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Objectives: To investigate the cumulative incidence proportion of disseminated or local Bacillus Calmette‐Guérin (BCG) infections after adjuvant BCG instillations in patients with non‐muscle‐invasive bladder cancer (NMIBC). Patients and Methods: We analysed the timing and occurrence of BCG infections and absolute and relative risk in relation to patient characteristics available in the Swedish nationwide database 'BladderBaSe 2.0'. The cumulative incidence proportion of a BCG infection was indicated by a reported diagnosis of tuberculosis (TB) in the patient registry or filing a prescription for tuberculostatic drugs. Results: The cumulative incidence proportion was 1.1% at the 5‐year follow‐up in 5033 patients exposed to adjuvant BCG instillations. The incidence rate was highest during the first 2 years after start of BCG instillations. Women had a lower risk than men (hazard ratio 0.23, 95% confidence interval 0.07–0.74). Age and calendar time at diagnosis, comorbidity, tumour risk group, previous medication with corticosteroids, immunosuppressive drugs, or time between transurethral resection of the bladder tumour and commencing the adjuvant BCG instillation were not associated with risk. Conclusions: These data further supports that the overall risk of a BCG infection after BCG‐instillation treatment for NMIBC is low. The great majority of infections occur in the first 2 years, calling for an awareness of the diverse symptoms of BCG infection during this period. We provide evidence for male sex as a risk factor; however, the statistical precision is low and with a risk of selection bias, making it difficult to rule out the other suggested risk factors without further studies with different approaches. [ABSTRACT FROM AUTHOR]

Objectives: To investigate long‐term disease trajectories among men with high‐risk localized or locally advanced prostate cancer (HRLPC) treated with radical radiotherapy (RT) or radical prostatectomy (RP). Material and Methods: Men diagnosed with HRLPC in 2006–2020, who received primary RT or RP, were identified from the Prostate Cancer data Base Sweden (PCBaSe) 5.0. Follow‐up ended on 30 June 2021. Treatment trajectories and risk of death from prostate cancer (PCa) or other causes were assessed by competing risk analyses using cumulative incidence for each event. Results: In total, 8317 men received RT and 4923 men underwent RP. The median (interquartile range) follow‐up was 6.2 (3.6–9.5) years. After RT, the 10‐year risk of PCa‐related death was 0.13 (95% confidence interval [CI] 0.12–0.14) and the risk of death from all causes was 0.32 (95% CI 0.31–0.34). After RP, the 10‐year risk of PCa‐related death was 0.09 (95% CI 0.08–0.10) and the risk of death from all causes was 0.19 (95% CI 0.18–0.21). The 10‐year risks of androgen deprivation therapy (ADT) as secondary treatment were 0.42 (95% CI 0.41–0.44) and 0.21 (95% CI 0.20–0.23) after RT and RP, respectively. Among men who received ADT as secondary treatment, the risk of PCa‐related death at 10 years after initiation of ADT was 0.33 (95% CI 030–0.36) after RT and 0.27 (95% CI 0.24–0.30) after RP. Conclusion: Approximately one in 10 men with HRLPC who received primary RT or RP had died from PCa 10 years after diagnosis. Approximately one in three men who received secondary ADT, an indication of PCa progression, died from PCa 10 years after the start of ADT. Early identification and aggressive treatment of men with high risk of progression after radical treatment are warranted. [ABSTRACT FROM AUTHOR]

A 5-tier grouping of Gleason scores has recently been proposed. Studies have indicated prognostic heterogeneity within these groups. We assessed prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) for men diagnosed with Gleason score 3 + 5 = 8, 4 + 4 = 8 and 5 + 3 = 8 acinar adenocarcinoma on needle biopsy in a population-based national cohort. The Prostate Cancer data Base Sweden 5.0 was used for survival analysis with PCSM and ACM at 5 and 10 years as endpoints. Multivariable Cox regression models controlling for socioeconomic factors, stage and primary treatment type were used for PCSM and ACM. Among 199,620 men reported with prostate cancer in 2000–2020, 172,112 were diagnosed on needle biopsy. In 18,281 (11%), there was a Gleason score of 8 in needle biopsies, including a Gleason score of 3 + 5, 4 + 4 and 5 + 3 in 11%, 86% and 2.3%, respectively. The primary treatment was androgen deprivation therapy (55%), deferred treatment (8%), radical prostatectomy (16%) or radical radiotherapy (21%). PCSM in men with Gleason scores of 3 + 5, 4 + 4 and 5 + 3 at 5 years of follow-up was 0.10 (95% CI 0.09–0.12), 0.22 (0.22–0.23) and 0.32 (0.27–0.36), respectively, and at 10 years 0.19 (0.17–0.22), 0.34 (0.33–0.35) and 0.44 (0.39–0.49), respectively. There was a significantly higher PCSM after 5 and 10 years in men with Gleason score 5 + 3 cancers than in those with 4 + 4 and in Gleason score 4 + 4 cancers than in those with 3 + 5. Grouping of Gleason scores will eliminate the prognostic granularity of Gleason scoring, thus diminishing the prognostic significance of this proposed grading system. [ABSTRACT FROM AUTHOR]

