Publications by authors named "Hans Garmo"

203 Publications

Time on treatment with abiraterone and enzalutamide in the Patient-overview Prostate Cancer in The National Prostate Cancer Register of Sweden.

Acta Oncol 2021 Sep 17:1-8. Epub 2021 Sep 17.

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Background: There are little and inconsistent data from clinical practice on time on treatment with the androgen receptor-targeted drugs (ART) abiraterone and enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC). We assessed time on treatment with ART and investigated predictors of time on treatment.

Material And Methods: Time on treatment with ART in men with mCRPC in the patient-overview prostate cancer (PPC), a subregister of the National Prostate Cancer Register (NPCR) of Sweden, was assessed by use of Kaplan-Meier plots and Cox regression. To assess the representativity of PPC for time on treatment, a comparison was made with all men in NPCR who had a filling for ART in the Prescribed Drug Registry.

Results: 2038 men in PPC received ART between 2015 and 2019. Median time on treatment in chemo-naïve men was 10.8 (95% confidence interval 9.1-13.1) months for abiraterone and 14.1 (13.5-15.5) for enzalutamide. After the use of docetaxel, time on treatment was 8.2 (6.5-12.4) months for abiraterone and 11.1 (9.8-12.6) for enzalutamide. Predictors of a long time on treatment with ART were long duration of ADT prior to ART, low serum levels of PSA at start of ART, absence of visceral metastasis, good performance status, and no prior use of docetaxel. PPC captured 2522/6337 (40%) of all men in NPCR who had filled a prescription for ART. Based on fillings in the Prescribed Drug Registry, men in PPC had a slightly longer median time on treatment with ART compared to all men in NPCR, 9.6 (9.1-10.3) vs. 8.6 (6.3-9.1) months.

Conclusions: Time on treatment in clinical practice was similar or shorter than that in published RCTs, due to older age, poorer performance status and more comorbidities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0284186X.2021.1978539DOI Listing
September 2021

Association between serum markers of the humoral immune system and inflammation in the Swedish AMORIS study.

BMC Immunol 2021 Sep 6;22(1):61. Epub 2021 Sep 6.

Translational Oncology and Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, Guy's Hospital, 3rd Floor, Bermondsey Wing, London, SE1 9RT, UK.

Background: Although the onset of inflammatory cascades may profoundly influence the nature of antibody responses, the interplay between inflammatory and humoral (antibody) immune markers remains unclear. Thus, we explored the reciprocity between the humoral immune system and inflammation and assessed how external socio-demographic factors may influence these interactions. From the AMORIS cohort, 5513 individuals were identified with baseline measurements of serum humoral immune [immunoglobulin G, A & M (IgG, IgA, IgM)] and inflammation (C-reactive protein (CRP), albumin, haptoglobin, white blood cells (WBC), iron and total iron-binding capacity) markers measured on the same day. Correlation analysis, principal component analysis and hierarchical clustering were used to evaluate biomarkers correlation, variation and associations. Multivariate analysis of variance was used to assess associations between biomarkers and educational level, socio-economic status, sex and age.

Results: Frequently used serum markers for inflammation, CRP, haptoglobin and white blood cells, correlated together. Hierarchical clustering and principal component analysis confirmed the interaction between these main biological responses, showing an acute response component (CRP, Haptoglobin, WBC, IgM) and adaptive response component (Albumin, Iron, TIBC, IgA, IgG). A socioeconomic gradient associated with worse health outcomes was observed, specifically low educational level, older age and male sex were associated with serum levels that indicated infection and inflammation.

Conclusions: These findings indicate that serum markers of the humoral immune system and inflammation closely interact in response to infection or inflammation. Clustering analysis presented two main immune response components: an acute and an adaptive response, comprising markers of both biological pathways. Future studies should shift from single internal marker assessment to multiple humoral and inflammation serum markers combined, when assessing risk of clinical outcomes such as cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12865-021-00448-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420021PMC
September 2021

Data Resource Profile: Breast Cancer Data Base Sweden (BCBaSe 2.0).

Int J Epidemiol 2021 Sep 2. Epub 2021 Sep 2.

Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Sweden.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ije/dyab139DOI Listing
September 2021

A drug comorbidity index to predict mortality in men with castration resistant prostate cancer.

PLoS One 2021 28;16(7):e0255239. Epub 2021 Jul 28.

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Background: The Charlson Comorbidity Index is a poor predictor of mortality in men with castration resistant prostate cancer (CRPC). To improve this prediction, we created a comorbidity index based on filled prescriptions intended to be used in registry-based studies.

Materials And Methods: In a population-based cohort of men with CPRC a drug comorbidity index (DCI-CRPC) was calculated based on prescriptions filled during a 365-day period before the date of CRPC diagnosis to predict mortality. Five risk categories for men with CRPC were defined based on PSA kinetics. Mortality rates were described by Kaplan-Meier curves. The predictive ability of the DCI-CRPC was compared in univariable models to that of the original DCI, derived from men in the general population, and to that of the Charlson Comorbidity Index.

Results: In 1,885 men with CRPC the median overall survival ranged from 3.0 years (95% confidence interval [CI] 2.8 to 3.4) in the first tertile of the DCI-CRPC, to 1.0 year (95% CI 0.9 to 1.1) in the third tertile of the DCI-CRPC. The index had higher discriminative ability (C-index 0.667) than the Charlson Comorbidity Index (C-index 0.508). The discriminative ability of the DCI-CRPC was highest in the subgroup with least aggressive cancer (C-index 0.651) and lowest in men with most aggressive cancer (C-index 0.618). The performance of the DCI-CRPC was comparable to that of the original DCI.

Conclusion: Our newly created comorbidity index using filled prescriptions predicted death in men with CRPC better than the Charlson Comorbidity Index.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255239PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318265PMC
July 2021

Aromatase inhibitors use and risk for cardiovascular disease in breast cancer patients: A population-based cohort study.

Breast 2021 Oct 7;59:157-164. Epub 2021 Jul 7.

Department of Oncology, Faculty of Medicine and Health, Örebro University, SE 70182, Örebro, Sweden. Electronic address:

Background: Prior studies regarding use of Aromatase inhibitors (AIs) and risk for cardiovascular disease (CVD) have shown conflicting results. This retrospective cohort study aimed to investigate whether AIs use affects risk for CVD events in postmenopausal breast cancer survivors.

