Recent trends in incidence, survival and treatment of multiple myeloma in Finland - a nationwide cohort study.

This study aimed to determine the incidence and prevalence of multiple myeloma (MM) in Finland in 2015-2019, to characterize adult patients newly diagnosed with MM, and to follow-up their overall survival (OS) and treatment patterns until the end of 2020. We sourced the data on inpatient and outpatient diagnoses, outpatient medication use, and date of death from comprehensive, nationwide registers. We identified 2037 incident patients with MM in 2015-2019. On average, the annual crude incidence was 8.8 and the age-standardized incidence (World Standard Population) was 3.3 per 100,000. The crude prevalence at the end of 2019 was 32.7 cases per 100,000 inhabitants ≥ 18 years of age. Median age of the patients at first diagnosis (index date) was 71 years, and 48% were female, the median follow-up being 2.4 years. The median OS was estimated at 4.5 years. The proportion of the patients receiving autologous stem cell transplantation (ASCT) within one year since the index date was 24%, with little variation across study years. Conversely, the proportion of all patients receiving lenalidomide within one year since the index date increased from 27 to 48% overall, and from 39 to 81% among ASCT recipients. The estimated median relapse-free survival after ASCT was 2.9 years. Information on in-hospital MM medication administrations was available for a subset of the study cohort. In this subset, 85.8% of the patients received immunomodulatory drugs and/or proteasome inhibitors within the first year after the index date.

Randomised double-blind phase 3 clinical study testing impact of atorvastatin on prostate cancer progression after initiation of androgen deprivation therapy: study protocol.

INTRODUCTION: Blood cholesterol is likely a risk factor for prostate cancer prognosis and use of statins is associated with lowered risk of prostate cancer recurrence and progression. Furthermore, use of statins has been associated with prolonged time before development of castration resistance (CR) during androgen deprivation therapy (ADT) for prostate cancer. However, the efficacy of statins on delaying castration-resistance has not been tested in a randomised placebo-controlled setting.This study aims to test statins' efficacy compared to placebo in delaying development of CR during ADT treatment for primary metastatic or recurrent prostate cancer. Secondary aim is to explore effect of statin intervention on prostate cancer mortality and lipid metabolism during ADT. METHODS AND ANALYSIS: In this randomised placebo-controlled trial, a total of 400 men with de novo metastatic prostate cancer or recurrent disease after primary treatment and starting ADT will be recruited and randomised 1:1 to use daily 80 mg of atorvastatin or placebo. All researchers, study nurses and patients will be blinded throughout the trial. Patients are followed until disease recurrence or death. Primary outcome is time to formation of CR after initiation of ADT. Serum lipid levels (total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and trigyserides) are analysed to test whether changes in serum cholesterol parameters during ADT predict length of treatment response. Furthermore, the trial will compare quality of life, cardiovascular morbidity, changes in blood glucose and circulating cell-free DNA, and urine lipidome during trial. ETHICS AND DISSEMINATION: This study is approved by the Regional ethics committees of the Pirkanmaa Hospital District, Science centre, Tampere, Finland (R18065M) and Tarto University Hospital, Tarto, Estonia (319/T-6). All participants read and sign informed consent form before study entry. After publication of results for the primary endpoints, anonymised summary metadata and statistical code will be made openly available. The data will not include any information that could make it possible to identify a given participant. TRIAL REGISTRATION NUMBER: Clinicaltrial.gov: NCT04026230, Eudra-CT: 2016-004774-17, protocol code: ESTO2, protocol date 10 September 2020 and version 6.

Outcomes of Screening for Prostate Cancer Among Men Who Use Statins.