Background: Studies identifying risk factors for death from breast cancer after ductal carcinoma in situ (DCIS) are rare. In this retrospective nested case–control study, clinicopathological factors in women treated for DCIS and who died from breast cancer were compared with those of patients with DCIS who were free from metastatic disease. Methods: The study included patients registered with DCIS without invasive carcinoma in Sweden between 1992 and 2012. This cohort was linked to the National Cause of Death Registry. Of 6964 women with DCIS, 96 were registered with breast cancer as cause of death (cases). For each case, up to four controls (318; women with DCIS, alive and without metastatic breast cancer at the time of death of the corresponding case) were selected randomly by incidence density sampling. Whole slides of tumour tissue were evaluated for DCIS grade, comedo necrosis, and intensity of periductal lymphocytic infiltrate. Composition of the immune cell infiltrate, expression of oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and proliferation marker Ki-67 were scored on tissue microarrays. Clinical information was obtained from medical records. Information on date, site, and histological characteristics of local and distant recurrences was obtained from medical records for both cases and controls. Results: Tumour tissue was analysed from 65 cases and 195 controls. Intense periductal lymphocytic infiltrate around DCIS was associated with an increased risk of later dying from breast cancer (OR 2.21. 95% c.i. 1.01 to 4.84). Tumours with more intense lymphocytic infiltrate had a lower T cell/B cell ratio. None of the other biomarkers correlated with increased risk of breast cancer death. Conclusion: The immune response to DCIS may influence the risk of dying from breast cancer. Current management of ductal carcinoma in situ (DCIS) is unsatisfactory because low- and high-risk groups of DCIS cannot be defined accurately and reproducibly. This study is the first to show that the degree of tumour infiltrating lymphocytes in DCIS affects the risk of dying from breast cancer. This means that the degree and composition of the immune environment, needs to be consider in order to risk stratify DCIS accurately and personalize treatment. [ABSTRACT FROM AUTHOR]

Assessment of comorbidity is crucial for confounding adjustment and prediction of mortality in register-based studies, but the commonly used Charlson comorbidity index is not sufficiently predictive. We aimed to develop a multidimensional diagnosis-based comorbidity index (MDCI) that captures comorbidity better than the Charlson Comorbidity index. The index was developed based on 286,688 men free of prostate cancer randomly selected from the Swedish general population, and validated in 54,539 men without and 68,357 men with prostate cancer. All ICD-10 codes from inpatient and outpatient discharges during 10 years prior to the index date were used to define variables indicating frequency of code occurrence, recency, and total duration of related hospital admissions. Penalized Cox regression was used to predict 10-year all-cause mortality. The MDCI predicted risk of death better than the Charlson comorbidity index, with a c-index of 0.756 (95% confidence interval [CI] = 0.751, 0.762) vs 0.688 (95% CI = 0.683, 0.693) in the validation cohort of men without prostate cancer. Men in the lowest vs highest MDCI quartile had distinctively different survival in the validation cohort of men with prostate cancer, with an overall hazard ratio [HR] of 5.08 (95% CI = 4.90, 5.26). This was also consistent within strata of age and Charlson comorbidity index, e.g. HR = 5.90 (95% CI = 4.65, 7.50) in men younger than 60 years with CCI 0. These results indicate that comorbidity assessment in register-based studies can be improved by use of all ICD-10 codes and taking related frequency, recency, and duration of hospital admissions into account. [ABSTRACT FROM AUTHOR]

Background: Breast angiosarcoma is a rare disease mostly observed in breast cancer (BC) patients who have previously received radiotherapy (RT). Little is known about angiosarcoma aetiology, management, and outcome. The study aim was to estimate risk and to characterize breast angiosarcoma in a Swedish population-based cohort. Methods: The Swedish Cancer Registry was searched for breast angiosarcoma between 1992 and 2018 in three Swedish healthcare regions (population 5.5 million). Information on previous BC, RT, management, and outcome were retrieved from medical records. Results: Overall, 49 angiosarcomas located in the breast, chest wall, or axilla were identified, 8 primary and 41 secondary to BC treatment. Median age was 51 and 73 years, respectively. The minimum latency period of secondary angiosarcoma after a BC diagnosis was 4 years (range 4-21 years). The cumulative incidence of angiosarcoma after breast RT increased continuously, reaching 1.4‰ after 20 years. Among 44 women with angiosarcoma treated by surgery, 29 developed subsequent local recurrence. Median recurrence-free survival was 3.4 and 1.8 years for primary and secondary angiosarcoma, respectively. The 5-year overall survival probability for the whole cohort was 50 per cent (95 per cent c.i., 21 per cent-100 per cent) for primary breast angiosarcoma and 35 per cent (95 per cent c.i., 23 per cent-54 per cent) for secondary angiosarcoma. Conclusion: Breast angiosarcoma is a rare disease strongly associated with a history of previous BC RT. Overall survival is poor with high rates of local recurrences and distant metastasis. [ABSTRACT FROM AUTHOR]

