Reliability and Efficiency of the CAPRI-3 Metastatic Prostate Cancer Registry Driven by Artificial Intelligence

Background: Manual data collection is still the gold standard for disease-specific patient registries. However, CAPRI-3 uses text mining (an artificial intelligence (AI) technology) for patient identification and data collection. The aim of this study is to demonstrate the reliability and efficiency of this AI-driven approach. Methods: CAPRI-3 is an observational retrospective multicenter cohort registry on metastatic prostate cancer. We tested the patient-identification algorithm and automated data extraction through manual validation of the same patients in two pilots in 2019 and 2022. Results: Pilot one identified 2030 patients and pilot two 9464 patients. The negative predictive value of the algorithm was maximized to prevent false exclusions and reached 94.8%. The completeness and accuracy of the automated data extraction were 92.3% or higher, except for date fields and inaccessible data (images/pdf) (10–88.9%). Additional manual quality control took over 3 h less time per patient than the original fully manual CAPRI registry (105 vs. 300 min). Conclusions: The CAPRI-3 patient-identification algorithm is a sound replacement for excluding ineligible candidates. The AI-driven data extraction is largely accurate and complete, but manual quality control is needed for less reliable and inaccessible data. Overall, the AI-driven approach of the CAPRI-3 registry is reliable and timesaving.</p

Alcohol consumption patterns across Europe and adherence to the European guidelines in coronary patients : findings from the ESC-EORP EUROASPIRE V survey

Background and aims: Alcohol consumption is an important risk factor for cardiovascular morbidity and mortality worldwide. The highest levels of alcohol consumption are observed in Europe, where alcohol as contributing cause of coronary heart disease (CHD) is also most significant. We aimed to describe alcohol consumption patterns across European regions and adherence to the current guidelines in patients with a recent CHD event. Methods: The ESC-EORP survey (EUROASPIRE V) has been conducted in 2016-2017 at 131 centers in 27 Eu-ropean countries in 7350 patients with a recent CHD. Median alcohol consumption, as well as the proportion of abstainers and excessive drinkers (i.e. >70 g/week for women and >140 for men, as recommended by the European guidelines on cardiovascular prevention), was calculated for each region. To assess adherence to guidelines, proportions of participants who were advised to reduce excessive alcohol consumption and participants who were incorrectly not advised were calculated per region. Results: Mean age was 64 years (SD: 9.5), 75% were male. Abstention rates were 53% in males and 77% in females, whereas excessive drinking was reported by 9% and 5% of them, respectively. Overall, 57% of the participants were advised to reduce alcohol consumption. In the total population, 3% were incorrectly not advised, however, this percentage differed per region (range: 1%-9%). In regions where alcohol consumption was highest, participants were less often advised to reduce their consumption. Conclusion: In this EUROASPIRE V survey, the majority of CHD patients adhere to the current drinking guidelines, but substantial heterogeneity exists between European regions

Symptomatic Skeletal Events and the Use of Bone Health Agents in a Real-World Treated Metastatic Castration Resistant Prostate Cancer Population:Results From the CAPRI-Study in the Netherlands

Background: Patients with metastatic castration resistant prostate cancer (mCRPC) are at risk of symptomatic skeletal events (SSE). Bone health agents (BHA, ie bisphosphonates and denosumab) and new life-prolonging drugs (LPDs) can delay SSEs. The aim of this study is to investigate the use of BHAs in relation to SSEs in treated real-world mCRPC population. Patients and Methods: We included patients from the CAPRI registry who were treated with at least one LPD and diagnosed with bone metastases prior to the start of first LPD (LPD1). Outcomes were SSEs (external beam radiation therapy (EBRT) to the bone, orthopedic surgery, pathologic fracture or spinal cord compression) and SSE-free survival (SSE-FS) since LPD1. Results: One-thousand nine hundred and twenty-three patients were included with a median follow-up from LPD1 of 16.7 months. Fifty-two percent (n = 996) started BHA prior or within 4 weeks after the start of LPD1 (early BHA). In total, 41% experienced at least one SSE. SSE incidence rate was 0.29 per patient year for patients without BHA and 0.27 for patients with early BHA. Median SSE-FS from LPD1 was 12.9 months. SSE-FS was longer in patients who started BHA early versus patients without BHA (13.2 vs. 11.0 months, P =.001). Conclusion: In a real-world population we observed an undertreatment with BHAs, although patients with early BHA use had lower incidence rates of SSEs and longer SSE-FS. This finding was irrespective of type of SSE and presence of risk factors. In addition to LPD treatment, timely initiation of BHAs is recommended in bone metastatic CRPC-patients with both pain and/or opioid use and prior SSE

Third-line Life-prolonging Drug Treatment in a Real-world Metastatic Castration-resistant Prostate Cancer Population:Results from the Dutch Castration-resistant Prostate Cancer Registry

Third-line life-prolonging drugs (LPDs) might not be appropriate for all metastatic castration-resistant prostate cancer patients. We developed a prognostic model and identified a high-risk subgroup in which no meaningful benefit from third-line LPDs is derived in clinical practice

