Cumulative incidence of second primary cancers in a large nationwide cohort of Danish cancer survivors: a population-based retrospective cohort study.

BACKGROUND: A new primary cancer is a serious late effect of a pre-existing cancer diagnosis, and can be attributed to hereditary cancer syndromes, immune or hormonal factors, cancer treatment, or modifiable lifestyle or environmental factors. We investigated the absolute and relative incidence of second primary cancers in a large cohort of Danish cancer survivors. Furthermore, we examined the association between alcohol-related, smoking-related, virus-related, and hormone-related first and second primary cancers. METHODS: In this retrospective cohort study, we identified a cohort of Danish adults (aged ≥40 years) diagnosed with cancer from Jan 1, 1997, to Dec 31, 2014 and alive 1 year after diagnosis. Follow-up was from date of first cancer diagnosis and lasted up to 24 years, ending on Dec 31, 2020. Cohort identification and information on second primary cancers was obtained from the Danish Cancer Registry, and comorbidity and sociodemographic information was obtained from Danish population-based registries. Overall, and for 27 cancer types, cumulative incidence functions and Cox proportional hazard regression models were used to estimate the incidence of second primary cancer and death, and hazard ratios (HRs) and 95% CIs of second primary cancer adjusted for sex, age and year of diagnosis, cohabitation status, income, and comorbidity. FINDINGS: 457 334 Danish adults were included in our study (230 150 [50·3%] male individuals and 227 184 [49·7%] female individuals; median age at diagnosis 68·3 years, IQR 59·7-76·6; median follow-up 3·6 years, IQR 0·6-9·3). The cumulative incidence of second primary cancer increased over time from 6·3% (95% CI 6·2-6·4) 5 years after diagnosis to 10·5% (10·4-10·6) 10 years after diagnosis and to 13·5% (13·4-13·7) 15 years after diagnosis. The highest cumulative incidence of second primary cancer 10 years after diagnosis was observed in survivors of cancers in the larynx (21·8%, 20·5-23·1), oropharynx and oral cavity (19·5%, 18·7-20·3), and bladder and urinary tract (18·5%, 18·0-19·0). Survivors of cancers related to alcohol (HR 1·09, 95% CI 1·06-1·13), smoking (1·73, 1·68-1·78), diet high in red or processed meat (1·32, 1·24-1·39), or virus (1·23, 1·13-1·35) were at increased risk of developing a second cancer with the same aetiology, whereas having had a hormone-related first cancer was associated with lower risk of a second hormone-related cancer (0·77, 0·73-0·81). INTERPRETATION: Our results could help optimise prevention efforts targeting modifiable risk factors to reduce risk of developing a second primary cancer. FUNDING: Nordic Cancer Union and The Health Foundation (Helsefonden).

Early experience with targeted and combination biopsies in prostate cancer work-up in Denmark from 2012 to 2016.

PURPOSE: To investigate the early implementation of combined systematic and targeted (cBx) primary biopsy in prostate cancer diagnosis and define the concordance in Gleason grading (GG) of different biopsy techniques with radical prostatectomy (RP) pathology. METHODS: This population-based analysis includes data on all men in Denmark who underwent primary cBx or standalone systematic (sBx) prostate biopsy between 2012 and 2016. Biopsy results were compared to RP pathology if performed within a year. Concordance measurement was estimated using Cohen's Kappa, and the cumulative incidence of cancer-specific death was estimated at 6 years with the Aalen-Johansen estimator. RESULTS: Concordance between biopsy and RP pathology was 0.53 (95CI: 0.43-0.63), 0.38 (95CI: 0.29-0.48), and 0.16 (95CI: 0.11-0.21) for cBx, targeted biopsy (tBx), and sBx, respectively. For standalone sBx and RP, concordance was 0.29 (95CI: 0.27-0.32). Interrelated GG concordance between tBx and sBx was 0.67 (95CI: 0.62-0.71) in cBx. The proportion of correctly assessed GG based on RP pathology was 54% in both cBx and standalone sBx. Incidence of prostate cancer-specific death was 0% regardless of biopsy technique in GG 1, and 22% (95CI: 11-32), 30% (95CI: 15-44), and 19% (95CI: 7.0-30) in GG 5 for cBx, tBx, or sBx, respectively. CONCLUSION: Overall, the cBx strategy demonstrates higher concordance to RP pathology than the standalone sBx. However, cBx exhibits more overgrading of the GG of RP pathology compared to sBx. Ultimately, the classic grading system does not take change in the diagnostic pathway into account, and grading should be altered accordingly to ensure appropriate treatment.