Oncological outcome after radical radiotherapy (RRT) combined with neoadjuvant and adjuvant androgen suppression therapy (AST) may differ according to type of AST. The aim of this nationwide register-based study was to investigate risk of prostate cancer (Pca) death after different neoadjuvant and adjuvant ASTs; (i) bicalutamide, (ii) gonadotropin-releasing hormone agonists (GnRH) or (iii) combined bicalutamide and GnRH (CAB), together with RRT. Data for 6882 men diagnosed with high-risk Pca between 2007 and 2020 and treated with primary RRT was retrieved from Prostate Cancer data Base Sweden (PCBaSe) 5.0. Time to Pca death according to type of neoadjuvant and adjuvant AST was assessed by use of Kaplan–Meier plots and Cox proportional hazard models adjusted for putative confounders. Data were stratified by RRT type since the effect of AST in risk of Pca death differed according to type of RRT. Compared with the reference RRT combined with neoadjuvant CAB/adjuvant GnRH, risk of Pca death for men treated with CAB/bicalutamide and conventionally fractionated external beam radiotherapy (CF-EBRT) was hazard ratio (HR) 0.73 (95% CI: 0.50–1.04), hypofractionated EBRT (HF-EBRT), HR 1.35 (95% CI: 0.65–2.81) and EBRT with high dose rate brachytherapy (EBRT-HDRBT), HR 0.85 (95% CI: 0.37–1.95). Risk of Pca death for men treated with bicalutamide/bicalutamide and: (i) CF-EBRT was HR 2.35 (95% CI: 1.42–3.90), (ii) HF-EBRT, HR 0.70 (95% CI: 0.26–1.85), (iii) HF-EBRT, HR 4.07 (95% CI: 1.88–8.77) vs the reference. In this observational study, risk of Pca death between men receiving different combinations of AST varied according to RRT type. No difference was found in risk of Pca death for men treated with bicalutamide or GnRH as adjuvant therapy to RRT following neoadjuvant CAB. Risk of Pca death was increased for men with monotherapy neo-/adjuvant bicalutamide in combination with CF-EBRT or EBRT-HDRBT. [ABSTRACT FROM AUTHOR]

Purpose: The safety of local estrogen therapy in patients on adjuvant endocrine treatment is questioned, but evidence on the issue is scarce. This nested case–control registry-based study aimed to investigate whether estrogen therapy affects breast cancer mortality risk in women on adjuvant endocrine treatment. Methods: In a cohort of 15,198 women diagnosed with early hormone receptor (HR)-positive breast cancer and adjuvant endocrine treatment, 1262 women died due to breast cancer and were identified as cases. Each case was matched with 10 controls. Exposure to estrogen therapy with concurrent use of aromatase inhibitors (AIs), tamoxifen, or both sequentially, was compared between cases and controls. Results: No statistically significant difference in breast cancer mortality risk was seen in patients with exposure to estrogen therapy concurrent to endocrine treatment, neither in short-term or in long-term estrogen therapy use. Conclusions: The study strengthens current evidence on local estrogen therapy use in breast cancer survivors, showing no increased risk for breast cancer mortality in patients on adjuvant AIs or tamoxifen. [ABSTRACT FROM AUTHOR]

Objective: To assess the strength of the evidence indicative of prostate cancer (PCa) progression as the adjudicated cause of death, according to age at death and PCa risk category. Patients and Methods: Using data from the Prostate Cancer data Base Sweden, we identified a study frame of 5543 men with PCa registered as the cause of death according to the Cause of Death Register. We assessed the evidence of PCa progression through a review of healthcare records for a stratified sample of 495/5543. We extracted data on prostate‐specific antigen levels, presence of metastases on imaging, and PCa treatments, and quantified the evidence of disease progression using a points system. Results: Both no evidence and moderate evidence for PCa progression was more common in men aged >85 years at death than those aged <85 years (29% vs 14%). Among the latter, the proportion with no evidence or moderate evidence for PCa progression was 21% for low‐risk, 14% for intermediate‐risk, 8% for high‐risk, and 0% for metastatic PCa. In contrast, in men aged >85 years, there was little difference in the proportion with no evidence or moderate evidence of PCa progression between PCa risk categories; 31% for low‐risk, 29% for intermediate‐risk, 29% for high‐risk, and 21% for metastatic PCa. Of the 5543 men who died from PCa, 13% (95% confidence interval 5–19%) were estimated to have either no evidence or moderate evidence of PCa progression. Conclusions: Weak evidence for PCa progression as cause of death was more common in older men with PCa and in those with low‐risk PCa. This has implications for interpretation of mortality statistics especially when assessing screening and early treatment of PCa because the beneficial effect of earlier diagnosis could be masked by erroneous adjudication of PCa as cause of death in older men, particular those with localised disease at diagnosis. [ABSTRACT FROM AUTHOR]

