Socioeconomic inequality in prostate cancer diagnostics, primary treatment, rehabilitation, and mortality in Sweden.

We designed a nationwide study to investigate the association between socioeconomic factors (household income and education) and different aspects of prostate cancer care, considering both individual- and neighbourhood-level variables. Data were obtained from Prostate Cancer data Base Sweden (PCBaSe), a research database with data from several national health care registers including clinical characteristics and treatments for nearly all men diagnosed with prostate cancer in Sweden. Four outcomes were analysed: use of pre-biopsy magnetic resonance imaging (MRI) in 2018-2020 (n = 11,843), primary treatment of high-risk non-metastatic disease in 2016-2020 (n = 6633), rehabilitation (≥2 dispensed prescriptions for erectile dysfunction within 1 year from surgery in 2016-2020, n = 6505), and prostate cancer death in 7770 men with high-risk non-metastatic disease diagnosed in 2010-2016. Unadjusted and adjusted odds and hazard ratios (OR/HRs) with 95% confidence intervals (CIs) were calculated. Adjusted odds ratio (ORs) comparing low versus high individual education were 0.74 (95% CI 0.66-0.83) for pre-biopsy MRI, 0.66 (0.54-0.81) for primary treatment, and 0.82 (0.69-0.97) for rehabilitation. HR gradients for prostate cancer death were significant on unadjusted analysis only (low vs. high individual education HR 1.41, 95% CI 1.17-1.70); co-variate adjustments markedly attenuated the gradients (low vs. high individual education HR 1.10, 95% CI 0.90-1.35). Generally, neighbourhood-level analyses showed weaker gradients over the socioeconomic strata, except for pre-biopsy MRI. Socioeconomic factors influenced how men were diagnosed with prostate cancer in Sweden but had less influence on subsequent specialist care. Neighbourhood-level socioeconomic data are more useful for evaluating inequality in diagnostics than in later specialist care.

Body mass index, triglyceride-glucose index, and prostate cancer death: a mediation analysis in eight European cohorts.

BACKGROUND: Insulin resistance is a hypothesised biological mechanism linking obesity with prostate cancer (PCa) death. Data in support of this hypothesis is limited. METHODS: We included 259,884 men from eight European cohorts, with 11,760 incident PCa's and 1784 PCa deaths during follow-up. We used the triglyceride-glucose (TyG) index as indicator of insulin resistance. We analysed PCa cases with follow-up from PCa diagnosis, and the full cohort with follow-up from the baseline cancer-free state, thus incorporating both PCa incidence and death. We calculated hazard ratios (HR) and the proportion of the total effect of body mass index (BMI) on PCa death mediated through TyG index. RESULTS: In the PCa-case-only analysis, baseline TyG index was positively associated with PCa death (HR per 1-standard deviation: 1.11, 95% confidence interval (CI); 1.01-1.22), and mediated a substantial proportion of the baseline BMI effect on PCa death (HRtotal effect per 5-kg/m2 BMI: 1.24; 1.14-1.35, of which 28%; 4%-52%, mediated). In contrast, in the full cohort, the TyG index was not associated with PCa death (HR: 1.03; 0.94-1.13), hence did not substantially mediate the effect of BMI on PCa death. CONCLUSIONS: Insulin resistance could be an important pathway through which obesity accelerates PCa progression to death.

Population-based study of disease trajectory after radical treatment for high-risk prostate cancer.

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.

Association between atherogenic lipids and GnRH agonists for prostate cancer in men with T2DM: a nationwide, population-based cohort study in Sweden.

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.

Risk of colorectal adenocarcinoma in men receiving androgen deprivation therapy for prostate cancer; a nationwide cohort study.

PURPOSE: To assess whether androgens play a role in explaining the sex related differences in the incidence of colorectal cancer (CRC). METHODS: A nationwide matched cohort study was conducted employing the Prostate Cancer data Base Sweden (PCBaSe) 4.0 during the study period 2006-2016. Prostate cancer (PC) patients receiving androgen deprivation therapy (ADT) were treated as exposed. Prostate cancer-free men from the general population were randomly selected and matched to the index case by birth year and county of residence, forming the unexposed group. All were followed until a diagnosis of CRC, death, emigration, or end of the study period. The risk of CRC among ADT exposed PC patients compared to unexposed cancer-free men was calculated using a flexible parametric survival model and expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: There was an increased risk of CRC among ADT exposed PC patients compared to unexposed cancer-free men (HR 1.27 [95% CI 1.15-1.41]), in particular an increased risk of adenocarcinoma of the colon (HR 1.33 [95% CI 1.17-1.51]) and more specifically an increased risk of adenocarcinoma of the distal colon (HR 1.53 [95% CI 1.26-1.85]). Examination of latency effects yielded significantly decreased HRs over time for CRC (p = 0.049 for trend). CONCLUSIONS: This population-based study found an increased risk of CRC among PC patients exposed to ADT, specifically adenocarcinoma of the distal colon, which indicates an increased association between ADT (PC + ADT) and CRC but not a positive dose-response trend questioning a true causal effect.

