Association between medical androgen deprivation therapy and long-term cardiovascular disease and all-cause mortality in nonmetastatic prostate cancer

Studies have suggested that prostate cancer (PCa) patients receiving androgen deprivation therapy (ADT) are at increased risk of developing or exacerbating cardiovascular disease (CVD). We aimed to explore the association between ADT for PCa and subsequent CVD and all-cause mortality in this nationwide, longitudinal study. We also evaluated the role of cardiovascular risk and ADT duration to determine effect modification. Norwegian registry data were used to identify patients with PCa from 2008-18 and who received primary ADT in the first year after diagnosis. The associations between ADT and composite cardiovascular events, and the individual components of myocardial infarction, stroke and heart failure, in addition to atrial fibrillation and all-cause mortality, were explored using time-varying Cox regression models. We included 30 923 PCa patients, of whom 8449 (27%) received primary ADT. Mean follow-up was 2.9 and 3.8 years for CVD events and mortality, respectively. We found an association between ADT and composite CVD (adjusted HR 1.13: 95% CI 1.05-1.21), myocardial infarction (1.18: 1.05-1.32), stroke (1.21: 1.06-1.38), heart failure (1.23: 1.13-1.35) and all-cause mortality (1.49: 1.39-1.61). These associations persisted in those with low and moderate CVD risk and ADT longer than 7 months. A relationship between ADT and composite CVD and all-cause mortality was observed, especially in those with moderate CVD risk and longer treatment duration. Future studies with more detailed cancer data are needed to verify the clinical relevance of these results, especially when considering all-cause mortality within the context of treatment guidelines and benefits of ADT.publishedVersio

Cardiovascular outcomes after curative prostate cancer treatment: A population-based cohort study

Objective: To investigate differences in cardiovascular disease (CVD) morbidity and mortality after radical prostatectomy or definitive radiotherapy with or without androgen deprivation therapy (ADT). Materials and methods: We used population-based data from the Cancer Registry of Norway, the Norwegian Patient Registry and the Norwegian Cause of Death Registry including 19 289 men ≤80 years diagnosed with non-metastatic prostate cancer during 2010-2019. Patients were treated with radical prostatectomy or definitive radiotherapy. We used competing risk models to compare morbidity from overall CVD, acute myocardial infarction (AMI), cerebral infarction, thromboembolism, and CVD-specific mortality for the overall cohort and stratified by prognostic risk groups. Results: After a median follow-up time of 5.4 years (IQR 4.6 years), there were no differences in adjusted rates of AMI, cerebral infarction, and CVD-specific death between radical prostatectomy and definitive radiotherapy in any of the prognostic risk groups. Rates of overall CVD (0.82; 95% CI 0.76-0.89) and thromboembolism (0.30; 95% CI 0.20-0.44) were lower for definitive radiotherapy than radical prostatectomy during the first year of follow-up. After this overall CVD rates (1.19; 95% CI 1.11-1.28) were consistently higher across all risk groups in patients treated with definitive radiotherapy, but there were no differences regarding thromboembolism. Conclusions: During the first years after treatment, no differences were found in rates of AMI, cerebral infarction, and CVD-specific death between radiotherapy and radical prostatectomy in any of the prognostic risk groups. This suggests that ADT use in combination with radiotherapy may not increase the risks of these outcomes in a curative setting. The increased overall CVD rate for definitive radiotherapy after the first year indicates a possible relationship between definitive radiotherapy and other CVDs than AMI and cerebral infarction.publishedVersio

Treatment and 30-day mortality after myocardial infarction in prostate cancer patients: A population-based study from Norway

Introduction: There is limited knowledge about the use of invasive treatment and mortality after acute myocardial infarction (AMI) in prostate cancer (PCa) patients. We therefore wanted to compare rates of invasive treatment and 30-day mortality between AMIs in patients with PCa and AMIs in the general Norwegian male population. Methods: Norwegian population-based registry data from 2013 to 2019 were used in this cohort study to identify AMIs in patients with a preceding PCa diagnosis. We compared invasive treatment rates and 30-day mortality in AMI patients with PCa to the same outcomes in all male AMI patients in Norway. Invasive treatment was defined as performed angiography with or without percutaneous coronary intervention or coronary artery bypass graft surgery. Standardized mortality (SMR) and incidence ratios, and logistic regression were used to evaluate the association between PCa risk groups and invasive treatment. Results: In 1,018 patients with PCa of all risk groups, the total rates of invasive treatment for AMIs were similar to the rates in the general AMI population. In patients with ST-segment elevation AMIs, rates were lower in metastatic PCa compared to localized PCa (OR 0.15, 95% CI: 0.04–0.49). For non-ST-segment elevation AMIs, there were no differences between PCa risk groups. The 30-day mortality after AMI was lower in PCa patients than in the total population of similarly aged AMI patients (SMR 0.77, 95% CI: 0.61–0.97). Conclusion: Except for patients with metastatic PCa experiencing an ST-segment elevation AMI, PCa patients were treated as frequent with invasive treatment for their AMI as the general AMI population. 30-day all-cause mortality was lower after AMI in PCa patients compared to the general AMI population.publishedVersio