Background: Gonadotropin-releasing hormone agonists (GnRH) used in prostate cancer (PCa) are associated with atherogenic dyslipidaemia. It can be assumed that GnRH need to be used with greater caution in men with type 2 diabetes mellitus (T2DM). This study investigated association of GnRH with atherogenic lipids (AL) in PCa men with T2DM. Methods: Two cohorts including 38,311 men with 11 years follow-up based on Swedish national registers were defined (PCa-Exposure cohort and GnRH-Exposure cohort). Based on European guidelines on cardiovascular diseases (CVD), primary outcomes were defined as: 1.0 mmol/L increase in AL and lipid-lowering therapy (LLT) intensification. We used Cox proportional-hazards models and Kaplan–Meier curves to assess the association. Results: There was an association between GnRH and increased AL (i.e., triglyceride, PCa-Exposure cohort: HR 1.77, 95% CI 1.48–2.10; GnRH-Exposure cohort: HR 1.88, 95% CI 1.38–2.57). There was also an association between PCa diagnosis and increased AL. In contrast, no association between LLT intensification and GnRH was found. Conclusion: In this large population-based study, men with T2DM on GnRH for PCa had an increased risk of increased atherogenic lipids. These results highlight the need to closely monitor lipids and to be ready to intensify lipid-lowering therapy in men with T2DM on GnRH for PCa. [ABSTRACT FROM AUTHOR]

An inverse association between use of antiepileptic drugs (AEDs) and prostate cancer (PCa) has been suggested, putatively due to the histone deacetylases inhibitory (HDACi) properties of the AEDs. In a case-control study in Prostate Cancer data Base Sweden (PCBaSe), PCa cases diagnosed between 2014 and 2016 were matched to five controls by year of birth and county of residence. AED prescriptions were identified in the Prescribed Drug Registry. Odds ratios (ORs) and 95% confidence intervals for risk of PCa were estimated using multivariable conditional logistic regression, adjusted for civil status, education level, Charlson comorbidity index, number of outpatient visits, and cumulative duration of hospital stay. Dose responses in different PCa risk categories and HDACi properties of specific AED substances were further explored. 1738/31591 (5.5%) cases and 9674/156802 (6.2%) controls had been exposed to AED. Overall, users of any AED had a reduced risk of PCa as compared to nonusers (OR: 0.92; 95% CI: 0.87–0.97) which was attenuated by adjustment to healthcare utilisation. A reduced risk was also observed in all models for high-risk or metastatic PCa in AED users compared to nonusers (OR: 0.89; 95% CI: 0.81–0.97). No significant findings were observed for dose response or HDACi analyses. Our findings suggest a weak inverse association between AED use and PCa risk, which was attenuated by adjustment for healthcare utilisation. Moreover, our study showed no consistent dose-response pattern and no support for a stronger reduction related to HDAC inhibition. Further studies focusing on advanced PCa and PCa treatments are needed to better analyse the association between use of AED and risk of PCa. [ABSTRACT FROM AUTHOR]

Background: Randomised controlled trials have demonstrated prolonged survival with new upfront treatments in addition to standard androgen deprivation therapy (ADT) in men with de novo metastatic castration-sensitive prostate cancer. We describe patient characteristics, time trends and regional differences in uptake of these new treatment strategies in clinical practice. Material and methods: This descriptive study consisted of men registered in the National Prostate Cancer Register of Sweden from 1 January 2018 to 31 March 2022 with de novo metastatic castration-sensitive prostate cancer defined by the presence of metastases on imaging at the time of diagnosis. Life expectancy was calculated based on age, Charlson Comorbidity Index and a Drug Comorbidity Index. Results: Within 6 months from diagnosis, 57% (1,677/2,959) of men with de novo metastatic castration-sensitive prostate cancer and more than 3 years of life expectancy had received docetaxel, abiraterone, enzalutamide, apalutamide and/or radiotherapy. Over time, there was a 2-fold increase in uptake of any added treatment, mainly driven by a 6-fold increase in use of abiraterone, enzalutamide or apalutamide, with little change in use of other treatments. Conclusions: Slightly more than half of men diagnosed with de novo metastatic castration-sensitive prostate cancer and a life expectancy of at least 3 years received additions to standard ADT as recommended by national guidelines in 2019-2022 in Sweden. There was a 2-fold increase in use of these treatments during the study period; however, efforts to further increase adherence to guidelines are warranted. [ABSTRACT FROM AUTHOR]

