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).

Outcomes of Biopsy Grade Group 1 Prostate Cancer Diagnosis in the Danish Population.

BACKGROUND: Debate regarding a nomenclature change for grade group 1 (GG 1) prostate cancer to noncancer has been revived, as this could be a powerful tool in reducing the overtreatment of indolent disease. OBJECTIVE: To describe outcomes for all men diagnosed with GG 1 prostate cancer in the Danish population, with a focus on men followed conservatively. DESIGN, SETTING, AND PARTICIPANTS: This was a population-based observational study using data from the Danish Prostate Registry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured the cumulative incidence of curative treatment, endocrine treatment, and cause-specific mortality. RESULTS AND LIMITATIONS: The cumulative incidence of endocrine therapy at 10 yr was 5.3% (95% confidence interval [CI] 4.3-6.3%) for men with initial active surveillance and 21% (95% CI 19-23%) for men with initial watchful waiting for localized GG 1. In the GG1 cohort, the prostate cancer-specific mortality rate at 15 yr was 14% (95 CI% 11-16%) for men on watchful waiting, 10% (95 CI% 6.7-14%) for men with prostate-specific antigen <10 ng/ml on watchful waiting, and 16% (95 CI% 13-19%) for men who did not receive curative-intent treatment or histological assessment. The study is limited by the historic nature of the observations over a period during which diagnostic procedures and treatments have evolved. CONCLUSIONS: GG 1 cancer can lead to disease-specific mortality in men with localized prostate cancer, and changing the nomenclature for all men may lead to undertreatment. PATIENT SUMMARY: Key opinion leaders have suggested that prostate cancers of Gleason grade group 1 (GG 1) should be renamed as noncancer to reduce overtreatment. The argument is that low-grade cancer does not metastasize. However, our nationwide population-based study showed that death from prostate cancer can occur in some men diagnosed with GG 1 disease. These men should be considered in discussions on changing the name for GG 1 prostate cancer.

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.

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.

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.

Selective arterial embolization of renal angiomyolipomas: A 10-year experience.

Objectives: To study safety and efficacy of selective endovascular trans-arterial embolization (TAE) of renal angiomyolipoma (AML) in a 10-year period at a regional tertiary referral center in Denmark. Patients and methods: All 56 patients who underwent TAE of renal AML at Departments of Urology and Radiology, Copenhagen University Hospital - Rigshospitalet, Denmark, from 2009 to 2020 were included. Seven without preoperative and postoperative imaging were excluded, leaving 49 patients for analysis. From national electronic medical records, we retrieved patient characteristics, surgical data, and follow-up data. Tumor size at the time of embolization and during follow-up was compared using Student's paired t test. Estimated glomerular filtration rate (eGFR) pre- and post-embolization were compared using Wilcoxon rank sum test. Results: We included 49 patients of whom 4 had two tumors treated in the same TAE procedure. Median age was 50 years (interquartile range [IQR]: [29-67 years]), and the median follow-up time was 4.6 years [IQR: 3.0-6.7 years]. Post-embolization syndrome (PES) was experienced in 27 patients, and non-PES in 5 patients. Median length of hospital stay was 0 days [IQR, 0-1]. Postoperative Everolimus immunosuppressive treatment was offered to seven patients. Median tumor size was 6.0 cm [IQR: 4.6-7.9 cm] and was significantly reduced to 3.7 cm [IQR: 2.5-5.2 cm] after treatment (p < 0.001). Kidney function was not affected by TAE. Three deaths, not related to AML, were noted during follow-up. Conclusion: Embolization of AML was in this cohort effective to significantly reduce tumor size without serious adverse events and loss of renal function. TAE is a safe and efficacious treatment and the preferred minimally invasive treatment option of AML.

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 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.

Diagnostic radiological examinations and risk of intracranial tumours in adults-findings from the Interphone Study.

