bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platinum eligibility (PE) criteria for patients with metastatic urothelial carcinoma (mUC): Results of a physician survey in 5 European countries.
Authors: Gupta Shilpa , Powles Thomas , Kearney Mairead , Panattoni Laura , Land Natalie , Flottemesch Thomas , Sullivan Patrick , Kirker Melissa , Bharmal Murtuza , Guenther Silke , Costa Nuno , Grande Enrique 
Published: January 2024

696 Background: The standard of care for mUC is platinum-based chemotherapy (PBC) followed by avelumab first-line (1L) maintenance in patients without disease progression. Guidelines for mUC recommend 1L treatment based on eligibility for PBC (cisplatin or carboplatin), but the definition of PE remains unclear, and little is known about criteria used by European physicians to define PE in clinical practice. In this cross-sectional study, we assessed treatment decision-making factors and clinical thresholds used by European physicians determine PE and examined their alignment with published US physician thresholds. Methods: Physicians from France, Germany, Italy, Spain, and the UK completed a quantitative online survey in Aug/Sep 2022. We adapted Gupta et al’s ASCO-GU 2019 and ASCO 2022 US-based surveys, which identified thresholds for clinical criteria used by US physicians to define PE. This EU survey included clinical parameters with different age and creatinine clearance (CrCl) thresholds, plus Eastern Cooperative Oncology Group performance status (ECOG PS) and other relevant criteria. Participants reported the percentage of patients they perceived were platinum eligible and ranked criteria to determine PE. All analyses used descriptive statistics. Results: 503 physicians (69% oncologists, 31% urologists) completed the quota-based survey. Most had been in practice for >10 years (69%), treated 5-19 patients with mUC per month (58%), and practiced in a public teaching hospital (40%). Most patients who received 1L systemic treatment were PE (77%), ranging from 75% in Italy to 79% in Spain. Most respondents chose >80 years (33.2%) or >75 years (24.1%) as the age threshold for platinum ineligibility. Age thresholds selected were significantly different across countries, years of practice, and practice settings (p<0.001). Responses for ECOG PS and peripheral neuropathy thresholds for platinum ineligibility were evenly split between ECOG PS ≥2 (40.6%) and ≥3 (45.3%) and between grade ≥2 (44.3%) and ≥3 (41.7%) peripheral neuropathy. The most frequent responses are summarized (Table). Conclusions: Physicians in Europe considered most patients with mUC to be platinum eligible. Criteria to determine PE were broadly consistent with previous US-based studies, except for age. The low age threshold observed is at odds with the older age of the mUC patient population. Wider use of these criteria could support clinical decision-making, reduce variations in care, and improve patient outcomes. [Table: see text]
Testosterone suppression and recovery in patients with advanced prostate cancer treated with intermittent androgen deprivation therapy (iADT) with relugolix.
Authors: Campbell Patrick , Gebrael Georges , Narang Arshit , Hage Chehade Chadi , Mathew Thomas Vinay , Galarza Fortuna Gliceida , Sayegh Nicolas , Tripathi Nishita , Tandar Clara , Dal Emre , Li Haoran , Swami Umang , Agarwal Neeraj , Maughan Benjamin L. 
