bluuebunny/crossref_metadata_2025_split huggingface dataset:
A national questionnaire survey of Japanese urologists on the treatment perspective for elderly patients with prostate cancer.
Authors: Kato Takuma , Tohi Yoichiro , Honda Tomoko , Matsuda Iori , Osaki Yu , Naito Hirohito , Matsuoka Yuki , Okazoe Homare , Taoka Rikiya , Ueda Nobufumi , Sugimoto Mikio 
Published: March 2023

327 Background: Physicians' attitudes toward elderly prostate cancer patients in Japan remain unknown. So, we conduct a national questionnaire survey of Japanese urologists from a treatment perspective for elderly patients with prostate cancer. Methods: A questionnaire was sent to 922 Japanese urological association teaching base hospitals. The following items were included: years of experience as a urologist, gender, workplace, treatment equipment owned, specialty area of daily practice, specialty area of urological cancer, reference items for treatment of the elderly, upper age limit for radical treatment, medication, and two hypothetical cases of Gleason grade Group 2 prostate cancer with or without oligometastasis. For examined the correlation between experience for urological practice and the answer, “not considering the upper age limit”, Cochran-Armitage trend test was used. For comparison of the rate of answering with “not considering the upper age limit” between variables, z-tests were conducted repeatedly and Bonferroni adjustments were made. In this analysis, the statistical significance was set at a P-value <0.05. Results: Altogether, 1,732 questionnaires were analyzed. The responses were almost equally distributed among all age groups. Workplaces included general hospitals (49.4%), university hospitals (40.3%), and cancer centers (4.2%). Performance status was the most frequently referenced item in treating the elderly, followed by the presence of comorbidities and cognitive function. Furthermore, 13.3% of respondents used the geriatric assessment. There was no upper age limit for total prostatectomy, brachytherapy, and external radiation therapy. Antiandrogens, androgen receptor-axis-targeted agents, chemotherapy, PARP inhibitors, and immune-checkpoint inhibitors were selected by 6.8%, 35.6%, 47.3%, 89%, 62.8%, 24.7%, 41.9%, and 41.7% of the respondents, respectively. The answers for the administration of hormone therapy for hypothetical cases of Gleason grade Group 2 prostate cancer with or without oligometastasis were 96.8% and 61.2%, respectively. The answers for the administration of hormone therapy for hypothetical cases of Gleason grade Group 2 prostate cancer with or without oligometastasis were 96.8% and 61.2%, respectively. Conclusions: Fewer than 10% of urologists used geriatric assessments. Many urologists responded that they would set age limits for highly invasive radical and systemic therapies. [Table: see text]
Awareness of genetic risk for prostate cancer (PCa) in men from families with germline mutations in DNA-repair genes.
Authors: Lazzeri Massimo , Fasulo Vittorio , Buffi NicolòMaria , Lughezzani Giovanni , Casale Paolo , Benetti Alessio , Saita Alberto , Hurle Rodolfo , Guazzoni Giorgio Ferruccio , Chiarelli Giuseppe , Asselta Rosanna , Soldà Giulia 
Published: March 2023

328 Background: Although one of the most important risk factors for prostate cancer (PCa) is a family history of the disease, there is a poor awareness of genetic risk. The aim of the current study is to investigate the awareness of genetic risk for PCa in men belonging to female families with germline variants in DNA-repair genes (DRGs). Methods: Data were extracted by a prospective observational study designed to select men with germline pathogenic variants (PVs) and offer them a dedicated PCa screening. The selection of probands was performed by genetic counseling and testing of male grade I relatives of female patients with a PVs. Male candidates were identified after reviewing the genealogical trees of all women who had received the diagnosis of breast and/or ovarian cancer and tested positive for a PVs. All the probands, 35-69 yrs old, who resulted positive for PVs were offered to participate to a specific PCa screening based on annually digital rectal examination (DRE), detection of PHI, which is a blood test including total PSA, free PSA, free/total PSA and -2proPSA, and multiparametric MRI. The primary outcome was the “willing to be tested”, defined as a proxy for male awareness of PCa risk. The secondary endpoint was the acceptance rate to be screened. Results: We reviewed the genealogical trees of breast/ovarian cancer female patients from January 2017 to December 2021 and we identified, over 1256 families, 139 positive cases for PVs in DRGs. Among 139 families, we identified 378 “healthy” 35-69 yrs old men, who were offered a genetic counseling, and if they agree a genetic testing. Overall 117/378 (31%) healthy males declared to be interested to be tested. Out of the 51 new tests (66 men already tested out of the study), we found 30 (58.8%) positive men. All the new positive tested men accepted to attend the PCa screening. Living in Northern Italy, having at least one child and higher (degree) level of education were the strongest predictors of willing for testing (p<0.01). Conclusions: Our data reveals a limited will to be tested, but all men tested positive for PVs accepted to participate to the PCa screening. These findings strongly support the urgent need to implement awareness of genetic risk for PCa.
Real world prospective evaluation of clinical outcomes in patients with non-metastatic castrate resistant prostate cancer treated with darolutamide.
Authors: Challapalli Amarnath , Renninson Emily , White Paul , Elumalai Thiraviyam , Parikh Omi , Vickers Alexander , Birtle Alison Jane , Brocklehurst Andrew , Bhana Rajanee , Wickramasinghe Kanchana , Jayaprakash Kamalram Thippu , Gray Emma , Sephton Matthew , Bowzyk Al-Naeeb Anna , Foulstone Emily , Soundy Alexandra , Ashurst Lauren , Bahl Amit 
Published: March 2023