Standardized prostate cancer incidence and mortality rates following initial non-malignant biopsy result.

OBJECTIVES: To compare the incidence of subsequent prostate cancer diagnosis and death following an initial non-malignant systematic transrectal ultrasonography (TRUS) biopsy with that in an age- and calendar-year matched population over a 20-year period. SUBJECTS AND METHODS: This population-based analysis compared a cohort of all men with initial non-malignant TRUS biopsy in Denmark between 1995 and 2016 (N = 37 231) with the Danish population matched by age and calendar year, obtained from the NORDCAN 9.1 database. Age- and calendar year-corrected standardized prostate cancer incidence (SIR) and prostate cancer-specific mortality ratios (SMRs) were calculated and heterogeneity among age groups was assessed with the Cochran's Q test. RESULTS: The median time to censoring was 11 years, and 4434 men were followed for more than 15 years. The corrected SIR was 5.2 (95% confidence interval [CI] 5.1-5.4) and the corrected SMR was 0.74 (95% CI 0.67-0.81). Estimates differed among age groups (P < 0.001 for both), with a higher SIR and SMR among younger men. CONCLUSION: Men with non-malignant TRUS biopsy have a much higher incidence of prostate cancer but a risk of prostate cancer death below the population average. This underlines that the oncological risk of cancers missed in the initial TRUS biopsy is low. Accordingly, attempts to increase the sensitivity of initial biopsy are unjustified. Moreover, current follow-up after non-malignant biopsy is likely to be overaggressive, particularly in men over the age of 60 years.

Impact of previous depression on the risk of suicide among prostate cancer patients.

BACKGROUND: Prior studies of suicide risk among prostate cancer patients are conflicting. We compared the risk of suicide in prostate cancer patients to cancer-free men including adjustment for clinical stage, socioeconomic position, somatic comorbidity, and previous depression. MATERIALS AND METHODS: A cohort of 37,527 men diagnosed with prostate cancer in Denmark during 1998-2011 was identified in the Danish Prostate Cancer Registry (DaPCaR) and compared with 357,384 cancer-free men matched by age at the time of diagnosis. The primary outcome was death from suicide. Data were analyzed using cumulative incidence functions and multivariable Cox regression models. RESULTS: Among prostate cancer patients, 3813 had a previous depression, defined as filed antidepressant prescription within three years before diagnosis. In the study period, 108 prostate cancer patients were registered with suicide as the cause of death, hereof 26 with previous depression. There was no difference in the cumulative incidence of suicide between prostate cancer patients and cancer-free men. There was no effect modification of previous depression on the risk of suicide (p = .12). The hazard ratio (HR) for suicide varied with time since diagnosis. A sensitivity analysis showed that the risk of suicide was highest within the first year of diagnosis where prostate cancer patients had a 1.70-fold increased hazard compared with cancer-free men (95% CI, 1.11-2.59). Men with prostate cancer and previous depression had a three-fold increased hazard for suicide compared with prostate cancer patients without a history of depression (HR 2.84, 95% CI, 1.82-4.45). CONCLUSION: The absolute risk of suicide is low following a prostate cancer diagnosis. Time since diagnosis and a history of depression was associated with the highest risk of suicide. Healthcare professionals should be aware of an increased risk of suicide among men with previous depression, especially in the immediate aftermath of the diagnosis.

Cardiovascular events after elective colorectal cancer surgery in patients with stage I-III disease with no previous cardiovascular disease.

