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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]

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]

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.

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]

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]

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]

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]

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]

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]

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]

Numerous pretreatment risk classification tools are available for prostate cancer. Which tool is best in predicting prostate cancer death is unclear. To systematically compare the prognostic performance of the most commonly used pretreatment risk stratification tools for prostate cancer. A nationwide cohort study was conducted, including 154 811 men in Prostate Cancer data Base Sweden (PCBaSe) 4.0 diagnosed with nonmetastatic prostate cancer during 1998–2016 and followed through 2016. We compared the D'Amico, National Institute for Health and Care Excellence (NICE), European Association of Urology (EAU), Genito-Urinary Radiation Oncologists of Canada (GUROC), American Urological Association (AUA), National Comprehensive Cancer Network (NCCN), and Cambridge Prognostic Groups (CPG) risk group systems; the Cancer of the Prostate Risk Assessment (CAPRA) score; and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram in predicting prostate cancer death by estimating the concordance index (C-index) and the observed versus predicted cumulative incidences at different follow-up times. A total of 139 515 men were included in the main analysis, of whom 15 961 died from prostate cancer during follow-up. The C-index at 10 yr of follow-up ranged from 0.73 (95% confidence interval [CI]: 0.72–0.73) to 0.81 (95% CI: 0.80–0.81) across the compared tools. The MSKCC nomogram (C-index: 0.81, 95% CI: 0.80–0.81), CAPRA score (C-index: 0.80, 95% CI: 0.79–0.81), and CPG system (C-index: 0.78, 95% CI: 0.78–0.79) performed the best. The order of performance between the tools remained in analyses stratified by primary treatment and year of diagnosis. The predicted cumulative incidences were close to the observed ones, with some underestimation at 5 yr. It is a limitation that the study was conducted solely in a Swedish setting (ie, case mix). The MSKCC nomogram, CAPRA score, and CPG risk grouping system performed better in discriminating prostate cancer death than the D'Amico and D'Amico-derived systems (NICE, GUROC, EAU, AUA, and NCCN). Use of these tools may improve clinical decision making. There are numerous pretreatment risk classification tools that can aid treatment decision for prostate cancer. We systematically compared the prognostic performance of the most commonly used tools in a large cohort of Swedish men with prostate cancer. The Memorial Sloan Kettering Cancer Center nomogram, Cancer of the Prostate Risk Assessment score, and Cambridge Prognostic Groups performed best in predicting prostate cancer death. The use of these tools may improve treatment decisions. There are numerous pretreatment risk classification tools for prostate cancer. In a head-to-head comparison, the Memorial Sloan Kettering Cancer Center nomogram, Cancer of the Prostate Risk Assessment score, and Cambridge Prognostic Groups system performed best in predicting prostate cancer death. The use of these tools may improve clinical decision making. [ABSTRACT FROM AUTHOR]

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]

Background: Metabolites are genetically and environmentally determined. Consequently, they can be used to characterize environmental exposures and reveal biochemical mechanisms that link exposure to disease. To explore disease susceptibility and improve population risk stratification, we aimed to identify metabolic profiles linked to carcinogenesis and mortality and their intrinsic associations by characterizing subgroups of individuals based on serum biomarker measurements. We included 13,615 participants from the Swedish Apolipoprotein MOrtality RISk Study who had measurements for 19 biomarkers representative of central metabolic pathways. Latent Class Analysis (LCA) was applied to characterise individuals based on their biomarker values (according to medical cut-offs), which were then examined as predictors of cancer and death using multivariable Cox proportional hazards models. Results: LCA identified four metabolic profiles within the population: (1) normal values for all markers (63% of population); (2) abnormal values for lipids (22%); (3) abnormal values for liver functioning (9%); (4) abnormal values for iron and inflammation metabolism (6%). All metabolic profiles (classes 2-4) increased risk of cancer and mortality, compared to class 1 (e.g. HR for overall death was 1.26 (95% CI: 1.16-1.37), 1.67 (95% CI: 1.47-1.90), and 1.21 (95% CI: 1.05-1.41) for class 2, 3, and 4, respectively). Conclusion: We present an innovative approach to risk stratify a well-defined population based on LCA metabolic-defined subgroups for cancer and mortality. Our results indicate that standard of care baseline serum markers, when assembled into meaningful metabolic profiles, could help assess long term risk of disease and provide insight in disease susceptibility and etiology. [ABSTRACT FROM AUTHOR]

The article reports on the use of androgen deprivation therapy for the treatment of prostate cancer and whether it causes dementia. It mentions previous studies which have found an increased risk, the present study which found no real correlation, and discusses the need to study men who have had an orchiectomy or who are on GnRh agonists.

