bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing genomic alterations in patients with metastatic urothelial carcinoma (mUC) treated with enfortumab-vedotin (EV) with a focus on 1q23.3.
Authors: Saliby Renee Maria , Semaan Karl , Epstein Ilana B. , Liria Sonsoles , Dall Christopher , Saad Eddy , Eid Marc , Canniff John , Kwak Lucia , Berg Stephanie A. , Mantia Charlene , McGregor Bradley Alexander , Braun David A. , CHOUEIRI Toni K. , Bellmunt Joaquim
Published: June 2024

e16570

Background: EV has improved outcomes for patients with mUC whether used as monotherapy or in combination. Limited studies have explored EV's efficacy and toxicity using combined genomic data from multiple platforms. We explored the association of genomic alterations with clinical outcomes in patients with mUC receiving EV treated at a single institution. Methods: Clinical and genomic data from patients with mUC treated with EV at the Dana-Farber Cancer Institute was analyzed. Genomic data was obtained using the targeted Oncopanel platform. Overall survival (OS), progression-free survival (PFS), and toxicity-free survival (TFS) as well as objective response rate (ORR) and progressive disease (PD) as best response according to RECIST 1.1 criteria were studied. Patients were categorized based on genomic alterations employing log-rank tests and univariate Cox regression for OS, PFS, and TFS, and Fisher’s exact test for ORR and PD. Results: We identified 286 patients treated for advanced UC since the approval of EV in 2021, of whom 65 received EV monotherapy, had available genomic data and were included in our analysis. Two genomic regions, 1q23.3 and 9p21.3 were found of interest. 17% (N=11) exhibited gain or amplification at the 1q23.3 cytoband ( PVRL4 cytoband) while 35% (N=23) had a two-copy deletion or loss at 9p21.3 ( MTAP, CDKN2A/B cytoband). While none of the results were statistically significant, gain or amplification of 1q23.3 was associated with a trend towards worse OS (Table). ORR was 29% compared to 60% in those without, but this difference was not statistically significant (p.value = 0.62). Two-copy deletion or loss at 9p21.3 was associated with numerically longer OS (Table) ORR was 57% in patients with the alteration versus 50% in those without, and 9% versus 17% for PD, respectively. These differences also did not reach statistical significance (p.value = 0.46). Conclusions: Our study did not find significant correlations between specific somatic alterations and clinical outcomes in patients with metastatic UC treated with EV though limited by small sample size. The observed trends in alterations of 1q23.3 and 9p21.3 warrant further investigation in larger cohorts. [Table: see text]
First-line (1L) systemic therapy in locally advanced/metastatic urothelial cancer (Ia/mUC): A living interactive systematic review and network meta-analysis.
Authors: Saxena Akshat , Riaz Irbaz Bin , Naqvi Syed Arsalan Ahmed , Bibi Arifa , Channar Aneeta , Tripathi Nikita , Khan Muhammad Ali , Raina Ammad , Khakwani Kaneez Zahra Rubab , Childs Daniel S , Bryce Alan Haruo , Singh Parminder
Published: June 2024

e16579

Background: Recent results from EV 302 and CheckMate 901 have transformed the treatment landscape of untreated locally advanced/metastatic urothelial cancer (Ia/mUC). Here, we present the most up-to-date evidence of comparative efficacy and safety of first line (1L) treatment options in Ia/mUC with emphasis on Enfortumab vedotin (EV)-pembrolizumab (P) and gemcitabine (Gem)-cisplatin (Cis)-nivolumab (N). Methods: This living systematic review used the living interactive evidence (LIvE) synthesis framework. Full-text and abstract publications of phase II/III randomized clinical trials comparing 1L immunotherapy combined with chemotherapy (IO+C) or immunotherapy alone (IO) regimens with platinum-based chemotherapy (Plat) in Ia/mUC were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS) and treatment-related grade 3 or greater adverse events (≥G3 TRAE). Mixed treatment comparisons were made using network meta-analysis. P-scores were computed to assess relative treatment rankings. Results: A total of 5 trials (8 references) with 4,749 patients and 9 unique treatments were included. EV-P and Gem-Cis-N were ranked first and second in terms of OS and PFS improvement. EV-P improved OS compared to Gem-Cis-N (HR: 0.60; 0.45-0.81), Gem-Plat-atezolizumab(A) (0.55; 0.42-0.72), durvalumab(D)- tremelimumab(T) (0.55; 0.42-0.72), Gem-Plat-P (0.55; 0.42-0.72), P (0.51; 0.39-0.68), D (0.47; 0.36-0.63), A (0.48; 0.36-0.63) and Gem-Plat (0.47; 0.38-0.58). EV-P also improved PFS compared to Gem-Cis-N (0.63; 0.48-0.82), Gem-Plat-A (0.55; 0.43-0.69), D-T (0.42; 0.33-0.53), Gem-Plat-P (0.58; 0.45-0.74), P (0.34; 0.26-0.44), D (0.35; 0.27-0.44) and Gem-Plat (0.45; 0.38- 0.54). For ≥G3 TRAE, A was ranked first with the lowest adverse events compared to others. EV-P (rank 5) had significantly fewer events compared to Gem-Plat, Gem-Plat-A, Gem-Cis-N and Gem-Plat-P. Gem-Cis-N was ranked last with significantly greater events compared to A, P, D, D-T, Gem-Plat, EV-P, and Gem-Plat-A (Table with ranks [p-scores]). Conclusions: Current evidence suggests that patients with untreated la/mUC experience improved survival and slower disease progression with EV-P when compared to other contemporary options. Gem-Cis-N may be a reasonable alternative in patients who are cisplatin-eligible. Cost and access to these treatments are crucial and should be considered to facilitate shared decision making. [Table: see text]
In-hospital outcomes of acute pulmonary embolism admissions in individuals with genitourinary cancers: Insights from a national population study in the United States.
Authors: Benjamin David Joseph , Rezazadeh Arash , Shafi Irfan , Yazdanpanah Omid
Published: June 2024