Published: January 2024

70 Background: Many patients with advanced prostate cancer do not want to pursue continuous androgen deprivation therapy (cADT) because of concerns about side effects, and pursue iADT. However, even intermittent treatment with GNRH agonist therapy may not lead to rapid recovery of testosterone during the off-treatment period. In the pivotal HERO trial of relugolix (GNRH antagonist) the testosterone recovery time was in weeks [PMID 32469183]. The objective of the study was to measure the time to testosterone suppression to castrate level and time to recovery of serum testosterone to non-castrate level in real-world patients with advanced prostate cancer undergoing intermittent relugolix therapy. Methods: In this IRB-approved retrospective study, the eligibility was: patients with advanced prostate cancer undergoing iADT with relugolix. iADT with relugolix was defined as initiating relugolix at PSA ≥ 10 ng/ml and holding relugolix when PSA ≤ 4 ng/ml. The primary endpoints were: 1) time to serum castrate level of testosterone after relugolix initiation and 2) time to recovery to non-castrate level after discontinuation of relugolix. Castrate level of serum testosterone was defined as serum testosterone level ≤ 50 ng/dL. Results: Overall 25 consecutive patients with advanced prostate cancer treated with iADT with relugolix were eligible and included. The median age was 75 [range 68-88]. Patients with a Gleason score of ≥ 8 comprised 44% of the cohort. The median PSA at the start of therapy was 18.2 ng/ml [5.1 – 99.1 ng/ml]. Median time to testosterone ≤ 50 ng/dl after relugolix initiation was 1.13 months [0.67 – 2.5 months], and median time to testosterone recovery after relugolix discontinuation was 1.4 months [0.83 – 6.57 months]. The median PSA nadir achieved with relugolix was 2.02 ng/ml [0.1 – 4.8], and median time to PSA nadir was 1.35 months from initiation of therapy (0.67 – 4.8 months). Median time to PSA relapse ≥ 10 ng/dl after holding relugolix was 3.4 months (0.9 – 8.23 months). Conclusions: This is the first real-world study to show that iADT with relugolix is associated with a rapid time to testosterone suppression and recovery. These results may guide patients’ counseling, monitoring of serum testosterone and PSA levels in patients wishing to pursue iADT for advanced prostate cancer. These hypothesis-generating data need external validation.
Risk factors for neoadjuvant chemotherapy-induced acute kidney injury in patients with muscle-invasive bladder cancer: A multicenter retrospective study.
Authors: Fujita Naoki , Momota Masaki , Tanaka Toshikazu , Hosogoe Shogo , Hatakeyama Shingo , Yoneyama Takahiro , Hashimoto Yasuhiro , Ohyama Chikara 
Published: January 2024

700 Background: Neoadjuvant chemotherapy (NAC)-induced acute kidney injury (AKI) is one of the frequent complications in patients with muscle-invasive bladder cancer (MIBC) and we previously have reported the negative impact of NAC-induced AKI on oncological outcomes. However, its risk factors remain unclear. Methods: This multi-institutional retrospective study included 517 patients with MIBC who received 2–4 cycles of NAC followed by radical cystectomy. AKI was defined according to the KDIGO criteria. Patients were divided into two groups: patients who developed any stage AKI during NAC (AKI group) and patients who did not (non-AKI group). Multivariable logistic regression analysis was performed to identify the risk factors for NAC-induced AKI. The predictive abilities for AKI were evaluated using the area under the receiver operating characteristic curve. Results: The median age was 69 years. Of the 517 patients, 188 (36%) received cisplatin-based regimens and 92 (18%) developed any stage AKI. Approximately 86% AKI were stage 1 AKI. In the univariable analyses, hypertension, impaired renal function, and cisplatin-based regimen were significantly associated with increased risk of AKI. In the multivariable analysis, hypertension, impaired renal function, and cisplatin-based regimen were independently and significantly associated with increased risk of AKI (Table). The optimal cutoff value of estimated glomerular filtration rate for AKI was 65.0 mL/min/1.73m2. ROC analysis showed that the AUC of hypertension plus eGFR <65.0 mL/min/1.73m2 plus cisplatin-based regimen was 0.748 (95% confidence interval [CI]: 0.697–0.799]. Conclusions: Hypertension, impaired renal function, and cisplatin-based regimens were risk factors for NAC-induced AKI in patients with MIBC. [Table: see text]
Does use of apalutamide enhance outcomes in combination with radiotherapy in metastatic hormone-sensitive prostate cancer? A real-world experience from the UK.