Background: Studies of survival comparing radical cystectomy (RC) and radiotherapy for muscle‐invasive bladder cancer have provided inconsistent results and have methodological limitations. The aim of the study was to investigate risk of death after radiotherapy as compared to RC. Methods: We selected patients with muscle‐invasive urothelial carcinoma without distant metastases, treated with radiotherapy or RC from 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe) and estimated absolute and relative risk of bladder cancer death and all‐cause death. In a group of patients, theoretically eligible for a trial comparing radiotherapy and RC, we calculated risk difference in an instrumental variable analysis. We have not investigated chemoradiotherapy as this treatment was not used in the study time period. Results: The study included 3 309 patients, of those 17% were treated with radiotherapy and 83% with RC. Patients treated with radiotherapy were older, had more advanced comorbidity, and had a higher risk of death as compared to patients treated with RC (relative risks of 1.5‐1.6). In the "trial population," all‐cause death risk difference was 6 per 100 patients lower after radiotherapy at 5 years of follow‐up, 95% confidence interval −41 to 29. Conclusion(s): Patient selection between the treatments make it difficult to evaluate results from conventionally adjusted and propensity‐score matched survival analysis. When taking into account unmeasured confounding by instrumental variable analysis, no differences in survival was found between the treatments for a selected group of patients. Further clinical studies are needed to characterize this group of patients, which can serve as a basis for future comparison studies for treatment recommendations. [ABSTRACT FROM AUTHOR]

Abstract Background Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias. Objective To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study. Design, setting, and participants Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n = 2078) or GnRH agonists (n = 4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5 yr before through to 5 yr after starting androgen deprivation therapy (ADT). Outcome measures and statistical methods Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses. Results and limitations Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p < 0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20–1.44). Conclusions Impact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment. Patient summary Hormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy. Take Home Message The increase in overall comorbidity following androgen androgen deprivation therapy for advanced prostate cancer was significantly higher for gonadotrophin gonadotrophin-releasing hormone agonists than for anti-androgen (AA) monotherapy. More consideration should be given to AA monotherapy as an alternative first-line therapy. [ABSTRACT FROM AUTHOR]

Objective: To investigate if results in terms of absolute risk in mature randomised trials are relevant for contemporary decision‐making. To do so, we compared the outcome for men in the radical prostatectomy (RP) arm of the Scandinavian Prostate Cancer Group Study number 4 (SPCG‐4) randomised trial with matched men treated in a contemporary era before and after compensation for the grade migration and grade inflation that have occurred since the 1980s. Patients and methods: A propensity score‐matched analysis of prostate cancer mortality and all‐cause mortality in the SPCG‐4 and matched men in the National Prostate Cancer Register (NPCR) of Sweden treated in 1998–2006 was conducted. Cumulative incidence of prostate cancer mortality and all‐cause mortality was calculated. Cox proportional hazards regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for a matching on original Gleason Grade Groups (GGG) and second, matching with GGG increased one unit for men in the NPCR. Results: Matched men in the NPCR treated in 2005–2006 had half the risk of prostate cancer mortality compared to men in the SPCG‐4 (HR 0.46, 95% CI 0.19–1.14). In analysis of men matched on an upgraded GGG in the NPCR, this difference was mitigated (HR 0.73, 95% CI 0.36–1.47). Conclusions: Outcomes after RP for men in the SPCG‐4 cannot be directly applied to men in the current era, mainly due to grade inflation and grade migration. However, by compensating for changes in grading, similar outcomes after RP were seen in the SPCG‐4 and NPCR. In order to compare historical trials with current treatments, data on temporal changes in detection, diagnostics, and treatment have to be accounted for. [ABSTRACT FROM AUTHOR]

There is evidence that derangement in serum electrolytes like sodium and potassium is associated with increased morbidity and mortality among hospitalized critically ill patients, but their role in the context of cancer survival remains poorly understood. We sought to investigate the association of pre-diagnostic serum sodium and potassium with risk of overall, cancer-specific, and cardiovascular (CV) death among 11,492 men diagnosed with prostate cancer (PCa) from the Swedish AMORIS study. Multivariable Cox proportional hazards regression was used to assess the risk of death by clinical categories of pre-diagnostic serum sodium and potassium. During a mean follow-up of 5.7 years, 1649 men died of PCa. Serum levels of sodium were not indicative of PCa-specific or CV death. A weak positive association was found between pre-diagnostic higher serum potassium (> 5 mEq/L) and overall death [HR: 1.26 (95% CI: 1.01-1.59)] as compared to low/normal levels of clinical cut-offs. The current study did not find strong evidence for a role of electrolytes in PCa mortality. To further disentangle the potential role of electrolytes in cancer development, future studies should use repeated measurement of serum electrolytes.This research project was reviewed and approved by the Stockholm Ethical Committee (Dnr 2010/1:7). [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between lower urinary-tract infections, their associated antibiotics and the subsequent risk of developing PCa. Subjects/Patients (or materials) and methods: Using data from the Swedish PCBaSe 3.0, we performed a matched case-control study (8762 cases and 43806 controls). Conditional logistic regression analysis was used to assess the association between lower urinary-tract infections, related antibiotics and PCa, whilst adjusting for civil status, education, Charlson Comorbidity Index and time between lower urinary-tract infection and PCa diagnosis. Results: It was found that lower urinary-tract infections did not affect PCa risk, however, having a lower urinary-tract infection or a first antibiotic prescription 6–12 months before PCa were both associated with an increased risk of PCa (OR: 1.50, 95% CI: 1.23–1.82 and 1.96, 1.71–2.25, respectively), as compared to men without lower urinary-tract infections. Compared to men with no prescriptions for antibiotics, men who were prescribed ≥10 antibiotics, were 15% less likely to develop PCa (OR: 0.85, 95% CI: 0.78–0.91). Conclusion: PCa was not found to be associated with diagnosis of a urinary-tract infection or frequency, but was positively associated with short time since diagnoses of lower urinary-tract infection or receiving prescriptions for antibiotics. These observations can likely be explained by detection bias, which highlights the importance of data on the diagnostic work-up when studying potential risk factors for PCa. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether curative prostate cancer (PCa) treatment was received less often by men with both PCa and Type 2 diabetes mellitus (T2DM) as little is known about the influence of T2DM diagnosis on the receipt of such treatment in men with localized PCa. Subjects and Methods: The Prostate Cancer database Sweden (PCBaSe) was used to obtain data on men with T2DM and PCa (n = 2210) for comparison with data on men with PCa only (n = 23 071). All men had intermediate‐ (T1–2, Gleason score 7 and/or prostate‐specific antigen [PSA] 10–20 ng/mL) or high‐risk (T3 and/or Gleason score 8–10 and/or PSA 20–50 ng/mL) localized PCa diagnosed between 1 January 2006 and 31 December 2014. Multivariate logistic regression was used to calculate the odds ratios (ORs) for receipt of curative treatment in men with and without T2DM. Overall survival, for up to 8 years of follow‐up, was calculated both for men with T2DM only and for men with T2DM and PCa. Results: Men with T2DM were less likely to receive curative treatment for PCa than men without T2DM (OR 0.78, 95% confidence interval 0.69–0.87). The 8‐year overall survival rates were 79% and 33% for men with T2DM and high‐risk PCa who did and did not receive curative treatment, respectively. Conclusions: Men with T2DM were less likely to receive curative treatment for localized intermediate‐ and high‐risk PCa. Men with T2DM and high‐risk PCa who received curative treatment had substantially higher survival times than those who did not. Some of the survival differences represent a selection bias, whereby the healthiest patients received curative treatment. Clinicians should interpret this data carefully and ensure that individual patients with T2DM and PCa are not under‐ nor overtreated. [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]