IMPORTANCE: Prostate-specific antigen (PSA) screening for prostate cancer has resulted in a slight reduction in prostate cancer mortality but also a concomitant overdiagnosis of low-risk tumors. Prostate-specific antigen levels are affected by use of cholesterol-lowering statin drugs, but the association of statin use with PSA screening performance is unknown. OBJECTIVE: To investigate whether statin use was associated with outcomes of a randomized PSA-based prostate cancer screening intervention. DESIGN, SETTING, AND PARTICIPANTS: This post hoc subgroup analysis of a cohort from a population-based randomized clinical trial used data from the population-based Finnish Randomized Study of Prostate Cancer Screening, which randomized men to PSA screening or routine care from March 1, 1996, to December 31, 1999, with follow-up continuing until December 31, 2015. The population included all men aged 55 to 67 years at baseline and residing in the Tampere or Helsinki districts of Finland. Information on statin purchases from 1996 to 2009 was obtained from a national prescription registry. Eligible men were identified from the population registry of Finland. Prevalent prostate cancer cases at baseline were excluded. Data were analyzed from January 1, 2019 to March 31, 2021. INTERVENTIONS: Three invitations for PSA screening at 4-year intervals from 1996 to 2007 vs routine care. MAIN OUTCOMES AND MEASURES: Risk for prostate cancer overall, high-risk disease, and prostate cancer mortality in the screening group vs the control group as an intention-to-treat analysis. The analysis was stratified by statin use. RESULTS: The study comprised 78 606 men (median age, 59 years [range, 55-67 years]) with statin purchase data available. Although PSA screening was associated with increased prostate cancer incidence among statin nonusers (screening vs control, 11.2 vs 8.6 per 1000 person-years); rate ratio [RR], 1.31; 95% CI, 1.24-1.38), no similar increase in incidence was observed among statin users (6.9 vs 5.9 per 1000 person-years; RR, 1.02; 95% CI, 0.95-1.10; P < .001 for interaction). Incidence of low-risk (Gleason score 6) and localized tumors was lower among statin users, whereas detection of tumors with a Gleason score of 8 to 10 was similar. Screening was associated with a lower incidence of metastatic tumors regardless of statin use. CONCLUSION AND RELEVANCE: In this post hoc subgroup analysis of a cohort from a population-based randomized clinical trial, PSA screening among statin users was associated with a decreased incidence of advanced prostate cancer that was similar among statin nonusers, but with less increase in detection of low-grade localized tumors in statin users than in nonusers. These findings suggest that statin use does not materially compromise benefits of PSA-based screening.

Nationwide infection control strategy lowered seasonal respiratory infection rate: occupational health care perspective during the COVID-19 epidemic in Finland.

BACKGROUND: Respiratory infection is the 4th most common reason for absence from work in Finland. There is limited knowledge of how social distancing affects the spread of respiratory infections during respiratory epidemics. We assessed the effect of nationwide infection control strategies against coronavirus disease in 2020 on various respiratory infections (International Statistical Classification of Diseases and Related Health Problems code J06) in occupational outpatient clinics. METHODS: We used occupational healthcare data of respiratory infection J06 diagnoses from 2017 to 2020 obtained from the largest health service provider in Finland. The data was divided into three 252 day-long pieces and was weekday-matched and smoothed by 7-day-moving average. The difference in the J06 diagnosis rate between the follow-up years was measured using Pearson correlation. Possible confounding by sex, age, and region was investigated in a stratified analysis. Confounding by respiratory syncytial virus was analysed using nationwide data of confirmed cases obtained from the national registry. RESULTS: In the second quarter of 2020, the trend in the daily number of J06 diagnoses was significantly different from the follow-up years 2019 and 2018. The number of J06 diagnoses peaked between March and April 2020 with roughly 2-fold higher count compared to normal. The timing of these peaks matched with the government issued infection control strategies and lockdowns. Based on stratified analysis, the increase in the number of J06 diagnoses was not confounded by region, age, or sex. Moreover, the rapid increase in the number of J06 diagnoses was not governed by the respiratory syncytial virus. CONCLUSION: Nationwide infection control strategies were effective to slow down the spread of common respiratory infectious diseases in the occupational population.

Atorvastatin induces adrenal androgen downshift in men with prostate cancer: A post Hoc analysis of a pilot adaptive Randomised clinical trial.