BACKGROUND: The risk of cardiovascular events in patients treated for colorectal cancer is debated due to diverging results in previous studies. Colorectal cancer and cardiovascular disease share several risk factors such as physical inactivity, obesity, and smoking. Information about confounding covariates and follow-up time are therefore essential to address the issue. This study aims to investigate the risk of new-onset cardiovascular events for patients with stage I-III colorectal cancer receiving elective surgery compared to a matched population. MATERIAL AND METHODS: Using a prospective cohort, we compared cardiovascular events among 876 patients treated with elective surgery for incident stage I-III colorectal cancer diagnosed between January 1st, 2001 and December 31st, 2016 to a cancer-free cohort matched by age, sex, and time since enrollment (N = 3504). Regression analyses were adjusted for lifestyle, cardiovascular risk factors, and comorbidity. Multivariable analyses were used to identify risk factors associated with cardiovascular events in the postoperative (<90 days of elective surgery) and long-term phase (>90 days after elective surgery). RESULTS: After a median follow-up of 3.9 years, the hazard ratio (HR) for incident heart failure was 1.53 (95% CI 1.02-2.28) among patients operated for colorectal cancer. The postoperative risk of myocardial infarction or angina pectoris was associated with the use of lipid-lowering drugs. Long-term risks of cardiovascular events were ASA-score of III+IV and lipid-lowering drugs with HRs ranging from 2.20 to 15.8. Further, the use of antihypertensive drugs was associated with an HR of 2.09 (95% CI 1.06-4.13) for angina pectoris or acute myocardial infarction. Heart failure was associated with being overweight, diabetes, and anastomosis leakage. CONCLUSION: We observed an increased hazard of heart failure in patients operated on for stage I-III colorectal cancer compared to cancer-free comparisons. We identified several potential risk factors for cardiovascular events within and beyond 90 days of elective surgery.

Educational differences in healthcare use among survivors after breast, prostate, lung, and colon cancer - a SEQUEL cohort study.

BACKGROUND: Many cancer survivors experience late effects after cancer. Comorbidity, health literacy, late effects, and help-seeking behavior may affect healthcare use and may differ among socioeconomic groups. We examined healthcare use among cancer survivors, compared with cancer-free individuals, and investigated educational differences in healthcare use among cancer survivors. METHODS: A Danish cohort of 127,472 breast, prostate, lung, and colon cancer survivors from the national cancer databases, and 637,258 age- and sex-matched cancer-free individuals was established. Date of entry was 12 months after diagnosis/index date (for cancer-free individuals). Follow-up ended at death, emigration, new primary cancer, December 31st, 2018, or up to 10 years. Information about education and healthcare use, defined as the number of consultations with general practitioner (GP), private practicing specialists (PPS), hospital, and acute healthcare contacts 1-9 years after diagnosis/index date, was extracted from national registers. We used Poisson regression models to compare healthcare use between cancer survivors and cancer-free individuals, and to investigate the association between education and healthcare use among cancer survivors. RESULTS: Cancer survivors had more GP, hospital, and acute healthcare contacts than cancer-free individuals, while the use of PPS were alike. One-to-four-year survivors with short compared to long education had more GP consultations (breast, rate ratios (RR) = 1.28, 95% CI = 1.25-1.30; prostate, RR = 1.14, 95% CI = 1.10-1.18; lung, RR = 1.18, 95% CI = 1.13-1.23; and colon cancer, RR = 1.17, 95% CI = 1.13-1.22) and acute contacts (breast, RR = 1.35, 95% CI = 1.26-1.45; prostate, RR = 1.26, 95% CI = 1.15-1.38; lung, RR = 1.24, 95% CI = 1.16-1.33; and colon cancer, RR = 1.35, 95% CI = 1.14-1.60), even after adjusting for comorbidity. One-to-four-year survivors with short compared to long education had less consultations with PPS, while no association was observed for hospital contacts. CONCLUSION: Cancer survivors used more healthcare than cancer-free individuals. Cancer survivors with short education had more GP and acute healthcare contacts than survivors with long education. To optimize healthcare use after cancer, we need to better understand survivors' healthcare-seeking behaviors and their specific needs, especially among survivors with short education.

Prescription rates for commonly used drugs before and after a prostate cancer diagnosis.