Androgen deprivation therapy (ADT) has been hypothesized to protect against COVID‐19, but previous observational studies of men with prostate cancer on ADT have been inconsistent regarding mortality risk from coronavirus disease 2019 (COVID‐19). Using data from the Prostate Cancer data Base Sweden (PCBaSe), we identified a cohort of 114 547 men with prevalent prostate cancer on the start of follow‐up in February 2020, and followed them until 16 December 2020 to evaluate the association between ADT and time to test positive for COVID‐19. Among men testing positive for COVID‐19, we used regression analyses to estimate the association between ADT and risk of COVID‐19‐related hospital admission/death from any cause within 30 days of the positive test. In total, 1695 men with prostate cancer tested positive for COVID‐19. In crude analyses, exposure to ADT was associated with a 3‐fold increased risk of both testing positive for COVID‐19 infection and subsequent hospital admission/death. Adjustment for age, comorbidity and prostate cancer risk category substantially attenuated the associations: HR 1.3 (95% CI: 1.1‐1.5) for testing positive for COVID‐19, and OR 1.4 (95% CI: 1.0‐1.9) for risk of subsequent hospital admission/death. In conclusion, although these results suggest increased risks of a positive COVID‐19 test, and COVID‐19‐related hospital admission/death in men on ADT, these findings are likely explained by confounding by old age, cancer‐associated morbidity and other comorbidities being more prevalent in men on ADT, rather than a direct effect of the therapy. [ABSTRACT FROM AUTHOR]

The main aim of the study was to determine the impact of diagnostic activity and life expectancy on the lifetime risk of a prostate cancer diagnosis. We used a state transition simulation model based on Swedish population-based data to simulate life trajectories for 2,000,000 men from age 40 to 100 in order to estimate the lifetime risk of a prostate cancer diagnosis. Risk estimates were determined by the level of diagnostic activity and estimated life expectancy. Higher exposure to diagnostic activity resulted in more prostate cancer diagnoses. This was especially true for men diagnosed with low or intermediate grade disease. Men exposed to high diagnostic compared to low diagnostic activity had a five-fold increased lifetime risk (22% vs. 5%) of being diagnosed with a low or intermediate-risk prostate cancer and half the risk of being diagnosed with a high-risk prostate cancer (6% vs. 13%). Men with a long life expectancy had a higher lifetime risk of a prostate cancer diagnosis both overall (21% vs. 15%) and in all risk categories when compared to men with a short life expectancy. The lifetime risk of a prostate cancer diagnosis is strongly influenced by diagnostic activity and to a lesser degree by life expectancy. [ABSTRACT FROM AUTHOR]

Objectives: To predict castration-resistant prostate cancer (CRPC) and prostate cancer (Pca) death by use of clinical variables at Pca diagnosis and PSA levels after start of gonadotropin-releasing hormone agonists (GnRH) in men with non-metastatic castration sensitive prostate cancer (nmCSPC). Materials and Methods: PSA values for 1603 men with nmCSPC in the National Prostate Cancer Register of Sweden who received GnRH as primary treatment were retrieved from Uppsala-Örebro PSA Cohort and Stockholm PSA and Biopsy Register. All men had measured PSA before (pre-GnRH PSA) and 3–6 months after (post-GnRH PSA) date of start of GnRH. Unadjusted and adjusted Cox models were used to predict CRPC by PSA levels. PSA levels and ISUP grade were used to construct a risk score to stratify men by tertiles according to risk of CRPC and Pca death. Results: 788 (49%) men reached CRPC and 456 (28%) died of Pca during follow-up. Post-GnRH PSA predicted CRPC regardless of pre-GnRH PSA. CRPC risk increased with higher post-GnRH PSA, HR 4.7 (95% CI: 3.4–6.7) for PSA > 16 ng/mL vs 0–0.25 ng/mL and with ISUP grade, HR 3.7 (95%: 2.5–5.4) for ISUP 5 vs ISUP 1. Risk of Pca death in men above top vs bellow bottom tertile of post-GnRH PSA and ISUP grade was HR 4.1 (95% CI: 3.0–5.5). Conclusion: A risk score based on post-GnRH PSA and ISUP grade could be used for early identification of a target group for future clinical trials on additional therapy to GnRH. [ABSTRACT FROM AUTHOR]