Evidence of cancer progression as the cause of death in men with prostate cancer in Sweden.

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.

Risk of prostate cancer death after radical radiotherapy with neoadjuvant and adjuvant therapy with bicalutamide or gonadotropin-releasing hormone agonists.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Susceptibility to SARS-Cov-2 infection and risk for severe COVID-19 in patients with prostate cancer on androgen deprivation therapy.

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.

Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia.

Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet  = .0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.

Risk of severe late toxicity after radiotherapy following radical prostatectomy - a nationwide study.

OBJECTIVE: To estimate the long-term risks of severe late toxicities for radiation therapy (RT) following radical prostatectomy (RP) in an unselected nationwide cohort, as severe side-effects are rare but may occur years later. PATIENTS AND METHODS: The study population comprised all men undergoing RP between 1997 and 2016 in the Prostate Cancer database Sweden (PCBaSe) (n = 40 962). By (1:2) matching, two cohorts were created: 2789 men exposed to postoperative RT and 5578 unexposed men with comparable age, comorbidities, and year of surgery. Cumulative incidences and rate ratios were calculated for the following outcomes: symptoms and interventions of the urinary or intestinal tract demanding inpatient care, secondary malignancies, and non-prostate cancer mortality. RESULTS: The largest differences were seen for late toxicities affecting the urinary tract. The 10-year cumulative incidences among those exposed to postoperative RT vs the RP-only group were: 17.8% vs 10.5% for procedures of the urinary tract (difference 7.3%, 95% confidence interval [CI] 4.4 to 10.3; relative risk [RR] 1.74, 95% CI 1.47 to 2.05); 6.0% vs 1.2% for haematuria (difference 4.8%, 95% CI 3.1 to 6.5; RR 6.50, 95% CI 4.31 to 10.10); and 2.4% vs 1.1% for bladder cancer (difference 1.4%, 95% CI 0.4 to 2.3; RR 2.71, 95% CI 1.72 to 4.33). The groups were similar regarding intestinal toxicity, other secondary malignancies, and non-prostate cancer mortality. Adjustments for preoperative tumour risk factors did not importantly affect the rate ratios. CONCLUSION: Severe late toxicity after postoperative RT following RP predominately affects the bladder and can appear many years after RT.

The 90-day cause-specific mortality after radical prostatectomy: a nationwide population-based study.

OBJECTIVE: To investigate the cause-specific mortality in the postoperative period after radical prostatectomy (RP) for prostate cancer (PCa). METHODS: In the National Prostate Cancer Register of Sweden (NPCR), we identified all men who died within 90 days after RP performed 1998-2018 and we assessed cause of death in a chart review. We compared the adjudications of death from our medical record review with those in in the Swedish Cause of Death Registry (CDR). RESULTS: Out of 44 635, 58 (0.13%) men who had undergone RP from 1998 through 2018 died within 90 days after RP. Per medical record review the most common causes of death were cardiac disease (30%) and venous thromboembolic events (VTE; 21%). No men died of metastatic PCa as was first indicated in the CDR. After robot-assisted RP (RARP) or open retropubic RP (RRP), the postoperative mortality was 0.09% (19/21 520) and 0.19% (37/19 635), respectively. The effect off modality was confounded mainly by year of surgery, age at surgery, Charlson Comorbidity Index score and the concomitant pelvic lymph node dissection. CONCLUSION: The validated absolute 90-day mortality after RP was 1.3/1000 during the 21-year study period. Cardiovascular diseases were the most common causes of death after RP. Our validation of the CDR refuted the occurrence of postoperative deaths from metastatic PCa. There were differences in rates and type of mortality between RRP and RARP, but the RARP cohort was more recent than the RRP cohort, which likely explain the differences.

Population-based study of long-term anticoagulation for treatment and secondary prophylaxis of venous thromboembolism in men with prostate cancer in Sweden.

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.

Population-based estimates of age and comorbidity specific life expectancy: a first application in Swedish males.

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.

Metabolic factors and the risk of small intestine cancers: Pooled study of 800 000 individuals in the metabolic syndrome and cancer project.

To explore the largely unknown etiology of small intestine cancer, we examined metabolic factors and risk of small intestine cancer overall and by subtypes. Among 404 220 women and 403 265 men in six European cohorts, we applied Cox regression with adjustment for smoking and body mass index (BMI), to calculate sex-specific hazard ratios (HRs) of small intestine cancer by levels of BMI, mean arterial pressure (MAP) and plasma total cholesterol, triglycerides and glucose. We also calculated HRs for these factors combined (metabolic score; MetS) and used Wald test statistics to investigate pairwise interactions between metabolic factors on risk. We also performed analyses separately per subtype (neuroendocrine tumors [NETs] and adenocarcinomas). During a median follow-up of 16.9 years, 144 women and 195 men were diagnosed with small intestine cancer, including 184 NETs and 99 adenocarcinomas. Among men, no main associations or interactions between metabolic factors were observed in relation to the risk of small intestine cancer. Among women, triglycerides were positively and linearly associated with risk (HR per standard deviation [SD]: 1.23, 95% confidence interval [CI]: 1.04-1.46), and a positive association was also observed for the MetS (HR per SD: 1.25, 95% CI: 1.02-1.52). Positive interactions were observed among women between triglycerides and cholesterol (P = .0005), and between MAP and glucose (P = .009), on risk. Glucose was positively associated with adenocarcinomas among women. This large, prospective study suggests that elevated triglycerides, and metabolic factors in interaction, confer an increased risk of small intestine cancer among women, but not among men.