PURPOSE: To investigate differences in prescription rates of commonly used drugs among prostate cancer patients and cancer-free comparisons and between patients diagnosed with localized and non-localized disease. METHODS: We conducted a register-based study including all men aged 50-85 years diagnosed with prostate cancer in Denmark from 1998 to 2015 and an age-matched cancer-free comparison cohort. We calculated the number of new and total prescriptions from three years before to three years after the date of diagnosis of the case for selected drug classes divided by the number of person-months and stratified by stage at diagnosis. RESULTS: We included 54,286 prostate cancer patients and 249,645 matched comparisons. 30,712 patients were diagnosed with localized disease and 12,884 with non-localized disease. The rates of new prescriptions increased considerably among patients within the year before the diagnosis. Hereafter the rates varied between drug classes. For most drug classes, total prescription rates for patients and comparisons increased similarly in the study period. Total prescription rates varied between men with localized and non-localized disease for all drug classes apart from statins. CONCLUSION: Our findings indicate that a large proportion of prostate cancer cases are likely diagnosed during medical work-up for other reasons than prostate cancer. Increased rates occur within the last year before diagnosis and future studies on the interaction between drug use and prostate cancer should at least include a one year pre-diagnostic lag-time. Post-diagnostic prescription rates demonstrated an increased use of drugs most likely associated with the consequences of the disease.

A Nationwide Analysis of Risk of Prostate Cancer Diagnosis and Mortality following an Initial Negative Transrectal Ultrasound Biopsy with Long-Term Followup.

PURPOSE: Magnetic resonance imaging (MRI) targeted prostate biopsy has been shown to find many high-grade prostate cancers in men with concurrent negative transrectal ultrasound (TRUS) systematic biopsy. The oncologic risk of such tumors can be explored by looking at long-term outcomes of men with negative TRUS biopsy followed without MRI. The aim was to analyze the mortality after initial and second negative TRUS biopsy. MATERIALS AND METHODS: All men who underwent initial TRUS biopsies between January 1, 1995 and December 31, 2016 in Denmark were included. A total of 37,214 men had a negative initial TRUS biopsy and 6,389 underwent a re-biopsy. Risk of cause-specific mortality was analyzed with competing risks. Diagnosis of Gleason score ≥7 prostate cancer following negative biopsies was analyzed with multivariable logistic regression including time to re-biopsy, prostate specific antigen (PSA), age and digital rectal examination. RESULTS: The 15-year prostate cancer-specific mortality was 1.9% (95% CI: 1.7-2.1). Prostate cancer-specific mortality was 1.3% (95% CI: 0.9-1.6) and 4.6% (95% CI: 3.4-5.8) for men with PSA <10 and >20 ng/ml, respectively. Of the TRUS re-biopsies 12% were Gleason score ≥7 and risk of Gleason score ≥7 increased with longer time to re-biopsy (p <0.001). Mortality after re-biopsy was similar to after initial biopsy. CONCLUSIONS: Men with negative TRUS biopsies have a very low prostate cancer-specific mortality, especially with PSA <10 ng/ml. This raises serious questions about the routine use of MRI targeting for initial prostate biopsy and suggests that MRI targeting should only be recommended for men with PSA >10 ng/ml after negative biopsy.

Prescription rates for drugs used in treatment of benign prostatic hyperplasia and erectile dysfunction before and after prostate cancer diagnosis.

BACKGROUND: Symptoms and treatment of benign prostatic hyperplasia (BPH) or erectile dysfunction (ED) may lead to prostate cancer workup, and patterns of prescriptions before diagnosis may affect findings of pharmacoepidemiological studies. Usage of BPH and ED drugs after diagnosis may be related to prostate cancer treatment. We investigated differences in prescription rates of BPH and ED drugs among prostate cancer patients and cancer-free comparisons and between patients with localized and non-localized disease. MATERIAL AND METHODS: A nationwide register-based study, including all Danish men aged 50-85 years diagnosed with prostate cancer during 1998-2015 and an age-matched comparison cohort without cancer. We calculated rates of new and total prescriptions in 1-month intervals from 3 years before to 3 years after cancer diagnosis for drugs used to treat BPH and ED, overall and stratified by clinical stage. RESULTS: We identified 54,286 men with prostate cancer and a comparison cohort of 249,645 age-matched men. The new prescription rate for BPH drugs increased for men with prostate cancer in the year before diagnosis and peaked 1 month before diagnosis with an 18-fold higher rate. Men with prostate cancer had a higher total prescription rate of BPH drugs 3 years before diagnosis, notably among men with localized disease. Before diagnosis, the new prescription rates for ED drugs were similar among men with prostate cancer and comparisons. After diagnosis, men with prostate cancer had a 7-fold higher rate of new prescriptions for ED drugs. Among men with localized disease, the total prescription rate of ED drugs increased in the months following diagnosis. CONCLUSION: Differences in prescription rates suggest increased prostate cancer surveillance among men receiving BPH drugs, whereas the post-diagnostic increase in ED drugs among men with localized disease is compatible with the increased risk of ED following prostate cancer treatment.