Androgens facilitate entrance of the severe acute respiratory syndrome coronavirus 2 into respiratory epithelial cells, and male sex is associated with a higher risk of death from corona virus disease (COVID-19). Androgen deprivation therapy (ADT) could possibly improve COVID-19 outcomes. In a case–control study nested in the Prostate Cancer data Base Sweden (PCBaSe) RAPID 2019, we evaluated the association between ADT and COVID-19 as registered cause of death in men with prostate cancer. Each case was matched to 50 controls by region. We used conditional logistic regression to adjust for confounders and also evaluated potential impact of residual confounding. We identified 474 men who died from COVID-19 in March–December 2020. In crude analyses, ADT exposure was associated with an increased risk of COVID-19 death (odds ratio [OR] 5.05, 95% CI: 4.18–6.10); however, the OR was substantially attenuated after adjustment for age, comorbidity, prostate cancer characteristics at diagnosis, recent healthcare use, and indicators of advanced cancer (adjusted OR 1.25, 95% CI: 0.95–1.65). If adjustment has accounted for at least 85% of confounding, then the true effect could be no more than a 5% reduction of the odds for COVID-19 death. The increased mortality from COVID-19 in men with prostate cancer treated with ADT was mainly related to high age, comorbidity, and more advanced prostate cancer. There was no evidence to support the hypothesis that ADT is associated with improved COVID-19 outcomes. [ABSTRACT FROM AUTHOR]

The article informs about time on treatment with abiraterone in men with de novo metastatic castration sensitive prostate cancer. Topics include demonstrated an increased overall survival by addition of the androgen receptor targeted agent abiraterone acetate to gonadotropin-releasing hormone (GnRH) agonist treatment in men; and drug utilization in routine care to detect signals suggesting a potentially different effectiveness in clinical practice.

Introduction: For clinical decision-making, an estimate of remaining lifetime is needed to assess benefit against harm of a treatment during the remaining lifespan. Here, we describe how to predict life expectancy based on age, Charlson Comorbidity Index (CCI) and a Drug Comorbidity Index (DCI), whilst also considering potential future changes in CCI and DCI using population-based data on Swedish men.Methods: Simulations based on annual updates of vital status, CCI and DCI were used to estimate life expectancy at population level. The probabilities of these transitions were determined from generalised linear models using prostate cancer-free comparison men in PCBaSe Sweden. A simulation was performed for each combination of age, CCI, and DCI. Survival curves were created and compared to observed survival. Life expectancy was then calculated as the area under the simulated survival curve.Results: There was good agreement between observed and simulated survival curves for most ages and comorbidities, except for younger men. With increasing age and comorbidity, there was a decrease in life expectancy. Cross-validation based on six regions in Sweden also showed that simulated and observed survival was similar.Conclusion: Our proposed method provides an alternative statistical approach to estimate life expectancy at population level based on age and comorbidity assessed by routinely collected information on diagnoses and filled prescriptions available in nationwide health care registers. [ABSTRACT FROM AUTHOR]

Background: Epidemiological data on anticoagulation for venous thromboembolism (VTE) in prostate cancer are sparse. We aimed to investigate associations between anticoagulation duration and risks of VTE recurrence after treatment cessation and major on-treatment bleeding in men with prostate cancer in Sweden.Methods: Using nationwide prostate cancer registry and prescribing data, we followed 1413 men with VTE and an outpatient anticoagulant prescription following prostate cancer diagnosis. Men were followed to identify cases of recurrent VTE, and hospitalized major bleeding. We calculated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) to quantify the association between anticoagulation duration (reference ≤ 3 months) and recurrent VTE using Cox regression. We estimated 1-year cumulative incidences of major bleedings from anticoagulation initiation.Results: The outpatient anticoagulation prescribed was parenteral (64%), direct oral anticoagulant (31%), and vitamin K antagonist (20%). Median duration of anticoagulation was 7 months. Adjusted HRs (95% CI) for off-treatment recurrent pulmonary embolism (PE) were 0.32 (0.09-1.15) for > 3-6 months' duration, 0.21 (0.06-0.69) for > 6-9 months and 0.16 (0.05-0.55) for > 9 months; corresponding HRs for deep vein thrombosis (DVT) were 0.67 (0.27-1.66), 0.80 (0.31-2.07), and 1.19 (0.47-3.02). One-year cumulative incidences of intracranial, gastrointestinal and urogenital bleeding were 0.9%, 1.7%, 3.0% during treatment, and 1.2%, 0.9%, 1.6% after treatment cessation.Conclusion: The greatest possible benefit in reducing recurrent VTE risk occurred with > 9 months anticoagulation for PE and > 3-6 months for DVT, but larger studies are needed to confirm this. Risks of major bleeding were low overall. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background: Gonadotropin Releasing Hormones agonists (GnRH), which are first line treatment for metastatic prostate cancer (PCa), increase risk of type 2 diabetes mellitus (T2DM). This study aims to quantify the association of use of GnRH with diabetes control in PCa men with T2DM.Methods: Nationwide population-based cohort study in the Swedish National Diabetes Register and Prostate Cancer data Base Sweden 4.1, on the association between GnRH and diabetes control in T2DM men with PCa by comparing T2DM men with PCa vs. without PCa, as well as comparing T2DM men with PCa on or not on GnRH. The primary exposure was use of GnRH. Worsening diabetes control was the primary outcome, defined as: 1) HbA1c rose to 58 mmol/mol or higher; 2) HbA1c increase by 10 mmol/mol or more; 3) Start of antidiabetic drugs or switch to insulin. We also combined all above definitions. Cox proportional hazards regression was used to analyze the association.Results: There were 5714 T2DM men with PCa of whom 692 were on GnRH and 28,445 PCa-free men with T2DM with similar baseline characteristics. Diabetes control was worse in men with GnRH vs. PCa-free men (HR: 1.24, 95% CI: 1.13-1.34) as well as compared with PCa men without GnRH (HR:1.58, 95% CI: 1.39-1.80), when we defined the worsening control of diabetes by combining all definitions above.Conclusion: Use of GnRH in T2DM men with PCa was associated with worse glycemic control. The findings highlight the need to closely monitor diabetes control in men with T2DM and PCa starting GnRH. [ABSTRACT FROM AUTHOR]