e16581

Background: Management of acute pulmonary embolism (PE) in patients with genitourinary (GU) malignancies is usually challenging. It is usually associated with adverse outcomes and can significantly contribute to morbidity and mortality and detrimentally impacts quality of life among cancer patients. There has been scarce previous national population study on patients with PE and GU malignancies. Here, we studied the rate of readmissions and mortality for patients admitted for PE with GU cancers in the U.S. and its burden on health care system. Methods: Utilizing the Nationwide Readmissions Database (NRD), we conducted a retrospective cohort study on patients admitted with PE and segregated the individuals with GU cancers (GUC) including renal cell carcinoma (RCC), urothelial Carcinoma (UC), prostate cancer (PCa), testicular cancer (TC), and penile cancer (Pen Ca) between 2016 and 2019 across the United States. We used multivariable logistic regression to determine the predictors of unplanned readmissions within 30 days and mortality. Results: A total of 402,054 patients hospitalized with PE and 44,373 (11%) were readmitted within the next 30 days. Mean length of stay was 4.64 days (95% CI 4.62-4.65). Total charge for index hospitalization was $51,409 (95% CI 51,174-51,643). A total of 8,998 patients were found to have GU cancers. Following baseline comorbidities were associated with highest risk of readmission: Atrial fibrillation, proximal and caval deep vein thrombosis, obesity, hypertension, smoking, and diabetes mellites ( P <0.001). Among GUC, rate of readmission was highest for UC (P<0.01; OR 2.49, 95% CI 1.76 - 3.5) as shown in the table. Risk of in hospital mortality was also highest for UC (P<0.01; OR 2.40, 95% CI 1.39-4.14) followed by RCC (P<0.01; OR 2.06, 95% CI 1.62-2.5). Conclusions: There was higher risk of readmission and mortality for patients with GU malignancies who were hospitalized for PE. UC was the leading GU cancer for rate of readmission and mortality. These readmissions were lengthy and costly for the health care system. This study suggests that more aggressive intervention might be needed in this population to prevent readmission and mortality. [Table: see text]
Efficacy and safety of neoadjuvant therapy with disitamab vedotin plus toripalimab in treating muscle invasive urothelial bladder cancer followed by selective bladder-preserving or radical cystectomy.
Authors: Ou ZHENYU , Hu Jiao , Chen Minfeng , Li Yangle , Zu Xiongbing
Published: June 2024

e16590

Background: Neoadjuvant cisplatin-based chemotherapy remains the standard systemic therapy for cisplatin-eligible patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). However, its application is constrained due to suboptimal efficacy and considerable safety concerns. The combination of immunotherapy with antibody-drug conjugates is being actively explored as an innovative approach to neoadjuvant therapy for MIBC. Disitamab vedotin (DV) has demonstrated encouraging outcomes in HER2-positive locally advanced or metastatic urothelial carcinoma. Thereby our study aimed to assess the effectiveness and safety of DV combined with toripalimab (PD-1 inhibitor) as neoadjuvant therapy in patients with HER2-expressing MIBC followed by either selective bladder preservation or RC. Methods: This retrospective, single-arm study included patients with histopathologically diagnosed MIBC (T2-4N0-1M0). The regimens comprised DV at a dose of 2.0 mg/kg and toripalimab at 3.0 mg/kg, both delivered intravenously biweekly. Following the neoadjuvant therapy, patients achieving a complete response (CR) or downstaged to non-MIBC were given the choice of either RC or opting for bladder-sparing. Patients not meeting the criteria underwent RC. The primary endpoint was the complete clinical response (cCR) rate. Secondary endpoints included bladder intact disease-free survival (BI-DFS), pathological downstaging (pDS) rate, and safety. Furthermore, we investigated the correlation between cCR and HER2 expression levels. Results: This study enrolled 47 patients between June27, 2022, and October 20, 2023. The median age was 66.0 years, with male representation at 85.1%. Baseline molecular profiling revealed varying levels of HER2 expression: HER2 IHC 3+ (17.0%), HER2 IHC 2+ (48.9%), and HER2 IHC 1+ (34.0%). The median number of treatment cycles administered was 4 ( 3.0-9.0). Remarkably, out of 47 patients, 29 achieved cCR (61.7%). This cCR rate positively correlated with the levels of HER2 expression. Additionally, 37 of the 47 patients achieved pDS (78.7%). Post neoadjuvant therapy, 30 patients opted for bladder-preserving and the rest underwent RC. Over a median follow-up period of 8.0 months (3.0-14.0), the median BI-DFS was not reached, with a 1-year BI-DFS rate of 100%. The most common TRAEs of any grade included anorexia (68.1%), peripheral sensory neuropathy (66.0%), and fatigue (61.7%). Grade 3 or worse TRAEs occurred in 25% of patients, primarily involving anemia, elevated ALT, and fatigue. Conclusions: The combination of DV and Toripalimab as neoadjuvant therapy demonstrated notable efficacy and a manageable safety profile in patients with HER2-expressing MIBC followed by either selective bladder preservation or RC.
Practice patterns of high-risk non-muscle invasive bladder cancer (HR-NMIBC) in real-world Canadian practice.
Authors: Gotto Geoffrey T. , Alimohamed Nimira S. , Kulkarni Girish S. , Black Peter C. , Kassouf Wassim , Sridhar Srikala S. , Kokorovic Andrea , Eigl Bernhard J. , Blais Normand , Lalani Aly-Khan A. , Osborne Brendan J.W. , Wallis Christopher J.D.
Published: June 2024