Methods: Using a retrospective cohort study design, four CVD outcomes; heart failure or cardiomyopathy, arrhythmia, acute ischemic heart disease and ischemic stroke or Transient Ischemic Attack were compared with uni- and multivariate Cox regression analyses according to exposure to endocrine therapy (use of AI, tamoxifen or AI/tamoxifen sequentially) or no endocrine therapy.

Results: In total 15815 postmenopausal women, surgically treated to early breast cancer during 2006-2012, were included. No significantly increased risk for CVD events was observed in patients with AI use in the whole cohort. However, two subgroup analyses showed increased risk for CVD events in the AI/tamoxifen sequential group; heart failure in patients older than 75 years (Hazard Ratio (HR) 2.44; 95% Confidence Interval (CI): 1.32-4.54) and arrhythmia in patients without prior CVD (HR 1.45; 95% CI: 1.01-2.10). An increased risk for arrhythmia and acute ischemic heart disease in patients with at least four years of AI treatment compared with no or short-time exposure was observed (HR 2.12; 95% CI: 1.40-3.25 for arrhythmia; HR 2.03; 95% CI: 1.15-3.58 for ischemic heart disease).

Conclusion: Our results indicate an increased risk for ischemic heart disease and arrhythmia in patients treated for more than four years with AIs. This should be considered in the risk-benefit assessment concerning endocrine therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.breast.2021.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281646PMC
October 2021

Temporal changes in cause-specific death in men with localised prostate cancer treated with radical prostatectomy: a population-based, nationwide study.

J Surg Oncol 2021 Oct 18;124(5):867-875. Epub 2021 Jun 18.

Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.

Background And Objective: Changes in diagnostic work-up, histopathological assessment, and treatment of men with prostate cancer during the last 20 years have affected the prognosis. The objective was to investigate the risk of prostate cancer death in men with clinically localised prostate cancer treated with radical prostatectomy in Sweden in 2000-2010.

Methods: Population-based, nationwide, study on men with clinically localised prostate cancer treated with radical prostatectomy in the period 2000-2010. Cox regression analyses were used to assess differences in risk of prostate cancer death according to calendar period for diagnosis and stratified on risk category.

Results: The study included 19 330 men with a median follow-up of 12.4 years. Men diagnosed in 2007-2008 and 2009-2010 had a significantly lower risk of prostate cancer death compared to men diagnosed in 2000-2002. The reduced risk of prostate cancer death was restricted to men with intermediate-risk prostate cancer with no differences observed in men with low- or high-risk prostate cancer.

Conclusion: During the study period, the risk of prostate cancer death decreased in the total population of men with localised prostate cancer treated with radical prostatectomy. The decrease was restricted to men with intermediate-risk prostate cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jso.26579DOI Listing
October 2021

Risk of primary lung cancer after adjuvant radiotherapy in breast cancer-a large population-based study.

NPJ Breast Cancer 2021 Jun 1;7(1):71. Epub 2021 Jun 1.

Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.

Adjuvant radiotherapy (RT) for breast cancer (BC) has been associated with an increased risk of later radiation-induced lung cancer (LC). We examined the risk of primary LC in a population-based cohort of 52300 women treated for BC during 1992 to 2012, and 253796 age-matched women without BC. Cumulative incidence of LC was calculated by the Kaplan-Meier method, and the risk of LC after BC treatment was estimated by Cox proportional hazards regression analyses. Women with BC receiving RT had a higher cumulative incidence of LC compared to women with BC not receiving RT and women without BC. This became apparent 5 years after RT and increased with longer follow-up. Women with BC receiving RT had a Hazard ratio of 1.59 (95% confidence interval 1.37-1.84) for LC compared to women without BC. RT techniques that lower the incidental lung doses, e.g breathing adaption techniques, may lower this risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41523-021-00280-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169889PMC
June 2021

Comparison of Relative Survival and Cause-specific Survival in Men with Prostate Cancer According to Age and Risk Category. Nationwide, Population-based Study.

Am J Epidemiol 2021 May 19. Epub 2021 May 19.

Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.

Net survival, estimated in a relative survival (RS) or cause-specific survival (CSS) framework, is a key measure of the effectiveness of cancer management. We compared RS and CSS in men with prostate cancer (PCa) according to age and risk category, using Prostate Cancer data Base Sweden, including 168 793 men below age 90 diagnosed 1998-2016 with PCa. RS and CSS were compared according to age and risk category based on TNM stage, Gleason, and PSA. Each framework requires assumptions that are unlikely to be appropriate for PCa. Ten-year RS was substantially higher than CSS in men age 80-89 with low-risk PCa, 125% (95% CI 113-138%) vs 85% (95% CI 82-88%). In contrast, RS and CSS were similar for men below age 70 and for all men with regional or distant metastases. Both RS and CSS produce biased estimates of net survival for men with low and intermediate-risk PCa, in particular for men above 80. Due to biases, net survival is overestimated in analysis of RS but underestimated in analysis of CSS. These results highlight the importance of evaluating the underlying assumptions for each method, as the 'true' net survival is expected to lie between the limits of RS and CSS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kwab146DOI Listing
May 2021

Variation in Prostate-Specific Antigen Testing Rates and Prostate Cancer Treatments and Outcomes in a National 20-Year Cohort.

JAMA Netw Open 2021 May 3;4(5):e219444. Epub 2021 May 3.

Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.

Importance: The diagnostic activity for prostate cancer has increased during the past decades. However, the benefit and harm of the increased diagnostic activity have not been quantified in detail for a country or a large region.

Objective: The aim of this study was to evaluate and quantify the association between increases in diagnostic activity driven by prostate-specific antigen testing and incidence of prostate cancer diagnosis, treatment, and mortality.

Design, Setting, And Participants: This cohort study used the Proxy-Based Risk-Stratified Incidence Simulation Model-Prostate Cancer to examine observed data on all Swedish men with prevalent prostate cancer and compare them with a corresponding, hypothetical, simulated scenario with more restrictive diagnostic activity. All men aged 40 to 100 years living in Sweden during the time period 1996 to 2016 with incident and prevalent prostate cancer were included. The second scenario is the corresponding, hypothetical, simulated scenario where diagnostic activity remained constant as of 1996 (the beginning of the prostate-specific antigen testing era) throughout the study period.