Authors: Das Prantik , Sharma Anand , Vengalil Salil , Khan Yakhub , Lim JunHao , Elmasry Abdelfattah , Mohammed Rania , Ghose Aruni , Bandyopadhyay Seheli , Nillegoda Hasanthi , Baraka Bahaaeldin , Tasmia Syeda , Mathiyalagan Navin 
Published: January 2024

73 Background: Management of metastatic prostate cancer has undergone a significant change over the past decade, with the introduction of several novel agents and repurposing of others. Latest update from STAMPEDE trials shown prostate radiotherapy (RT) improves OS, without detriment in QoL in metastatic home sensitive prostate cancer mHSPC along with Docetaxel in those with low volume metastatic disease. There is no published data on impact of radiotherapy to prostate on Apalutamide treated mHSPC patients. Here we report our real-world experience of Apalutamide in mHSPC with radiotherapy. Methods: Patients with mHSPC (N = 266) from 5 UK centres, were treated with Apalutamide (240 mg) and ADT along with radiotherapy to prostate as per treating clinician’s discretion. The primary endpoint was objective rate (ORR) as determined by patients achieving a PSA decline of ≥90% (PSA90) and ≥50% (PSA50) and secondary endpoints included biochemical progression free survival (bPFS) and safety. Results: The median age for the whole cohort was 73.4 years (interquartile range 52 - 91), A total of 11.6% had received prior radical treatment (prostatectomy or radiotherapy for localised disease) and 88.4% had de novo metastatic disease. Median baseline PSA was 47 ng/ml (range 0.4-17100). The proportion of patients PSA90 and PSA50 at 3, 6 and 12 months is shown in the Table. Median PSA nadir was 0.1 ng/ml(rage 0.01- 48.2) and median time to reach nadir was 6 months (range 3-24 months). 13.5% (35) patients were treated with radiotherapy (RT) after at least 3 months (range 3 -6 months) of starting apalutamide. Patients received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) of radiotherapy (68 % vs 32%). Higher number of patients in RT group had achieved PSA90 compared to no radiotherapy cohort (97.14 % vs 87.3%, p =0.15). Patients treated with RT had median post treatment of PSA 0.01 ng/ml compared to 0.1 ng/ml in non RT group (p=0.0062). After median follow up of 8.4 months, proportion of patients shown biochemical progression in RT vs non RT group were 5.7 % vs 15 % respectively (p= 0.04). Patients with de novo metastatic disease have shown poor PSA response and higher chance of progression compared to patients who had initial radical treatment. Radiotherapy was well tolerated, with 17 % adverse events (Radiation Therapy Oncology Group grade 3–4) reported in radiotherapy group. Conclusions: Early experience of using apalutamide and radiotherapy in mHSPC showed improved PSA response and delayed progression. Treatment was well tolerated. Further follow up and clinical trials are needed to understand the impact on overall survival. [Table: see text]
Cardiovascular medications and overall survival in metastatic hormone-sensitive prostate cancer.
Authors: Ingram Kara , Pickett Carley , Eaton Daniel B. , Tohmasi Steven , Karunanandaa Krishny , Gopukumar Deepika , Puri Varun , Schoen Martin W. 
Published: January 2024

75 Background: The assessment of comorbid cardiovascular disease can predict health outcomes and may risk-stratify patients for adverse events and death. Current methods used to estimate patient risk, such as the Charlson Comorbidity Index (CCI), are based on International Classification of Diseases (ICD) codes, which are a poor indicator of severity and complexity of comorbid disease. Alternatively, the number of cardiovascular drugs could be an efficient tool for estimating patient risk. In this study, we examined the relationship between cardiovascular medications and survival in patients being treated for metastatic hormone-sensitive prostate cancer (mHSPC). Methods: A nationwide retrospective observational study of US Veterans with de novo mHSPC in the Veterans Health Administration between 2011-2021 with at least 1 prescription medicine of any class. We determined the number of cardiovascular drugs from Anatomic Therapeutic Chemical (ATC) drug class C prescribed in the year prior up to 14 days before initiation of treatment. Multivariable logistic regression and Cox proportional hazard modeling was used to assess the association between number of drugs with overall survival (OS) while accounting for important covariates including age, body-mass index (BMI), prostate specific antigen (PSA), CCI, race, and weight change. Results: Among 7,875 veterans, a median (IQR) of 2 (1-4) unique cardiovascular medications were filled in the year prior to treatment. The mean age was 74.3 years (SD 10.0) with a median CCI of 3 (3-6). Age was associated with increased number of cardiac medicines with a mean of 1.6 drugs in <60 years, 2.2 drugs in 60-69, 2.5 drugs in 70-80, and 2.5 drugs in 80+ years (p<0.001). Increased number of medications was associated with decreased OS using the Kaplan-Meier method (p<0.001, see table). After adjusting for age, race, BMI, weight change, PSA, and CCI, the number of medications was independently associated with increased mortality with an adjusted hazard ratio (aHR) of 1.05 (1.03-1.06) for each additional cardiac drug. Increased mortality was observed in patients treated with 2 or more cardiac drugs (see table). Conclusions: The number of cardiovascular medications is associated with decreased survival in veterans undergoing treatment for mHSPC, even after accounting for important covariates including age, BMI, PSA, and CCI. The assessment of cardiovascular medications may provide a simple and reliable tool to estimate comorbid disease and survival in patients with cancer. [Table: see text]
Impact of exposure to clinical trials and standard-of-care therapy in metastatic or recurrent prostate cancer: An update.