BACKGROUND: Prostate cancer (PCa) progression depends on androgen receptor activity. Cholesterol is required for biosynthesis of all steroid hormones, including androgens. Impact of cholesterol-lowering statins on androgens is unknown. We explored atorvastatin influence on serum and prostatic tissue steroidomic profiles (SP) to expose novel pathways for limiting androgen concentration in men with PCa. METHODS: This is a pre-planned post hoc analysis of ESTO-1 pilot randomised, double-blinded, clinical trial. Statin naïve men, scheduled for radical prostatectomy due to localised PCa, were randomised 1:1 to use daily 80 mg of atorvastatin or placebo before the surgery for a median of 28 days. Participants were recruited and treated at the Pirkanmaa Hospital District, Tampere, Finland. 108 of the 158 recruited men were included in the analysis based on sample availability for hormone profiling. Serum and prostatic tissue steroid profiles were determined using liquid chromatography mass spectrometry. Wilcoxon rank sum test and bootstrap confidence intervals (CI) were used to analyse the difference between placebo and atorvastatin arms. FINDINGS: Most serum and prostatic steroids, including testosterone and dihydrotestosterone, were not associated with atorvastatin use. However, atorvastatin use induced serum SP changes in 11-ketoandrostenedione (placebo 960pM, atorvastatin 617.5pM, p-value <0.0001, median difference -342.5; 95% CI -505.23 - -188.98). In the prostatic tissue, atorvastatin was associated with plausible downshift in 11- ketodihydrotestosterone (placebo 25.0pM in 100 mg tissue/1 mL saline, atorvastatin 18.5pM in 100 mg tissue/1 mL saline, p-value 0.027, median difference -6.53; 95% CI -12.8 - -0.29); however, this association diminished after adjusting for multiple testing. No serious harms were reported. INTERPRETATION: Atorvastatin was associated with adrenal androgen downshift in the serum and possibly in the prostate. The finding warrants further investigation whether atorvastatin could improve androgen deprivation therapy efficacy. FUNDING: Funded by grants from the Finnish Cultural Foundation, Finnish Cancer Society, Academy of Finland, and the Expert Responsibility Area of the Tampere University Hospital. CLINICALTRIALS. GOV IDENTIFIER: NCT01821404.

Antidiabetic Drugs and Prostate Cancer Prognosis in a Finnish Population-Based Cohort.

BACKGROUND: Hyperinsulemia and glycemic control may play a role as prostate cancer prognostic factors, whereas use of certain antidiabetic drugs, that is metformin, could improve the prognosis. We examined the link between antidiabetic medication use and prostate cancer survival taking into account simultaneous use of multiple drugs. METHODS: The study cohort composed of 6,537 men in The Finnish Randomized Study of Screening for Prostate Cancer with prostate cancer diagnosed 1996 to 2009. Use of medication was attained from the nationwide prescription database of the Social Insurance Institution of Finland. Median follow-up was 9.2 years postdiagnosis. A total of 1,603 (24,5%) men had used antidiabetic medication. A total of 771 men died of prostate cancer during the follow-up. We used multivariable-adjusted Cox regression to evaluate the risk of prostate cancer death and onset of androgen deprivation therapy (ADT) with adjustment for prostate cancer clinical characteristics, comorbidities and use of other drugs. Separate analyses were further adjusted for blood glucose. RESULTS: Risk of prostate cancer death was higher among antidiabetic drug users overall (HR = 1.42; 95% CI, 1.18-1.70) compared with nonusers, separately among insulin and metformin users. Adjustment for blood glucose level abolished the risk increase. Risk of ADT initiation was increased among the medication users (HR = 1.26; 95% CI, 1.05-1.49). CONCLUSIONS: Men with prostate cancer using antidiabetic medication are generally at increased risk of dying from prostate cancer compared with nonusers. The risk association is driven by underlying diabetes, as adjustment for blood glucose level ameliorates the risk increase. IMPACT: Type 2 diabetes should be considered as a risk factor when considering prostate cancer prognosis.

Circulatory and prostatic tissue lipidomic profiles shifts after high-dose atorvastatin use in men with prostate cancer.

Prostate cancer patients using cholesterol-lowering statins have 30% lower risk of prostate cancer death compared to non-users. The effect is attributed to the inhibition of the mevalonate pathway in prostate cancer cells. Moreover, statin use causes lipoprotein metabolism changes in the serum. Statin effect on serum or intraprostatic lipidome profiles in prostate cancer patients has not been explored. We studied changes in the serum metabolomic and prostatic tissue lipidome after high-dose 80 mg atorvastatin intervention to expose biological mechanisms causing the observed survival benefit. Our randomized, double-blind, placebo-controlled clinical trial consisted of 103 Finnish men with prostate cancer. We observed clear difference in post-intervention serum lipoprotein lipid profiles between the study arms (median classification error 11.7%). The atorvastatin effect on intraprostatic lipid profile was not as clear (median classification error 44.7%), although slightly differing lipid profiles by treatment arm was observed, which became more pronounced in men who used atorvastatin above the median of 27 days (statin group median classification error 27.2%). Atorvastatin lowers lipids important for adaptation for hypoxic microenvironment in the prostate suggesting that prostate cancer cell survival benefit associated with statin use might be mediated by both, local and systemic, lipidomic/metabolomic profile changes.