Patient-reported outcome measures after treatment for prostate cancer: Results from the Danish Prostate Cancer Registry (DAPROCAdata).

PURPOSE: This study compares the side effects of active surveillance, prostatectomy, radiation with or without adjuvant endocrine therapy, watchful waiting, and palliative therapy on patient-reported outcomes in a nationwide, population-based cohort of Danish men with prostate cancer. METHODS: A total of 15,465 participants completed questionnaires over a 5 year period (2011-2016). Condition-specific quality of life, focusing on urinary function, bowel incontinence, sexual function, and hormonal symptoms were investigated using the validated EPIC-26 questionnaire at diagnosis, 1 year- and 3- year follow-up. Patients were identified from the Danish Prostate Cancer Registry with data-linked to several national healthcare registries. Longitudinal analysis with linear mixed effects models were fitted to compare changes over time on quality of life symptom scores for five treatment modalities, adjusting for age, clinical TNM stage, PSA value, Gleason score, Charlson Comorbidity score, education, disposable income, and urbanization measured at time of prostate cancer diagnosis. RESULTS: There was a more than10-point decrease in mean scores across all symptom domains at 1-year follow-up. Thereafter mean scores for all symptom domains improved marginally and remained relatively unchanged at 3-year follow-up. Prostatectomy had the greatest negative effect on sexual function and urinary incontinence. Overall quality of life was most adversely affected by sexual function, regardless of treatment modality. CONCLUSION: Clinical interventions for improving symptoms should focus particularly on the first year after prostate cancer diagnosis. Greater emphasis on improving sexual function should be practiced in clinical and rehabilitative care, since this area has the single greatest impact on symptom-specific QoL after primary treatment for prostate cancer.

Causes of death in men with prostate cancer: Results from the Danish Prostate Cancer Registry (DAPROCAdata).

BACKGROUND: Current knowledge of the validity of registry data on prostate cancer-specific death is limited. We aimed to determine the underlying cause of death among Danish men with prostate cancer, to estimate the level of misattribution of prostate cancer death, and to examine the risk of death from prostate cancer when accounting for competing risk of death. MATERIAL AND METHODS: We investigated a nationwide cohort of 15,878 prostate cancer patients diagnosed in 2010-2014; with 3343 deaths occurring through 2016. Blinded medical chart review was carried out for 670 deaths and compared to the national cause of death registry. Five death categories were defined: 1) prostate cancer-specific death, 2) other unspecified urological cancer death, 3) other cancer death 4) cardiovascular disease death, and 5) other causes of death. Competing risk analyses compared Cox cause-specific and Fine-Gray regression models. RESULTS: Chart review attributed 51.2% of deaths to prostate cancer, 17.0% to cardiovascular disease, and 16.7% to other causes. The Danish Register of Causes of Death attributed 71.7% of deaths to prostate cancer when including all registered contributing causes of death, and 57.0% of deaths when including only the primary registered cause of death. The probability of death by prostate cancer was 10% at 2-year survival. CONCLUSIONS: More than half of the deceased men in our study cohort died of their prostate cancer disease within a mean of 2.4 years of follow up. Data from the death registry is prone to misclassification, potentially overestimating the proportion of deaths from prostate cancer.

The Danish Prostate Cancer Database.

AIM OF DATABASE: The Danish Prostate Cancer Database (DAPROCAdata) is a nationwide clinical cancer database that has prospectively collected data on patients with incident prostate cancer in Denmark since February 2010. The overall aim of the DAPROCAdata is to improve the quality of prostate cancer care in Denmark by systematically collecting key clinical variables for the purposes of health care monitoring, quality improvement, and research. STUDY POPULATION: All Danish patients with histologically verified prostate cancer are included in the DAPROCAdata. MAIN VARIABLES: The DAPROCAdata registers clinical data and selected characteristics for patients with prostate cancer at diagnosis. Data are collected from the linkage of nationwide health registries and supplemented with online registration of key clinical variables by treating physicians at urological and oncological departments. Main variables include Gleason scores, cancer staging, prostate-specific antigen values, and therapeutic measures (active surveillance, surgery, radiotherapy, endocrine therapy, and chemotherapy). DESCRIPTIVE DATA: In total, 22,332 patients with prostate cancer were registered in DAPROCAdata as of April 2015. A key feature of DAPROCAdata is the routine collection of patient-reported outcome measures (PROM), including data on quality-of-life (pain levels, physical activity, sexual function, depression, urine and fecal incontinence) and lifestyle factors (smoking, alcohol consumption, and body mass index). PROM data are derived from questionnaires distributed at diagnosis and at 1-year and 3-year follow-up. Hitherto, the PROM data have been limited by low completeness (26% among newly diagnosed patients in 2014). CONCLUSION: DAPROCAdata is a comprehensive, yet still young clinical database. Efforts to improve data collection, data validity, and completeness are ongoing and of high priority.