Background Active surveillance (AS) is commonly used for men with low-risk prostate cancer (PCa). When life expectancy becomes too short for curative treatment to be beneficial, a change from AS to watchful waiting (WW) follows. Little is known about this change since it is rarely documented in medical records. Objective To model transition from AS to WW and how this is affected by age and comorbidity among men with very low-risk PCa. Design, setting, and participants National population-based healthcare registers were used for analysis. Outcome measurements and statistical analysis Using data on PCa characteristics, age, and comorbidity, a state transition model was created to estimate the probability of changes between predefined treatments to estimate transition from AS to WW. Results and limitations Our estimates indicate that 48% of men with very low-risk PCa starting AS eventually changed to WW over a life course. This proportion increased with age at time of AS initiation. Within 10 yr from start of AS, 10% of men aged 55 yr and 50% of men aged 70 yr with no comorbidity at initiation changed to WW. Our prevalence simulation suggests that the number of men on WW who were previously on AS will eventually stabilise after 30 yr. A limitation is the limited information from clinical follow-up visits (eg, repeat biopsies). Conclusions We estimated that changes from AS to WW become common among men with very low-risk PCa who are elderly. This potential change to WW should be discussed with men starting on AS. Moreover, our estimates may help in planning health care resources allocated to men on AS, as the transition to WW is associated with lower demands on outpatient resources. Patient summary Changes from active surveillance to watchful waiting will become more common among men with very low-risk prostate cancer. These observations suggest that patients need to be informed about this potential change before they start on active surveillance. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the association between commonly measured serum biomarkers of inflammation and penile and testicular cancer risk in the Swedish Apolipoprotein-related MORtality RISk (AMORIS) study. Materials and methods: A total of 205,717 subjects had baseline measurements of C-reactive protein, albumin, and haptoglobin. The association between quartiles and dichotomised values of inflammatory markers and penile and testicular cancer risk were analysed by using multivariate Cox proportional hazard models. Results: A total of 125 men were diagnosed with testicular cancer and 50 with penile cancer during a mean follow-up of 20.3 years. No statistically significant trends were seen between serum inflammatory markers and risk of penile cancer, but higher albumin levels increased the risk of testicular cancer [HR for albumin (g/L): 1.10 (95% CI: 1.03-1.18)]. However, this trend was not observed when using medical cut-offs of albumin. Conclusions: In the present study, we did not find support for an association between commonly used markers of inflammation and risk of testicular or penile cancer. The role of inflammation may be more complicated and require assessment of more specialised measurements of inflammation in future studies. [ABSTRACT FROM AUTHOR]