e16594

Background: There is a paucity of evidence pertaining to real-world treatment of localized bladder cancer, particularly in Canada. We sought to investigate real-world treatment patterns in HR-NMIBC patients, treated in Alberta to understand current treatment practices, predictors of BCG utilization and real-world survival outcomes. Methods: We conducted a retrospective, observational cohort study of de novo HR-NMIBC patients diagnosed between 2010-2022 using population-level administrative databases in Alberta. Data sources included Alberta Cancer Registry (ACR), Vital Statistics, Pharmaceutical Information Network (PIN), Health Practitioner Claims, Discharge Abstract Database (DAD) and National Ambulatory Care Report System (NACRS) databases. HR-NMIBC was defined as AJCC stage N0 and M0 with either Tis, T1, or high-grade Ta (HG-Ta). Patients were followed from diagnosis to last known contact with healthcare system, end of 2021, or death. Multivariable logistic regression analysis was used to identify features associated with receipt of BCG. Results: In this cohort, 3874 HR-NMIBC patients were identified: 82% were male and mean age was 71 years. Tumor stage was T1 in 50%, HG-Ta in 33% and Tis in 17%. Following TURBT, 60.8% of the cohort received no intravesical therapy while 35.6% received BCG treatment, 2.9% intravesical gemcitabine, and 0.6% mitomycin C. Patients who received BCG were predominantly male (83.9%), had T1 tumors (52%) and had a CCI of 0-1 (83.5%). Few (<10%) patients underwent cystectomy. In patients who received BCG, 28.3% completed only one dose 56.9% completed five induction doses, and 32% received “adequate” dosing (≥5 induction doses + ≥2 maintenance doses). In multivariable regression analysis, the strongest predictor of receipt of BCG was high-grade disease (OR 1.62; 95% CI: 1.25-2.10; p < 0.001). Other features associated with higher BCG utilization were younger age, fewer comorbidities, and rural residence and being diagnosed closer to 2010. Overall survival was 10.3 years (95% CI: 116-131 years). Conclusions: In this large, population-based retrospective study, we identify relatively poor utilization of BCG among patients with HR-NMIBC with 32% of patients receiving adequate BCG therapy, per FDA definitions. These data, while concordant with other jurisdictions, do not address underlying causes which may relate to BCG supply issues, patient preference, or fitness to receive therapy, or physician beliefs regarding treatment efficacy. Additional research is needed to identify strategies to improve utilization of guideline recommended therapy among HR-NMIBC patients in real-world settings.
Real-world study of urine-based NGS liquid biopsy in organ preservation therapy of muscle-invasive bladder cancer (MIBC).
Authors: Zhang Ruiyun , Jin Di , Zang Jingyu , Xue Wei , Huang Yiran , Zhuang Guanglei , Tang Haoran , Jia Cancan , Xie Feng , Zhang Yue , Jia Shidong , Chen Haige
Published: June 2024

e16602

Background: Bladder cancer is a common malignancy of the urinary system. For those diagnosed with muscle-invasive bladder cancer (MIBC), radical cystectomy (RC) is the conventional treatment but is associated with a high risk of complications and diminished life expectancy. Consequently, trimodal therapy (TMT)—consisting of maximal transurethral resection of the bladder tumor (TURBT) followed by combined chemotherapy and radiation therapy—has been established as an alternative, bladder-preserving treatment for MIBC patients. Nevertheless, concerns persist regarding disease relapse, and the detection of recurrence at the molecular level poses significant challenges. Methods: In this real-world prospective study, 100 patients with MIBC, either candidates for or having undergone bladder-preserving TMT, were enrolled. Blood and urine samples were collected at each follow-up visit to the cancer center. The study utilized PredicineCARE, a targeted next-generation sequencing (NGS) liquid biopsy assay, to detect somatic changes in urinary tumor DNA (utDNA), including single nucleotide variations (SNVs), gene fusions, and copy number variations (CNVs). These molecular alterations were analyzed to determine the tumor fraction, aiming to identify molecular recurrence among the patients. Results: Within the cohort of 100 patients, 98 underwent urine testing and 94 blood testing, with 92 patients having both. Baseline urine samples revealed TP53 (38%), TERT (30%), FGFR3 (19%), ARID1A (16%), and PIK3CA (14%) as the most common mutant genes. For baseline blood samples, prevalent mutations included TP53 (17%), BRCA2 (13%), ATM (9%), FGFR3 (7%), and ERBB2 (5%). Urine samples showed a significantly higher mutation prevalence associated with MIBC, especially in TP53 (p<0.001), FGFR3 (p=0.004), and PIK3CA (p=0.006), suggesting urine as a more effective medium for mutation profiling in MIBC. The study also monitored disease progression during bladder preservation treatment by tracking tumor fractions in sequential urine and blood samples. Results indicated a ctDNA reduction in tumor fraction levels in urine for 38 patients and in blood for 25 patients, with a consistent overlap in 13 patients, aligning with the observed clinical treatment response. Notably, four patients exhibited no detectable tumor fraction at the latest follow-up, suggesting they may have achieved molecular clearance of MIBC. Conclusions: This study confirms that urine-based NGS liquid biopsy is a promising method for identifying molecular markers in MIBC patients undergoing bladder preservation therapy. Furthermore, the reduction in ctDNA tumor fractions may associate with effective treatment and the possibility of disease eradication.
Non-invasive detection of urothelial carcinoma through ensembled methylation profiles and fragmentomic patterns in urinary cell-free DNA.
Authors: Zhao Huan , Dong Hang , Gan Shuang , Tang Haoran , Zhang Zhihui , Wei Na , Xu Jingjing , Bonora Giancarlo , Dai Chao , Du Pan , Jia Shidong , Xiao Ting , Guo Huiqin
Published: June 2024

