bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection rate of 18F-rhPSMA-7.3 PET in patients with suspected prostate cancer recurrence: Results from a phase 3, prospective, multicenter study (SPOTLIGHT)
Authors: Schuster David M. ,   SPOTLIGHT Study Group
Published: February 2022

9 Background: 18F-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) ligands offer a longer half-life and improved spatial resolution compared with 68Ga-PSMA. Here, we report the detection rate (DR) of 18F-rhPSMA-7.3, a novel high affinity theranostic PET ligand with potential for low bladder activity. Methods: SPOTLIGHT (NCT04186845) assessed the coprimary endpoints of patient level Correct Detection Rate (CDR - % of all patients scanned with ≥1 true positive lesion) and region level Positive Predictive Value (all PET positive regions combined) of 18F-rhPSMA-7.3 using histopathology and/or conventional imaging as a composite Standard of Truth (SoT). These metrics were also evaluated in a subset of patients with a histopathology-only SoT. Prespecified statistical thresholds of at least 36.5% and 62.5% were set for CDR and PPV, respectively. Overall DR stratified by PSA was also documented. Men with prostate cancer recurrence underwent PET 50-70 minutes after IV administration of 296 MBq 18F-rhPSMA-7.3. Image guided biopsies of PET lesions took place ≤60 days post-PET and any confirmatory imaging took place ≤90 days. Three blinded central readers evaluated the scans with majority read accepted as final interpretation. A separate Truth Panel established SoT for each patient. Results: The overall DR in the 389 men (median [range] PSA, 1.10 [0.03-134.6] ng/mL) who had an evaluable 18F-rhPSMA-7.3 scan is 83% by majority read (See Table). In the 366 men (median [range] PSA, 1.27 [0.03-134.6] ng/mL) with a composite SoT, the patient level CDR is 56.8% (95% CI, 51.6-62.0), meeting the prespecified threshold. The region level PPV is 59.7% (54.7-64.7), not meeting the prespecified threshold. In the subset of patients with a histopathology-only SoT, the patient level CDR and region level PPV are higher at 81.2% (69.9-89.6) and 71.6% (62.5-80.7), respectively. Both of these values would have met the prespecified thresholds. Conclusions: 18F-rhPSMA-7.3 has a clinically meaningful CDR that meets the prespecified threshold. While the region level PPV does not meet the prespecified threshold, the data in patients with a composite SoT are limited by the high proportion of prostate/bed scans (92%) that relied on conventional imaging, a suboptimal SoT. For the subset of patients with the more robust histopathology SoT for at least one region per patient, a high PPV is seen and the lower bound of the 95% CI would have exceeded the prespecified threshold. Together, these data support the clinical utility of 18F-rhPSMA-7.3 PET in men with recurrent prostate cancer across a wide PSA range. Clinical trial information: NCT04186845. [Table: see text]
Prostate-specific antigen (PSA) outcomes in black (B) and white (W) chemotherapy-naïve (CN) prostate cancer (PC) patients (pts) treated with enzalutamide (ENZA).
Authors: Morgans Alicia K. , Hong Agnes , Murty Sharanya , El-Chaar Nader N. , Ramaswamy Krishnan , Coutinho Anna D. , Nimke David , Freedland Stephen J. 
Published: February 2022

20 Background: Population-level data suggest that B men are more likely to be diagnosed and die from PC. In juxtaposition, across multiple treatments for advanced PC, studies suggest B men have better survival than W men, including with novel hormone therapies (NHTs) such as ENZA. Whether improved survival is driven by better clinical response is unknown as data on racial differences in treatment response for ENZA are limited. This study assessed real-world PSA outcomes (response and progression) of ENZA-treated B vs W CN PC pts in the US. Methods: This retrospective cohort study included PC pts who initiated ENZA in the IntrinsiQ Specialty Solutions urology electronic medical records database from Sept 1, 2014 to Feb 28, 2018. The index date was the first prescription for ENZA. Patients with evidence of prior chemotherapy and/or abiraterone were excluded. Baseline characteristics, PSA response (PSA decline ≥50% or ≥90%), and clinical progression-free survival (cPFS) were assessed by race. Kaplan-Meier and Cox models adjusting for baseline characteristics were used to estimate PSA response and cPFS. Results: The study included 214 B and 1,332 W CN PC pts. Black pts were younger and had a higher baseline median PSA than W pts. Charlson Comorbidity Index (CCI), median duration of therapy, follow-up time, and number of post-index PSA tests were similar between races. In adjusted analyses, the chances of pts achieving ≥50% PSA decline was similar, whereas a numerically higher trend was observed for ≥90% PSA decline in B pts (Table). In addition, B men had significantly better cPFS (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.68, 0.98; p=0.03) [Table]. Conclusions: This real-world study found similar PSA response in B and W CN PC pts treated with ENZA but suggests that B pts may have better cPFS than W pts. Further research is warranted to validate these findings.[Table: see text]
Hormonal treatment for newly diagnosed metastatic prostate cancer: A population-based study of 15,435 cases from the California Cancer Registry (2009-2018).
Authors: Benjamin David Joseph , Fellman Dimitra , Shrestha Anshu , Rezazadeh Arash 
Published: February 2022