Background: The lipid and glucose metabolisms are postulated as possible intermediary mechanisms in linking obesity and breast cancer (BC). Links between serum lipid and glucose biomarkers and BC risk has been observed in the Swedish Apolipoprotein MORtality RISk (AMORIS) cohort. We conducted a follow-up analysis including information on tumour characteristics.Methods: One thousand eight hundred twenty-four women diagnosed with BC, with serum biomarker levels of glucose, triglycerides, cholesterol (total, HDL, and LDL), and apolipoproteins A-1 and B recorded in a routine health check at baseline were included. BC severity was split into categories (good, moderate, and poor prognosis) based on ER status, TNM stage, and age at diagnosis. Proportional odds models were used to obtain odds ratios (ORs) and 95% confidence intervals (CI), with the interval time between baseline measurement and BC diagnosis accounted for.Results: Serum glucose and the ApoB/ApoA-1 ratio showed a non-statistically significant positive association with BC severity (proportional OR: 1.25 (95%CI: 0.92-1.70) for glucose (Conclusions: Despite the size and detail of data in AMORIS, we only found a modest positive association between serum levels of glucose, apoB/ApoA-1 and BC severity, suggesting that these factors are not the main players in linking obesity and BC aggressiveness. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the risk of thromboembolic disease (TED) after radiation therapy (RT) with curative intent for prostate cancer (PCa).Patients and Methods: We identified all men who received RT as curative treatment (n=9410) and grouped according to external beam RT (EBRT) or brachytherapy (BT). By comparing with an age- and county-matched comparison cohort of PCa-free men (n=46,826), we investigated risk of TED after RT using Cox proportional hazard regression models. The model was adjusted for tumor characteristics, demographics, comorbidities, PCa treatments, and known risk factors of TED, such as recent surgery and disease progression.Results: Between 2006 and 2013, 6232 men with PCa received EBRT, and 3178 underwent BT. A statistically significant association was found between EBRT and BT and risk of pulmonary embolism in the crude analysis. However, upon adjusting for known TED risk factors these associations disappeared. No significant associations were found between BT or EBRT and deep venous thrombosis.Conclusion: Curative RT for prostate cancer using contemporary methodologies was not associated with an increased risk of TED. [ABSTRACT FROM AUTHOR]

Purpose To determine the inter-observer variation in delineating the coronary arteries as organs at risk (OAR) in breast cancer (BC) radiotherapy (RT) and how this variation affects the estimated coronary artery radiation dose. Method Delineation of the left main and the left anterior descending coronary artery (LMCA and LAD), and the right coronary artery (RCA), by using the heart atlas by Feng et al., was performed by three radiation oncologists in 32 women who had received adjuvant RT for BC. Centres of the arteries were calculated and distances between artery centres were measured and the artery radiation doses were estimated. The intraclass correlation coefficient (ICC) was used to quantify the variability in doses. Results Along the extent of RCA, the median distance between centres of arteries varied from 2 to 9 mm with similar patterns over pairs of oncologists. For the LMCA-LAD the median distance varied from 1 to 4 mm. The estimated maximum radiation doses showed an ICC variation from 0.82 to 0.97. Conclusion The coronary arteries can be reliably identified and delineated as OARs in BC RT. The spatial variance is limited and the total variation in radiation dose is almost completely determined by the between patient variation. [ABSTRACT FROM AUTHOR]

Background and aims Previous epidemiological studies have shown positive associations between serum calcium concentration and risk of cardiovascular disease (CVD), but results differ by definition of CVD. We examined the association of circulating calcium with incident and fatal CVD, myocardial infarction (MI), and stroke in the Swedish AMORIS cohort. Methods We included 441,738 participants of the AMORIS database linked for follow-up information on morbidity and mortality. Concentrations of total calcium were fully automated measured using a colorimetric method; concentrations of albumin were measured with a bromocresol green method between 1985 and 1995. The association of albumin-corrected calcium concentration and risk of incident and fatal CVD, MI, and stroke, respectively, was assessed with multivariable adjusted Cox proportional hazards models. Results Until December 31, 2011, during a median follow-up time of 21 years, 90,866 incident cases of CVD, 21,271 of MI, and 25,810 of stroke were identified. High serum calcium concentrations were associated with increased risk of non-fatal CVD (Hazard ratio [HR] = 1.12, 95% CI 1.10–1.14, top [≥2.40 nmol/L] vs. bottom [≤2–25 nmol/L] quintile), MI (1.19, 1.14–1.25), and stroke (1.11, 1.06–1.15) and fatal disease (CVD: 1.41, 1.35–1.47; MI: 1.41, 1.31–1.51; stroke: 1.30, 1.20–1.41). Effect modification by sex was observed for incident disease such that associations were stronger among women than men. Serum calcium was positively associated with both incident and fatal ischemic stroke and with fatal hemorrhagic stroke, but not with incident hemorrhagic stroke. In a sub-groups analysis, the results remained significant after adjustment for smoking. Conclusions The results support a modest positive association between serum calcium and risk of CVD, but the underlying mineral metabolism and the exact mechanisms are currently unclear. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Many men diagnosed with localised prostate cancer will eventually be treated with androgen deprivation therapy (ADT). ADT is associated with adverse effects and its timing is controversial. Data on patterns of use are scarce. We describe patterns of ADT use, defined as castration (medical and surgical) or antiandrogen monotherapy initiated after primary treatment, in a population-based cohort. Methods and materials: Data were extracted from the population-based Prostate Cancer data Base Sweden (PCBaSe). Totally 45,147 men diagnosed between 1997 and 2009 with clinical stage T1–2, N0–NX, M0–MX and prostate specific antigen (PSA)<50ng/ml without primary ADT were included. Outcomes in the period 2006 through 2010 were analysed using a period analysis approach. Results: The cumulative incidence of castration at 10years after diagnosis was 11.6% (95% confidence interval (CI), 11.0–12.2%). The corresponding proportion of antiandrogen monotherapy was 10.8% (95% CI, 10.2–11.4%). Castration was the dominant therapy among men on deferred treatment. The probability of receiving castration rather than antiandrogen monotherapy increased with age. Estimated median durations of castration ranged from 4years in the deferred treatment high-risk group to 17years in the prostatectomy low-risk group. The main limitation was the lack of information on progression to metastatic disease and PSA at the time for initiation of ADT. Conclusion: When initiated early after curative treatment, the duration of castration can be decades. The findings indicate that more accurate tools are necessary to guide which men should be selected for ADT as secondary treatment. [Copyright &y& Elsevier]

