Risk of cardiovascular disease following gonadotropin-releasing hormone agonists vs antagonists in prostate cancer: Real-world evidence from five databases.

Observational studies in prostate cancer (PCa) have shown an increased risk of cardiovascular disease (CVD) following gonadotropin-releasing hormone (GnRH) agonists, whereas randomised-controlled trials have shown no associations. Compared to GnRH agonists, GnRH antagonists have shown less atherosclerotic effects in preclinical models. We used real-world data from five countries to investigate CVD risk following GnRH agonists and antagonists in PCa men. Data sources included cancer registries, primary and secondary healthcare databases. CVD event was defined as an incident or fatal CVD. Multivariable Cox proportional hazard models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled using random-effects meta-analysis. Stratified analyses were conducted by history of CVD and age (75 years). A total of 48 757 men were on GnRH agonists and 2144 on GnRH antagonists. There was no difference in risk of any CVD for men on GnRH antagonists and agonists (HR: 1.25; 95% CI: 0.96-1.61; I2 : 64%). Men on GnRH antagonists showed increased risk of acute myocardial infarction (HR: 1.62; 95% CI: 1.11-2.35; I2 : 0%) and arrhythmia (HR: 1.55; 95% CI: 1.11-2.15, I2 : 17%) compared to GnRH agonists. Having a history of CVD was found to be an effect modifier for the associations with some CVD subtypes. Overall, we did not observe a difference in risk of overall CVD when comparing GnRH antagonists with agonists-though for some subtypes of CVD we noted an increased risk with antagonists. Further studies are required to address potential confounding caused by unadjusted variables such as severity of CVD history and PCa stage.

Combining data to perform population-based observational studies: know your sources. The case of thyroid cancer in Belgium.

BACKGROUND: Large scale observational studies are crucial to study thyroid cancer incidence and management, known to vary in time and place. Combining cancer registry data with other data sources enables execution of population-based studies, provided data sources are accurate. The objective was to compare thyroid tumour and treatment information between the available data sources in Belgium. METHODS: We performed a retrospective national population-based cohort study. All patients with thyroid cancer diagnosis in Belgium between 2009 and 2011 (N = 2659 patients) were retrieved from the Belgian Cancer Registry database, containing standard patient and tumour characteristics. Additionally, information was obtained from the following sources: a) detailed pathology reports b) the health insurance company database for reimbursed performed therapeutic acts (both available for N = 2400 patients) c) registration forms for performed and/or planned treatments at the time of the multidisciplinary team meeting (available for N = 1819 patients). More precisely, information was retrieved regarding characteristics of the tumour (histologic subtype, tumour size, lymph node status (source a)) and the treatment (thyroid surgery (a,b,c), lymph node dissection (a,b), postoperative administration of radioactive iodine (b,c)). RESULTS: High concordance in histological cancer subtype (> 90%), tumour size (96.2%) and lymph node involvement (89.2%) categories was found between the cancer registry database and the pathology reports. Tumour subcategories (such as microcarcinoma, tumor ≤1 cm diameter) were more specified in the pathology reports. The therapeutic act of thyroid surgery as mentioned in the pathology reports and health insurance company database was concordant in 92.7%, while reports from multidisciplinary team meetings showed 88.5% of concordance with pathology reports and 86.1% with health insurance data. With regard to postoperative radioiodine administration, reports from multidisciplinary teams and health insurance data were concordant in 76.8%. CONCLUSION: Combining registered and/or administrative data results in sufficiently accurate information to perform large scale observational studies on thyroid cancer in Belgium. However, thorough and continuous quality control and insight in strengths and limitations of each cancer data source is crucial.

The survival gap between young and older patients after surgical resection for colorectal cancer remains largely based on early mortality: A EURECCA comparison of four European countries.