335 Background: The RECORD Study is a real world data, prospective evaluation of clinical outcomes in patients with nmCRPC treated with Darolutamide. This study will increase the understanding of treatment response and management and in particular inform regarding use of next generation imaging in this setting. Methods: Patient data from 9 UK centres was collected based on the recommendation of NICE for Darolutamide as an option for the treatment of non-metastatic castrate resistant prostate cancer (nmCRPC) from November 2020. Data cut-off was 15 September 2022. The study is ongoing. Results: 87 patients were analysed with a median age of 78 (range 61-92). Median pre-treatment PSA and PSA doubling time (PSAdT) were 13 (range 1.99-110.6) mg/L and 5.05 (range 0.6 - 10) months. 42 patients (49.4%) had pre-treatment PSAdT of <6 months and 43 (50.6%) patients had PSAdT of ≥6 months (2 patients had no pre-treatment PSAdT data). 6 patients (6.90%) had next generation imaging prior to initiation of Darolutamide. Median duration of treatment on Darolutamide was 17 months for patients with pre-treatment PSAdT <6 months but median duration had not been reached for patients with pre-treatment PSAdT ≥6 months after 24 months of treatment, a significant difference p=0.018 (HR=0.385, 95% CI 0.17-0.88). 30 patients have come off treatment so far (34.5%); 21 (70%) for disease progression, 5 (16%) for a medical cause unrelated to the drug (e.g. COVID infection, reduced performance status secondary to pre-existing Parkinson's), 3 (10%) for unacceptable toxicity (rash, Grade3 fatigue, muscle aches, memory issues), and 1 patient died (unrelated). Conclusions: In the RECORD study, predominantly the diagnosis of nmCRPC is based on conventional imaging. The majority of patients respond and tolerate Darolutamide well, comparable with the ARAMIS trial. There is a significant difference between time on Darolutamide for those with pre-treatment PSAdT of <6 months compared with ≥6 months. Further long-term toxicity, MFS and OS data will continue to be collected prospectively within the study.
Sexual function after primary external beam radiation therapy (EBRT) for prostate cancer in a large cohort of men with long-term follow-up.
Authors: Escobar Domenique , Wang Lufan , Banton Jasmin , Cowan Janet E. , Washington Samuel L. , Mohamad Osama , Carroll Peter 
Published: March 2023