Dietary pattern analyses have increased the possibilities to detect associations between diet and disease. However, studies on dietary pattern and prostate cancer are scarce. Food intake data in the Uppsala Longitudinal Study of Adult Men cohort was determined by 7-day food records. Adherence to a modified Mediterranean Diet Score (mMDS) and a low carbohydrate–high protein (LCHP) score were grouped as low, medium, or high in the whole study population (n= 1,044) and in those identified as adequate reporters of energy intake (n= 566), respectively. Prostate cancer risk was analyzed with Cox proportional hazard regression (median follow-up 13 years) and competing risk of death was considered. There were no associations between dietary patterns and prostate cancer (n= 133) in the whole study population. Among adequate reporters the mMDS was not associated with prostate cancer (n= 72). The LCHP score was inversely related to prostate cancer in adequate reporters, adjusted hazard ratios; 0.55 (0.32–0.96) for medium and 0.47 (0.21–1.04) for high compared to low adherent participants (P-for-trend 0.04). Risk relations were not attributable to competing risk of death. In this study, a LCHP diet was associated with lower prostate cancer incidence. Relations emerged in adequate reporters, underscoring the importance of high-quality dietary data. [ABSTRACT FROM AUTHOR]

Abstract: Background: Studies enumerating the dynamics of physical and emotional symptoms following prostate cancer (PCa) treatment are needed to guide therapeutic strategy. Yet, overcoming patient selection forces is a formidable challenge for observational studies comparing treatment groups. Objective: To compare patterns of symptom burden and distress in men with localized PCa randomized to radical prostatectomy (RP) or watchful waiting (WW) and followed up longitudinally. Design, setting, and participants: The three largest, Swedish, randomization centers for the Scandinavian Prostate Cancer Group-4 trial conducted a longitudinal study to assess symptoms and distress from several psychological and physical domains by mailed questionnaire every 6 mo for 2 yr and then yearly through 8 yr of follow-up. Intervention: RP compared with WW. Outcome measurements and statistical analysis: A questionnaire was mailed at baseline and then repeatedly during follow-up with questions concerning physical and mental symptoms. Each analysis of quality of life was based on a dichotomization of the outcome (yes vs no) studied in a binomial response, generalized linear mixed model. Results and limitations: Of 347 randomized men, 272 completed at least five questionnaires during an 8-yr follow-up period. Almost all men reported that PCa negatively influenced daily activities and relationships. Health-related distress, worry, feeling low, and insomnia were consistently reported by approximately 30–40% in both groups. Men in the RP group consistently reported more leakage, impaired erection and libido, and fewer obstructive voiding symptoms. For men in the WW group, distress related to erectile symptoms increased gradually over time. Symptom burden and distress at baseline was predictive of long-term outlook. Conclusions: Cancer negatively influenced daily activities among almost all men in both treatment groups; health-related distress was common. Trade-offs exist between physiologic symptoms, highlighting the importance of tailored treatment decision-making. Men who are likely to experience profound long-term distress can be identified early in disease management. [Copyright &y& Elsevier]

Background. Chemotherapy prolongs life and relieves symptoms in men with castration resistant prostate cancer (CRPC). There is limited information on a population level on the use of chemotherapy for CRPC. Material and methods. To assess the use of chemotherapy in men with CRPC we conducted a register-based nationwide population-based study in Prostate Cancer data Base Sweden (PCBaSe) and a nationwide in-patient drug register (SALT database) between May 2009 and December 2010. We assumed that men who died of prostate cancer (PCa) underwent a period of CRPC before they died. Results. Among the 2677 men who died from PCa during the study inclusion period, 556 (21%) had received chemotherapy (intravenous or per oral) detectable within the observation period in SALT database. Specifically, 239 (61%) of men < 70 years had received chemotherapy, 246 (30%) of men between 70 and 79 years and 71 (5%) men older than 80 years. The majority of men 465/556 (84%) had received a docetaxel-containing regimen. Among chemotherapy treated men, 283/556 (51%) received their last dose of chemotherapy during the last six months prior to death. Treatment with chemotherapy was more common among men with little comorbidity and high educational level, as well as in men who had received curatively intended primary treatment. Conclusion. A majority of men younger than 70 years with CRPC were treated with chemotherapy in contrast to men between 70 and 79 years of whom half as many received chemotherapy. Chemotherapy treatment was often administered shortly prior to death. The low uptake of chemotherapy in older men with CRPC may be caused by concerns about tolerability of treatment, as well as treatment decisions based on chronological age rather than global health status. [ABSTRACT FROM AUTHOR]