Diagnostic and Therapeutic Strategies for Prostate Cancer.

Prostate cancer (PC) is a major disease that affects men's health worldwide. It is the second most common form of cancer in men, surpassed only by nonmelanoma skin cancers such as basal and squamous cell carcinomas. Diagnostic strategies with population screening for prostate cancer using prostate-specific antigen (PSA) has been surrounded with controversy and debated intensively ever since the PSA protein was first purified in 1979 by Wang et al. At the same time, advances in diagnostic imaging, surgery, radiation, and chemotherapy have increased the opportunity to effectively diagnose, treat, and manage PC. Given the sheer burden of PC disease in Denmark and worldwide, new and innovative strategies for cancer diagnosis and care are needed. This article is a short review of current diagnostic and therapeutic strategies for the care and management of prostate cancer in Denmark.

Survival of ovarian cancer patients in Denmark: Results from the Danish gynaecological cancer group (DGCG) database, 1995-2012.

BACKGROUND: Ovarian cancer has a high mortality rate, especially in Denmark where mortality rates have been reported higher than in adjacent countries with similar demographics. This study therefore examined recent survival and mortality among Danish ovarian cancer patients over an 18-year study period. METHODS: This nationwide registry-based observational study used data from the Danish Gynecology Cancer Database, Danish Pathology Registry, and Danish National Patient Registry. All patients with ovarian cancer diagnosed between 1995 and 2012 were included in the study. The data sources were linked via the patients' personal identification number and the analyses included data on cancer stage, age, survival, surgery status and comorbidity. The computed outcome measures were age-adjusted mortality rates and age-adjusted overall and relative survival rates for one and five years. RESULTS: We identified 9972 patients diagnosed with ovarian cancer in the period 1995-2012. The absolute one-year mortality rate decreased from 42.8 (CI 40.3-45.6) in 1995-1999 to 28.3 (CI 25.9-30.9) in 2010-2012, and the five-year mortality rate decreased from 28.2 (CI 27.0-29.5) in 1995-1999 to 23.9 (CI 22.9-25.0) in 2005-2009. After stratification by age, comorbidity and cancer stage, the decrease in one-year mortality was most substantial in the 65-74 year old age group 41.1 (CI 38.8-43.5) to 26.5 (CI 24.4-28.7) and for stage III 39.1 (CI 35.1-43.6) to 22.9 (CI 19.9-26.5) and stage IV 91.3 (CI 80.8-103.2) to 41.9 (CI 35.5-49.5). For overall survival, we showed an increase in one-year survival from 68% (CI 66-69%) in 1995-1999 to 76% (CI 74-78%) in 2010-2012 and an increase in five-year survival from 33% (CI 32-35%) in 1995-1999 to 36% (CI 34-38%) in 2005-2009. Relative survival showed similar increases through the period. CONCLUSIONS: Ovarian cancer survival in Denmark has improved substantially from 1995 to 2012, bringing Denmark closer to the standards set by adjacent countries.

The incidence of metastatic basal cell carcinoma (mBCC) in Denmark, 1997-2010.

BACKGROUND: Few data exist on the occurrence of metastatic basal cell carcinoma (mBCC). OBJECTIVE: To identify all cases of mBCC in Denmark over a 14-year period. METHODS: We searched the Danish National Patient Registry covering all Danish hospitals, the Danish Cancer Registry, the National Pathology Registry and the Causes of Death Registry during the period 1997 to 2010 for potential cases of mBCC registered according to the International classification of diseases ICD-10 and the International Systemized Nomenclature of Medicine (SNOMED). RESULTS: We identified 126,627 patients with a history of primary basal cell carcinoma (BCC) in the registries during the 14-year study period. Using case identifications from the four registries, a total of 170 potential mBCC cases were identified. However, after a pathology review, only five cases could be confirmed, of which three were basosquamous carcinomas. The 14-year cumulative incidence proportion of mBCC was 0.0039% (95% CI 0.0016-0.0083) among individuals with a history of previous BCC (n = 126,627) and 0.0001% (95% CI 0.0000-0.0002) in the general population. CONCLUSION: MBCC is a rare disease and only a small proportion of potential cases identified in automated clinical databases or registries can be confirmed by pathology and medical record review.