Risk of depression after diagnostic prostate cancer workup - A nationwide, registry-based study.

OBJECTIVE: To compare the risk of depression after diagnostic workup for prostate cancer (PCa), regardless of the histopathologic outcome, with that of a cancer-free population. METHODS: A nationwide cohort of Danish men who had a prostatic biopsy sample in 1998-2011 was identified from the Danish Prostate Cancer Registry and compared to an age-matched cohort from the background population. Men with other cancers, major psychiatric disorder, or prior use of antidepressants were excluded. The risk of depression defined as hospital contact for depression or prescription for antidepressants was determined from cumulative incidence functions and multivariate Cox regression models. RESULTS: Of 54,766 men who underwent diagnostic workup for PCa, benign results were found for 21,418 and PCa was diagnosed in 33,347. During up to 18 years of follow-up, the adjusted hazard of depression was higher in men with PCa than in the background population, with the highest risk in the two years after diagnosis (hazard ratio (HR) 2.77, 95% CI 2.66-2.87). Comorbidity and lowest or highest income were significant risk factors for depression and the cumulative incidence was substantially higher in men with metastatic or high-risk disease. In men with benign histopathology the HR for depression was 1.22 (95% CI 1.14-1.31) in the first two years but no different from the background population after that. CONCLUSIONS: Diagnostic workup for PCa is associated with an increased risk of depression, mainly among men with a diagnosis of PCa. Clinicians should be aware of depressive symptoms in prostate cancer patients.

Associations of low-dose aspirin or other NSAID use with prostate cancer risk in the Danish Diet, Cancer and Health Study.

PURPOSE: Epidemiologic studies suggest that use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce prostate cancer risk. We examined these associations overall and according to clinical and lifestyle parameters. METHODS: We identified male participants in the Danish Diet, Cancer and Health Study (n = 26,339), holding information on anthropometric measures and lifestyle factors. From Danish nationwide registries and medical records, we retrieved complete prescription histories and prostate cancer occurrence and characteristics. Cox regression was used to estimate hazard ratios (HRs) for prostate cancer associated with low-dose aspirin or nonaspirin NSAID use, overall and by clinical characteristics, anthropometric measures, and lifestyle factors. RESULTS: We identified 1,927 prostate cancer cases during a median follow-up of 17.0 years. Low-dose aspirin use was not associated with overall prostate cancer risk, but a reduced HR for nonaggressive prostate cancer (high use [≥ 1,825 tablets]: 0.79; 95% confidence interval (CI) 0.60-1.04) and an increased HR for aggressive disease (high use: 1.27; 95% CI 1.00-1.61) was observed with low-dose aspirin use. Long-term, high-intensity use (≥ 10 years with ≥ 0.25 defined daily doses/day) of nonaspirin NSAIDs was associated with an increased HR for prostate cancer (1.35, 95% CI 0.99-1.84), confined to localized and nonaggressive disease. No consistent variation in HRs was seen in analyses stratified by height, body mass index, smoking, and alcohol use. CONCLUSION: Low-dose aspirin or other NSAID use was not associated with reduced prostate cancer risk, neither overall nor according to anthropometric measures, smoking, or alcohol use. The variation according to outcome characteristics warrants further investigation.

Use of Low-Dose Aspirin and Mortality After Prostate Cancer Diagnosis: A Nationwide Cohort Study.