Exposures: High or low diagnostic activity for prostate cancer.

Main Outcomes And Measures: Incidence of prostate cancer diagnosis, treatment (deferred treatment, curative treatment, and hormonal treatment), and prostate cancer mortality.

Results: During the study period from 1996 to 2016, 188 884 men were diagnosed with prostate cancer at a median (interquartile range) age of 71 (64-77) years. Compared with the low-diagnostic activity scenario, in the high-diagnostic activity scenario, the number of men diagnosed with prostate cancer was 48% higher (423 vs 286 [95% CI, 271-302] per 100 000 men per year), 148% more men were diagnosed with low- or intermediate-risk cancer (221 vs 89 [95% CI, 73-105] per 100 000 men per year), and 108% more men received curative treatment (152 vs 73 [95% CI: 66-85] per 100 000 men per year). There were up to 15% fewer prostate cancer deaths in the scenario with high-diagnostic activity (incidence rate ratio, 0.85; 95% CI, 0.82-0.88).

Conclusions And Relevance: This study's results suggest that increased prostate-specific antigen testing and diagnostic activity are associated with a larger number of men being diagnosed with prostate cancer, predominately with low- and intermediate-risk disease. The increased diagnostic activity was associated with a 2-fold increase in curative treatment and a modest decrease in mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2021.9444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129820PMC
May 2021

An Aggregated Comorbidity Measure Based on History of Filled Drug Prescriptions: Development and Evaluation in Two Separate Cohorts.

Epidemiology 2021 07;32(4):607-615

From the Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Background: The ability to account for comorbidity when estimating survival in a population diagnosed with cancer could be improved by using a drug comorbidity index based on filled drug prescriptions.

Methods: We created a drug comorbidity index from age-stratified univariable associations between filled drug prescriptions and time to death in 326,450 control males randomly selected from the general population to men with prostate cancer. We also evaluated the index in 272,214 control females randomly selected from the general population to women with breast cancer.

Results: The new drug comorbidity index predicted survival better than the Charlson Comorbidity Index (CCI) and a previously published prescription index during 11 years of follow-up. The concordance (C)-index for the new index was 0.73 in male and 0.76 in the female population, as compared with a C-index of 0.67 in men and 0.69 in women for the CCI. In men of age 75-84 years with CCI = 0, the median survival time was 7.1 years (95% confidence interval [CI] = 7.0, 7.3) in the highest index quartile. Comparing the highest to the lowest drug comorbidity index quartile resulted in a hazard ratio (HR) of 2.2 among men (95% CI = 2.1, 2.3) and 2.4 among women (95% CI = 2.3, 2.6).

Conclusions: A new drug comorbidity index based on filled drug prescriptions improved prediction of survival beyond age and the CCI alone. The index will allow a more accurate baseline estimation of expected survival for comparing treatment outcomes and evaluating treatment guidelines in populations of people with cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/EDE.0000000000001358DOI Listing
July 2021

Short-term ciprofloxacin prophylaxis for prostate biopsy and risk of aortic aneurysm. Nationwide, population-based cohort study.

Scand J Urol 2021 Jun 28;55(3):221-226. Epub 2021 Apr 28.

Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.

Introduction: The use of quinolones has recently been questioned due to reports on side effects including an increased risk of aortic aneurysm. The aim of the study was to examine the risk of aortic aneurysm (AA) after short-term ciprofloxacin as prophylaxis for prostate biopsy.

Materials And Methods: We used the Prostate Cancer data Base Sweden and investigated 192,024 prostate biopsy exposures vs. 554,974 non-exposures for risk of AA.Prostate biopsy was used as a proxy for quinolone use as short-term ciprofloxacin is the recommended and documented prophylaxis in Sweden for this procedure.The outcome was the hazard ratio (HR) of AA in men who underwent a biopsy vs. those that did not.

Results: The absolute risk of AA was small, 39/10,000 person years for all AÁs and for ruptured AÁs 3.5/10,000 person years. In multivariate analyses, there were small, non-significant increases in risk of all AA's (adjusted HR = 1.13, 95% CI: 0.91 to 1.39) and ruptured AÁs (adjusted HR = 1.05, 95% CI: 0.52 to 2.15) in men who underwent biopsy. A significantly increased risk of AA was observed in men diagnosed with high-risk prostate cancer on biopsy (HR = 1.50, 95% CI: 1.15-2.21). The use of prostate biopsy as a proxy for exposure to ciprofloxacin was a limitation of the study.

Conclusions: Short-term ciprofloxacin was not associated with an increased risk of aortic aneurysm and the increased risk in men with high-risk prostate cancer was likely due detection bias caused by imaging more commonly performed in these men.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21681805.2021.1916072DOI Listing
June 2021

The Value of Real-World Data in Understanding Prostate Cancer Risk and Improving Clinical Care: Examples from Swedish Registries.

Cancers (Basel) 2021 Feb 19;13(4). Epub 2021 Feb 19.

Department of Surgical Sciences, Uppsala Hospital University, SE-75185 Uppsala, Sweden.

Real-world data (RWD), that is, data from sources other than controlled clinical trials, play an increasingly important role in medical research. The development of quality clinical registers, increasing access to administrative data sources, growing computing power and data linkage capacities have contributed to greater availability of RWD. Evidence derived from RWD increases our understanding of prostate cancer (PCa) aetiology, natural history and effective management. While randomised controlled trials offer the best level of evidence for establishing the efficacy of medical interventions and making causal inferences, studies using RWD offer complementary evidence about the effectiveness, long-term outcomes and safety of interventions in real-world settings. RWD provide the only means of addressing questions about risk factors and exposures that cannot be "controlled", or when assessing rare outcomes. This review provides examples of the value of RWD for generating evidence about PCa, focusing on studies using data from a quality clinical register, namely the National Prostate Cancer Register (NPCR) Sweden, with longitudinal data on advanced PCa in Patient-overview Prostate Cancer (PPC) and data linkages to other sources in Prostate Cancer data Base Sweden (PCBaSe).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13040875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923148PMC
February 2021

Risk of cardiovascular events in men on abiraterone or enzalutamide combined with GnRH agonists: nation-wide, population-based cohort study in Sweden.