Comparison of Relative Survival and Cause-Specific Survival in Men With Prostate Cancer According to Age and Risk Category: A Nationwide, Population-Based Study.

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.

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

BACKGROUND: The ability to account for comorbidity when estimating survival in a population diagnosed with cancer could be improved by using a drug comorbidity index based on filled drug prescriptions. METHODS: We created a drug comorbidity index from age-stratified univariable associations between filled drug prescriptions and time to death in 326,450 control males randomly selected from the general population to men with prostate cancer. We also evaluated the index in 272,214 control females randomly selected from the general population to women with breast cancer. RESULTS: The new drug comorbidity index predicted survival better than the Charlson Comorbidity Index (CCI) and a previously published prescription index during 11 years of follow-up. The concordance (C)-index for the new index was 0.73 in male and 0.76 in the female population, as compared with a C-index of 0.67 in men and 0.69 in women for the CCI. In men of age 75-84 years with CCI = 0, the median survival time was 7.1 years (95% confidence interval [CI] = 7.0, 7.3) in the highest index quartile. Comparing the highest to the lowest drug comorbidity index quartile resulted in a hazard ratio (HR) of 2.2 among men (95% CI = 2.1, 2.3) and 2.4 among women (95% CI = 2.3, 2.6). CONCLUSIONS: A new drug comorbidity index based on filled drug prescriptions improved prediction of survival beyond age and the CCI alone. The index will allow a more accurate baseline estimation of expected survival for comparing treatment outcomes and evaluating treatment guidelines in populations of people with cancer.

Exploring the association between use of gonadotropin releasing hormones agonists and prostate cancer diagnosis per se and diabetes control in men with type 2 diabetes mellitus: a nationwide, population-based cohort study.

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.

Simulation model of disease incidence driven by diagnostic activity.

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.

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

BACKGROUND AND OBJECTIVE: Changes in diagnostic work-up, histopathological assessment, and treatment of men with prostate cancer during the last 20 years have affected the prognosis. The objective was to investigate the risk of prostate cancer death in men with clinically localised prostate cancer treated with radical prostatectomy in Sweden in 2000-2010. METHODS: Population-based, nationwide, study on men with clinically localised prostate cancer treated with radical prostatectomy in the period 2000-2010. Cox regression analyses were used to assess differences in risk of prostate cancer death according to calendar period for diagnosis and stratified on risk category. RESULTS: The study included 19 330 men with a median follow-up of 12.4 years. Men diagnosed in 2007-2008 and 2009-2010 had a significantly lower risk of prostate cancer death compared to men diagnosed in 2000-2002. The reduced risk of prostate cancer death was restricted to men with intermediate-risk prostate cancer with no differences observed in men with low- or high-risk prostate cancer. CONCLUSION: During the study period, the risk of prostate cancer death decreased in the total population of men with localised prostate cancer treated with radical prostatectomy. The decrease was restricted to men with intermediate-risk prostate cancer.

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

BACKGROUND: There are little and inconsistent data from clinical practice on time on treatment with the androgen receptor-targeted drugs (ART) abiraterone and enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC). We assessed time on treatment with ART and investigated predictors of time on treatment. MATERIAL AND METHODS: Time on treatment with ART in men with mCRPC in the patient-overview prostate cancer (PPC), a subregister of the National Prostate Cancer Register (NPCR) of Sweden, was assessed by use of Kaplan-Meier plots and Cox regression. To assess the representativity of PPC for time on treatment, a comparison was made with all men in NPCR who had a filling for ART in the Prescribed Drug Registry. RESULTS: 2038 men in PPC received ART between 2015 and 2019. Median time on treatment in chemo-naïve men was 10.8 (95% confidence interval 9.1-13.1) months for abiraterone and 14.1 (13.5-15.5) for enzalutamide. After the use of docetaxel, time on treatment was 8.2 (6.5-12.4) months for abiraterone and 11.1 (9.8-12.6) for enzalutamide. Predictors of a long time on treatment with ART were long duration of ADT prior to ART, low serum levels of PSA at start of ART, absence of visceral metastasis, good performance status, and no prior use of docetaxel. PPC captured 2522/6337 (40%) of all men in NPCR who had filled a prescription for ART. Based on fillings in the Prescribed Drug Registry, men in PPC had a slightly longer median time on treatment with ART compared to all men in NPCR, 9.6 (9.1-10.3) vs. 8.6 (6.3-9.1) months. CONCLUSIONS: Time on treatment in clinical practice was similar or shorter than that in published RCTs, due to older age, poorer performance status and more comorbidities.