22 Background: Androgen deprivation therapy (ADT) is considered standard of care in the treatment of metastatic prostate cancer (mPC). Over the past ten years, the approval of novel androgen receptor-axis-targeted therapies has changed the treatment landscape of mPC. All these novel therapies have only been approved for use in addition to ADT. Despite these new therapeutic advances, it remains unclear how often men with mPC receive standard of care treatment with ADT. Methods: Male adults aged 20 years and older with newly diagnosed metastatic (stage IV) prostate cancer between 2009 and 2018 were identified through the California Cancer Registry (n = 15,435). Patient characteristics including age, year of diagnosis, race/ethnicity, insurance status, socioeconomic status (SES), Charlson co-morbidity score, and death within 3 months of diagnosis were analyzed. Results: 23.1% (n = 3,568) of men with newly diagnosed mPC did not receive ADT. The highest rate of receiving ADT was in men between ages 75-84 (79.6%), and the lowest rate was in men aged over 85 (72.0%) as shown in the table. There was a trend toward more newly diagnosed men receiving ADT in 2018 (81.3%) compared to 2009 (68.8%). Asian men (n = 1077) had a larger proportion of receiving ADT (79.7%), followed by American Indian men (n = 152; 76.4%), Hispanic men (n = 2,368; 75.1%), non-Hispanic White (n = 6,790; 75.6%), and lastly non-Hispanic Black men (n = 1,312; 74.8%). Men from the highest SES had the highest rate of receiving ADT (77.3%), and lowest rate was in lowest SES (73.5%). There was no significant difference among men not receiving hormonal therapy based off Charlson comorbidity score: 0 (26.0%), 1-2 (25.3%), and 3+ (24.9%). Conclusions: Despite significant advancements in the treatment of mPC in recent years, nearly a quarter of patients in California did not receive ADT, which is the backbone for all new systemic therapies. Further statistical analysis of this data set is currently ongoing. This data set might be able to help addressing some of the prostate cancer care disparities in California. [Table: see text]
Predictive factors for effectiveness from novel androgen-receptor-axis-targeted agents in patients with metastatic prostate cancer.
Authors: Nishimoto Koshiro , Nakajima Kenichi , Oyama Masafumi , Kaneko Go , Takahashi Satoru , Matsuyama Hideyasu , Shiina Hiroaki , Ichikawa Tomohiko , Horikoshi Hiroyuki , Hashine Katsuyoshi , Sugiyama Yutaka , Miyao Takeshi , Kamiyama Manabu , Harada Kenichi , Ito Akito , Mizokami Atsushi ,   PROSTAT-BSI Investigators
Published: February 2022