e16604

Background: The detection of epigenetic markers in urinary cell-free DNA (ucfDNA) has shown promise for tumor identification. However, the reliance on changes in methylation patterns presents challenges in the early detection of urothelial carcinoma, particularly when the tumor DNA present in urine is scarce. The incorporation of fragmentomic characteristics could enhance the detection of tumor signals. Methods: This study presents a single-assay approach, PredicineEPIC, which is a genome-wide methylation assay capable of analyzing both methylation and fragmentomic patterns in ucfDNA. Our cohort included 187 subjects: 66 with malignancies, 52 with benign conditions, and 69 healthy controls, divided into training and validation groups at a 2:1 ratio. We used the XGBoost machine learning algorithm for model development, followed by logistic regression to create an ensemble classifier. The training set utilized leave-one-out cross-validation to mitigate sample size constraints and prevent overfitting, with the classifier's performance assessed in the validation set. Results: The classifier's performance was evaluated using beta values of differentially methylated regions, the count of abnormally methylated fragments, and fragmentomic patterns (fragment sizes and transcription factor accessibility), with sensitivities of 0.75, 0.9, and 0.75, and a specificity of 0.86, respectively. The integrated features model showed a notable increase in sensitivity to 0.92 without losing specificity compared to models based on single features. This model also demonstrated precision on par with other methylation-based diagnostics, particularly in detecting early-stage tumors. Conclusions: Our study underscores an approach that differentiates malignant from benign lesions using a combination of omic features, enhancing the potential and precision of non-invasive liquid biopsy methods for early urothelial carcinoma detection.
Correlation of circulating tumor DNA (ctDNA) dynamics with clinical response in patients with muscle-invasive bladder cancer (MIBC) undergoing trimodality therapy (TMT).
Authors: Epstein Ilana B. , Berg Stephanie A. , Mantia Charlene , Mossanen Matthew , Saraf Anurag , Preston Mark A. , Ravi Arvind , Carvalho Filipe Lf , Clinton Timothy , Roberts Daniel Aaron , Peng Luke , McGregor Bradley Alexander , Bellmunt Joaquim , Berchuck Jacob E. , Mouw Kent William
Published: June 2024

e16606

Background: Trimodality therapy (TMT) is a curative treatment option for patients with muscle-invasive bladder cancer (MIBC). Plasma circulating tumor DNA (ctDNA) is associated with treatment response and clinical outcomes following cystectomy for bladder cancer, but the association of plasma ctDNA with treatment response and clinical outcomes in patients with MIBC treated with TMT is poorly understood. Methods: Select patients with MIBC who received TMT at Dana-Farber/Brigham and Women’s Cancer Center between June 2023 and January 2024 who underwent pre-TMT ctDNA evaluation with the commercially available Signatera assay were included in this analysis. Individual chart review was performed to collect demographic and clinical data including disease stage, histopathology, imaging, and treatment details. Results: Pre-treatment ctDNA results were available for 16 patients. Nine of the 16 patients had at least one post-treatment result available while the remaining 7 patients have not yet completed their first post-TMT ctDNA test. Seven of 16 patients had detectable ctDNA prior to TMT initiation. Of these 7 patients, 4 had at least one post-treatment ctDNA result available (median 11.2 weeks following TMT), and 3 of 4 patients converted to having undetectable ctDNA following TMT and were also free of disease as determined by routine post-TMT surveillance including radiographic, cytologic and cystoscopic assessment. The single patient who had persistent detectable ctDNA following TMT developed radiographic evidence of metastatic disease 3 months following TMT and died from bladder cancer 2 months later. Five patients with undetectable ctDNA prior to TMT had at least one post-TMT ctDNA result available. All five of these patients remained ctDNA-negative following TMT and have had no clinical evidence of recurrence. Conclusions: Plasma ctDNA measured using the Signatera assay can be performed in MIBC patients undergoing TMT and appears to correlate with clinical response to TMT at early time points. Larger cohorts with longer follow-up will be required to define the association between plasma ctDNA status and clinical outcomes following TMT. [Table: see text]
Comparative outcomes of radical nephroureterectomy and kidney-sparing surgery in the treatment of high-grade upper tract urothelial carcinoma.
Authors: Moore Kyle , Gao Helen , Delgado Jennifer , Kulkarni Anirudh , Lichtbroun Benjamin , Chua Kevin J. , Pfail John , Srivastava Arnav , Packiam Vignesh T. , Golombos David , Jang Thomas L , Ghodoussipour Saum
Published: June 2024