Background: Recent studies suggest that aspirin use may improve survival in patients with prostate cancer. Objective: To assess the association between postdiagnosis use of low-dose aspirin and prostate cancer mortality. Design: Nationwide cohort study. Setting: Denmark. Patients: Men with incident prostate adenocarcinoma between 2000 and 2011. Measurements: Nationwide registry data on tumor characteristics, drug use, primary prostate cancer therapy, comorbidity, and socioeconomic parameters. Postdiagnosis use of low-dose aspirin (75 to 150 mg) was defined as 2 or more prescriptions filled within 1 year after prostate cancer diagnosis. Follow-up started 1 year after prostate cancer diagnosis. In secondary analyses, low-dose aspirin use was assessed within exposure periods of 5 or 7.5 years after prostate cancer diagnosis. Results: Of 29 136 patients (median age, 70 years), 7633 died of prostate cancer and 5575 died of other causes during a median follow-up of 4.9 years (interquartile range, 3.1 to 7.2 years), through 2015. Postdiagnosis low-dose aspirin use was associated with adjusted hazard ratios (HRs) of 0.95 (95% CI, 0.89 to 1.01) for prostate cancer-specific mortality and 1.12 (CI, 1.05 to 1.20) for other-cause mortality. The secondary analyses showed that prostate cancer mortality was slightly reduced with low-dose aspirin use after the 5-year (HR, 0.91 [CI, 0.83 to 1.01]) and 7.5-year (HR, 0.84 [CI, 0.72 to 0.97]) postdiagnosis exposure periods, notably among patients filling prescriptions for a large quantity of low-dose aspirin tablets during the 7.5-year period. Limitations: Data on over-the-counter aspirin use were unavailable. Some residual confounding was possible as a result of incomplete data on some prognostic factors. Conclusion: The study did not support an overall effect of postdiagnosis low-dose aspirin use on prostate cancer mortality. However, results for extended exposure periods suggest that low-dose aspirin use might be inversely associated with prostate cancer mortality after 5 years from cancer diagnosis. Primary Funding Source: Danish Cancer Society.

Risk of cardiovascular events in men treated for prostate cancer compared with prostate cancer-free men.

BACKGROUND: The effect of lifestyle, anthropometry and cardiovascular risk factors on cardiovascular disease in men with prostate cancer (PCa) remains unclear. METHODS: Using a population-based cohort of 25,436 Danish, cancer-free men aged 50-64 years, we obtained information on self-reported pre-cancer lifestyle, objectively measured anthropometry and cardiovascular risk factors, and linked them to national health registers for information on major cardiovascular outcomes. We assessed hazard ratios (HRs) of incident acute myocardial infarction (MI), ischaemic stroke (IS) and heart failure (HF) among 1546 men diagnosed with PCa treated with first-line active surveillance, watchful waiting, intended curative or palliative treatment compared with PCa-free men during 18 years of follow-up. RESULTS: Men who received first-line palliative treatment had higher rates of IS and HF with adjusted HRs of 2.09 (95% CI 1.49-2.93) and 2.05 (95% CI 1.43-2.94), respectively, compared with PCa-free men. The risks were increased from start of treatment. We did not find the same relation for men in any other treatment group. No differences between men treated for PCa and cancer-free controls were observed for MI after adjustment for lifestyle, anthropometry, and cardiovascular risk factors. CONCLUSION: Pre-diagnosis lifestyle, anthropometry or cardiovascular risk factors did not explain the risk of IS and HF in PCa patients receiving palliative treatment. The results emphasise the need for balancing disease management and monitoring of cardiovascular health in this patient group.

The association between education and risk of major cardiovascular events among prostate cancer patients: a study from the Diet, Cancer and Health study.

Background: High socioeconomic position is associated with better prognosis in prostate cancer patients but it is unknown if part of this association may be explained by socioeconomic differences in severe late effects. We investigated the association between education as an indicator for socioeconomic position and cardiovascular events after prostate cancer and if such associations were mediated by differences in lifestyle, cardiovascular risk factors and prostate cancer treatment. Material and methods: We identified 1980 men diagnosed with prostate cancer from 1993 to 2014 among participants in the Danish Diet, Cancer and Health study. Individual level information on education, lifestyle, cardiovascular risk factors and prostate cancer clinical information were obtained from questionnaires, registries and medical records. The Cox proportional hazards models were used to evaluate the risk of incident acute myocardial infarction, ischemic stroke and heart failure during up to 18 years of follow-up for men with short (<9 years) or medium (9-12 years) compared with long education (>12 years). Results: Compared to men with long education, we found an increased risk of acute myocardial infarction in men with medium and short education (HR 3.14, 95% CI 1.53-6.47 and HR 2.14, 95% CI 0.82-5.58, respectively). Adjusting for stage, first-line treatment, lifestyle and cardiovascular risk factors did not change the HRs substantially (adjusted HRs 3.04, 95% CI 1.47-6.31 and 2.07, 95% CI 0.78-5.53, respectively). There were no educational differences in risk for ischemic stroke or heart failure. Conclusions: The risk of acute myocardial infarction was increased in prostate cancer patients with short or medium education compared with long education. Although the educational inequality did not seem to be explained by differences in treatment, lifestyle or cardiovascular risk factors, monitoring of cardiovascular health and health promotion should involve all prostate cancer patients regardless of social position to ensure best prognosis for all.