33 Background: About a half of men with prostate cancer progress to metastatic castration-resistant prostate cancer (mCRPC) one year after the initiation of androgen-deprivation therapy (ADT), whereas approximately 20 % of men keep the sensitivity to ADT more than 5 years. Several novel androgen-receptor-axis-targeted agents (ARATAs) were developed for the treatment of mCRPC, and improved overall survival (OS) in patients with mCRPC; however, to which patients these ARATAs were more beneficial is yet to be determined. We conducted this study to identify factors that predict effectiveness from ARATAs for mCRPC. Methods: We previously performed a multicenter study to determine prognostic factors including bone scan index (BSI) in patients with metastatic hormone sensitive prostate cancer (n = 148) and mCRPC (n = 99), which showed that BSI was one of the significant determinants of 3-year OS (PROSTAT-BSI study). The patients with mHSPC progressed to mCRPC (n = 101). Among these mCRPC patients, 69 patients received treatments with or without ARATAs, because the patients were recruited before and after approval of ARATAs in Japan. We used the data of the 69 patients to identify predictors for effective use of ARTA. The cohort was divided into two groups according to patient factors by several thresholds, and these two cohorts were further divided into two subgroups: those who received and did not receive ARATAs (abiraterone or enzalutamide). OS was compared between these two cohort groups to evaluate contribution of each factor. Categorical values were analyzed in the same way, although no threshold setting was required. Results: Factors, in which the significant treatment effect from ARATAs was observed between subgroups in only one group (eg. age < 71.4 vs age ≥ 71.4), were age ( < 71.4 years); serum levels of C-reactive protein (≥0.16 ng/mL), alkaline phosphatase (≥548 U/L), and type 1 collagen C-terminal telopeptide ( < 6.4 ng/mL); time to PSA progression after ADT ( < 8.9 months); lowest PSA level (≥1 ng/mL) after ADT; and rate of PSA decline 3 month after ADT ( <.987). Whereas, no significant difference was observed between two groups in cohorts divided by hemoglobin level, PSA before ADT, Gleason score, and BSI. Conclusions: This study identified the predictors of the effectiveness from ARATAs. In addition, the number of bone metastases (corresponding to BSI) and Gleason score, which were considered as high-risk factors in the LATITUDE study and disease volume in the CHAARTED criteria, may not be useful for predicting the effectiveness from ARATAs.
Novel framework for treatment response evaluation using PSMA-PET/CT in patients with metastatic castration-resistant prostate cancer (RECIP): An international multicenter study.
Authors: Gafita Andrei , Rauscher Isabel , Weber Manuel , Hadaschik Boris A. , Wang Hui , Armstrong Wesley R , Tauber Robert , Grogan Tristan , Czernin Johannes , Rettig Matthew , Herrmann Ken , Calais Jeremie , Weber Wolfgang A , Benz Matthias R. , Fendler Wolfgang Peter , Eiber Matthias 
Published: February 2022

42 Background: We aimed to develop a novel framework for Response Evaluation Criteria In PSMA-PET/CT (RECIP) 1.0 and a composite response classification which combines responses by PSA measurements and by RECIP 1.0 (PSA+RECIP). Methods: This was an international, multicenter, retrospective study. 124 men with mCRPC who underwent 177Lu-PSMA therapy and received PSMA-PET/CT at baseline (bPET) and at interim at 12 weeks (iPET) were included. Pairs of bPET and iPET were interpreted by consensus among three blinded readers for appearance of new lesions. Tumor lesions were segmented and total PSMA-positive tumor volume (PSMA-VOL) was obtained. Appearance of new lesions and changes in PSMA-VOL were combined to develop RECIP 1.0, which was defined as: complete response (RECIP-CR: absence of any PSMA-ligand uptake on iPET), partial response (PSMA-PR: decline ≥30% in PSMA-VOL and no appearance of new lesions), progressive disease (RECIP-PD: increase ≥20% in PSMA-VOL and appearance of new lesions), stable disease (RECIP-SD: any condition but RECIP-PR or RECIP-PD). Changes in PSA levels at 12 weeks by PCWG3 were recorded. Responses by PSA+RECIP were defined as: response (PSA decline ≥50% or RECIP-PR/CR) and progression (PSA increase ≥25% or RECIP-PD). Study's primary outcome measure was the prognostic value of RECIP 1.0 for overall survival (OS). Secondary outcome measure was the prognostic accuracy (C-index) of PSA+RECIP vs PSA responses. Results: Patients with progressive disease (RECIP-PD; n=39; 8.3 mo) had shorter OS compared to patients with stable disease (RECIP-SD; n=47; 13.1 mo; p<0.001) and to those with partial response (RECIP-PR; n=38; 21.7 mo; p<0.001). PSA+RECIP had superior C-indices in identifying responders and progressors compared to PSA only: 0.65 vs 0.62 (p=0.028) and 0.66 vs 0.63 (p=0.044), respectively. Conclusions: PSMA-PET/CT by RECIP 1.0 is prognostic for OS and can be used as a response biomarker to monitor efficacy of 177Lu-PSMA in men with mCRPC. PSA+RECIP may be used as a novel composite endpoint in mCRPC clinical trial design.
Comparison of major adverse cardiovascular events risk after androgen deprivation therapy initiation by body mass index.
Authors: Gordan Lucio N. , Atkinson Stuart , Boldt-Houle Deborah , Lee Andrew K. 
Published: February 2022