BACKGROUND: Exposure to high doses of ionizing radiation is among the few well-established brain tumour risk factors. We used data from the Interphone study to evaluate the effects of exposure to low-dose radiation from diagnostic radiological examinations on glioma, meningioma and acoustic neuroma risk. METHODS: Brain tumour cases (2644 gliomas, 2236 meningiomas, 1083 neuromas) diagnosed in 2000-02 were identified through hospitals in 13 countries, and 6068 controls (population-based controls in most centres) were included in the analysis. Participation across all centres was 64% for glioma cases, 78% for meningioma cases, 82% for acoustic neuroma cases and 53% for controls. Information on previous diagnostic radiological examinations was obtained by interviews, including the frequency, timing and indication for the examinations. Typical brain doses per type of examination were estimated based on the literature. Examinations within the 5 years before the index date were excluded from the dose estimation. Adjusted odds ratios were estimated using conditional logistic regression. RESULTS: No materially or consistently increased odds ratios for glioma, meningioma or acoustic neuroma were found for any specific type of examination, including computed tomography of the head and cerebral angiography. The only indication of an elevated risk was an increasing trend in risk of meningioma with the number of isotope scans, but no such trends for other examinations were observed. No gradient was found in risk with estimated brain dose. Age at exposure did not substantially modify the findings. Sensitivity analyses gave results consistent with the main analysis. CONCLUSIONS: There was no consistent evidence for increased risks of brain tumours with X-ray examinations, although error from selection and recall bias cannot be completely excluded. A cautious interpretation is warranted for the observed association between isotope scans and meningioma.

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.

Detection of Clinically Significant Prostate Cancer by Systematic TRUS-Biopsies in a Population-Based Setting Over a 20 Year Period.

OBJECTIVE: To assess the performance of systematic TRUS-biopsies in a population-based setting to detect clinically significant PCa (csPCa) in combination with age, clinical tumor category (cT), and prostate-specific antigen (PSA) in men referred for the first biopsy. METHODS: We identified all men referred for PCa work-up because of elevated PSA who underwent initial TRUS-biopsies in the nationwide Danish Prostate Cancer Registry (DaPCaR) between January 1st, 1995 and December 31st, 2016, in Denmark. Risk of histologic findings in initial TRUS-biopsies categorized as non-malignant, insignificant PCa, or significant PCa (csPCa). We defined csPCa as any biopsy containing Gleason score 3 + 4 or above as in the PRECISION trial. We assessed risk of csPCa with absolute risk, logistic regression model, and predicted risks. RESULTS AND LIMITATIONS: After exclusions, our cohort included 39,886 men. The diagnostic hit rate for csPCa was 40.8 %. Men with PSA > 20 ng/mL and ≥cT2 harbor a risk >75% for finding csPCa in the first TRUS biopsy-set. Men with cT1 tumors and PSA < 20 ng/mL have a risk of non-malignant histology of at least 58%. Limitations include the high number of exclusions based on missing information. CONCLUSION: The diagnostic accuracy of systematic TRUS-biopsies is high for men with palpable tumors and high PSA. Our data point to the fact that not all men need pre-biopsy MRI to find csPCa.

Risk of Pharmacological or Hospital Treatment for Depression in Patients with Colorectal Cancer-Associations with Pre-Cancer Lifestyle, Comorbidity and Clinical Factors.

We investigated the risk of depression in colorectal cancer (CRC) patients and associated risk factors. The 1324 patients with CRC and 6620 matched cancer-free participants from the Diet, Cancer and Health study were followed for up to 16 years for either a first hospitalization for depression or antidepressant prescription after diagnosis of CRC cancer or study entry date. Information on the outcome and covariates was retrieved from the Danish Colorectal Cancer Group database, the national health registries and questionnaires. Cumulative incidence of depression was estimated, and Cox regression models were used to evaluate the association between risk factors and depression incidence. During follow-up, 191 (14.4%) patients with CRC and 175 (2.6%) cancer-free comparison persons experienced depression. After adjustments, in the first year after cancer diagnosis, patients with CRC had a 12-fold higher hazard compared with the cancer-free population (HR, 12.01; 95% CI, 7.89-18.28). The risk decreased during follow-up but remained significantly elevated with an HR of 2.65 (95% CI, 1.61-4.36) after five years. Identified risk factors were presence of comorbidities, advanced disease stage and use of radiotherapy, while life style factors (pre-cancer or at diagnosis) and chemotherapy did not seem to contribute to the increased risk.

Antidepressant prescriptions and associated factors in men with prostate cancer and their female partners.