Survival and PSA-markers for mortality and metastasis in nonmetastatic prostate cancer treated with androgen deprivation therapy.

BACKGROUND: Few studies have examined the risk of developing castration-resistant prostate cancer (CRPC), metastasis, and mortality among nonmetastatic prostate cancer (M0-PC) patients treated with androgen deprivation therapy (ADT). We estimated the incidence of these outcomes among M0-PC patients on ADT and identified prostate-specific antigen (PSA) based biomarkers for mortality and metastasis. METHODS: This population-based cohort study included all nonmetastatic prostate cancer patients in Northern and Central Denmark Regions during 1997-2010, identified through registry data. Primary outcomes were metastasis, overall survival, and bone metastasis-free survival (BMFS). We estimated relative risks (RR) associated with PSA and PSA doubling-time (PSA-DT), measured as time-varying variables beginning at ADT treatment start. RESULTS: We included 2494 M0-PC patients treated with ADT, of whom 1617 (80%) developed CRPC during follow-up. One-fourth of the patients developed metastases within 5 years; bone metastases (BM) accounted for 81% of all metastases. Median survival time was 4.4 years. Compared with PSA <8 ng/mL, PSA ≥8 ng/mL was associated with an adjusted RR of 14.0 (95% confidence interval [CI]: 10.2, 19.0) for BM, 4.4 (CI: 3.9, 5.0) for all-cause mortality, and RR of 4.8 (CI: 4.3, 5.4) for the inverse of BMFS. PSA-DT ≤6 months was associated with an adjusted RR of 7.6 (95% CI: 6.1, 9.5) for BM, RR of 5.9 (CI: 5.2, 6.6) for all-cause mortality, and RR 6.6 (CI: 5.9, 7.4) for the inverse of BMFS. CONCLUSIONS: PSA ≥8 ng/mL and PSA-DT ≤6 months are strong predictors of mortality and bone metastasis. The poor prognosis observed in this study may reflect inclusion of patients with severe prostate cancer by requiring repeated PSA measurements.

Validation of algorithms to detect distant metastases in men with prostate cancer using routine registry data in Denmark.

OBJECTIVE: Among patients with prostate cancer, diagnostic codes for bone metastases in the Danish National Registry of Patients have a sensitivity of 44%. In an attempt to improve the sensitivity of registry-based identification of metastases from prostate cancer, we tested a series of algorithms, combining elevated prostate-specific antigen (PSA) levels, use of antiresorptive therapy, and performed bone scintigraphy. PATIENTS AND METHODS: We randomly selected 212 men diagnosed with prostate cancer in 2005-2010 in the Central Denmark Region with prespecified PSA values, antiresorptive therapy, and bone scintigraphy who did not have a registry-based diagnostic code indicating presence of distant metastases. We defined three candidate algorithms for bone metastases: 1) PSA >50 µg/L and bone scintigraphy, 2) PSA >50 µg/L and antiresorptive therapy, and 3) PSA ≤50 µg/L with antiresorptive therapy or bone scintigraphy. An algorithm for distant metastasis site other than bone was defined as PSA >50 µg/L alone. Medical chart review was used as the reference standard to establish the presence or absence of metastases. Validity was expressed as a positive predictive value (PPV) or a negative predictive value, based on whether the algorithms correctly classified metastases compared with the reference standard. RESULTS: We identified 113 men with evidence of metastases according to the candidate algorithms, and 99 men without evidence of metastases according to the candidate algorithm. The PPVs of PSA >50 µg/L were 0.10 (95% confidence interval [CI] 0.04-0.19) for bone metastases and 0.14 (95% CI 0.07-0.24) for nonbone metastases, regardless of receipt of antiresorptive therapy or presence of bone scintigraphy. The PPVs for any metastases were 0.16 (95% CI 0.06-0.32) for PSA >50 µg/L and 0.28 (95% CI 0.14-0.47) for PSA >50 µg/L with bone scintigraphy. Adding antiresorptive treatment to the algorithm did not improve PPV. All negative predictive values approached 1.00. CONCLUSION: Algorithms based on elevated PSA, antiresorptive therapy, or bone scintigraphy are not suitable for supplementing diagnostic codes to identify additional cases of distant metastases among men with prostate cancer. However, it is possible that in this setting, medical chart review is not a gold standard to identify metastases.