44 Background: The association between androgen deprivation therapy (ADT) and increased cardiovascular (CV) risk in prostate cancer (PCa) patients is controversial.1-2 Major adverse cardiovascular events (MACE) occurred in 3-6% of patients in a 48-week ADT trial,2 but meta-analysis from a 2011 study found no association between ADT and increased risk of CV death.1 Body mass index (BMI) is a potential risk factor; Lee et al. found a lower risk of MACE in patients with high BMI than those with a normal weight, and patients with low BMI had a higher risk of all-cause mortality.3 This study evaluates the association between BMI and MACE risk in PCa patients on ADT using real-world data. Methods: Analyses of US electronic medical records (2010 to 2020) of PCa patients (n=36,249) receiving LHRH agonist/antagonist injections were conducted to calculate the risk of MACE since ADT initiation for the following BMI groups: <18.5, 18.5 to <25, 25 to <30, 30 to <35, and >35. BMI groups were based on the standard weight status associated with each BMI range (underweight, normal or healthy weight, overweight, obese, and severely obese, respectively).4 The database contained 178,388 LHRH agonist/antagonist injection entries and 965 documented MACE events. Exclusion criteria included lack of ADT initiation date, lack of BMI data, and MACE within 6 months prior to ADT initiation. MACE was defined as myocardial infarction, stroke, and death from any cause based on a recent study in this field.2 Kaplan-Meier event-free survival curves were constructed to compare the risk of MACE between BMI groups. Statistical significance between survival curves was evaluated by log-rank test. Results: Differences in MACE incidence between BMI groups were not significant. (Table). Conclusions: MACE risk was similar across BMI subgroups after ADT initiation. This is consistent with the literature that higher BMIs do not confer additional CV/MACE risk as might be expected (a lower risk of MACE in patients with high BMI than those with normal weight).3 This 10-year analysis in >35,000 patients is likely reflective of the real world, but further study is recommended to evaluate whether BMI should be considered a predisposing risk factor for CV disease in PCa patients undergoing ADT. As the association between ADT and increased CV risk in PCa patients is controversial, future studies evaluating the role of co-morbidities on MACE risk for PCa patients during ADT may be helpful to identify other CV predictors.[Table: see text]
Real-world analyses of major adverse cardiovascular event risk by drug class after initiation of androgen deprivation therapy.
Authors: Crawford E. David , Atkinson Stuart , Boldt-Houle Deborah , Gordan Lucio N. 
Published: February 2022

46 Background: Recent literature has suggested an association between androgen deprivation therapy (ADT) and increased cardiovascular (CV) risk in prostate cancer (PCa) patients.1,2 The 1-year incidence of major adverse cardiovascular events (MACE) in patients ≥45 years old was 1.4%,3 whereas a recent study of PCa patients on ADT reported MACE in 2.9% of patients treated with an LHRH antagonist (relugolix) and 6.2% of patients treated with an LHRH agonist (leuprolide acetate) over 48 weeks.4 Thus, MACE risk is an important consideration for PCa patients on ADT. This study aims to evaluate MACE risk after ADT initiation with LHRH agonists vs. LHRH antagonists using real-world data. 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 the rate of MACE-free survival after ADT initiation by drug class. The database contained 178,388 LHRH agonist and antagonist injection entries and 965 documented MACE events. Exclusion criteria included taking more than one class of ADT and MACE within 6 months prior to ADT initiation. MACE was defined as myocardial infarction, stroke, and death from any cause based on a recent study in this field.4 Kaplan-Meier event-free survival curves were constructed to compare the risk of MACE between patients on agonist vs. antagonist. Statistical significance between survival curves was evaluated by log-rank test. Results: Overall MACE risk for all patients was 1.0% at one year. MACE risk was significantly higher for patients treated with LHRH antagonist compared to agonists in the first seven years after ADT initiation. Conclusions: Risk of MACE was lower than previously reported. Although this may potentially be due to underreporting, our analysis of data over 10 years from >45,000 PCa patients is likely an accurate reflection of the real world. A recent study using large real-world dataset with >50,000 PCa patients over approximately 2 years showed no difference in CV risk following treatment with GnRH agonists and antagonists.5 However, in our analyses MACE risk was lower in patients treated with LHRH agonists vs. antagonists in the first seven years after ADT initiation. Further, we plan to evaluate baseline comorbidities and demographics for imbalances. Future studies evaluating the impact of ADT class and comorbidities on MACE risk for PCa patients during ADT may be helpful to identify CV predictors. 1Ng C-F, et al. Scientific Reports. 2020. 2Zhao J, et al. PLoS One. 2014. 3Miao B, et al. J of the American Heart Association. 2020. 4Shore ND, et al. New England Journal of Medicine. 2020. 5George G, et al. Int J Cancer. 2021.
Statin type and survival of patients with metastatic castrate-resistant prostate cancer receiving abiraterone and enzalutamide: A nationwide retrospective cohort study.
Authors: Yoon Harrison , Luo Suhong , Sanfilippo Kristen Marie , Linneman Travis , Whitmer Alison , Schoen Martin W. 
Published: February 2022