PURPOSE: To estimate the risk of first-time antidepressant prescriptions as a proxy for depression or anxiety and associated risk factors in patients with prostate cancer and their female partners. METHODS: We followed all men (n = 25,126) and their female cohabiting partners (n = 8785) without a history of cancer or antidepressants from the Danish Diet, Cancer and Health cohort from 1997 to 2014 or 2010, respectively. We estimated the cumulative incidence of first-time antidepressant prescriptions in men with prostate cancer compared with cancer-free men and their respective female partners, using the Danish National Prescription Registry. Sociodemographic, lifestyle-related, and clinical risk factors were assessed using Cox regression models. RESULTS: A total of 1828 men were diagnosed with prostate cancer of whom 15% received antidepressants. The unadjusted hazard ratio of antidepressant prescription was 2.18 (95%CI, 1.92, 2.48) for men with prostate cancer and 1.27 (95%CI, 0.87, 1.85) for their partners, compared with cancer-free men and their partners, respectively. After adjusting for sociodemographic, lifestyle-related, and comorbidity factors, this risk was 2-fold to 4-fold increased among patients, but not significantly increased among partners. Significant risk factors among patients were curative and palliative treatment (vs. active surveillance and watchful waiting), nonlocalized disease, and short education. CONCLUSIONS: Men with prostate cancer have a higher risk of receiving antidepressant medication than cancer-free men. Clinical characteristics can help clinicians in identifying patients at a high risk of depression or anxiety. IMPLICATIONS FOR CANCER SURVIVORS: Men with prostate cancer who experience symptoms of depression or anxiety should seek professional help early on. Patient education could aid in raising awareness and reducing the stigma associated with mental disorders.

Risk of Depression After Radical Prostatectomy-A Nationwide Registry-based Study.

BACKGROUND: Development of depression in prostate cancer patients depends on multiple disease- and patient-related factors. OBJECTIVE: To investigate the risk of depression following radical prostatectomy focussing on the impact of surgery and subsequent treatment with salvage radiation or androgen deprivation therapy. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study of 5570 men who underwent radical prostatectomy in Denmark from 1998 to 2011 was identified in the Danish Prostate Cancer Registry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data on covariates and primary outcome defined as a hospital contact for depression or a redeemed antidepressant prescription were obtained from nationwide Danish registries. The risk of depression was evaluated using cumulative incidence functions and Cox models with time since surgery as an underlying time scale. Exposure to salvage procedures was included as time-varying covariates, and analyses were adjusted for confounders. RESULTS AND LIMITATIONS: The cumulative incidence of depression was increased in men who had undergone surgery compared with cancer-free men throughout follow-up of up to 18yr, particularly among men on androgen deprivation therapy. Compared with no subsequent treatment, the risk of depression was increased with subsequent androgen deprivation therapy (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.4-2.3), salvage radiation (HR 1.3, 95% CI 1.0-1.6), and the treatments combined (HR 2.2, 95% CI 1.8-2.8) after adjustments for age, year of surgery, income, and cohabitation status. Further adjustment for comorbidity hardly changed the estimates. CONCLUSIONS: Radical prostatectomy and subsequent salvage procedures increase the risk of depression, and men with subsequent androgen deprivation therapy are mainly at risk. Clinicians should thus be aware of depressive symptoms in patients receiving treatment for postsurgical relapse. PATIENT SUMMARY: In a population-based study, we found that radical prostatectomy and subsequent treatments with either radiation or endocrine manipulation significantly increased the risk of developing clinical depression.

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.

Educational level and first-time PSA testing in general practice.

Introduction: Different patterns in the use of prostate-specific antigen (PSA) testing might explain socioeconomic differences in prostate cancer incidence and mortality. We examined the association between socioeconomic position, measured as education and first-time PSA testing in general practice.Material and Methods: A population-based cohort study of men aged 45-79 years without prior prostate cancer diagnosis living in the Capital Region of Denmark between 2000 and 2014. Information on socioeconomic indicators (education, income, cohabitation status and work market affiliation), prostate cancer diagnoses, and vital status were obtained from national registries. Date of first PSA test was obtained from the Copenhagen Primary Care Laboratory database. Temporal trends of PSA testing were calculated as annual age-standardised incidence rates and the association was examined by a multivariable Cox proportional hazards model.Results: The cohort consists of 431,997 men of which 105,476 (24%) had a first-time PSA test in the study period. Men with longer education, higher income, living with a partner, and employed had higher rates of PSA testing. For men with short education, the rate of PSA test was 28.3 tests per 1000 person-years compared to 31.2 tests among men with long education. The fully adjusted hazard ratio for a first PSA test among men with short education was 0.87 (95% CI, 0.85-0.89) compared to men with long education.Conclusion: The association between education and first-time PSA testing indicates socioeconomic disparities in health care utilisation, which could explain part of the observed socioeconomic difference in prostate cancer incidence and mortality.