Pre-diagnostic changes in body mass index and mortality among breast cancer patients.

PURPOSE: We investigated whether changes in body mass index (BMI) before a breast cancer diagnosis affected mortality and whether trajectories more accurately predict overall mortality compared to a single measure of BMI. METHODS: Our prospective cohort comprised 2012 women with breast cancer who reported their weight in each decade from 20 to 50-64 years of age. We used trajectory analysis to identify groups with similar development patterns in BMI and Cox proportional hazards models to examine the association between trajectory groups and mortality, and interactions with oestrogen receptor status and smoking. We used c-index statistics to compare the trajectory model with the single measure model of BMI. RESULTS: We identified three distinct trajectory groups, with a mean BMI at age 20 of 19, 22 and 24 increasing to 23 (normal-to-normal), 29 (normal-to-overweight) and 37 (normal-to-obese) at 50-64 years of age, respectively. Women in the normal-to-obese trajectory group experienced significantly higher overall mortality than those in the normal-to-normal trajectory group (HR 1.76, 95% CI 1.21‒2.56). The association declined to a non-significant level after adjustments for clinical prognostic factors. Although not significant, the same tendency was seen for breast cancer-specific mortality. The association was strongest in women with oestrogen receptor-negative tumours. Weight changes over time were not significantly different from a single BMI measure before diagnosis to predict survival. CONCLUSION: Weight gain affects overall mortality after breast cancer but clinical prognostic factors largely eliminate the association. Using trajectories of weight changes did not improve the predictive value compared to a single measure of BMI.

Socioeconomic position and mortality among patients with prostate cancer: influence of mediating factors.

INTRODUCTION: Men with low socioeconomic position experience higher mortality after a prostate cancer diagnosis compared to men with a higher socioeconomic position, however, the specific mediators of this association are unclear. We therefore evaluated the influence of potential mediators on the association between socioeconomic position, and prostate cancer-specific and all-cause death in prostate cancer patients. MATERIALS AND METHODS: We conducted a cohort study of prostate cancer patients in the Danish Diet, Cancer and Health study. All patients completed questionnaires and anthropometric measurements at enrollment. Information on educational level, income, comorbidity and vital status was obtained by linkage to Danish nationwide registries. Clinical data and anthropometric measures were collected from medical records at diagnosis. Cox proportional hazard models were used to compute hazard ratios (HR) for all-cause and prostate cancer-specific death according to socioeconomic position and potential mediators. RESULTS: We included 953 prostate cancer patients identified among 27 179 male participants in the Diet, Cancer and Health study who were followed for a median of 6.5 years (interquartile range 6.4-11.2 years). Patients with low socioeconomic position were more often overweight or obese at baseline. Low socioeconomic position was associated with increased prostate cancer-specific and all-cause death. The increased mortality could largely be explained by tumor aggressiveness, comorbidity, treatment and metabolic indicators, except for patients in the lowest income group. DISCUSSION: Our study confirmed the a priori assumption that socioeconomic position is associated with increased mortality after prostate cancer. The increased mortality could largely be explained by lifestyle and clinical parameters.

Early life risk factors for testicular cancer: a case-cohort study based on the Copenhagen School Health Records Register.