e16609

Background: Patients with upper tract urothelial carcinoma (UTUC) can be managed via radical nephroureterectomy (RNU) or kidney-sparing surgery (KSS) depending on pathology and patient characteristics. Unfortunately, UTUC is a rare disease lacking high-level evidence regarding clinical and oncologic outcomes after management. This study compares outcomes of RNU to KSS for high-grade (HG) UTUC. Methods: We retrospectively reviewed all patients with >1 year follow-up treated for HG UTUC at our institution from 2015-2021. Oncologic and clinical outcomes were recorded. Procedure burden was analyzed as total procedures under anesthesia, anesthesia time, days hospitalized, and estimated cost of care. Results: We identified 17 patients treated with KSS and 46 with RNU. There was no significant difference in 5-year overall survival, 3-year metastasis-free survival, or 3-year recurrence-free survival with KSS compared to RNU (Table). The average change in GFR was 17.9 ± 18.3 mL/min/1.73 m² and 24.8 ± 21.0 mL/min/1.73 m² for patients who underwent KSS and RNU, respectively (p = 0.33). Renal function was preserved (GFR decline <10 mL/min/1.73 m²) 2 years after surgery in 100.0% of patients who had KSS compared to 97.1% of patients who had RNU (p = 0.081). Patients who had KSS experienced a higher total number of procedures but fewer perioperative complications than those who had RNU with 3.4 ± 1.7 procedures vs 2.1 ± 1.7 procedures, respectively (p = 0.016), and 0% vs 41% of patients experiencing complications, respectively (p = 0.0098). Total anesthesia time and days hospitalized for KSS were similar to RNU at 400 ± 218 minutes vs 474 ± 185 minutes (p = 0.26) and 5.5 ± 4.3 days vs 6.8 ± 4.6 days, respectively (p = 0.36). Patients with KSS experienced a lesser in network but similar out of network cost of care to RNU patients at $7881 ± $4438 vs $10799 ± $4539 (p = 0.020) and $22159 ± $12401 vs $24523 ± $11282, respectively (p = 0.46). Conclusions: There were similar oncologic and clinical outcomes in HG UTUC patients treated with KSS or RNU. Patients treated with KSS endured a greater procedural load than patients who had RNU but at a reduced in network cost and with fewer complications. Larger datasets are needed to further evaluate outcomes and treatment burdens of RNU vs KSS as HG UTUC treatment. [Table: see text]
Analysis of the efficacy and tolerance or darolutamide in combination with chemotherapy and ADT in patients with metastatic castration-sensitive prostate cancer (mCSPC) in the Spanish population in a daily clinic.
Authors: Cassinello Espinosa Javier , Garcia Sanchez Lourdes , Gallegos Sancho Isabel , Sanchez-Escribano Morcuende Ricardo , Perezagua Marin Carmen , Sanchez Cendra Alicia , Fiorini Talavera Aldo Bruno
Published: June 2024

e17069

Background: Darolutamide is an inhibitor of the androgen receptor signaling pathway that increases overall survival both in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and in patients with high-volume mCSPC [Smith et al. N Eng J Med 2022]. Our objective is to analyze the efficacy and tolerance of darolutamide, in combination with chemotherapy and ADT (triplet therapy), in real-life data in several Spanish hospitals. Methods: A multicentric, observational, prospective study was performed in patients with mCSPC which started treatment with triplet therapy including darolutamide between 2022 and 2023 in some Spanish hospitals. A statistical analysis has been carried out with the SPSS v19 platform. Results: Between 2022 and 2023, 11 patients have been included, of which 10 have been analyzed. The mean age was 64 years (57-75 years), most patients with ECOG = 0 (60%) and ECOG = 1 (10%); the mean PSA diagnosis was 1025 ng/ml (12-4735 ng/ml). The majority of patients had a Gleason 9 (70%), 60% with extra regional lymph node metastases (M1a), 70% with bone metastases (M1b) and 60% with visceral metastases (M1c). The median time from diagnosis to statistical analysis was 580 days (366-700 days). The first patient was included in January 2022 and the last one was included in April 2023. Most patients started docetaxel and darolutamide was added a few weeks later. All patients achieved progression-free survival (PFS) with median of 14,5 months. The overall survival (OS) has not been reached. The median response time to 50% PSA was 3 months (2-8 months) and the median response time to 90% was 6 months (2-9 months); 30% of patients achieved complete PSA response. In relation to the objective response evaluation, 70% of the patients achieved a partial response, 30% stable disease and 11% presented disease progression; no complete radiological responses have been observed. Only 2 patients became castration resistant (one in 1 month and another in 11 months). Regarding adverse effects, 5 patients (50%) presented asthenia, 4 patients (40%) hematological toxicity (20% grade 3 neutropenia), 3 patients (30%) hot flashes, 2 patients (20%) elevated transaminases and 1 patient (10%) hyperglycemia; no patient had high blood pressure, weight gain, urinary tract infection or falls. Conclusions: The results of this analysis of real-life data confirm the efficacy of darolutamide within the triplet combination with chemotherapy and ADT in mCSPC patients, similar to the results of the already published phase III trial. Treatment with darolutamide was well tolerated. This analysis is limited by the retrospective nature and the small number of patients included.
Real-world intensification beyond androgen deprivation therapy (ADT) in metastatic hormone sensitive prostate cancer (mHSPC) in the United States 2017-2023: An administrative claims database study.
Authors: Raval Amit D , Lunacsek Orsolya , Korn Matthew J. , Littleton Natasha , Constantinovici Niculae , George Daniel J.
Published: June 2024