346 Background: Clinically localized prostate cancer can be treated with prostatectomy, radiation or focal therapy, with known impacts on sexual function. We sought to characterize long term sexual function in a large cohort of men treated with primary EBRT and to differentiate between those who have high vs low sexual function scores at baseline. Methods: Patients enrolled in CaPSURE, a national registry of men diagnosed with prostate cancer, from 1995 - 2017 with clinically localized prostate cancer (cN0M0/X, PSA < = 50) and treated with primary EBRT were included. Sexual function (SF) was self-reported using the UCLA Prostate Cancer Index (PCI). We performed repeated measures mixed models to evaluate SF after EBRT, stratified by baseline SF and adjusted for age, BMI, comorbidities, smoking, clinical risk, receipt of brachytherapy and/or hormonal therapy, and type of clinical site. Results: 1193 patients were included for analysis. Mean age was 70, mean number of comorbidities was 2, and median PSA was 7.5 at diagnosis. Baseline PCI scores were available for 43% of the cohort (data not collected before 1998). The mean PCI score was 38 out of 100 at baseline and after EBRT, declined gradually to 16 by 10 years. When only those men with good SF at baseline were assessed (scores 80 – 100), the initial rate of decline was more severe, but the nadir in this group was higher than those with lower baseline scores. Unadjusted mean PCI scores showed a similar decline amongst both groups, although those with good baseline SF consistently had better scores. 63% of patients were treated for erectile dysfunction (PDE5 inhibitors, intracavernosal injections or both), 13% of whom started therapy before EBRT. In the repeated measures mixed models analysis, we found that SF changed significantly over time and scores differed significantly by age, comorbidities, baseline SF, receipt of brachytherapy boost and concurrent ADT. Conclusions: SF after EBRT declines and persists. The most affected are those who had better PCI scores at baseline, although their overall PCI scores are consistently higher compared to those with baseline scores less than 80. Among both groups however, there was a similar decline that was statistically significant.
Major adverse cardiovascular events after androgen deprivation therapy in patients with prostate cancer with hypercholesterolemia.
Authors: Twardowski Przemyslaw , Henry Jacqueline , Atkinson Stuart 
Published: March 2023

348 Background: Prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) may experience major adverse cardiovascular events (MACE). It is unclear how much of MACE is caused by ADT itself. High cholesterol has been associated with lower MACE risk in older men, not on statin therapy. This study evaluates MACE risk after ADT initiation for patients with and without hypercholesterolemia using real-world data. Methods: US electronic medical records (2010-2020) of PCa patients (n=45,059) receiving LHRH agonist/antagonist injections were analyzed to calculate the risk of MACE since ADT initiation in patients with and without hypercholesterolemia. Hypercholesterolemia was defined as having taken hypercholesterolemia medication or diagnosis with hypercholesterolemia prior to the first MACE event after ADT start. Exclusion criteria included lack of ADT initiation date or MACE within six months prior to ADT initiation. MACE was defined as myocardial infarction, stroke, and death from any cause. Kaplan-Meier event-free survival curves and cox regression were used to compare MACE risk between patients with and without hypercholesterolemia. Results: The dataset contained 178,388 LHRH injection entries and 7,681 MACE. MACE risk was only 1.8% lower (19.0% vs 20.8%) after 4 years for patients with hypercholesterolemia compared to those without (across 10 years, unadjusted: HR=0.88, 95% CI [0.83, 0.92] and adjusted: HR=0.85, 95% CI [0.77, 0.94]). Conclusions: Patients with hypercholesterolemia appear to have slightly lower MACE rates. This may be due to the use of statins, which can reduce the incidence of CV events in a general population. Our analysis of data over the most recent decade from ~45,000 PCa patients is likely an accurate reflection of the real world. Clinicians should monitor PCa patients with underlying CV risk factors and help educate them on lifestyle changes that could impact treatment outcomes.
Major adverse cardiovascular event risk following androgen deprivation therapy initiation by personal history of cardiovascular events.
Authors: Lee Andrew , Henry Jacqueline , Atkinson Stuart 
Published: March 2023

