Coverage with evidence development program on stereotactic body radiotherapy in Belgium (2013-2019): a nationwide registry-based prospective study.

Background: Although stereotactic body radiotherapy (SBRT) was progressively adopted in clinical practice in Belgium, a reimbursement request in 2011 was not granted because of remaining clinical and economic uncertainty. A coverage with evidence development (CED) program on SBRT started in 2013, with the aim to assess clinical and technical patterns-of-care in Belgium and monitor survival per indication, in view of supporting inclusion in the reimbursement system. Methods: The Belgian National Institute for Health and Disability Insurance (NIHDI) initiated this prospective observational registry. Participating departments, using SBRT in clinical practice, signed the 'NIHDI convention'. Eligible patients had a primary tumour (PT) or oligometastatic disease (OMD). Patient, tumour, and treatment characteristics were collected through an online module of the Belgian Cancer Registry, prerequisite for financing. Five-year overall survival (5YOS) and 30- and 90-days mortality were primary outcomes, derived from vital status information. Findings: Between 10/2013 and 12/2019, 20 of the 24 accredited radiotherapy departments participated, 6 were academic. Registered cases per department ranged from 21 to 867. Of 5675 registrations analysed, the majority had good performance status and limited number of lesions. Enrolment of PTs remained stable over time, OMDs almost doubled. Peripheral lung lesions dominated in PTs as in OMDs. Other metastases were (para)spinal, 'non-standard' and hepatic. Thirty- and 90-days mortalities remained below 0.5% [95% CI 0.3%-0.8%] respectively 2.1% [95% CI 1.6%-2.7%]. 5YOS varied by indication, primary prostate patients performing best (85%, 95% CI [76%, 96%]), those with liver metastases worst (19%, 95% CI [15%, 24%]). Better OS was observed in academic departments, department size did not significantly impact survival. OMD survival was better in 2018-19. Interpretation: CED can be used to define patterns-of-care and real-life outcome of innovative radiotherapy. As the observed survival for different indications was in line with outcome in emerging literature, SBRT was included in the Belgian reimbursement system as of January 2020. Funding: NIHDI financed participating departments per registered case.

Delayed treatment in breast cancer patients during the COVID-19 pandemic: a population health information research infrastructure (PHIRI) case study.

BACKGROUND: The indirect impact of the coronavirus disease 2019 pandemic on healthcare services was studied by assessing changes in the trend of the time to first treatment for women 18 or older who were diagnosed and treated for breast cancer between 2017 and 2021. METHODS: An observational retrospective longitudinal study based on aggregated data from four European Union (EU) countries/regions investigating the time it took to receive breast cancer treatment. We compiled outputs from a federated analysis to detect structural breakpoints, confirming the empirical breakpoints by differences between the trends observed and forecasted after March 2020. Finally, we built several segmented regressions to explore the association of contextual factors with the observed changes in treatment delays. RESULTS: We observed empirical structural breakpoints on the monthly median time to surgery trend in Aragon (ranging from 9.20 to 17.38 days), Marche (from 37.17 to 42.04 days) and Wales (from 28.67 to 35.08 days). On the contrary, no empirical structural breakpoints were observed in Belgium (ranging from 21.25 to 23.95 days) after the pandemic's beginning. Furthermore, we confirmed statistically significant differences between the observed trend and the forecasts for Aragon and Wales. Finally, we found the interaction between the region and the pandemic's start (before/after March 2020) significantly associated with the trend of delayed breast cancer treatment at the population level. CONCLUSIONS: Although they were not clinically relevant, only Aragon and Wales showed significant differences with expected delays after March 2020. However, experiences differed between countries/regions, pointing to structural factors other than the pandemic.

Breast cancer incidence, stage distribution, and treatment shifts during the 2020 COVID-19 pandemic: a nationwide population-level study.