e17082

Background: Severalguidelines recommended the use of androgen receptor pathway inhibitors (ARPIs) and/or docetaxel along with ADT for mHSPC based on improved clinical outcomes demonstrated in clinical trials. Given the evolving treatment landscape since 2016, there is a need to understand the translation of clinical evidence and guidelines into clinical practice. Therefore, we examined the use of, and factors associated with intensification beyond ADT in men with mHSPC. Methods: A retrospective cohort of men treated for mHSPC was selected from private insurance claims of the Komodo Research Dataset (Jan 2017-Sep 2023). Men with mHSPC were identified based on their earliest claim for metastasis on or after prostate cancer diagnosis date without evidence of castration resistance. Index date was the earliest claim of ADT following mHSPC. Continuous insurance coverage for ≥ 12 months pre- (baseline) and ≥ 4 months post-index was required. Intensification beyond ADT was defined as the addition of ARPIs, docetaxel or both within ±4 months of the index date. Multinomial regression was conducted to examine factors associated with ADT intensification. Results: The study cohort comprised of 10,717 men with mHSPC with a median age of 65 years. Most had de novo mHSPC (62%), bone-only metastases (49%), hypertension (68%), diabetes (29%), and received opioids (59%) at baseline. Overall, in addition to ADT, 28% received ARPI (abiraterone: 18%, androgen receptor inhibitors: 10%), 9% docetaxel and 2.5% ARPI + docetaxel. From 2017 to 2023, there has been an increase in the intensification of ADT with ARPI from 13% to 47% and with docetaxel + ARPI from 0.8% to 15%, while the use of ADT + docetaxel declined from 12% to 3% and ADT alone from 74% to 36%. Key factors (age, comorbidity, de novo mHSPC, bone metastases) associated with intensification with either docetaxel or ARPI are listed in Table. Conclusions: There was a linear increase in intensification with ARPI and/or docetaxel in mHSPC between 2017-2023 in the US. Findings highlight a gradual uptake of guideline-recommended treatment for men with mHSPC, while over a third are still receiving ADT alone. [Table: see text]
Triplet therapy in metastatic hormone-sensitive prostate cancer: A real-world Indian multicentre study.
Authors: Mondal Debapriya , Roy Somnath , Bhattacharjee Arnab , Roy Rakesh , Meyur Suman , Biswas Bivas
Published: June 2024

e17086

Background: The survival benefit of upfront triplet therapy in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has been demonstrated in two prospective randomised trials using a combination of androgen deprivation therapy (ADT), docetaxel and an androgen receptor signalling inhibitor (ARSi) among abiraterone or darolutamide. This study aimed to evaluate the real-world outcomes of first-line triplet therapy in treating Indian mHSPC patients. Methods: In this multicentre retrospective study, patients with mHSPC started on upfront triplet therapy at three Eastern Indian centres between May 2022 and December 2023 were included. Patients were included if they received at least one cycle of triplet therapy. Descriptive statistics were used for reporting baseline patient and disease characteristics, treatments, and adverse events. Kaplan-Meier and life-table analyses were used for survival estimates. Results: Fifty-eight patients with mHSPC were included in this study. Most of the patients had de novo metastatic disease (93.1%). The mean age was 64 years (range 49-82), and the majority had Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (90%). High-volume disease was present in 94.8%, and 69% of patients had a Gleason score of 8 or higher. Comorbidities were present in 89.7% (2 or more in 37.9%). All the patients received a triplet combination of docetaxel, ADT, and abiraterone. The median number of triplet cycles received was 6. Grade 3 or worse adverse events occurred in 22.4% of patients without any treatment-related deaths. The most common grade ≥3 adverse events were hypertension (6.9%), febrile neutropenia (5.2%), hyperglycemia (5.2%), and urinary tract infection (3.4%). Dose reduction was required in 24.1%. Undetectable PSA (<0.2 ng/mL) as response was achieved in 62%. The 12-month overall survival rate was 98.3%, and the 12-month biochemical progression-free survival rate was 96.6%. Conclusions: First-line triplet therapy in Indian mHSPC patients was effective and tolerable with rare serious adverse events.
Comparing overall survival in patients with metastatic prostate cancer using PSA levels: A multivariate analysis using a national database.
Authors: Albawaliz Anas , Kumar Rohit , Pachika Pranali Santhoshini
Published: June 2024

e17089

Background: Prostate - specific antigen (PSA) is a useful biomarker for detection of prostate cancer and for risk classification in addition to TNM classification and Gleason score. Data is limited in determining its role in prognostication. The purpose of our study is to learn the impact of PSA value at the time of diagnosis on overall survival in patients with de novo metastatic prostate cancer. Methods: The National Cancer Database (NCDB) 2016-17 was queried to identify all patients diagnosed with de novo metastatic prostate adenocarcinoma. The demographic and clinical characteristics were compared using Pearson’s chi-square test between patients with PSA<98 ng/mL versus >=98 ng/mL. A multivariate cox regression analysis was done to determine the survival difference between the two groups. Results: The NCDB database found a cohort of 18,157 patients with de novo metastatic prostate cancer. A total of 8593 patients had PSA values below 98, while 9564 patients had PSA levels equal to or above 98. Multivariate cox regression analysis was done, and results indicated HR of 1.11 with 95% CI 1.07-1.13 and p value <0.001, indicating 11% worse survival in patients with higher PSA. Patients were further stratified based on age, race, and sites of metastasis. The results were consistent across all groups, with a significant p-value of <0.001. Conclusions: Our study indicates that a higher PSA value at the time of diagnosis is associated with a lower overall survival in patients with de novo metastatic prostate cancer. Further prospective studies with potentially higher PSA thresholds are needed to validate this correlation. Should concordant results be obtained, this may suggest utilizing more aggressive treatment strategies in this subset of patients to improve clinical outcomes. [Table: see text]
Addition of MRI or DRE to clinical data and risk prediction for clinically significant prostate cancer.
Authors: Wallis Christopher J.D. , Paproski Robert J , Hyndman M Eric , Fairey Adrian S. , Marks Leonard , Pavlovich Christian P. , Fletcher Sean , Zachoval Roman , Adamcova Vanda , Stejskal Jiri , Aprikian Armen G. , Kinnaird Adam , Pink Desmond , Vasquez Catalina , Beatty Perrin H , Lewis John D
Published: June 2024