Background: Hip fractures are associated with increased mortality and are a known adverse effect of androgen deprivation therapy (ADT) for prostate cancer (PCa). It was our aim to evaluate how mortality after hip fracture is modified by PCa and ADT. Methods: PCa dataBase Sweden (PCBaSe 2.0) is based on the National PCa Register and also contains age and county-matched PCa-free men. We selected all men (n = 14,205) who had been hospitalized with a hip fracture between 2006 and 2010; 2,300 men had a prior PCa diagnosis of whom 1,518 (66%) were on ADT prior to date of fracture. Risk of death was estimated with cumulative incidence and standardized mortality ratios (SMRs) to make comparisons with the entire PCa population and the general population. Results: Cumulative incidences indicated that there was a higher risk of death following a hip fracture for PCa men on ADT than for PCa men not on ADT or PCa-free men, particularly in the first year. The SMRs showed that PCa men on ADT with a hip fracture were 2.44 times more likely to die than the comparison cohort of all PCa men (95%CI: 2.29-2.60). This risk was especially increased during the first month (5.64 (95%CI: 4.16–7.48)). In absolute terms, hip fractures were associated with 20 additional deaths per 1,000 person-years in PCa men not on ADT, but 30 additional deaths per 1,000 person-years for PCa men on ADT, compared to all PCa men. Conclusion: Hip fractures are associated with higher all-cause mortality in PCa men on ADT than in PCa men not on ADT or PCa-free men, especially within the first three months. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Many men diagnosed with localised prostate cancer will eventually be treated with androgen deprivation therapy (ADT). ADT is associated with adverse effects and its timing is controversial. Data on patterns of use are scarce. We describe patterns of ADT use, defined as castration (medical and surgical) or antiandrogen monotherapy initiated after primary treatment, in a population-based cohort. Methods and materials: Data were extracted from the population-based Prostate Cancer data Base Sweden (PCBaSe). Totally 45,147 men diagnosed between 1997 and 2009 with clinical stage T1–2, N0–NX, M0–MX and prostate specific antigen (PSA)<50ng/ml without primary ADT were included. Outcomes in the period 2006 through 2010 were analysed using a period analysis approach. Results: The cumulative incidence of castration at 10years after diagnosis was 11.6% (95% confidence interval (CI), 11.0–12.2%). The corresponding proportion of antiandrogen monotherapy was 10.8% (95% CI, 10.2–11.4%). Castration was the dominant therapy among men on deferred treatment. The probability of receiving castration rather than antiandrogen monotherapy increased with age. Estimated median durations of castration ranged from 4years in the deferred treatment high-risk group to 17years in the prostatectomy low-risk group. The main limitation was the lack of information on progression to metastatic disease and PSA at the time for initiation of ADT. Conclusion: When initiated early after curative treatment, the duration of castration can be decades. The findings indicate that more accurate tools are necessary to guide which men should be selected for ADT as secondary treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background: Prostate cancer (PCa) and surgery are both associated with increased risk of thromboembolic diseases (TED). Objective: We assessed risk of TED among men undergoing different types of urologic surgery. Design, setting, and participants: Using the Prostate Cancer Database Sweden (PCBaSe) Sweden, we identified all men (n =45 065) undergoing pelvic lymph node dissection (PLND), radical prostatectomy (RP) with or without PLND, orchiectomy due to PCa, or a transurethral resection of the prostate (TURP). We identified a comparison cohort from the population. Outcome measurements and statistical analysis: Main outcomes were deep venous thrombosis (DVT) and pulmonary embolism (PE) as primary diagnoses in the National Patient Register or Cause of Death Register (2002–2010). We calculated hazard ratios (HR) and 95% confidence intervals (CI) using multivariable Cox proportional hazards models. Results and limitations: All surgical procedures were associated with increased risk of TED; laparoscopic and open RP with a PLND were the most strongly associated with TED (HR for PE: 8.1 [95% CI, 2.9–23.0] and 7.8 [95% CI, 4.9–13], respectively). For surgery including a PLND, the risk increased during the second half of the first postoperative month. The HR for PE after TURP in men with PCa was 3.0 (95% CI, 1.8–5.1). Patients with a history of TED had a strongly increased risk of TED (HR for DVT: 4.5; 95% CI, 2.6–8.0). A limitation is lack of information on TED prophylaxis, but its use was standardized during the study period for RP and PLND. Other limitations are lack of information on extent of PLND and lifestyle factors. Conclusions: Surgeries for PCa, including TURP, are associated with hospitalization for TED. Patients with a history of TED and patients undergoing a PLND were at highest risk. The largest risk was observed from days 14 to 28 postoperatively. Thus, our results suggest that prophylactic measures may be beneficial during the first 4 wk in these patients. [Copyright &y& Elsevier]

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]