BACKGROUND: A decade ago, it was demonstrated that the difference in survival between older patients and younger patients with colorectal cancer (CRC) was mainly due to mortality in the first postoperative year. Over the last few years, improvements - especially in perioperative care - have increased survival. The current research investigates whether a survival gap between younger and older patients with CRC still exists on a national level in four European countries. METHODS: Population-based data from Belgium, the Netherlands, Norway, and Sweden were collected from patients that underwent surgical resection for primary stage I-III CRC between 2007 and 2016. Relative survival and conditional relative survival (CS), with the condition of surviving the first postoperative year, were calculated for colon and rectal cancer separately, stratified for country and age category (<65, 65-75, ≥75 years). In addition, relative excess risk of death (RER) was estimated, and one-year excess mortality was calculated. RESULTS: Data of 206,024 patients were analyzed. In general, compared to patients <65 years, patients ≥75 years had a worse survival during the first year after surgery, which was most pronounced in Belgium (RER colon cancer 2.5 [95% confidence interval (CI) 2.3-2.8] and RER rectal cancer 2.6 [95% CI 2.3-2.9]). After surviving the first year, CS was mostly not statistically different between patients <65 years and patients ≥75 years with stage I-II, with the exception of stage II colon cancer in Belgium. However, CS remained worse in the largest part of the patients ≥75 years with stage III colon or rectal cancer (except for rectal cancer in Norway). CONCLUSIONS: Although differences exist between the countries, the survival gap between young and older patients is based mainly on early mortality and remains only for stage III disease after surviving the first year.

Socio-Economic Position, Cancer Incidence and Stage at Diagnosis: A Nationwide Cohort Study in Belgium.

Background: Socio-economic position is associated with cancer incidence, but the direction and magnitude of this relationship differs across cancer types, geographical regions, and socio-economic parameters. In this nationwide cohort study, we evaluated the association between different individual-level socio-economic and -demographic factors, cancer incidence, and stage at diagnosis in Belgium. Methods: The 2001 census was linked to the nationwide Belgian Cancer Registry for cancer diagnoses between 2004 and 2013. Socio-economic parameters included education level, household composition, and housing conditions. Incidence rate ratios were assessed through Poisson regression models. Stage-specific analyses were conducted through logistic regression models. Results: Deprived groups showed higher risks for lung cancer and head and neck cancers, whereas an inverse relation was observed for malignant melanoma and female breast cancer. Typically, associations were more pronounced in men than in women. A lower socio-economic position was associated with reduced chances of being diagnosed with known or early stage at diagnosis; the strongest disparities were found for male lung cancer and female breast cancer. Conclusions: This study identified population groups at increased risk of cancer and unknown or advanced stage at diagnosis in Belgium. Further investigation is needed to build a comprehensive picture of socio-economic inequality in cancer incidence.

Social Inequalities in Cancer Survival in Belgium: A Population-Based Cohort Study.

BACKGROUND: Socioeconomic status (SES) is an important factor in cancer survival; however, results are heterogeneous and linked to characteristics of the study population and health care system. This population-based cohort study evaluates the association between individual-level socioeconomic and demographic factors and cancer survival for the first time in Belgium. METHODS: From the Belgian Cancer Registry, we identified 109,591 patients diagnosed between 2006 and 2013 with one of eight common cancer types. Information on treatment, socioeconomic parameters, and vital status were retrieved from multiple data sources and linked using a unique personal identification number. The outcome was 5-year observed survival. Associations between survival and socioeconomic and demographic factors were assessed using multivariable Cox proportional-hazard regression models. RESULTS: Lower income, unemployment, and living alone were all associated with worse cancer survival. These associations were most pronounced for certain lifestyle-related cancer types (e.g., head and neck cancers) and those with good to moderate prognosis (e.g., colorectal and female breast cancer). CONCLUSIONS: These results indicate that, despite a comprehensive and nationwide health insurance program in which equity in rights and access to health care are pursued, SES is associated with disparities in cancer survival in Belgium. IMPACT: This population-based study with individual-level socioeconomic information of more than 100,000 patients with cancer identifies patient groups that may be at highest risk for socioeconomic disparities in cancer survival. Reasons behind the observed disparities are multiple and complex and should be further examined. Health policy interventions should consider the observed deprivation gap to plan targeted actions.

One-year excess mortality and treatment in surgically treated patients with colorectal cancer: A EURECCA European comparison.