Acta Oncol 2021 Apr 19;60(4):459-465. Epub 2021 Feb 19.

Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.

Background: Men with prostate cancer (PCa) on gonadotropin-releasing hormone agonists (GnRH) have an increased risk of cardiovascular disease (CVD) compared to men with PCa not on GnRH as well as compared with PCa-free men. Whether the addition of androgen receptor targeted (ART) drugs to GnRH further increases CVD risk, remains to be fully elucidated.

Material And Methods: We investigated risk of CVD for men with castration resistant PCa (CRPC) on GnRH plus ART; abiraterone or enzalutamide vs 5,127 and 12,079 respective matched comparator men on GnRH in Prostate Cancer data Base Sweden (PCBaSe) 4.1 between 1 June 2015 and 31 December 2018. PCBaSe links National Prostate Cancer Register of Sweden to other healthcare registries and demographic databases. We conducted multivariable Cox proportional hazard models adjusting for PCa risk category, Charlson comorbidity index (CCI), insulin or statin use, civil status, level of education, history of CVD events and number of CVD drugs, with any incident or fatal CVD as the outcome.

Results And Conclusion: 1,310 men were treated with abiraterone and 3,579 with enzalutamide. In multivariable analysis, CVD risk was increased in men on abiraterone (hazard ratio (HR): 1.19; 95% confidence interval (CI): 1.03-1.38) and in men on enzalutamide (HR: 1.10; 95% CI: 1.01-1.20). Men with a recent CVD (<12 months) including both men on ART as well as comparators had a much higher probability of a new CVD vs men with no prior CVD. CVD risk was mildly increased in men with PCa on GnRH plus abiraterone or enzalutamide vs comparator men on GnRH. Residual confounding and detection bias may at least partly explain this association.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0284186X.2021.1885058DOI Listing
April 2021

Observational study on time on treatment with abiraterone and enzalutamide.

PLoS One 2020 28;15(12):e0244462. Epub 2020 Dec 28.

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Introduction: The aim of this study was to assess time on treatment with abiraterone and enzalutamide, two androgen receptor targeted (ART) drugs, the impact on time on treatment of time interval without drug supply between prescription fillings, and adherence to treatment.

Material And Methods: By use of data from The National Prostate Cancer Register, The Prescribed Drug Registry and the Patient Registry, time on treatment with the abiraterone and enzalutamide was analyzed in all men with castration resistant prostate cancer (CRPC) in Sweden 2015-2019. Three time intervals between consecutive fillings, i.e. time without drug supply, were assessed. Adherence to the treatment was evaluated by use of the Medication Possession Ratio. Kaplan Meier analysis and multivariable Cox regression model were used to assess factors affecting time on treatment.

Results: Between January 2015 and October 2019, 1803 men filled a prescription for abiraterone and 4 534 men filled a prescription for enzalutamide. With a time interval of 30 days or less between two fillings, median time on treatment was 4.9 months (IQR 2.6-11.7) for abiraterone and 8.0 months (IQR 3.6-16.4) for enzalutamide. In sensitivity analyses, allowing for no more than 14 days without drug supply between fillings, median time on treatment was 3.9 months (IQR 2.1-9.0) for abiraterone and 5.9 months (IQR 2.8-12.1) for enzalutamide. Allowing for any time period without drug between fillings, median time on treatment was 5.7 months (IQR 2.7-14.0) for abiraterone and 9.8 months (IQR 4.4-21.0) for enzalutamide. Adherence to treatment was above 90% for both drugs.

Conclusion: Time on treatment with abiraterone and enzalutamide was shorter in clinical practice than in randomized controlled trials and varied almost two-fold with time interval without drug. Adherence to treatment was high. The main limitation of our study was the lack of data on use of chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244462PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769419PMC
March 2021

Simulation model of disease incidence driven by diagnostic activity.

Stat Med 2021 02 25;40(5):1172-1188. Epub 2020 Nov 25.

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

It is imperative to understand the effects of early detection and treatment of chronic diseases, such as prostate cancer, regarding incidence, overtreatment and mortality. Previous simulation models have emulated clinical trials, and relied on extensive assumptions on the natural history of the disease. In addition, model parameters were typically calibrated to a variety of data sources. We propose a model designed to emulate real-life scenarios of chronic disease using a proxy for the diagnostic activity without explicitly modeling the natural history of the disease and properties of clinical tests. Our model was applied to Swedish nation-wide population-based prostate cancer data, and demonstrated good performance in terms of reconstructing observed incidence and mortality. The model was used to predict the number of prostate cancer diagnoses with a high or limited diagnostic activity between 2017 and 2060. In the long term, high diagnostic activity resulted in a substantial increase in the number of men diagnosed with lower risk disease, fewer men with metastatic disease, and decreased prostate cancer mortality. The model can be used for prediction of outcome, to guide decision-making, and to evaluate diagnostic activity in real-life settings with respect to overdiagnosis and prostate cancer mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/sim.8833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894333PMC
February 2021

Risk of cardiovascular disease following gonadotropin-releasing hormone agonists vs antagonists in prostate cancer: Real-world evidence from five databases.

Int J Cancer 2021 05 23;148(9):2203-2211. Epub 2020 Nov 23.

King's College London, Translational Oncology and Urology Research, London, UK.