351 Background: Associations between androgen deprivation therapy (ADT) and increased cardiovascular (CV) risk in prostate cancer (PCa) patients have been reported; however, how many of these major adverse CV events (MACE) are caused by ADT itself has been debated. One risk factor for increased CV risk is a prior history of CV events; an analysis found that each new CV event increased the probability of a future event. This study aims to evaluate the incidence of MACE after ADT initiation for patients with and without a prior medical history of MACE. Methods: Analyses of US electronic medical records (2010 to 2020) of PCa patients (n=45,059) receiving LHRH agonist and antagonist injections were conducted to evaluate MACE incidence after ADT initiation in patients with and without MACE history. Exclusion criteria included lack of ADT initiation date or myocardial infarction (MI)/stroke within 6 months prior to ADT initiation. MACE was defined as MI, stroke, and death from any cause. Kaplan-Meier event-free survival curves were constructed, and Cox regression was used to compare the MACE hazard rates between patients with and without a personal history of MACE. Multivariate Cox regression adjusted for agonists vs antagonist, increasing age per year, BMI (<18.5 vs ≥18.5 kg/m2), race (White vs Black), family MACE history, ethnicity (Hispanic vs non-Hispanic), urology vs oncology setting, history of hypertension, and history of hypercholesterolemia. Results: Overall, MACE incidence was 3.9% and 19.6% for the cohort at one year and four years after ADT initiation, respectively. MACE risk following ADT initiation was higher for patients with history of prior MACE (unadjusted: (HR=2.76, 95% CI [2.49, 3.06], p<0.001); adjusted: HR=2.29, 95% CI [1.93, 2.71], p<0.001). When MACE was divided into component events, the risks of myocardial infarction and stroke were higher for patients with a prior MACE history compared to those without (8 vs. 1% and 8 vs. 2%, respectively), and the risk of any-cause death was similar (13 vs. 14%). Conclusions: MACE incidence in PCa patients in the first year of ADT was consistent with previous publications.(3). When MACE risk was analyzed in detail, ADT patients with a personal history of stroke or myocardial infarction (MI) had a 4- and 8-fold greater risk of a subsequent stroke and MI, respectively, compared to those without a history of stroke or MI. Given the large sample size (~45,000 PCa patients) of this data set over the recent past decade, these results likely reasonably reflect the real world. Urologists and oncologists should work with cardiologists, cardio-oncologists, and primary care practitioners to ensure the highest quality CV care is delivered.
Oncological outcomes with wide resection in robot-assisted radical prostatectomy as primary treatment for very high-risk prostate cancer.
Authors: Miura Noriyoshi , Hashine Katsuyoshi , Watanabe Ryuta , Noda Terutaka , Nishimura Kenichi , Fukumoto Tetsuya , Miyauchi Yuki , Kikugawa Tadahiko , Tacho Takatoshi , Yanagaki Takahiro , Oka Akihiro , Takeda Hajime , Watanabe Yuichi , Ninomiya Iku , Shirato Akitomi , Saika Takashi 
Published: March 2023

357 Background: Patients with very high-risk prostate cancer (VHRPCa) have earlier biochemical recurrences (BCRs) and higher mortality rates. It remains unclear whether extended robot-assisted radical prostatectomy (eRARP) with intended wide resection can improve the outcomes of VHRPCa patients. We aimed to compare the oncological outcomes of eRARP versus standard RALP (sRARP) for primary treatment of VHRPCa. Methods: We retrospectively evaluated 168 patients classified by the National Comprehensive Cancer Network (NCCN) as very high-risk who were treated with RARP without neoadjuvant/adjuvant therapy between September 2011 and December 2020. eRARP was performed using the extra-fascial approach as reported by Gandaglia G et al. (Eur Urol. 71:249-256, 2017). We performed 1:1 propensity score matching to account for potential differences between eRARP and sRARP. Kaplan-Meier analysis and Cox regression models were used to test the effect of eRARP on the biochemical progression-free survival (bPFS). This observational study was approved by the Institutional Review Board. Results: There were 93 patients in the eRARP group and 75 in the sRARP group. The eRARP group had a worse clinical stage than the sRARP group ( p< 0.001). Age, pretreatment prostate specific antigen (PSA), and pretreatment Gleason score were similar in the two groups. All patients in the eRARP group underwent pelvic lymph node dissection, compared with 89% in the sRARP group. The propensity-adjusted 3-year biochemical recurrence-free survival rates was 31.4% in the sRARP group and 67.4% in the eRARP group(p=0.001), respectively. The adjusted Cox regression analysis showed that the eRARP group had a significantly longer bPFS than the sRARP group (hazard ratio 0.415, p=0.0047). Conclusions: In patients with VHRPCa, eRARP was associated with a reduce risk of biochemical recurrence. These results suggest that eRARP may improve oncological outcomes in VHRPCa.
Cost-effectiveness of abiraterone acetate for high-risk nnon-metastatic prostate cancer.
Authors: Lester-Coll Nataniel Hernan , Ahmed Shahid Sattar , Wallace H. James , Sprague Brian L. , Ades Steven 
Published: March 2023