BACKGROUND: Mortality in the first postoperative year represents an accurate reflection of the perioperative risk after colorectal cancer surgery. This research compares one-year mortality after surgery divided into three age-categories (18-64, 65-74, ≥75 years), focusing on time trends and comparing treatment strategies. MATERIAL: Population-based data of all patients diagnosed and treated surgically for stage I-III primary colorectal cancer from 2007 to 2016, were collected from Belgium, the Netherlands, Norway, and Sweden. Stratified for age-category and stage, treatment was evaluated, and 30-day, one-year and one-year excess mortality were calculated for colon and rectal cancer separately. Results were evaluated over two-year time periods. RESULTS: Data of 206,024 patients were analysed. Postoperative 30-day and one-year mortality reduced significantly over time in all countries and age-categories. Within the oldest age category, in 2015-2016, one-year excess mortality varied from 9% in Belgium to 4% in Sweden for colon cancer and, from 9% in Belgium to 3% in the other countries for rectal cancer. With increasing age, patients were less likely to receive additional therapy besides surgery. In Belgium, colon cancer patients were more often treated with adjuvant chemotherapy (p < 0.001). For neoadjuvant treatment of rectal cancer, patients in Belgium and Norway were mostly treated with chemoradiotherapy. In the Netherlands and Sweden, radiotherapy alone was preferred (p < 0.001). CONCLUSIONS: Despite improvement over time in all countries and age-categories, substantial variation exists in one-year postoperative mortality. Differences in one-year excess postoperative mortality could be due to differences in treatment strategies, highlighting the consequences of under- and over-treatment on cancer survival.

Real-world insights into risk of developing cardiovascular disease following GnRH agonists versus antagonists for prostate cancer: a methodological protocol to a study using five European databases.

One of the more recently investigated adverse long-term side effects of gonadotropin-releasing hormone (GnRH) agonists for prostate cancer (PCa) is cardiovascular disease (CVD). Studies suggest lower risk of CVD following GnRH antagonists (degarelix) than GnRH agonists. This protocol describes precise codes used to extract variables from five European databases for a study that compares risk of CVD following GnRH agonists and antagonists for PCa. PCa men on primary GnRH agonists or antagonists were identified from the UK THIN (The Health Improvement Network) database, National Health Service (NHS) Scotland, Belgian Cancer Registry (BCR), Dutch PHARMO Database Network and French National Database (SNIIRAM). Cohort entry was defined as date of treatment initiation. CVD event was defined as any first incident or fatal CVD after cohort entry. Readcodes in THIN and ICD codes in NHS Scotland, BCR, PHARMO and SNIIRAM were used to extract variables. Risk of Bias in Non-randomised studies of Interventions (ROBINS-I) tool was used to assess the potential risk of biases in this study. 51 572 men with a median follow-up time of 2 years started on GnRH agonists and 2 417 men with a median follow-up time of 1 year started on GnRH antagonists between 2010 and 2017 in the UK, Scotland, Belgium, the Netherlands and France. Data from five countries improved the study power and internal validity required to compare risk of CVD between GnRH agonists and antagonists, the latter being a fairly new drug with limited data in individual countries.

Comparative performance of a modified landmark approach when no time of treatment data are available within oncological databases: exemplary cohort study among resected pancreatic cancer patients.

PURPOSE: The Mantel-Byar method is the gold standard analytical approach to avoid immortal time bias, but requires information on the time between start of follow-up and exposure initiation. Alternatively, a modified landmark approach might be used to mitigate the amount of immortal time bias, which assumes exposure initiation at a predefined landmark time. In the context of an expected positive association between adjuvant chemotherapy (ACT) and overall survival among resected pancreatic cancer (PCa) patients, this study aims to empirically assess the performance of this approach relative to the Mantel-Byar method. PATIENTS AND METHODS: Data from resected PCa patients diagnosed between 2003 and 2014 and registered in the national cancer registries of Belgium, the Netherlands, and Slovenia were used to estimate the association between ACT and overall survival using a Cox proportional hazards model by country and overall. Results derived from the immortal time bias (misclassifying the time to ACT initiation), Mantel-Byar method, and conventional and modified landmark analyses with assumed cutoff times of ACT initiation at 9, 12 and 15 weeks post-diagnosis were compared. RESULTS: In total, 5,668 patients with a total of 10,921 person-years of follow-up were eligible. All analytical approaches showed a significant survival benefit for resected PCa patients who received ACT, but immortal time bias analyses led to strong overestimation of ACT benefits compared to the Mantel-Byar method (immortal time bias: overall HR [95% CI] 0.68 [0.62-0.75] vs Mantel-Byar method: 0.82 [0.71-0.93]), whereas the conventional landmark approach generally provided rather conservative estimates (0.86 [0.75-1.00], 15 weeks landmark). HRs derived from modified landmark analyses depended on the cutoff time, but were similar compared to the Mantel-Byar method at 15 weeks (0.81 [0.70-0.94]). CONCLUSION: A modified landmark approach might be a valid alternative to the Mantel-Byar method if no time of treatment information is available. The performance depends on the chosen cutoff time.