Quality of venous thromboembolism diagnoses among prostate cancer patients in the Danish National Registry of Patients.

BACKGROUND AND AIM: It is well established that cancer patients have an increased risk of venous thromboembolism (VTE). However, no previous study has examined the quality of VTE diagnoses related to cancer patients in the Danish National Registry of Patients (DNRP). To support future studies on cancer and risk of VTE, this study aimed to estimate the positive predictive value (PPV) of VTE diagnoses among prostate cancer (PC) patients registered in the DNRP. MATERIALS AND METHODS: We conducted a validation study using data from hospitals within the Central Denmark Region, which covers a population of 1.3 million people. Using the DNRP, we identified a total of 120 PC patients registered with VTE within the period 1995-2012. We also identified a random sample of 120 PC patients with no VTE registration within the same period. Therefore, a total of 240 patients were selected for medical chart review. We compared data from the DNRP to data collected from medical record review (ie, reference standard). We then computed PPV, sensitivity, and specificity with corresponding 95% confidence intervals (CIs) using the Jeffreys method. RESULTS: The final study sample included 232 PC patients, of which 115 were registered with VTE and 117 had no registration of VTE in the DNRP. We found the overall PPV of VTE diagnoses in the DNRP to be 86.1% (95% CI 78.9%-91.5%). Sensitivity was 98.0% (95% CI 93.8%-99.6%), and specificity was 87.8% (95% CI 81.4%-92.6%). We also found the PPV of incident PC diagnoses in the DNRP to be 98.3% (95% CI 96.1%-99.4%). CONCLUSION: For PC patients, the registration of VTE diagnoses in the DNRP is associated with a high PPV. We provide evidence that data from the DNRP are valid for studies on risk of VTE among cancer patients.

Comorbidity and survival of Danish prostate cancer patients from 2000-2011: a population-based cohort study.

OBJECTIVE: We investigated temporal changes in overall survival among prostate cancer (PC) patients and the impact of comorbidity on all-cause mortality. METHODS: We conducted a population-based cohort study in the Central Denmark Region (1.2 million inhabitants). Using medical registries, we identified 7,654 PC patients with first-time PC diagnosis within the period 2000-2011 and their corresponding comorbidities within 10 years prior to the PC diagnosis. We estimated 1- and 5-year survival in four consecutive calendar periods using a hybrid analysis and plotted Kaplan-Meier survival curves. We used Cox proportional hazards regression to compute 1- and 5-year age-adjusted mortality rate ratios (MRRs) for different comorbidity levels. All estimates are reported with their corresponding 95% confidence intervals (CI). RESULTS: The annual number of PC cases doubled over the 12-year study period. Men aged <70 years accounted for the largest proportional increase (from 33% to 47%). The proportion of patients within each comorbidity category remained constant over time. One-year survival increased from 82% (CI: 80%-84%) in 2000-2002 to 92% (CI: 90%-93%) in 2009-2011, while 5-year survival increased from 43% (CI: 40%-46%) to 65% (CI: 62%-67%) during the same time intervals. Improvements in 5-year survival were most prominent among patients aged <80 years and among those with no comorbidity (from 51% to 73%) and medium comorbidity (from 32% to 54%). Improvements in survival were much smaller for those with high comorbidity (from 33% to 39%). The 1-year age-adjusted MRR for patients with high comorbidity (relative to patients with no comorbidity) increased over time from 1.84 (CI: 1.19-2.84) to 3.67 (CI: 2.49-5.41), while the 5-year age-adjusted MRR increased from 1.73 (CI: 1.34-2.23) to 2.38 (CI: 1.93-2.94). CONCLUSION: Overall survival of PC improved substantially during 2000-2011, although primarily among men with low comorbidity. All-cause mortality was highest among PC patients with high comorbidity, and their relative 1- and 5-year mortality increased over time compared to those without comorbidity.

Existing data sources for clinical epidemiology: Danish registries for studies of medical genetic diseases.