Observational studies in prostate cancer (PCa) have shown an increased risk of cardiovascular disease (CVD) following gonadotropin-releasing hormone (GnRH) agonists, whereas randomised-controlled trials have shown no associations. Compared to GnRH agonists, GnRH antagonists have shown less atherosclerotic effects in preclinical models. We used real-world data from five countries to investigate CVD risk following GnRH agonists and antagonists in PCa men. Data sources included cancer registries, primary and secondary healthcare databases. CVD event was defined as an incident or fatal CVD. Multivariable Cox proportional hazard models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled using random-effects meta-analysis. Stratified analyses were conducted by history of CVD and age (75 years). A total of 48 757 men were on GnRH agonists and 2144 on GnRH antagonists. There was no difference in risk of any CVD for men on GnRH antagonists and agonists (HR: 1.25; 95% CI: 0.96-1.61; I : 64%). Men on GnRH antagonists showed increased risk of acute myocardial infarction (HR: 1.62; 95% CI: 1.11-2.35; I : 0%) and arrhythmia (HR: 1.55; 95% CI: 1.11-2.15, I : 17%) compared to GnRH agonists. Having a history of CVD was found to be an effect modifier for the associations with some CVD subtypes. Overall, we did not observe a difference in risk of overall CVD when comparing GnRH antagonists with agonists-though for some subtypes of CVD we noted an increased risk with antagonists. Further studies are required to address potential confounding caused by unadjusted variables such as severity of CVD history and PCa stage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049028PMC
May 2021

Use of Warfarin or Direct Oral Anticoagulants and Risk of Prostate Cancer in PCBaSe: A Nationwide Case-Control Study.

Front Oncol 2020 8;10:571838. Epub 2020 Oct 8.

Translational Oncology and Urology Research Group, School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.

Existing literature examining warfarin's association with prostate cancer (PCa) risk provides conflicting results, while the association with direct oral anticoagulants (DOACs) has not yet been studied. We investigated the association of warfarin and DOAC use on PCa risk among men within the population-based Prostate Cancer database Sweden (PCBaSe), using a case-control design. The study population included PCa cases diagnosed 2014-2016 and five age-matched PCa-free controls. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CI) for PCa associated with warfarin and DOAC use, adjusted for marital status, education level, other drug use, and comorbidities. Among 31,591 cases and 156,802 controls, there were 18,522 (9.8%) warfarin and 4,455 (2.4%) DOAC users. Warfarin ever-use was associated with reduced risk of PCa overall (OR 0.92 95% CI 0.88-0.96) as were both past and current use. DOAC use was not associated with PCa risk. For some warfarin exposures, decreased risk was observed for unfavorable PCa (high risk/locally advanced/distant metastatic) but not with favorable PCa (low/intermediate risk). Increased risk of favorable PCa was observed for men whose initial warfarin exposure occurred in the 12 month period before diagnosis (OR 1.39; 95% CI 1.13-1.70). Our findings are consistent with previous publications reporting decreased PCa risk with warfarin exposure. Increased risk of favorable PCa suggests detection bias due to increased prostate specific antigen testing when starting on warfarin. Decreased overall PCa risk could reflect bias due to reduced biopsy rates among long-term warfarin users.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.571838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578339PMC
October 2020

Prescription-based prediction of baseline mortality risk among older men.

PLoS One 2020 29;15(10):e0241439. Epub 2020 Oct 29.

Dept. of Surgical Sciences, Urology, Uppsala University, Uppsala, Sweden.

Background: Understanding the association between patients' history of prescribed medications and mortality rate could optimize characterization of baseline risk when the Charlson Comorbidity Index is insufficient.

Methods: Using a Swedish cohort of men selected randomly as controls to men with prostate cancer diagnosed 2007-2013, we estimated the association between medications prescribed during the previous year and mortality rates, using Cox regression stratified for age.

Results: Among the 326,450 older men with median age of 69 years included in this study, 73% were categorized as free of comorbidity according to the Charlson Comorbidity Index; however, 84% had received at least one prescription during the year preceding the follow-up. This was associated with a 60% overall increase in mortality rate (hazard ratio [HR] = 1.60, 95% confidence interval [CI] 1.56 to 1.64). Some drugs that were unexpectedly associated with mortality included locally acting antacids (HR = 4.7, 95% CI 4.4 to 5.1), propulsives (HR = 4.7, 95% CI 4.4 to 5.0), vitamin A and D (HR = 4.6, 95% CI 4.3 to 4.9), and loop diuretics, for example furosemide (HR = 3.7; 95% CI 3.6 to 3.8). Thiazide diuretics, however, were only weakly associated with a mortality risk (HR = 1.5; 95% CI 1.4 to 1.5). Surprisingly, only weak associations with mortality were seen for major cardiovascular drug classes.

Conclusions: A majority of older men had a history of prescribed medications and many drug classes were associated with mortality rate, including drug classes not directly indicated for a specific comorbidity represented in commonly used comorbidity measures. Prescription history can improve baseline risk assessment but some associations might be context-sensitive.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241439PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595371PMC
December 2020

Changes in lifestyle among prostate cancer survivors: A nationwide population-based study.

Psychooncology 2020 10 1;29(10):1713-1719. Epub 2020 Sep 1.

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Objective: Long-term information on lifestyle changes among prostate survivors is lacking. In this nationwide, population-based study we investigated the prevalence of lifestyle changes, factors associated with lifestyle changes and associations between lifestyle changes and general quality of life.

Methods: All men registered in the National Prostate Cancer Register of Sweden diagnosed in 2008 with low-risk prostate cancer at age 70 years or younger were sent a questionnaire. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals for factors potentially associated with lifestyle change.

Results: Out of 1288, 1720 men (75%) were responded. A total of 279 (22%) reported a positive lifestyle change regarding diet or exercise. Poor functional outcomes after treatment was associated with exercising less (OR 1.6, 95% CI 1.2-2.1) and less interest in social activities and relationships (OR 1.8, 95% CI 1.5-2.1). Men who exercised more (OR 7.9, 95% CI 4.4-14) and men who had an increased interest in relationships and social activities (OR 5.2, 95% CI 2.1-13) reported higher general quality of life.

Conclusions: A considerable proportion of men reported making positive lifestyle changes after the prostate cancer diagnosis. The time after diagnosis may be a teachable moment that facilitates lifestyle interventions. Poor functional outcomes after treatment may reduce the willingness to engage in positive lifestyle change, which need be considered when supporting men after treatment. Men who made a positive lifestyle change, regardless of whether it was exercise or regarding relationships and social activities more often reported a high level of general quality of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pon.5513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589218PMC
October 2020

PSA testing patterns in a large Swedish cohort before the implementation of organized PSA testing.

Scand J Urol 2020 Oct 31;54(5):376-381. Epub 2020 Jul 31.