Abstract: Background: To date, adverse events of prostate cancer (PCa) treatment have only been studied as a single event, and little is known about the risk of subsequent adverse events. Objective: We assessed the frequency of multiple events (fractures, stroke, heart disease [HD], and thromboembolic disease [TED]) following PCa diagnosis. Design, setting, and participants: PCBaSe Sweden is based on the National Prostate Cancer Register (NPCR) that covers >96% of incident PCa cases in Sweden. Measurements: We evaluated the number of events (fractures, stroke, HD, and TED) leading to hospitalisation recorded in the National Hospital Discharge Registry after PCa diagnosis and conducted multivariate age-adjusted Cox proportional hazards regression to estimate the risk of developing multiple events. Results and limitations: Between 1997 and 2007, 30 642 men received primary endocrine treatment, 26 432 curative treatment, and 19 526 surveillance: 75% had no event during follow-up, 17% had one event, and 9% had more than one event. The incidence of any event was 102 in 1000 person-years. Men who already had experienced an event, particularly HD, before or after the date of PCa diagnosis were more likely to have multiple events afterwards. For example, the hazard ratio of developing a third event for those with two or more events of HD before PCa diagnosis was 1.40 (95% confidence interval, 1.28–1.52) compared with those with no events of HD before PCa diagnosis. Events treated without hospitalisation were not included, so the number of adverse events is possibly underestimated. Conclusions: A third of PCa patients with an adverse event after treatment subsequently experienced another adverse event, but apart from history of HD or stroke before PCa diagnosis, no specific characteristics were found for these men. Thus PCa management needs to take into account the risk of adverse events in all PCa patients, especially those with a history of adverse events before PCa diagnosis. [Copyright &y& Elsevier]

Abstract: Background: Outcomes for many cancer forms are associated with socioeconomic status (SES).We investigated if SES was associated with management and mortality in men with high risk prostate cancer. Material and methods: A nation-wide population-based cohort in Prostate Cancer Data Base Sweden (PCBaSe), a merged database including data on incident prostate cancer identified in the National Prostate Cancer Register (NPCR) between 1997 and 2006. High risk PCa was defined as T3 tumour, and/or Gleason score 8–10 and/or PSA 20–50ng/mL. Use of bone scan, curative treatment, and mortality in relation to SES was assessed by logistic, Cox, and competing risk regression with hazard ratios (HR), sub-distributed HR and 95% confidence intervals (CI) adjusted for co-morbidity, age, calendar period and clinical subgroups. Results: Amongst 17,522 high risk prostate cancer patients, a bone scan was more often performed in higher white-collar than in blue-collar workers (OR 1.30; 95% CI 1.21–1.40). Amongst men without metastases, the likelihood of intention to treat was higher in higher white-collar workers (OR 1.43; 95% CI 1.28–1.57). In men who received curative treatment, the likelihood was higher to undergo radical prostatectomy for higher white-collar patients (OR 1.29; 95% CI 1.10–1.47). In men without metastases, not only overall mortality was lower amongst higher white-collar workers (HR, 0.76; 95% CI 0.60–0.97), but also prostate cancer-specific mortality (sHR 0.70; 95% CI, 0.49–0.99). Conclusions: We conclude that socioeconomic disparities in the management and mortality in men with high risk prostate cancer exist also within the setting of a National Health Care System aiming to provide care on equal terms to all residents. [Copyright &y& Elsevier]

Background. Metabolic syndrome has been linked to an increased cancer risk, but the role of dyslipidaemia in gastrointestinal malignancies is unclear. We aimed to assess the risk of oesophageal, stomach, colon, and rectal cancers using serum levels of lipid components. Methods. From the Swedish Apolipoprotein Mortality Risk (AMORIS) study, we selected 540,309 participants (> 20 years old) with baseline measurements of total cholesterol (TC), triglycerides (TG), and glucose of whom 84,774 had baseline LDL cholesterol (LDL), HDL cholesterol (HDL), apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I). Multivariate Cox proportional hazards regression was used to assess glucose and lipid components in relation to oesophageal, stomach, colon, and rectal cancer risk. Results. An increased risk of oesophageal cancer was observed in persons with high TG (e.g. HR: 2.29 (95% CI: 1.42-3.68) for the 4th quartile compared to the 1st) and low LDL, LDL/HDL ratio, TC/HDL ratio, log (TG/HDL), and apoB/apoAI ratio. High glucose and TG were linked with an increased colon cancer risk, while high TC levels were associated with an increased rectal cancer risk. Conclusion. The persistent link between TC and rectal cancer risk as well as between TG and oesophageal and colon cancer risk in normoglycaemic individuals may imply their substantiality in gastrointestinal carcinogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To explore whether the self-reported psychological distress among men with prostate cancer was to the extent that it required psychiatric treatment. Methods: PCBaSe Sweden, a merged database based on the National Prostate Cancer Register including 97% of all prostate cancers registered as well as age-matched controls. We calculated relative risks and 95% confidence intervals to compare risks of psychiatric treatment due to depression, anxiety, and post-traumatic stress disorder controlling for age and socio-economic factors. We used odds ratios to compare use or no use of antidepressants. Findings: In total 72,613 men with prostate cancer and 217,839 men without prostate cancer were included for analyses. Psychiatric hospitalisation due to depression, anxiety and post-traumatic stress disorder were significantly increased (RR 1.29, (95% CI 1.14–1.45), RR 1.42 (95% CI 1.12–1.80) and RR 1.61 (95% CI 1.16–2.24), respectively). However, hospitalisations due to anxiety were only increased in men with more advanced tumours RR 2.28 (95% CI 1.45–3.57). The use of antidepressants was increased for all men with prostate cancer RR 1.65 (95% CI 1.54–1.77) and treatment strategies RR 1.93 (95% CI 1.75–2.13). Interpretation: Men diagnosed with prostate cancer had increased risk of psychiatric treatment for depression, post-traumatic stress disorder and use of antidepressants regardless of risk group and treatment strategy compared to age-matched controls, whilst more advanced prostate cancer was associated with severe anxiety disorders. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To explore whether the self-reported psychological distress among men with prostate cancer was to the extent that it required psychiatric treatment. Methods: PCBaSe Sweden, a merged database based on the National Prostate Cancer Register including 97% of all prostate cancers registered as well as age-matched controls. We calculated relative risks and 95% confidence intervals to compare risks of psychiatric treatment due to depression, anxiety, and post-traumatic stress disorder controlling for age and socio-economic factors. We used odds ratios to compare use or no use of antidepressants. Findings: In total 72,613 men with prostate cancer and 217,839 men without prostate cancer were included for analyses. Psychiatric hospitalisation due to depression, anxiety and post-traumatic stress disorder were significantly increased (RR 1.29, (95% CI 1.14–1.45), RR 1.42 (95% CI 1.12–1.80) and RR 1.61 (95% CI 1.16–2.24), respectively). However, hospitalisations due to anxiety were only increased in men with more advanced tumours RR 2.28 (95% CI 1.45–3.57). The use of antidepressants was increased for all men with prostate cancer RR 1.65 (95% CI 1.54–1.77) and treatment strategies RR 1.93 (95% CI 1.75–2.13). Interpretation: Men diagnosed with prostate cancer had increased risk of psychiatric treatment for depression, post-traumatic stress disorder and use of antidepressants regardless of risk group and treatment strategy compared to age-matched controls, whilst more advanced prostate cancer was associated with severe anxiety disorders. [Copyright &y& Elsevier]