Background: Men have a higher risk of death from COVID-19 than women and androgens facilitate entrance of the SARS-CoV-2 virus into respiratory epithelial cells. Thus, androgen deprivation therapy may reduce infection rates and improve outcomes for COVID-19. In the spring of 2020, Sweden was highly affected by COVID-19. The aim was to estimate the impact of androgen deprivation therapy on mortality from COVID-19 in men with prevalent prostate cancer by comparing all-cause mortality in the spring of 2020 to that in previous years. Patients and methods: Using the Prostate Cancer data Base Sweden all men with prostate cancer on March 1 each year in 2015–2020 were followed until June 30 the same year. Exposure to androgen deprivation therapy was ascertained from filled prescriptions for bicalutamide monotherapy, gonadotropin-releasing hormone agonists (GnRH), or bilateral orchidectomy. Results: A total of 9,822 men died in March-June in the years 2015–2020, of whom 5,034 men were on androgen deprivation therapy. There was an excess mortality in 2020 vs previous years in all men. The crude relative mortality rate ratio for 2020 vs 2015–2019 was 0.93 (95% confidence interval (CI) 0.83 to 1.04) in men on GnRH, and 0.90 (95% CI 0.78 to 1.05) in men on bicalutamide monotherapy. After multivariable adjustment these ratios were attenuated to 1.00 (95% CI 0.89 to 1.12) and 0.97 (95% CI 0.84 to 1.12), respectively. When restricting the analysis to the regions with the highest incidence of COVID-19 or to the time period between 2 April to 10 June when mortality in 2020 was increased >30% compared to previous years, the results were similar to the main analysis. Conclusions: In this large national population-based cohort of men with prevalent prostate cancer, there was no clear evidence in support for an effect of androgen deprivation therapy on COVID-19 mortality. [ABSTRACT FROM AUTHOR]

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 younger than age 90 years, diagnosed 1998–2016 with PCa. RS and CSS were compared according to age and risk category based on TNM (tumor, nodes, and metastases) stage, Gleason score, and prostate-specific antigen level. Each framework requires assumptions that are unlikely to be appropriate for PCa. Ten-year RS was substantially higher than CSS in men aged 80–89 with low-risk PCa: 125% (95% confidence interval: 113, 138) versus 85% (95% confidence interval: 82, 88). In contrast, RS and CSS were similar for men under 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 over 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, because the "true" net survival is expected to lie between the limits of RS and CSS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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; I2: 64%). Men on GnRH antagonists showed increased risk of acute myocardial infarction (HR: 1.62; 95% CI: 1.11‐2.35; I2: 0%) and arrhythmia (HR: 1.55; 95% CI: 1.11‐2.15, I2: 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. What's new? Prolonged use of gonadotropin‐releasing hormone (GnRH) agonists has been associated with an increased risk of cardiovascular disease (CVD). Preclinical studies have indicated that newer GnRH antagonists may cause fewer atherosclerotic effects than GnRH agonists. In this meta‐analysis of prostate cancer studies, however, the authors found little benefit of GnRH antagonists over GnRH agonists, in terms of CVD risk. If anything, men taking GnRH antagonists may have an increased risk of acute myocardial infarction and arrhythmia compared to GnRH agonists. Further studies are warranted. [ABSTRACT FROM AUTHOR]