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Background: Organized PSA testing for asymptomatic men aged 50-74 years will be implemented in Sweden to reduce opportunistic testing in groups who will not benefit. The aim of this study was to describe the opportunistic PSA testing patterns in a Swedish region before the implementation of organized PSA testing programs.

Method: We included all men in the Uppsala-Örebro health care region of Sweden who were PSA tested between 1 July 2012 and 30 June 2014. Information regarding previous PSA testing, prostate cancer diagnosis, socioeconomic situation, surgical procedures and prescribed medications were collected from population-wide registries to create the Uppsala-Örebro PSA cohort (UPSAC). The cohort was divided into repeat and single PSA testers. The background population used for comparison consisted of men 40 years or older, living in the Uppsala-Örebro region during this time period.

Results: Of the adult male population in the region, 18.1% had undergone PSA testing. Among men over 85 years old 21% where PSA tested. In our cohort, 62.1% were repeat PSA testers. Of men with a PSA level ≤1µg/l 53.8% had undergone repeat testing. Prostate cancer was found in 2.7% and 4.8% of the repeat and single testers, respectively.

Conclusion: Every fifth man in the male background population was PSA tested. Repeated PSA testing was common despite low PSA values. As repeated PSA testing was common, especially among older men who will not be included in organized testing, special measures to change the testing patterns in this group may be required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21681805.2020.1797871DOI Listing
October 2020

Association of type 2 diabetes mellitus and antidiabetic medication with risk of prostate cancer: a population-based case-control study.

BMC Cancer 2020 Jun 15;20(1):551. Epub 2020 Jun 15.

School of Cancer and Pharmaceutical Sciences, Translational Oncology and Urology Research (TOUR), King's College London, London, UK.

Background: Prostate cancer (PCa) and type 2 diabetes mellitus (T2DM) are prevalent conditions that often occur concomitantly. However, many aspects of the impact of T2DM, particularly the duration of T2DM and antidiabetic medications, on PCa risk are poorly understood.

Methods: To assess the association of duration of T2DM and antidiabetic medication with PCa risk, we designed a matched case-control study, including 31,415 men with PCa and 154,812 PCa-free men in Prostate Cancer data Base Sweden (PCBaSe) 4.1.

Results: Overall, a decreased risk of PCa was observed for men with T2DM (odds ratio (OR): 0.81, 95% confidence interval (CI): 0.78-0.84), as compared to men without T2DM. The decreased risk of PCa was consistently showed across duration of T2DM. With respect to use of antidiabetic drugs, this inverse association with duration was also found for all medications types, as compared to men without T2DM, including insulin, metformin and sulphonylurea (SU) (e.g. 3- < 5 yr insulin OR:0.69, 95%CI:0.60-0.80; 3- < 5 yr metformin OR: 0.82, 95%CI: 0.74-0.91; 3- < 5 yr SU OR: 0.72, 95%CI: 0.62-0.83). When stratifying by PCa risk categories, this decreased risk was most evident for diagnosis of low and intermediate-risk PCa (low-risk OR: 0.65, 95%CI: 0.66-0.70, intermediate-risk OR: 0.80, 95%CI: 0.75-0.85).

Conclusions: The study showed an inverse association between pre-existing T2DM and PCa across different durations of T2DM and all types of T2DM medication received. This inverse association was most evident for low- and intermediate-risk PCa, suggesting that whilst T2DM and its medication may protect some men from developing PCa, the relationship warrants further study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-020-07036-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294669PMC
June 2020

Comparative Effectiveness of Different Radical Radiotherapy Treatment Regimens for Prostate Cancer: A Population-Based Cohort Study.

JNCI Cancer Spectr 2020 Apr 14;4(2):pkaa006. Epub 2020 Feb 14.

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Background: It is unclear which radiotherapy technique and dose fractionation scheme is most effective in decreasing the risk of prostate cancer death.

Methods: We conducted a population-based cohort study among 15 164 men in the Prostate Cancer database Sweden (version 4.0) treated with primary radical radiotherapy for prostate cancer in Sweden from 1998 to 2016. We calculated hazard ratios with 95% confidence intervals (CIs) of the association between the following exposure groups and outcome: conventionally fractionated external beam radiotherapy (EBRT) to 78 Gy (39 × 2 Gy), EBRT combined with high dose-rate brachytherapy (HDR-BT) (25 × 2 Gy + 2 × 10 Gy), conventionally fractionated EBRT to 70 Gy (35 × 2 Gy), and moderately hypofractionated (M-HF) dose-escalated EBRT (29 × 2.5 Gy or 22 × 3 Gy).

Results: Of the men, 7296 received conventionally fractionated EBRT to 78 Gy, 4657 EBRT combined with HDR-BT, 1672 conventionally fractionated EBRT to 70 Gy, and 1539 M-HF EBRT. Using EBRT to 78 Gy as the reference, the multivariable hazard ratios (95% CIs) of prostate cancer death was 0.64 (0.53 to 0.78) for EBRT combined with HDR-BT, 1.00 (0.80 to 1.27) for EBRT to 70 Gy, and 1.51 (0.99 to 2.32) for M-HF EBRT. The multivariable hazard ratios (95% CIs) for death from any cause were 0.79 (0.71 to 0.88), 0.99 (0.87 to 1.14), and 1.12 (0.88 to 1.42), respectively. The lower risk of prostate cancer death comparing EBRT combined with HDR-BT with conventionally fractionated EBRT to 78 Gy was more pronounced for men with high-risk or poorly differentiated tumors.

Conclusions: In this study, EBRT combined with HDR-BT was the most effective radiotherapy treatment regimen, especially for poorly differentiated tumors. Randomized trials comparing EBRT combined with HDR-BT with dose-escalated EBRT should be a priority.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jncics/pkaa006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192027PMC
April 2020

Adherence to guidelines for androgen deprivation therapy after radical prostatectomy: Swedish population-based study.

Scand J Urol 2020 Jun 27;54(3):208-214. Epub 2020 Apr 27.