Authors: Kim Grace G , Mohamed Heba , Bhuiyan Ishmam , Macphail Corin , Sidhu Taylor , Emami Amir , Huang Longlong , Sun Shaun Zheng , Tyldesley Scott , Ko Jenny J. 
Published: January 2024

76 Background: Treatment (tx) options for metastatic prostate cancer (mPC) have advanced significantly. Literature shows that access to, and uptake of, clinical trials or standard intensified tx in mPC may be low. Methods: We conducted further survival analysis on all consecutive patients (pts) diagnosed with any stage of PC between 2016-2017 in British Columbia, and only included pts with de novo metastasis or later recurrence. We performed descriptive statistics, univariate and multivariate analysis to examine overall survival (OS). Results: This study included 796 pts with either de novo metastatic (n=554, 69.6%) or recurrent PC (N=242; 30.4%); 743 (93.3%) had metastasis by time of cutoff (Sep 1, 2022). Median age at diagnosis of mPC in all patients was 73 (range 45-98). 790 (99.2%) started androgen deprivation tx (ADT). 263 (35.4%) had additional line of tx started with ADT at hormone sensitive mPC (mHSPC); 309 (38.8%) had 1st line tx started at castrate resistant mPC (mCRPC). Radiotherapy (RT) to prostate for mPC were given to 93 (11.6%). 307 (38.6%) received 1 line of tx; 181 (22.7%), 2; 128 (16.1%), 3 or more. 432 (54.3%) received ≥1 androgen receptor pathway inhibitors (ARPI). At cutoff, 474 (59.5%) died; most (n=400; 84.4%) died of prostate cancer. 35 pts who went on trial had longer mOS than those who did not go on trial (63.6 vs 39.5m, p=0.025). Pts with 5 or 6 lines of therapy had numerically longer but statistically similar mOS than those who had 1 (51.7m vs. 63.7m vs. 38.1m, p=0.47). Pts who got 1 line of ARPI had statistically similar mOS than those not exposed to ARPI (43.3m vs. 39.5m, p=0.89). In pts with de novo mPC, more than 1 line (44.3m) or 1 line of ARPI (42.1m) were associated with numerically longer but statistically similar mOS compared to no ARPI (30.1m, p=0.47); pts with recurrent mPC showed an opposite trend (22.5 vs 48.5m vs. not reached, p=0.009). In multivariable analysis, RT to prostate for mPC was associated with better mOS in mHSPC (HR 0.409, 95% CI 0.180 – 0.92, p=0.032) but not mCRPC. None of age, PSA at metastasis, Gleason score, or ADT type was identified as an independent factor affecting mOS. No significant differences in mOS was seen with varying years of mPC diagnosis (2015-2022). Conclusions: Our multicentre data suggest that access to clinical trials and timely RT to prostate in appropriate pts with mPC are associated with longer mOS and should be considered standard of care. Access to clinical trials may be challenging for a significant proportion of pts. Exposure to as many lines of tx/ARPI as possible may potentially help in pts with de novo mPC, but more data are required to determine benefit in all subgroups.
Impact of TP53, RB1, and PTEN mutations on overall survival in metastatic prostate cancer: A multi-center study via the Guardian Research Network.