Denmark has an extensive collection of national and regional medical registries. There are many advantages to registry-based research when investigating genetic diseases which, due to their rarity, can be difficult to identify. In this study, we aimed to provide an updated overview of Danish registries for medical genetic conditions and describe how data linkage across registries can be used to collect data on genetic diseases at the individual level and at the family level. We present a list of medical genetic registries in Denmark at the national level, data sources from the departments of clinical genetics and other specialized centers, and project-specific data sources. We also summarize key general registries, such as the Danish National Registry of Patients, the Danish Medical Birth Registry, and the Civil Registration System, which are renowned for their comprehensive and high quality data, and are useful supplemental data sources for genetic epidemiology research. We describe the potential for data linkage across multiple registries, which allows for access to medical histories with follow-up time spanning birth to death. Finally, we provide a brief introduction to the Danish epidemiological research setting and legalities related to data access. The Danish collection of medical registries is a valuable resource for genetic epidemiology research.

The prevalence of X-linked hypohidrotic ectodermal dysplasia (XLHED) in Denmark, 1995-2010.

UNLABELLED: X-linked hypohidrotic ectodermal dysplasia (XLHED) is characterised by hypohidrosis, sparse hair, and teeth abnormalities. Infants with XLHED have an increased risk of death by hyperpyrexia. XLHED is the most common form of hypohidrotic ectodermal dysplasia (HED); however, no population-based prevalence estimates are available. We aimed to: 1) estimate the prevalence of XLHED in the Danish population per January 1, 2011; 2) identify the most frequent age at time of diagnosis; and 3) quantify the most frequent clinical feature associated with XLHED. MATERIALS AND METHODS: We conducted a nationwide cross-sectional study (1995-2010). We leveraged national medical registries and data from clinical departments to categorise XLHED cases into three groups: 1) Molecularly-confirmed XLHED; 2) Clinically-diagnosed HED (registered with ICD-10 Q 82.4); and 3) Possible HED (registered with sufficient clinical features based on a clinical algorithm that we designed). RESULTS: We identified 90 molecularly-confirmed XLHED, 146 clinically-diagnosed HED, and 988 possible HED cases between 1995 and 2010 (total n = 1224). The prevalence was 21.9 per 100,000 overall and 1.6 per 100,000 when restricting to molecularly-confirmed XLHED cases. The most frequent age at time of XLHED diagnosis occurred between the ages of 11 and 18 years. Teeth abnormalities occurred in 79% of all cases and 52% of molecularly-confirmed cases as a primary clinical marker. CONCLUSION: We present the first ever population-based prevalence estimates of XLHED and suggest that the prevalence of XLHED may be higher than previously estimated. Diagnosis occurs most frequently during adolescence and teeth abnormalities were the most frequent clinical marker of XLHED.

Completeness of prostate cancer staging in the Danish Cancer Registry, 2004-2009.

OBJECTIVE: To investigate the completeness of TNM (Tumor-Node-Metastasis) staging for prostate cancer (PC) in the Danish Cancer Registry (DCR). METHODS: We identified 20,184 men registered with first-time PC in the DCR between 2004 and 2009. These patients were linked to the Danish National Patient Register to obtain data on comorbidity according to the Charlson Comorbidity Index (CCI). We calculated the completeness and corresponding 95% confidence intervals (CI) of TNM staging overall and by the individual components. We also defined a clinically-based algorithm classifying PC into four stage categories: localized, regional, distant, and unknown. RESULTS: The overall completeness of TNM staging was 34.2% (95% CI: 0.34-0.35). TNM completeness improved gradually over time reaching 41.2% in 2009. TNM completeness decreased substantially with age from 75.0% among patients 0-39 years to 11.3% among patients 80 years or older. Similarly, completeness decreased with increasing comorbidity level from 37.6% among patients with low CCI to 20.3% among those with high CCI. When classifying T1 cancer as a complete registration regardless of missing N or M stage, the overall TNM completeness increased to 48.7% (95% CI: 0.48-0.49). According to the clinically-based staging algorithm, 70.5% of PC cases could be categorized into a definite clinical stage. CONCLUSION: One-third of PC patients had a complete registration of all TNM components in the DCR. Although TNM completeness improved over time, older age and high comorbidity were consistently associated with missing TNM staging. Research and monitoring based on cancer registries such as the DCR should account for missing TNM staging. Failing to do so could otherwise lead to biased results of stage-specific analyses.