e17105

Background: In patients suspected of prostate cancer, the decision to perform a biopsy hinges on available clinical data. Magnetic resonance imaging (MRI) and digital rectal exam (DRE) data are informative but may not be available. We created accurate models for clinically significant prostate cancer (csPCa), flexible to MRI and DRE data availability. Methods: Optimized ensembles of calibrated random forest models predicting csPCa (Grade Group ≥2) used total PSA, free PSA, prior negative biopsy status, and age, with or without DRE and MRI data (prostate volume and PI-RADS score). Risk models were derived (training cohorts n=1257 to 2191) and validated (validation cohorts n=317 to 1257) from different clinical sites. Models were evaluated by the area under the receiver operating characteristic curve (ROC AUC), sensitivity, specificity, positive predictive value, and negative predictive value, using thresholds providing ~ 95% sensitivity. Feature importance was determined by SHAP analysis. Results: All models had an AUC of at least 0.80, showing that predicting csPCa can be accurate without MRI or DRE data. Including MRI data significantly increased the AUC in the validation cohort (ClarityDX Prostate 0.80 vs ClarityDX Prostate +MRI 0.87). DRE had moderate value for models without MRI data (ClarityDX Prostate 0.80 vs ClarityDX Prostate +DRE 0.82) and minor value with MRI data (ClarityDX Prostate +MRI vs ClarityDX Prostate +DRE+MRI; AUC 0.87 vs 0.87; specificity 45% vs 47%, Table). Mean absolute SHAP values were highest for PI-RADS and prostate volume. Conclusions: These optimized risk models provide high accuracy for predicting csPCa in various clinical settings. Including MRI data greatly increases model accuracy, while DRE has a smaller effect on model accuracy. [Table: see text]
The silent burden: A SEER-based analysis of potential years of life lost due to genitourinary cancers in the United States (1975-2017).
Authors: Gor Rajvi , Gwalani Pranav , GOR DHAIRYA , Shah Anand , Thakur Rahul Kumar , Gartrell Benjamin Adam
Published: June 2024

e17107

Background: Genitourinary (GU) cancers significantly impact United States (US) public health, not just in mortality but also in premature deaths. We evaluated the potential years of life lost (PYLL) due to these cancers (prostate, kidney, bladder, testicular, penile, and others) from 1975 to 2017 using the SEER database and stratified it across racial groups. Methods: From 1975 to 2017, GU cancers were identified using SEER*Stat 8.4.2 using ICD-10 CM codes. We analyzed premature deaths and calculated PYLL as [Life expectancy minus (age at diagnosis + survival time)]. Due to non-homogeneity, the Kruskal-Wallis test (α = 5%) was employed for subgroup PYLL analysis. Spearman correlation coefficient (ρ) assessed the relationship between the year of diagnosis and PYLL. Analyses were conducted using SAS OnDemand. Results: Of the 1,715,763 GU cancer cases (1975-2017), 235,279 had premature deaths, totaling 2,406,551.20 PYLL. Testicular cancer showed the highest median PYLL (33.3 years) compared to other sites, followed by penile cancer with a median PYLL of 12.2 years. Non-Hispanic (NH) Blacks had higher PYLL for prostate, kidney, ureteral, and bladder cancers (p<0.05), while Hispanics had higher PYLL for penile and testicular cancers (p<0.0001). ρ value for PYLL and year of diagnosis was 0.23. Conclusions: Our study reveals a substantial impact of GU cancers on premature mortality and PYLL in the US. Despite the lower prevalence, testicular and penile cancers contribute significantly to PYLL, likely related to younger age at diagnosis. Racial disparities were evident, with NH-Blacks and Hispanics experiencing higher PYLL for specific GU cancers compared to other racial groups. These findings underscore the pressing need for targeted interventions to address disparities and enhance GU cancer management and prevention outcomes. [Table: see text]
Disparity in education and disease stage in patients with testicular germ cell tumors.
Authors: Chovanec Michal , Alzeer Rateb , Hapakova Nikola , Kalavska Katarina , Lesko Peter , Obertova Jana , Orszaghova Zuzana , Palacka Patrik , Rejlekova Katarina , Svetlovska Daniela , Sycova-Mila Zuzana , Vasilkova Lucia , Mego Michal
Published: June 2024

e17108

Background: Disparities may result in delayed staging and worse outcomes in cancer patients. Testicular germ cell tumors (GCTs) have excellent prognosis. However, disparities in education may have detrimental effect on early diagnosis and treatment. This study evaluated differences in staging and disease burden based on education in GCT patients treated at National Cancer Institute in Slovakia. Methods: Our institutional database was searched for GCT patients treated at National Cancer Institute in Slovakia between 1984 and 2023. Educational status was categorized as: basic/high-school and university. Educational status was correlated with disease stage, IGCCCG risk group, non-metastatic vs metastatic disease and size of retroperitoneal lymph nodes. Methods of descriptive statistics Chi-squared test and logistic regression were used for statistical analysis. Results: This retrospective study included 232 patients treated for stage I or metastatic GCT. Of the patients, 7 (3%), 114 (49%) and 111 (48%) had basic, high-school and university education, respectively. 46 patients (20%) had stage I disease and 186 patients (80%) were treated for metastatic disease. Patients who had basic/high-school education were diagnosed with metastatic disease more commonly compared to patients with university degree (p = 0.01). The Odds ratio for higher risk in patients without university education was 4.6 (95% CI 1.4-15.1). IGCCCG risk group, nodal stage or presence of non-pulmonary visceral metastases did not correlate with educational status (all p>0.05). Conclusions: GCT patients with basic- and/or high-school education are diagnosed with metastatic disease more frequently than those with university education. Our study may suffer from referral bias. Raising awareness in schools is imperative for early diagnosis of GCTs.
Clinician documentation of shared decision making for prostate cancer screening.
Authors: Le Phuong Nhi , Shungu Nicholas
Published: June 2024