PURPOSE: One established risk factors for testicular cancer is cryptorchidism. However, it remains unclear whether cryptorchidism is a risk factor in itself or whether the two conditions share common causes in early life (estrogen hypothesis), such as birth weight and birth order. The objective of this study is to utilize data from the Copenhagen School Health Records Register (CSHRR) to evaluate cryptorchidism, birth weight and birth order as risk factors for testicular cancer. METHODS: The study population consisted of 408 cases of testicular cancer identified by a government issued identification number linkage of the entire CSHRR with the Danish Cancer Registry and a random subsample of 4819 males from the CSHRR. The study design was case-cohort and the period of follow-up between 2 April 1968 and 31 December 2003. RESULTS: Cryptorchidism was significantly associated with testicular cancer in crude analyses [hazard ratio (HR) = 3.60, 95% CI 2.79-4.65]. Birth weight was inversely associated with testicular cancer and no clear association with birth order was observed. The positive association between cryptorchidism and testicular cancer was only slightly attenuated controlling for birth weight and birth order and stratified on birth cohort (HR = 3.46, 95% CI 2.67-4.48). CONCLUSION: This study confirmed the robustness of the association between cryptorchidism and testicular cancer even after adjustment for birth weight and birth order. Furthermore, the study showed an inverse association between birth weight and testicular cancer.

Low-dose aspirin or other nonsteroidal anti-inflammatory drug use and prostate cancer risk: a nationwide study.

PURPOSE: Increasing evidence suggests that aspirin use may protect against prostate cancer. In a nationwide case-control study, using Danish high-quality registry data, we evaluated the association between the use of low-dose aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of prostate cancer. METHODS: We identified 35,600 patients (cases) with histologically verified prostate cancer during 2000-2012. Cases were matched to 177,992 population controls on age and residence by risk-set sampling. Aspirin and nonaspirin NSAID exposure was defined by type, estimated dose, duration, and consistency of use. We used conditional logistic regression to estimate odds ratios (ORs), with 95 % confidence intervals (CIs), for prostate cancer associated with low-dose aspirin (75-150 mg) or nonaspirin NSAID use, adjusted for potential confounders. RESULTS: Use of low-dose aspirin was associated with an OR for prostate cancer of 0.94 (95 % CI 0.91-0.97). Slightly lower ORs were seen with increasing cumulative amount, duration, and consistency of low-dose aspirin use (continuous use, ≥5 years: OR 0.89; 95 % CI 0.82-0.97; ≥10 years: OR 0.86; 95 % CI 0.70-1.06). Nonaspirin NSAID use was associated with a slightly increased OR for prostate cancer (1.13; 95 % CI 1.10-1.15); however, this association was confined to localized disease and did not vary materially with amount, duration, or consistency of nonaspirin NSAID use. CONCLUSIONS: Our study indicates that long-term, consistent low-dose aspirin use may provide modest protection against prostate cancer. The slightly increased risk of only localized prostate cancer with nonaspirin NSAID use suggests a noncausal explanation of the observed association.

Prostate cancer incidence, clinical stage and survival in relation to obesity: a prospective cohort study in Denmark.

There is no clear link between obesity and prostate cancer incidence but an association has been reported between obesity and fatal prostate cancer. We report on two prospective cohort analyses on (i) the incidence of prostate cancer in relation to obesity in a cohort of men with no previous cancer, and on (ii) the stage distribution and prostate cancer specific mortality in relation to obesity among men with prostate cancer. The "Diet, Cancer and Health" prospective cohort study was established in Denmark in 1993-1997 and accrued 26,944 men aged 50-64 years. Data were extracted on height, weight, body mass index (BMI), waist circumference and body fat percentage. Information on cancer incidence and deaths were obtained by record linkage with the Danish Cancer Register and the Danish Death Register. The incidence rate of prostate cancer was similar or slightly lower in obese men compared with nonobese men, but obese men tended to be diagnosed with more advanced prostate cancer. The proportion of Stage 3-4 cancers was 37% in the lowest BMI quartile and 48% in the highest (p = 0.006). Obese men with prostate cancer had higher prostate cancer specific mortality. The hazard ratio comparing the highest and the lowest quartiles of BMI was 1.48 (95% confidence interval: 1.06-2.05; p-value for trend: 0.002). The association was attenuated but not eliminated by statistical adjustment for stage, and the data are suggestive of a stage-independent causal pathway where prostate cancer in obese men has higher fatality, even in early-stage disease.