Prescribed drugs in 27 000 individuals after diagnosis of colorectal cancer: A population-based cohort study

BACKGROUND: The prevalence of prescribed drugs in survivors of colorectal cancer (CRC) was evaluated. METHODS: Data from the Cancer Registry of Norway were linked to the Norwegian Prescription Database for a study population of 3.52 million individuals. Prevalence ratios (PRs) with 95% confidence intervals (CIs) of prescribed drugs in CRC-survivors compared to the cancer-free population, were estimated by log-binomial regression, adjusting for age and education. RESULTS: Almost 27 000 individuals, aged 20 to 84, were diagnosed with CRC during 2005 to 2014. The first year after diagnosis, the prevalence of prescribed drugs was higher in CRC-survivors compared with the cancer-free population, especially drugs for anxiety and tension, and steroid-responsive conditions. PRs for several drugs, especially drugs used for mental and behavioural disorders, decreased with time since diagnosis. The prevalence of drugs used for anxiety and tension was elevated 10 years after diagnosis; PRs the first year after diagnosis were 20 (95% CI: 18-22) in males and 17 (16-18) in females. Ten years after diagnosis PRs were 5.0 (3.1-7.9) and 2.0 (1.0-3.8), respectively. In absolute numbers, the largest increase, compared to the cancer-free population, was in drugs used for gastric acid disorders and pain. The prevalence of neuromodulatory drugs was higher in CRC-survivors. CONCLUSIONS: The prevalence of several drugs was higher in CRC-survivors than in the cancer-free population 10 years after diagnosis. The largest absolute excess in prevalence was for gastric acid disorder and pain medications, while the relative prevalence of drugs used for anxiety and tension was high in CRC-survivors. Long persisting neuropathia was indicated

Hva betyr tidligere hjerte- og karsykdom eller kreft for risiko for død etter påvist SARS-CoV-2?

BAKGRUNN Hjerte- og karsykdommer og kreft har vært beskrevet som mulige risikofaktorer for død av covid-19. Hensikten med studien er å undersøke om tidligere påvist hjerte- og karsykdom eller kreft har påvirket risiko for å dø etter påvist covid-19 i Norge. MATERIALE OG METODE Data fra Meldingssystem for smittsomme sykdommer, Nasjonalt register over hjerte- og karsykdommer og Kreftregisteret ble sammenstilt. Bi- og multivariable regresjonsmodeller ble brukt for å beregne både relativ og absolutt risiko. RESULTATER Første halvår 2020 fikk 8 809 personer påvist SARS-CoV-2 og 260 covid-19-assosierte dødsfall ble registrert. Økende alder, mannlig kjønn (relativ risiko (RR): 1,5; konfidensintervall (KI): 1,2 til 2,0), tidligere hjerneslag (RR: 1,5; KI: 1,0 til 2,1) og kreft med fjernspredning på diagnosetidspunktet (RR: 3,0; KI: 1,1 til 8,2) var uavhengige risikofaktorer for død etter påvist covid-19. Etter justering for alder og kjønn var hjerteinfarkt, atrieflimmer, hjertesvikt, hypertensjon og ikke-metastatisk kreft ikke lengre statistisk signifikante risikofaktorer for død. FORTOLKNING Den største risikofaktoren for død blant SARS-CoV-2-testpositive personer var alder. Mannlig kjønn, tidligere påvist hjerneslag og kreft med fjernspredning var også assosiert med forhøyet risiko for død etter påvist covid-19.publishedVersio

Identification and Validation of Leucine-rich α-2-glycoprotein 1 as a Noninvasive Biomarker for Improved Precision in Prostate Cancer Risk Stratification.