50 Background: Studies have suggested that statin use is associated with prostate cancer mortality. However, uncertainties exist in how the solubility profile of statins impact cancer outcomes. Lipophilic statins have greater accessibility in extrahepatic tissues, which may lead to stronger inhibitory effects on cancer cells, whereas hydrophilic statins exhibit greater hepato-selectivity and therefore less likely to cause drug interactions and adverse events. Abiraterone (ABI) and enzalutamide (ENZ) are antiandrogen agents used in metastatic castrate-resistant prostate cancer (mCRPC). In this study, we sought to examine whether statin usage and lipophilicity of statins is associated with survival benefits in mCRPC patients receiving ABI or ENZ. Methods: We conducted a nationwide retrospective cohort study of the Veteran Affairs population. Patients with mCRPC who received statin therapy one year prior to initiation of either ABI or ENZ between 9/10/2014 and 6/3/2017 were included and followed until April 2020. Statins were categorized as lipophilic (atorvastatin, simvastatin, lovastatin, fluvastatin, cerivastatin, pitavastatin) and hydrophilic (rosuvastatin and pravastatin). A cox proportional hazards model was used to estimate adjusted hazards ratio (aHR) with 95% confidence interval (CI) of overall survival after controlling for known prognostic factors including age, Charlson-Romano Comorbidity Index, use of bone-modifying agents, Body-Mass Index, and prostate specific antigen levels. Results: A total of 4919 patients (mean age 75.0 years) were included in our cohort. Of those, 969 patients (19.7%) received lipophilic statins and 452 patients (9.2%) received hydrophilic statins. After adjusting for known factors, statin use was not associated with improved overall survival (aHR 0.93; 95% CI 0.87 – 1.00). Similarly, the use of lipophilic statins (aHR 0.98; 95% CI 0.90 – 1.06) or hydrophilic statins (aHR 0.90; 95% CI 0.80 – 1.01) were not associated with improved overall survival in mCRPC. Conclusions: Our study found no differences in overall survival between mCRPC patients with statin use compared to those without statins. When analyzing statin lipophilicity, we saw a higher trend towards survival in the hydrophilic statin group compared to the lipophilic statin group, which contradicts the direct anticancer benefits of lipophilic statins, but neither group reached statistical significance. Further studies analyzing statin usage and types with specific outcome measures such as cardiovascular events, duration of antiandrogen therapy, and adverse events related to ABI or ENZ will support in optimal therapy choices for mCRPC.
Diagnosis codes overestimate the burden of prostate cancer cases.
Authors: Anglin-Foote Tori , Lee Kyung Min , Robison Brian , Alba Patrick , DuVall Scott L. , Lynch Julie Ann 
Published: February 2022

72 Background: Identifying cancer cases within the electronic health record (EHR) or claims data can be challenging because diagnosis codes are often entered into patient records during routine screenings or as “rule out” diagnosis codes when the patient is referred to a procedure. To improve accuracy of prostate cancer (PCa) case ascertainment, we compared algorithms that used diagnoses codes to natural language processing (NLP) tools applied to clinical notes and pathology reports to identify Veterans with prostate cancer (PCa). Methods: This is a retrospective observational cohort study using VA EHR data to identify veterans diagnosed with PCa between 2000 and 2020. Using International Classification of Diseases (ICD-10 CM or ICD-9 CM) diagnosis and procedure codes, we identified veterans who may have PCa. We deployed validated NLP tools to identify the presence of Gleason score, metastatic PCa, and castration sensitivity to identify evidence of PCa within the notes. We conducted a descriptive analysis to compare the results of algorithms that relied exclusively on diagnosis codes compared to use of NLP tools. Results: From 2000 through 2020,1,031,296 veterans had one or more PCa diagnosis code. This number decreased by 11% for each additional PCa diagnosis code required. When we required 4 or more PCa diagnosis codes to be present, only 746,350 veterans had PCa. When we deployed NLP tools to identify mention of a Gleason score or an indicator of mPCa, only 685,847 Veterans had these indicators of PCa, a 35% decrease in the number of PCa cases with a single diagnosis code. Chart review of patients with their first PCa diagnosis codes in 2019 and 4 or more codes in their records illustrated no evidence of Gleason score or mPCa disease in their EHR. Analysis of their pathology reports revealed that these patients had prostatic intraepithelial neoplasia or atypical small acinar proliferation and had not yet developed prostate cancer. Conclusions: Accurate ascertainment of PCa using EHR and claims data requires using NLP tools and clinical notes combined with structured data sources such as diagnosis codes. Relying on ICD diagnosis codes alone will overestimate the burden of PCa up to 30%.