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. 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 (PCBaSeTraject) 4.1 between 1 June 2015 and 31 December 2018. PCBaSeTraject 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Previous studies on the risk of cancer after total hip arthroplasty (THA) contradict each other, and many are hampered by small cohort sizes, residual confounding, short observation times or a mix of indications underlying the THA procedure. We evaluated the risk of cancer after total hip arthroplasty due to osteoarthritis in a nationwide cohort by comparing cancer incidences in individuals exposed to total hip arthroplasty due to osteoarthritis and in unexposed, sex‐, age‐ and residence matched individuals. To address some previous studies' shortcomings, information on comorbidity and socioeconomic background were obtained and adjusted for. We included 126,276 patients exposed to a cemented THA between 1992 and 2012, and 555,757 unexposed individuals. Follow‐up started on the day of surgery for exposed individuals and respective date for matched, unexposed individuals, and ended on the day of death, emigration, censuring or December 31st, 2012, whichever came first. The Swedish Hip Arthroplasty Registry (SHAR), the Swedish Cancer Registry, the Swedish National Patient Registry and Statistics Sweden were accessed to obtain information on procedural details of the THA, cancer diagnoses, comorbidities, and socioeconomic background. The primary outcome measure was the occurrence of any cancer after the index date. Exposed individuals had a slightly lower adjusted risk of developing any cancer than unexposed individuals (hazard ratio [HR] 0.97; CI 0.95–0.99). The only cancer with a statistically significant risk increase in exposed individuals was skin melanoma (HR 1.15; CI 1.05–1.24). We attained similar risk estimates in analyses stratified by sex, in individuals with minimum 5 years of follow‐up, in an analysis including individuals with a history of previous cancer, and in patients with cementless THA. In this study on a large and well‐defined population with long follow‐up, we found no increased overall risk of cancer after THA. These reassuring findings could be included in the guidelines on preoperative information given to THA patients. What's new? Some evidence has suggested an increase in cancer associated with total hip arthroplasty, but prior studies have been inconclusive. For this study, the authors recruited 126,276 patients who had received cemented THA and 555,575 age‐ and sex‐matched controls. They limited patients to those whose THA was due to primary osteoarthritis, which generated a relatively homogenous patient population in terms of age and general health. The patients were recruited from the Swedish national THA registry, and cancer incidence was compared between the two groups. They found no increase in cancer risk associated with total hip arthroplasty. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Material and methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

We aimed to investigate whether the concomitant use of tamoxifen with warfarin is associated with higher risk for bleeding among patients with early estrogen‐receptor (ER)‐positive breast in a population‐based nested case‐control study. We identified 1787 patients taking warfarin and 92 cases hospitalized for bleeding and found an adjusted odds ratio (OR) of 1.42 (95% confidence interval (CI): 0.84‐2.40) for the risk of bleeding in patients treated with warfarin that initiated tamoxifen within the previous 30 days. As a result, we could not definitively rule out a potential association between tamoxifen use during warfarin and bleeding risk in patients with breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: 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. Materials and methods: 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. Results: 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). Discussion: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: We selected all participants (≥20 years old) with baseline measurements of IgA, IgG or IgM (n = 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. Results: 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); P 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Aim: Gonadotropin-releasing hormone (GnRH) agonists are used to treat men with prostate cancer (PCa). To date, no study has fully assessed patterns of adherence to GnRH agonists. We investigated patterns of adherence to GnRH agonists using data from Prostate Cancer data Base Sweden (PCBaSe). Methods: PCBaSe links the National Prostate Cancer Register (NPCR) Sweden to other healthcare registers and demographic databases. Men on primary or secondary GnRH agonists between 2006–2013 entered the study 45 days after GnRH agonists' initiation (run-in period) and exited at 3 years. Medication possession ratio quantified adherents (≥80%). Multivariable logistic regression models included age, injection interval, PCa risk categories, Charlson Comorbidity Index, prior PCa treatment, civil status and year of GnRH initiation. Odds ratios (OR) and 95% confidence intervals (CI) expressed odds of adherence. Results: Men on primary GnRH agonists (n = 8,105) were more adherent with increasing age (75–84 years compared to ≤65 years OR: 1.49; 95% CI: 1.23–1.81), longer injection intervals (365 days compared to 90 days OR: 3.29; 95% CI: 2.52–4.30) and higher PCa risk categories at diagnosis (distant metastasis compared to low risk PCa OR: 3.56; 95% CI: 2.54–5.00). Men on secondary GnRH agonists (n = 4,738) were more adherent with increasing age (≥85 years compared to ≤65 years OR: 1.65; 95% CI: 1.23–2.22) and prior PCa treatment (anti-androgens compared to deferred treatment OR: 1.50; 95% CI: 1.23–1.82), (radiotherapy compared to deferred treatment OR: 1.35; 95% CI: 1.11–1.64). Conclusions: Longer injection intervals could be addressed in the clinical setting to improve adherence. [ABSTRACT FROM AUTHOR]