BACKGROUND: More accurate risk assessments are needed to improve prostate cancer management. OBJECTIVE: To identify blood-based protein biomarkers that provided prognostic information for risk stratification. DESIGN SETTING AND PARTICIPANTS: Mass spectrometry was used to identify biomarker candidates from blood, and validation studies were performed in four independent cohorts retrospectively collected between 1988 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome objectives were progression-free survival, prostate cancer-specific survival (PCSS), and overall survival. Statistical analyses to assess survival and model performance were performed. RESULTS AND LIMITATION: Serum leucine-rich α-2-glycoprotein 1 (LRG1) was found to be elevated in fatal prostate cancer. LRG1 provided prognostic information independent of metastasis and increased the accuracy in predicting PCSS, particularly in the first 3 yr. A high LRG1 level is associated with an average of two-fold higher risk of disease-progression and mortality in both high-risk and metastatic patients. However, our study design, with a retrospective analysis of samples spanning several decades back, limits the assessment of the clinical utility of LRG1 in today's clinical practice. Thus, independent prospective studies are needed to establish LRG1 as a clinically useful biomarker for patient management. CONCLUSIONS: High blood levels of LRG1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer, and LRG1 increased the accuracy of risk stratification of prostate cancer patients. PATIENT SUMMARY: High blood levels of leucine-rich α-2-glycoprotein 1 are unfavourable in newly diagnosed high-risk and metastatic prostate cancer

Association between medical androgen deprivation therapy and long-term cardiovascular disease and all-cause mortality in nonmetastatic prostate cancer

Studies have suggested that prostate cancer (PCa) patients receiving androgen deprivation therapy (ADT) are at increased risk of developing or exacerbating cardiovascular disease (CVD). We aimed to explore the association between ADT for PCa and subsequent CVD and all-cause mortality in this nationwide, longitudinal study. We also evaluated the role of cardiovascular risk and ADT duration to determine effect modification. Norwegian registry data were used to identify patients with PCa from 2008-18 and who received primary ADT in the first year after diagnosis. The associations between ADT and composite cardiovascular events, and the individual components of myocardial infarction, stroke and heart failure, in addition to atrial fibrillation and all-cause mortality, were explored using time-varying Cox regression models. We included 30 923 PCa patients, of whom 8449 (27%) received primary ADT. Mean follow-up was 2.9 and 3.8 years for CVD events and mortality, respectively. We found an association between ADT and composite CVD (adjusted HR 1.13: 95% CI 1.05-1.21), myocardial infarction (1.18: 1.05-1.32), stroke (1.21: 1.06-1.38), heart failure (1.23: 1.13-1.35) and all-cause mortality (1.49: 1.39-1.61). These associations persisted in those with low and moderate CVD risk and ADT longer than 7 months. A relationship between ADT and composite CVD and all-cause mortality was observed, especially in those with moderate CVD risk and longer treatment duration. Future studies with more detailed cancer data are needed to verify the clinical relevance of these results, especially when considering all-cause mortality within the context of treatment guidelines and benefits of ADT

Case completeness in the Norwegian Cardiac Arrest Registry

Introduction This study aimed to assess the case completeness of out-of-hospital cardiac arrests (OHCA) in the Norwegian Cardiac Arrest Registry (NorCAR) and describe the differences between the registered and missing patients identified from the case-control assessment. Methods We identified the relevant patients in the Norwegian Patient Registry and the Norwegian Cause of Death Registry and compared them with the patients in NorCAR. Data processors used patient records to confirm if the potential cardiac arrest cases met the inclusion criteria in NorCAR. Results Between 2015 and 2017, 8612 OHCA patients were registered in NorCAR. Through the Patient Registry and the Cause of Death Registry we identified 11,114 potential OHCA patients, 3469 of these were already registered in NorCAR. After evaluating the patient records for the remaining 7645 patients, we found 344 patients (4%), were eligible for inclusion in NorCAR, giving a case completeness of 96%. The registered and missing patients were similar in age and gender distribution. Initial shockable rhythm and presumed cause were also comparable. However, the missing patients more frequently achieved return of spontaneous circulation, were more often transported to hospital, and had higher survival rates. The already registered patients had more key variables registered than the missing patients. Conclusion Our results indicate high case completeness in NorCAR. The missing patients were too few to introduce significant changes in the distribution of patient characteristics, indicating that NorCAR is representative of the Norwegian OHCA population