Urinary Ethyl Glucuronide as Measure of Alcohol Consumption and Risk of Cardiovascular Disease:A Population-Based Cohort Study

Background Moderate alcohol consumption has been associated with a lower risk of cardiovascular disease (CVD) and all-cause mortality compared with heavy drinkers and abstainers. To date, studies have relied on self-reported consumption, which may be prone to misclassification. Urinary ethyl glucuronide (EtG) is an alcohol metabolite and validated biomarker for recent alcohol consumption. We aimed to examine and compare the associations of self-reported alcohol consumption and EtG with CVD and all-cause mortality. Methods and Results In 5676 participants of the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study cohort, EtG was measured in 24-hour urine samples and alcohol consumption questionnaires were administered. Participants were followed up for occurrence of first CVD and all-cause mortality. Cox proportional hazards regression models, adjusted for age, sex, and CVD risk factors, were fitted for self-reported consumption, divided into 5 categories: abstention, 1 to 4 units/month (reference), 2 to 7 units/week, 1 to 3 units/day, and ≥4 units/day. Similar models were fitted for EtG, analyzed as both continuous and categorical variables. Follow-up times differed for CVD (8 years; 385 CVD events) and all-cause mortality (14 years; 724 deaths). For both self-reported alcohol consumption and EtG, nonsignificant trends were found toward J-shaped associations between alcohol consumption and CVD, with higher risk in the lowest (hazard ratio for abstention versus 1-4 units/month, 1.42; 95% CI, 1.02-1.98) and highest drinking categories (hazard ratio for ≥4 units/day versus 1-4 units/month, 1.11; 95% CI, 0.68-1.84). Neither self-report nor EtG was associated with all-cause mortality. Conclusions Comparable associations with CVD events and all-cause mortality were found for self-report and EtG. This argues for the validity of self-reported alcohol consumption in epidemiologic research

Being Transparent About Brilliant Failures:An Attempt to Use Real-World Data in a Disease Model for Patients with Castration-Resistant Prostate Cancer

Background: Real-world disease models spanning multiple treatment lines can provide insight into the (cost) effectiveness of treatment sequences in clinical practice. Objective: Our objective was to explore whether a disease model based solely on real-world data (RWD) could be used to estimate the effectiveness of treatments for patients with castration-resistant prostate cancer (CRPC) that could then be suitably used in a cost-effectiveness analysis. Methods: We developed a patient-level simulation model using patient-level data from the Dutch CAPRI registry as input parameters. Time to event (TTE) and overall survival (OS) were estimated with multivariate regression models, and type of event (i.e., next treatment or death) was estimated with multivariate logistic regression models. To test internal validity, TTE and OS from the simulation model were compared with the observed outcomes in the registry. Results: Although patient characteristics and survival outcomes of the simulated data were comparable to those in the observed data (median OS 20.6 vs. 19.8 months, respectively), the disease model was less accurate in estimating differences between treatments (median OS simulated vs. observed population: 18.6 vs. 17.9 [abiraterone acetate plus prednisone], 24.0 vs. 25.0 [enzalutamide], 20.2 vs. 18.7 [docetaxel], and 20.0 vs. 23.8 months [radium-223]). Conclusions: Overall, the disease model accurately approximated the observed data in the total CRPC population. However, the disease model was unable to predict differences in survival between treatments due to unobserved differences. Therefore, the model is not suitable for cost-effectiveness analysis of CRPC treatment. Using a combination of RWD and data from randomised controlled trials to estimate treatment effectiveness may improve the model

Real-world Outcomes of Sequential Androgen-receptor Targeting Therapies with or Without Interposed Life-prolonging Drugs in Metastatic Castration-resistant Prostate Cancer:Results from the Dutch Castration-resistant Prostate Cancer Registry

BACKGROUND: Cross resistance between androgen-receptor targeting therapies (ARTs) (abiraterone acetate plus prednisone [ABI+P] or enzalutamide [ENZ]) for treatment of metastatic castration-resistant prostate cancer (mCRPC) may affect responses to second ART (ART2). OBJECTIVE: To establish treatment duration and prostate-specific antigen (PSA) response of ART2 in real-world mCRPC patients treated with or without other life-prolonging drugs (LPDs; ie, docetaxel, cabazitaxel, or radium-223) between ART1 and ART2. DESIGN, SETTING, AND PARTICIPANTS: Castration-resistant prostate cancer patients, diagnosed between 2010 and 2016 were retrospectively registered in Castration-resistant Prostate Cancer Registry (CAPRI). Patients treated with both ARTs were clustered into two subgroups: ART1>ART2 or ART1>LPD>ART2. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were ≥50% PSA response and treatment duration of ART2. Descriptive statistics and binary logistic regression after multiple imputations were performed. RESULTS AND LIMITATIONS: A total of 273 patients were included with a median follow-up of 8.4 mo from ART2. Patients with ART1>ART2 were older and had favourable prognostic characteristics at ART2 baseline compared with patients with ART1>LPD>ART2. No differences between ART1>ART2 and ART1>LPD>ART2 were found in PSA response and treatment duration. Multivariate analysis suggested that PSA response of ART2 was less likely in patients with visceral metastases (odds ratio [OR] 0.143, p=0.04) and more likely in patients with a relatively longer duration of androgen-deprivation treatment (OR 1.028, p=0.01) and with ABI + P before ENZ (OR 3.192, p=0.02). A major limitation of this study was missing data, a common problem in retrospective observational research. CONCLUSIONS: The effect of ART2 seems to be low, with a low PSA response rate and a short treatment duration irrespective of interposed chemotherapy or radium-223, especially in patients with short time on castration, visceral disease, and ENZ before ABI+P. PATIENT SUMMARY: We observed no differences in outcomes of patients treated with sequential abiraterone acetate plus prednisone (ABI+P) and enzalutamide (ENZ) with or without interposed chemotherapy or radium-223. In general, outcomes were lower than those in randomised trials, questioning the additional effect of second treatment with ABI+P or ENZ in daily practice

PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer : A Retrospective Study

Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from [177Lu]Lu-PSMA- (177Lu-PSMA) or [225Ac]Ac-PSMA-radioligand treatment (225Ac-PSMA). In this retrospective study, we analyzed the safety and efficacy of PSMARLT in early-stage and hormone-sensitive metastatic prostate cancer patients. Methods: A retrospective study was performed in patients who received 177Lu-PSMA and/or 225Ac-PSMA with early-stage metastatic prostate cancer. The primary outcome parameter evaluated in this study was the progression-free survival (PFS) after PSMA-RLT and toxicity according to the Common Terminology Criteria for Adverse Events. Secondary outcome parameters were prostate-specific antigen (PSA) response and the date of onset of CRPC state. Results: In total, 20 patients were included of which 18 patients received 177Lu-PSMA radioligand and two patients received tandem treatment with both 177Lu-PSMA and 225Ac-PSMA radioligands. Patients received a median of 2 treatment cycles (range 1–6) and a median activity of 6.2 GBq 177Lu-PSMA per cycle (interquartile range (IQR) 5.2–7.4 GBq). PSMA-RLT was overall well-tolerated. The most common grade 1–2 side effects were xerostomia (n = 6) and fatigue (n = 8), which were only temporarily reported. One patient that received 225Ac-PSMA developed grade 3–4 bone marrow toxicity. The median PFS was 12 months (95% confidence interval (CI), 4.09–19.9 months). Seventeen (85%) patients had a ≥50% PSA response following PSMA-RLT. One patient developed CRPC 9 months following PSMA-RLT. Conclusions: In this small cohort study, PSMA-RLT appeared safe and showed encouraging efficacy for (metastasized) early-stage and hormone-sensitive prostate cancer patients. Prospective studies are awaited and should include long-term follow-up

Talazoparib, a Poly(ADP-ribose) Polymerase Inhibitor, for Metastatic Castration-resistant Prostate Cancer and DNA Damage Response Alterations: TALAPRO-1 Safety Analyses

BACKGROUND: The phase II TALAPRO-1 study (NCT03148795) demonstrated durable antitumor activity in men with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). Here, we detail the safety profile of talazoparib. PATIENTS AND METHODS: Men received talazoparib 1 mg/day (moderate renal impairment 0.75 mg/day) orally until radiographic progression, unacceptable toxicity, investigator decision, consent withdrawal, or death. Adverse events (AEs) were evaluated: incidence, severity, timing, duration, potential overlap of selected AEs, dose modifications/discontinuations due to AEs, and new clinically significant changes in laboratory values and vital signs. RESULTS: In the safety population (N = 127; median age 69.0 years), 95.3% (121/127) experienced all-cause treatment-emergent adverse events (TEAEs). Most common were anemia (48.8% [62/127]), nausea (33.1% [42/127]), decreased appetite (28.3% [36/127]), and asthenia (23.6% [30/127]). Nonhematologic TEAEs were generally grades 1 and 2. No grade 5 TEAEs or deaths were treatment-related. Hematologic TEAEs typically occurred during the first 4-5 months of treatment. The median duration of grade 3-4 anemia, neutropenia, and thrombocytopenia was limited to 7-12 days. No grade 4 events of anemia or neutropenia occurred. Neither BRCA status nor alteration origin significantly impacted the safety profile. The median (range) treatment duration was 6.1 (0.4-24.9) months; treatment duration did not impact the incidence of anemia. Only 3 of the 15 (11.8% [15/127]) permanent treatment discontinuations were due to hematologic TEAEs (thrombocytopenia 1.6% [2/127]; leukopenia 0.8% [1/127]). CONCLUSION: Common TEAEs associated with talazoparib could be managed through dose modifications/supportive care. Demonstrated efficacy and a manageable safety profile support continued evaluation of talazoparib in mCRPC. CLINICALTRIALS.GOV IDENTIFIER: NCT0314879