADT, apalutamide, salvage RT, and six cycles of docetaxel for high-risk PSA recurrence, the 3-yr PFS rate improved to 71%, indicating feasible and efficacious treatment intensification, with durable remissions beyond historic data.</p><p><strong>Patient summary: </strong>Prostate cancer recurrence after surgical removal of the tumor occurs often, and current treatment options to limit recurrence after surgery are only partially effective. In this study, we found that the addition of an androgen receptor inhibitor and docetaxel chemotherapy to standard postsurgery radiation therapy and androgen deprivation therapy significantly improved progression-free survival at 3 yr after treatment. These results suggest that intensification of treatment after surgery can provide long-term benefit to a subset of patients with high-risk prostate cancer.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544674","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":"PTEN Loss Is Associated with Adverse Outcomes in the Setting of Salvage Radiation Therapy.","authors":"Emerson Lee, Lia DePaula Oliveira, Oluwademilade Dairo, Sanaz Nourmohammadi Abadchi, Eumee Cha, Adrianna A Mendes, Jarey H Wang, Daniel Y Song, Tamara L Lotan","doi":"10.1016/j.euo.2024.06.008","DOIUrl":"https://doi.org/10.1016/j.euo.2024.06.008","url":null,"abstract":"<p><strong>Background: </strong>Salvage radiation therapy (SRT) is a mainstay of treatment for biochemical relapse following radical prostatectomy; however, few studies have examined genomic biomarkers in this context.</p><p><strong>Objective: </strong>We characterized the prognostic impact of previously identified deleterious molecular phenotypes-loss of PTEN, ERG expression, and TP53 mutation-for patients undergoing SRT.</p><p><strong>Design, setting, and participants: </strong>We leveraged an institutional database of 320 SRT patients with available tissue and follow-up. Tissue microarrays were used for genetically validated immunohistochemistry assays.</p><p><strong>Intervention: </strong>All men underwent SRT with or without androgen deprivation therapy OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable Cox-proportional hazard models assessed the association of molecular phenotypes with biochemical recurrence-free (bRFS) and metastasis-free (MFS) survival after SRT.</p><p><strong>Results and limitations: </strong>Loss of PTEN (n = 123, 43%) and ERG expression (n = 118, 39%) were common in this cohort, while p53 overexpression (signifying TP53 missense mutation) was infrequent (n = 21, 7%). In univariable analyses, any loss of PTEN portended worse bRFS (hazard ratio [HR] 1.86; 95% confidence interval 1.36-2.57) and MFS (HR 1.89; 1.21-2.94), with homogeneous PTEN loss being associated with the highest risk of MFS (HR 2.47; 1.54-3.95). Similarly, p53 overexpression predicted worse bRFS (HR 1.95; 1.14-3.32) and MFS (HR 2.79; 1.50-5.19). ERG expression was associated with worse MFS only (HR 1.6; 1.03-2.48). On the multivariable analysis adjusting for known prognostic features, homogeneous PTEN loss remained predictive of adverse bRFS (HR 1.82; 1.12-2.96) and MFS (HR 2.08; 1.06-4.86). The study is limited by its retrospective and single-institution design.</p><p><strong>Conclusions: </strong>PTEN loss by immunohistochemistry is an independent adverse prognostic factor for bRFS and MFS in prostate cancer patients treated with SRT. Future trials will determine the optimal approach to treating SRT patients with adverse molecular prognostic features.</p><p><strong>Patient summary: </strong>Loss of the PTEN tumor suppressor protein is associated with worse outcomes after salvage radiotherapy, independent of other clinical or pathologic patient characteristics.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534013","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":"Current Treatment Paradigms and Clinical Outcomes in Oligometastatic Prostate Cancer Patients: A Targeted Literature Review.","authors":"Emmanuel S Antonarakis, Irene M Shui, Omer Zaidi, Mark Bernauer, Christian Gratzke","doi":"10.1016/j.euo.2024.06.002","DOIUrl":"https://doi.org/10.1016/j.euo.2024.06.002","url":null,"abstract":"<p><strong>Context: </strong>Prostate cancer is the most common noncutaneous malignancy among men in the USA and Europe. There is no consensus definition of oligometastatic prostate cancer (omPC), which is often considered in two subgroups, synchronous (de novo) and metachronous (oligorecurrent), and may include patients with a low metastatic disease burden.</p><p><strong>Objective: </strong>To summarize the epidemiology, disease definitions, mortality/survival outcomes, and treatment characteristics in both clinical trial and real-world settings among patients with synchronous, metachronous, and mixed-subtype (ie, synchronous and metachronous or undefined type) omPC, as well as low burden disease states.</p><p><strong>Evidence acquisition: </strong>We searched MEDLINE and Embase to identify publications reporting on epidemiology, disease definitions, clinical outcomes, and treatment characteristics of omPC. Gray literature sources (eg, ClinicalTrials.gov) were searched for ongoing trials.</p><p><strong>Evidence synthesis: </strong>We identified 105 publications. Disease definitions varied across publications and omPC subtypes on the number and location of lesions, type of imaging used, and type of oligometastatic disease. Most studies defined omPC as five or fewer metastatic lesions. Data on the epidemiology of omPC were limited. Mortality rates and overall survival tended to be worse among synchronous versus metachronous omPC cohorts. Progression-free survival was generally longer among synchronous than among metachronous omPC cohorts but was more similar at longer time points. A summary of ongoing clinical trials investigating a variety of local, metastasis-directed, and systemic therapies in men with omPC is also provided.</p><p><strong>Conclusions: </strong>Definitions of oligometastatic disease depend on the imaging technique used. Epidemiologic data for omPC are scarce. Survival rates differ between synchronous and metachronous cohorts, and heterogeneous treatment patterns result in varied outcomes. Ongoing clinical trials using modern imaging techniques are awaited and needed.</p><p><strong>Patient summary: </strong>Definitions of oligometastatic prostate cancer (omPC) vary depending on the imaging technique used. Different treatment patterns lead to different outcomes. Robust omPC epidemiologic data are lacking.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533982","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}