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Androgen deprivation therapy (ADT) is a non-curative but essential treatment of prostate cancer with severe side effects. Therefore, both over- and underuse should be avoided. We investigated adherence to guidelines for ADT following radical prostatectomy through Swedish population-based data. We used the database Uppsala/Örebro PSA cohort (UPSAC) to study men with localised or locally advanced prostate cancer at diagnosis (clinical stage T1-T3, N0-NX, M0-MX, and prostate-specific antigen (PSA) <50 ng/ml) who underwent radical prostatectomy 1997-2012. 114 men were treated with ADT and selected as cases; 1140 men with no ADT at the index date were selected as controls within 4-year strata of year of radical prostatectomy. All men with a biochemical recurrence and a PSA doubling time <12 months and/or a Gleason score of 8-10 were considered to have an indication for ADT according to the European Association of Urology (EAU) guidelines. No indication for ADT was found in 37% of the cases. Among these, 88% had clinical stage T1-2 at diagnosis, 57% had a biopsy Gleason score 2-6, 98% had an expected remaining lifetime over 10 years, 12% received castration, and 88% received antiandrogen monotherapy. 2% of controls were found to have an indication for ADT, and 96% of these had an expected remaining lifetime over 10 years. Our results indicate that overtreatment with ADT after radical prostatectomy is common, whereas undertreatment is unusual. Interventions to improve adherence to guidelines are needed to avoid unnecessary side-effects and long treatment durations with ADT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21681805.2020.1750475DOI Listing
June 2020

Changes in treatment and mortality in men with locally advanced prostate cancer between 2000 and 2016: a nationwide, population-based study in Sweden.

BJU Int 2020 07 8;126(1):142-151. Epub 2020 May 8.

Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.

Objective: To evaluate whether the effects of radical treatment in men with locally advanced prostate cancer (PCa) on PCa mortality observed in randomised clinical trials are applicable on a population basis.

Patients And Methods: We conducted a population-based cohort study using the Prostate Cancer data Base Sweden of 20 350 men diagnosed between 2000 and 2016 with locally advanced PCa, defined as clinical local stage T3/T4, M0, Mx and a prostate-specific antigen level of <100 ng/mL. Cumulative PCa mortality was examined using competing risk analysis of all men with locally advanced PCa, and also including men who did not undergo radical treatment. Multivariate regression analysis, including prognostic factors, was used to calculate hazard ratios (HRs) for all-cause and PCa-specific death.

Results: The proportion of men treated with primary radical radiotherapy (n = 4174) or prostatectomy (n = 1210) increased from 15% in 2000-2003, 25% in 2004-2007, 33% in 2008-2011 to 43% in 2012-2016. The corresponding 5-year PCa mortality decreased from 19%, 18%, 17%, to 15% for all men, with the steepest decrease in men aged 65-74 years, from 16% to 8%. The risk of PCa mortality in men aged <80 years was lower in the last period compared to the first period, with a HR of 0.65 (95% confidence interval 0.56-0.76) in multivariate analysis.

Conclusions: The threefold increase in use of radical treatment was accompanied by a modest decrease in PCa mortality in all men with newly diagnosed locally advanced PCa. For men aged 65-74 years, there was a 50% decrease in the relative risk of PCa death. This indicates that the benefits previously observed in randomised trials can also be achieved in a real-life setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bju.15077DOI Listing
July 2020

5α-Reductase Inhibitors and Risk of Prostate Cancer Death.

J Urol 2020 10 3;204(4):714-719. Epub 2020 Apr 3.

Department of Urology, Ryhov Hospital, Jonkoping, Sweden.

Purpose: 5α-Reductase inhibitors reduced the risk of prostate cancer in 25% in 2 randomized trials but increased the risk of Gleason 8-10 at biopsy. One explanation is that 5α-reductase inhibitors induce morphological changes in prostate cancer cells similar to higher Gleason grades but without its adverse biology. We compared risk of prostate cancer death between men on 5α-reductase inhibitors and men not on 5α-reductase inhibitors before prostate cancer diagnosis in each Gleason Grade Group.

Materials And Methods: Prostate Cancer data Base Sweden consists of linkages between the National Prostate Cancer Register, the Prescribed Drug Registry and the Cause of Death Registry. Of 89,227 men diagnosed with prostate cancer between July 2007 and December 2016, 5,816 had been on 5α-reductase inhibitors for more than 180 days before the date of diagnosis. Followup ended in December 2018. A Cox proportional hazard model was used to assess hazard ratio for prostate cancer death. Adjustments for age, comorbidity, education and curative treatment were made. Men with high risk cancer were stratified according to Gleason Grade Group.

Results: In men with high risk cancer the risk of prostate cancer death was similar among 5α-reductase inhibitor users and nonusers, with Gleason Grade Group 1 HR 1.02 (95% CI 0.53-1.95), Gleason Grade Group 2 HR 1.04 (95% CI 0.65-1.69), Gleason Grade Group 3 HR 1.27 (95% CI 0.89-1.80), Gleason Grade Group 4 HR 0.95 (95% CI 0.76-1.18) and Gleason Grade Group 5 HR 0.99 (95% CI 0.83-1.19), for 5α-reductase inhibitor users vs nonusers.

Conclusions: We found no evidence that 5α-reductase inhibitors affect Gleason grading as no difference in mortality was observed among 5α-reductase inhibitor users and nonusers in each Gleason group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JU.0000000000001038DOI Listing
October 2020

Serum Immunoglobulin G Is Associated With Decreased Risk of Pancreatic Cancer in the Swedish AMORIS Study.

Front Oncol 2020 28;10:263. Epub 2020 Feb 28.

Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.