e17109

Background: Prostate cancer is the second leading cause of cancer death among US men and disproportionally impacts Black men. Black men are 2.2 times more likely to die from prostate cancer than non-Hispanic white men. Guidelines recommend that men make an informed decision about prostate cancer screening following a conversation with their clinician about risks and benefits. Despite known racial prostate cancer disparities, Black men receive PSA screening at lower rates than Non-Hispanic White men. Black men also report inadequate education to make informed decisions about prostate cancer screening. Little is known contemporarily about how often shared decision-making (SDM) conversations occur and how they affect rates of PSA tests. The purpose of this project was to determine the extent to which clinicians are documenting prostate cancer shared decision making conversations in men aged 45 to 69, to investigate whether this documentation differs based on patient race, and to examine the relationship between SDM conversations and completion of prostate cancer screening. Methods: This retrospective chart review included 300 Black men and 300 age-matched White men between the ages of 45 and 69 who had an outpatient visit at a Medical University of South Carolina (MUSC) outpatient family medicine clinic from 2019-2020. Frequency of documented SDM conversations by patient race and frequency of PSA ordering by patient race were analyzed using Pearson chi-squares. Multivariable logistic regression was run with documented shared decision-making conversation and screening PSA ordered as dependent variables and patient demographic and clinical data as independent variables. Results: 28.1% of Black men and 29.1% of White men completed PSA screening (p=0.68). 12.1% of Black men and 6.5% of White men had SDM conversations documented (p=0.13). Among 300 Black men, SDM was associated with increased likelihood of screening PSA (p<0.01). SDM was not associated with family history of cancer, colon cancer screening, or insurance. Screening PSA was associated with insurance type among Black men (p = 0.03). Among 300 non-Black men, there was no association between SDM and screening PSA. There was also no association between insurance type and screening PSA. Conclusions: Rates of PSA screening and documented SDM conversations were strikingly low regardless of race at this large academic medical center. It is imperative that primary care clinicians engage in and appropriately document prostate cancer screening SDM conversations in order to uphold the current standard of care and reduce prostate cancer mortality. The increased likelihood of prostate cancer screening in Black men who had SDM conversations stresses the importance of these conversations in the fight to eliminate racial prostate cancer disparities.
Evaluation of persistence and adherence for oral and injectable androgen deprivation therapies (ADT) in United States (US) patients with prostate cancer (PC).
Authors: Hafron Jason , Hong Agnes , DePaauw-Holt Simon , Romdhani Hela , Kinkead Frédéric , Flanders Scott C , Ryan Michael J. , McKay Rana R.
Published: June 2024

e17110

Background: Relugolix (REL) is the only oral gonadotropin-releasing hormone (GnRH) antagonist available for patients (pts) with advanced PC. Other ADT options for these pts include the injectable GnRH antagonist degarelix (DEG) or injections or implants of GnRH agonists (i.e., leuprolide, goserelin, triptorelin, or histrelin). This study assessed persistence and adherence for REL, DEG, and GnRH agonists in US pts with PC. Methods: This retrospective study used the Merative MarketScan Research Claims Database (Commercial Claims and Medicare Supplemental; 01/2017–12/2022). Eligible pts were adult men with ≥1 claim with PC diagnosis who initiated REL, DEG, or a GnRH agonist (first claim was the index date) between 01/01/2021 and 06/30/2022. Pts were classified into these 3 mutually exclusive cohorts based on the index ADT. Kaplan–Meier (KM) analysis was used to assess persistence (i.e., time from index to treatment discontinuation defined as a gap in treatment of ≥60 days after the last day of supply, or switch to a new ADT). Treatment adherence was assessed at 6 and 12 months (mo) using proportion of days covered (PDC) defined as the sum of non-overlapping days of supply divided by the time period. Results: In total, 173 REL, 266 DEG, and 2,955 GnRH agonist pts were included. Median age was similar across cohorts and the proportion of pts with metastatic disease was slightly lower in GnRH agonist pts (Table). Median time on index ADT was 13.5 (REL), 3.1 (DEG), and 8.8 (GnRH agonist) mo. At 6 mo, persistence was 72.9% (REL), 24.2% (DEG), and 57.3% (GnRH agonist); and the proportion of pts with PDC ≥0.80 was numerically highest in REL and GnRH agonist pts and lowest in DEG. At 12 mo, persistence was 54.8% (REL), 9.9% (DEG), and 39.9% (GnRH agonist); and the proportion of pts with PDC ≥0.80 was also numerically highest in REL and GnRH agonist pts and lowest in DEG (Table). Conclusions: Despite differences in mode of administration, findings indicate that persistence and adherence are similar in pts with PC treated with REL and GnRH agonists while higher than those treated with DEG. Future research is needed to understand the factors associated with persistence and adherence. [Table: see text]