Abstract: Background: There are limited prognostic data for locally advanced prostate cancer PCa to guide in the choice of treatment. Objective: To assess mortality in different prognostic categories among men with locally advanced PCa managed with noncurative intent. Design, setting, and participants: We conducted a register-based nationwide cohort study within the Prostate Cancer DataBase Sweden. The entire cohort of locally advanced PCa included 14 908 men. After the exclusion of 2724 (18%) men treated with curative intent, 12 184 men with locally advanced PCa either with local clinical stage T3 or T4 or with T2 with serum levels of prostate-specific antigen (PSA) between 50 and 99 ng/ml and without signs of metastases remained for analysis. Measurements: We followed up the patient cohort in the Cause of Death Register for ≤11 yr and assessed cumulative incidence of PCa -specific death stratified by age and clinical characteristics. Results and limitations: The PCa -specific mortality at 8 yr of follow-up was 28% (95% confidence interval [CI], 25–32%) for Gleason score (GS) 2–6, 41% (95% CI, 38–44%) for GS 7, 52% (95% CI, 47–57%) for GS 8, and 64% (95% CI, 59–69%) for GS 9–10. Even for men aged >85 yr at diagnosis with GS 8–10, PCa was a major cause of death: 42% (95% CI, 37–47%). Men with locally advanced disease and a PSA<4 ng/ml at diagnosis were at particularly increased risk of dying from PCa. One important limitation is the lack of bone scans in 42% of the patient cohort, but results remained after exclusion of patients with unknown metastasis status. Conclusions: The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors. [Copyright &y& Elsevier]

The article investigates associations among triglycerides (TG), total cholesterol (TC), and prostate cancer (pCa) while taking into account glucose. The researchers found no association for hypercholesterolemia. The results also strengthened the hypothesis that factors of the glucose and lipid metabolism influence pCa risk.

Abstract: Background: Prostate-specific antigen (PSA) measurements are increasingly used to monitor men with localised prostate cancer (PCa), but there is little consensus about the method to use. Objective: To apply age-specific predictions of PSA level (developed in men without cancer) to one cohort of men with clinically identified PCa and one cohort of men with PSA-detected PCa. We hypothesise that among men with clinically identified cancer, the annual increase in PSA level would be steeper than in men with PSA-detected cancer. Design, setting, and participants: The Scandinavian Prostate Cancer Group 4 (SPCG-4) cohort consisted of 321 men assigned to the watchful waiting arm of the SPCG-4 trial. The UK cohort consisted of 320 men with PSA-detected PCa in the Prostate testing for cancer and Treatment (ProtecT) study who opted for monitoring. Multilevel models describing changes in PSA level were fitted to the two cohorts, and average PSA level at age 50, change in PSA level with age, and predicted PSA values were derived. Measurements: PSA level. Results and limitations: In the SPCG-4 cohort, mean PSA at age 50 was similar to the cancer-free cohort but with a steeper yearly increase in PSA level (16.4% vs 4.0%). In the UK cohort, mean PSA level was higher than that in the cancer-free cohort (due to a PSA biopsy threshold of 3.0ng/ml) but with a similar yearly increase in PSA level (4.1%). Predictions were less accurate for the SPCG-4 cohort (median difference between observed and predicted PSA level: −2.0ng/ml; interquartile range [IQR]: −7.6–0.7ng/ml) than for the UK cohort (median difference between observed and predicted PSA level: −0.8ng/ml; IQR: −2.1–0.1ng/ml). Conclusions: In PSA-detected men, yearly change in PSA was similar to that in cancer-free men, whereas in men with symptomatic PCa, the yearly change in PSA level was considerably higher. Our method needs further evaluation but has promise for refining active monitoring protocols. [Copyright &y& Elsevier]