Authors: Ganiyani Mohammad Arfat , Prabhakar Pushan , Khosla Atulya Aman , Bellur Shreyas S , Pon Avudaiappan Arjun , Bond Liz , Marada Suresh , McCracken Andrea , Hurmiz Charlie , Bastos Bruno R. , Garje Rohan 
Published: January 2024

82 Background: The treatment paradigm for metastatic prostate cancer has significantly improved in the past decade. Nevertheless, there remains an unmet need for novel biomarker-driven risk stratification. Studies have shown that genetic alterations in any of the PTEN, RB1, and TP53 genes influence the prognosis, potential for androgen independence and overall survival of individuals diagnosed with advanced prostate cancer. Based on these findings, we compared survival rates by contrasting patients with any of these mutations to those lacking them, using an extensive real-world sample from community oncology centers across the Guardian Research network (GRN). Methods: All patients diagnosed with metastatic prostate cancer who had undergone Next-Generation Sequencing (NGS) were included across an oncology-focused hospital consortium network database (GRN). Study participants were classified into two cohorts based on the presence or absence of biomarkers. Patients harboring at least one of the following genomic alterations— TP53, Rb, or PTEN—were categorized as "biomarker-positive." Those without these mutations were designated as "biomarker negative." Overall survival (OS) was compared between the two cohorts by Kaplan-Meier Curve analysis. Results: We identified 350 patients with metastatic prostate cancer, of which 140 were biomarker positive and 210 were biomarker negative. The biomarker-positive cohort had a lower overall survival (p=0.002) when compared to the biomarker-negative cohort. For the sub-group with a minimum follow up of four years, median survival was 35.8 months vs 67.2 months for biomarker marker positive and negative cohorts, respectively. Furthermore, the biomarker-positive cohort was associated with significantly higher number of patients with bone and liver metastases. Conclusions: Our study indicates poor overall survival in patients with TP53, RB1, and PTEN mutated prostate cancer, underscoring the need for novel treatment strategies for this aggressive disease genotype. Future studies based on genomic risk stratification are needed to customize therapies through appropriate intensification or de-intensification based on individual genomic profiles. [Table: see text]
Quality of treatment with targeted agents for advanced prostate cancer by treating specialist.
Authors: Faraj Kassem S , Oerline Mary , Kaufman Samuel , Caram Megan Veresh , Shahinian Vahakn B. , Hollenbeck Brent K. 
Published: January 2024

88 Background: Urologists are increasingly prescribing oral targeted agents to men with advanced prostate cancer, who traditionally have been cared for by medical oncologists. These agents require close monitoring, since they mechanistically affect androgen biosynthesis and can lead to cardiovascular and metabolic adverse events. It is unclear whether patients treated by urologists—whose practice scope typically does not involve systemic therapies—experience more frequent therapy-related adverse events. Further, these medications are expensive, often subjecting patients to high out-of-pocket costs, which can lead to coping strategies like treatment non-adherence. Urologists may have less experience discussing these costs and exploring cheaper alternatives. Methods: A 20% sample of National Medicare claims was used to perform a retrospective cohort study of Medicare beneficiaries with advanced prostate cancer between 2012-2020 who were treated with a targeted agent (abiraterone or androgen receptor blocker). The primary outcome was the composite of any hospital or emergency department visit for a cardiometabolic event within 1 year of starting a targeted agent. Secondary outcomes included monthly out-of-pocket costs in those without low-income subsidies and adherence to treatment in first 6 months after initiating treatment. Multivariable regression models were fitted to assess the association between prescribing specialist (urologist or medical oncologist) and each outcome. Results: There were 1,462 (25%) and 4,501 (75%) patients who were prescribed a targeted agent by a urologist and medical oncologist. Men who were managed by urologists were more often started on an androgen receptor blocker, compared to those managed by medical oncologists (67% vs 36%, p<0.001).There were no differences in the adjusted frequencies of composite adverse events of patients managed by urologists and medical oncologists in those who were started on abiraterone (7.7 % vs 8.1%, P=0.79) or an androgen receptor blocker (6.4% vs 6.2%, p=0.91). Out-of-pocket costs did not vary between patients who were managed by urologists vs medical oncologists in those who were started on abiraterone ($748 % vs $778%, P=0.48) or an androgen receptor blocker ($795 vs $834, p=0.33). Adherence to treatment was similar between the specialties in those prescribed abiraterone (67% vs 64%, P=0.15), but the likelihood of adherence was higher in men prescribed an androgen receptor blocker by a urologist (65% vs 61%, p=0.04). Conclusions: Although urologists may be less accustomed to primarily managing advanced prostate cancer than medical oncologists, patients fared no worse when assessing adverse events, out-of-pocket costs, or adherence to treatment. This study provides further support for urologists’ increased role in managing advanced prostate cancer.