358 Background: In a primary analysis of the STAMPEDE protocol, the addition of Abiraterone acetate to androgen deprivation therapy (ADT) in men with castration sensitive, high-risk, non-metastatic prostate cancer was associated with significantly higher rates of metastasis-free survival compared with ADT alone. However, the cost-effectiveness of Abiraterone in this population remains unaddressed. Methods: A decision model based on partitioned survival simulations estimated costs and quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICERs) associated with ADT with or without Abiraterone. This analysis was performed from a United States healthcare sector perspective. We estimated drug acquisition costs using the Federal Supply Schedule. Given current heterogeneity in prescription drug coverage, we used both brand-name and generic drug prices. The willingness-to-pay (WTP) threshold was $100,000 per QALY. Analyses were performed over the published STAMPEDE trial with median follow-up duration of 72 months. Model input parameters were based on the STAMPEDE trial data as well as best available and most recent data provided in the published literature. Sensitivity analyses explored uncertainty with regard to the model assumptions. Results: Using brand-name pricing, the addition of Abiraterone to ADT was associated with an increase in net costs by $217,616, and an increase in QALYS by 0.79. Therefore, the ICER associated with brand-name Abiraterone was $277,156 per QALY. Sensitivity analyses revealed that the monthly price of Abiraterone would need to be less than or equal to $2,581 in order to be cost-effective at a WTP threshold of $100,000 per QALY. In contrast, generic Abiraterone was associated with an increase in net costs by $45,325, and a cost-effective ICER of $57,726 per QALY. Conclusions: Abiraterone for high-risk non-metastatic prostate cancer is cost-effective using generic pricing. However, current brand-name pricing is roughly four times the threshold of cost-effectiveness, underscoring the need to increase access to generic drugs in the United States.
Testosterone Recovery Following Androgen Suppression and Prostate Radiotherapy (TRANSPORT): Individual patient data meta-analysis from the MARCAP Consortium.
Authors: Ong Wee Loon , Wilhalme Holly , Millar Jeremy Laurence , Steigler Allison , Denham James William , Joseph David John , Roy Soumyajit , Malone Shawn , Nickols Nicholas George , Rettig Matthew , Valle Luca Faustino , Steinberg Michael L. , Sun Yilun , Zaorsky Nicholas George , Spratt Daniel Eidelberg , Kishan Amar Upadhyaya 
Published: March 2023

366 Background: The kinetics of testosterone recovery (TR) vary following cessation of androgen deprivation therapy (ADT) of various durations when given in combination with radiotherapy for prostate cancer. Time to TR will impact on quality of life. We aim to identify factors affecting the time to TR following ADT use. Methods: We included trials of prostate radiotherapy and ADT in the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) consortium for which prospectively collected serial testosterone data is available. Time to non-hypogonadal TR (NHTR) (>8.0nmol/L) and time to full TR (FTR) (>10.5nmol/L) were estimated from the date of first available testosterone at trial enrolment to the date of TR using the Kaplan-Meier method. The effect of interactions between duration of ADT and patients’ age on TR was evaluated. Results: There were 1439 men with non-castrate testosterone at baseline (>1.7nmol/L) who met the inclusion criteria for analysis, of which 220, 765 and 454 men had 3-, 6-, and 18-months of ADT. There were 959 (67%) men who had FTR at last follow-up. For men who had 3-, 6-, and 18-months of ADT, the median time (range) to NHTR were 5.5 (1.6-76.3), 12.2 (0.8-53.6), and 30.1 (2.8-90.4) months respectively, while the median time (range) to FTR were 6.2 (1.8-75.7), 15.2 (0.8-86.0), and 36.0 (18.1-85.5) months respectively. In the subset of 1160 men who had normal testosterone at baseline (>10.5nmol/L), 851 (69%) men had FTR, with a median time (range) to FTR of 5.5 (1.8-75.7), 12.7 (1.8-86.0), and 30.8 (18.1-84.1) months for men who had 3-, 6- and 18-months ADT, respectively. For any given duration of ADT, men aged above 65 years were less likely to have FTR compared to those aged under 65 years – HR=0.67 (95%CI=0.46-0.99), HR=0.80 (95%CI=0.67-0.96), HR=0.64 (95%CI=0.51-0.81) for men who had 3-, 6-, and 18-months ADT respectively. There was no evidence of interaction between the effect of ADT duration on time to FTR and age (interaction P=0.3 for entire cohort). Conclusions: This is the largest pooled analysis of prospectively collected serial testosterone data from randomized trials, indicating substantial delay in FTR in men receiving longer durations of ADT. Approximately one-third of the men did not achieve FTR, which may have life-long impact on quality of life.