Emerging evidence points to potential roles of the humoral immune responses in the development of pancreatic cancer. Epidemiological studies have suggested involvement of viral and bacterial infections in pancreatic carcinogenesis. Experimental studies have reported high expression levels of antigens in pancreatic cancer cells. Therefore, we aimed to investigate the role of different components of humoral immunity in the context of pancreatic cancer. We evaluated associations between pre-diagnostic serum markers of the overall humoral immune system [immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM)], and the risk of pancreatic cancer in the Swedish Apolipoprotein-related MORtality RISk (AMORIS) study. We selected all participants (≥20 years old) with baseline measurements of IgA, IgG or IgM ( = 41,900, 136,221, and 29,919, respectively). Participants were excluded if they had a history of chronic pancreatitis and individuals were free from pancreatic cancer at baseline. Multivariate Cox proportional hazards regression was used to estimate risk of pancreatic cancer for medical cut-offs of IgA, IgG, and IgM. Compared to the reference level of 6.10-14.99 g/L, risk of pancreatic cancer was elevated among those with IgG levels <6.10 g/L [HR: 1.69 (95% CI 0.99-2.87)], and an inverse association was observed among those with IgG levels ≥15.00 g/L [0.82 (95% CI 0.64-1.05); trend = 0.027]. The association appeared to be stronger for women than men [HR: 0.64 (95% CI 0.43-0.97) and 0.95 (95% CI 0.69-1.29), respectively]. No associations were observed with IgA or IgM. An inverse association was observed between pre-diagnostic serum levels of IgG and risk of pancreatic cancer. Our findings highlight the need to further investigate the role of immune response in pancreatic cancer etiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.00263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059192PMC
February 2020

Spironolactone use is associated with lower prostate cancer risk: a population-wide case-control study.

Prostate Cancer Prostatic Dis 2020 09 2;23(3):527-533. Epub 2020 Mar 2.

Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Studies, King's College London, London, UK.

Background: Spironolactone, a cheap effective diuretic used to manage hypertension and heart failure, also has anti-androgenic effects through its non-selective binding to steroid receptors, and hence may affect prostate cancer (PCa) risk. This study investigated the association between spironolactone use and PCa risk. For comparison, we also examined associations with thiazide diuretics which do not have anti-androgenic properties.

Methods: A matched case-control study was undertaken using population-wide data from the Prostate Cancer Data Base Sweden (PCBaSe). All PCa cases diagnosed from 2014 to 2016 were matched by birth year and county with PCa-free controls selected from the general population (1:5). Multivariable conditional logistic regression was used to examine associations between spironolactone use (dose and duration) and PCa risk, and similarly for thiazides.

Results: Three percent of the 31,591 cases and 4% of the 156,802 controls had been prescribed spironolactone. Multivariable analyses indicated reduced risk of PCa among those ever exposed to spironolactone (odds ratio [OR] 0.83; 95% confidence interval [CI]: 0.76-0.89), with a stronger association for current users (OR: 0.77, 95% CI: 0.69-0.86) than past users (OR: 0.88; 95% CI: 0.79-0.97) and decreasing risk with increasing dose (p-trend < 0.001). No association was observed for thiazide exposure and PCa risk. Biases due to differences in prescribing patterns or frequency of PSA testing may have influenced these findings.

Conclusion: PCa risk was reduced among men exposed to the diuretic spironolactone. Further investigation of spironolactone's potential chemopreventive effects is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41391-020-0220-8DOI Listing
September 2020

Radical radiotherapy for prostate cancer: patterns of care in Sweden 1998-2016.

Acta Oncol 2020 May 3;59(5):549-557. Epub 2020 Mar 3.

Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.

Radiotherapy is an established treatment option for prostate cancer (PCa), both as primary treatment and secondary treatment after radical prostatectomy (RP). Since 1998, detailed data on radiotherapy delivered to Swedish men with PCa (e.g. treatment modalities, absorbed doses, fractionation) have been collated within PCa data Base Sweden (PCBaSe). This study reports patterns of radical radiotherapy for PCa in Sweden over the past two decades. All men with non-metastatic PCa (1998-2016) who received external beam radiotherapy (EBRT) or high or low dose-rate brachytherapy (HDR-BT/LDR-BT) were identified in PCBaSe. Analyses included: trends in radiation techniques, fractionation patterns and total doses over time; PCa-specific survival comparing treatment in 2007-2017 with 1998-2006; and regional variation in type of primary radiotherapy. About 20,876 men underwent primary radiotherapy. The main treatment modalities include conventionally fractionated (2.0 Gy/fraction) EBRT (51%), EBRT with HDR-BT boost (27%) and hypofractionated (>2.4 Gy/fraction) EBRT (11%). EBRT with photon or proton boost and HDR-BT and LDR-BT monotherapies were each used minimally. Use of dose-escalated EBRT (>74 Gy) and moderate hypofractionation increased over time, while use of HDR-BT declined. Considerable regional variation in treatment modalities was apparent. Risk of PCa death following primary radiotherapy had declined for intermediate-risk (HR: 0.60; 95%CI 0.47-0.87) and high-risk PCa (HR: 0.72; 95%CI 0.61-0.86). Increased use of dose escalation and hypofractionated EBRT has occurred in Sweden over the past two decades, reflecting current evidence and practice guidelines. Disease-specific outcomes have also improved. Data collected in PCBaSe provide an excellent resource for further research into RT use in PCa management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0284186X.2020.1730003DOI Listing
May 2020

Prediction of metastatic prostate cancer by prostate-specific antigen in combination with T stage and Gleason Grade: Nationwide, population-based register study.

PLoS One 2020 29;15(1):e0228447. Epub 2020 Jan 29.

Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.

The objective was to investigate the proportion of men with metastatic prostate cancer in groups defined by T stage, Gleason Grade Group (GGG) and serum levels of prostate-specific antigen (PSA) and if PSA can be used to rule in metastatic prostate cancer when combined with T stage and GGG. We identified 102,076 men in Prostate Cancer data Base Sweden 4.0 who were diagnosed with prostate cancer in 2006-2016. Risk of metastases was assessed for PSA stratified on T stage and five-tiered GGG. For men who had not undergone bone imaging, we used multiple imputation to classify metastatic prostate cancer. Advanced T stage, high GGG and high PSA were related to bone metastases. For example: only 79/38 190 (0.2%) of men with T1-2 and GGG 1 had PSA above 500 ng/mL, and 29/79 (44%) of these men had metastases; whereas 1 154/7 018 (16%) of men with T3-4 and GGG 5 had PSA above 500 ng/ml and 1 088/1 154 (94%) of these men had metastases. However, no PSA cut-off could accurately identify the majority of men with metastatic prostate cancer (i.e. high sensitivity) while also correctly classifying most men without metastasis (i.e. high specificity). In conclusion, these results support the use of imaging to confirm bone metastases in men with advanced prostate cancer as no PSA level in combination with T stage and GGG could accurately rule in metastatic prostate cancer and thereby safely omit bone imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228447PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988964PMC
April 2020
-->