BACKGROUND: The first COVID-19 wave in 2020 necessitated temporary suspension of non-essential medical services including organized cancer screening programs in Belgium. This study assessed the impact of the pandemic on breast cancer (BC) incidence, stage at diagnosis, and management in Belgium in 2020. METHODS: All Belgian residents diagnosed with in situ or invasive BC in 2015-2020 in the nationwide, population-based cancer registry database were included. Incidence trends for 2015-2019 were extrapolated to predict incidence and stage distribution for 2020 and compared with the observed values. National healthcare reimbursement data were used to examine treatment strategies. Exact tumor diameter and nodal involvement, extracted from pathology reports, were analyzed for 2019 and 2020. RESULTS: 74,975 tumors were selected for analysis of incidence and clinical stage. Invasive BC incidence declined by -5.0% in 2020, with a drop during the first COVID-19 wave (Mar-Jun; -23%) followed by a rebound (Jul-Dec; +7%). Predicted and observed incidence (in situ + invasive) was not different in patients < 50 years. In the 50-69 and 70 + age groups, significant declines of -4.1% and - 8.4% respectively were found. Excess declines were seen in clinical stage 0 and I in Mar-Jun, without excess increases in clinical stage II-IV tumors in Jul-Dec. There was no increase in average tumor diameter or nodal involvement in 2020. Patients diagnosed in Mar-Jun received significantly more neoadjuvant therapy, particularly neoadjuvant hormonal therapy for patients with clinical stage I-II BC. CONCLUSIONS: BC incidence decline in 2020 in Belgium was largely restricted to very early-stage BC and patients aged 50 and over. Delayed diagnosis did not result in an overall progression to higher stage at diagnosis in 2020. Observed treatment adaptations in Belgium were successful in prioritizing patients for surgery while preventing tumor progression in those with surgical delay. Continuation of monitoring BC incidence and stage in the future is crucial.

Functional Outcomes and Quality of Life in High-risk Prostate Cancer Patients Treated by Robot-assisted Radical Prostatectomy with or Without Adjuvant Treatments.

BACKGROUND: Robot-assisted laparoscopic prostatectomy (RALP) is used frequently to treat prostate cancer; yet, prospective data on the quality of life and functional outcomes are lacking. OBJECTIVE: To assess the quality of life and functional outcomes after radical prostatectomy in different risk groups with or without adjuvant treatments. DESIGN, SETTING, AND PARTICIPANTS: The Be-RALP database is a prospective multicentre database that covers 9235 RALP cases from 2009 until 2016. Of these 9235 patients, 2336 high-risk prostate cancer patients were matched with low/intermediate-risk prostate cancer patients. INTERVENTION: Patients were treated with RALP only or followed by radiotherapy and/or hormone treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used a mixed-model analysis to longitudinally analyse quality of life, urinary function, and erectile function between risk groups with or without additional treatments. RESULTS AND LIMITATIONS: Risk group was not significant in predicting quality of life, erectile function, or urinary function after RALP. Postoperative treatment (hormone and/or radiotherapy treatment) was significant in predicting International Index of Erectile Function (IIEF-5), sexual activity, and sexual functioning. CONCLUSIONS: Risk group was not linked with clinically relevant declines in functional outcomes after RALP. The observed functional outcomes and quality of life are in favour of considering RALP for high-risk prostate cancer. Postoperative treatment resulted in lower erectile function measures without clinically relevant changes in quality of life and urinary functions. Hormone therapy seems to have the most prominent negative effects on these outcomes. PATIENT SUMMARY: This study investigated the quality of life, and urinary and erectile function in patients with aggressive and less aggressive prostate cancer after surgery only or in combination with hormones or radiation. We found that quality of life recovers completely, while erectile and urinary function recovers only partially after surgery. Aggressiveness of the disease had a minimal effect on the outcomes; yet, postoperative treatments lowered erectile function further.

Incidence, survival, and mortality of cancer in children and young adolescents in Belgium and the Netherlands in 2004-2015: A comparative population-based study.

International comparisons of cancer surveillance measures may provide insight into inequalities in registration practices, etiological factors, and treatment strategies. This study aimed to compare incidence, survival, and mortality of cancer in children and young adolescents between Belgium and the Netherlands. All children (0-14 years) and young adolescents (15-17 years) diagnosed with cancer between 2004 and 2015 were selected from the population-based cancer registries of Belgium (N = 4739) and the Netherlands (N = 7322). Differences in incidence and mortality were expressed as standardized rate ratios (SRR; BE/NL). Five-year observed survival was calculated using the Kaplan-Meier method. During 2004-2015, the overall cancer incidence among children and young adolescents was similar in both countries. Incidence of neuroblastoma was significantly higher in Belgian children (2010-2015: SRR = 1.3, 95% CI 1.0-1.6). Five-year survival of all malignant cancers was comparable in 2010-2015, exceeding 80% in both age groups. Remarkable differences in survival existed in children for malignant central nervous system (CNS) tumors in 2004-2009 (BE = 62%, NL = 45%), for acute myeloid leukemia (BE = 68%, NL = 78%) and rhabdomyosarcomas (BE = 60%, NL = 79%) in 2010-2015, and for neuroblastoma in both periods (2004-2009: BE = 76%, NL = 64%; 2010-2015: BE = 82%, NL = 64%). Overall cancer mortality in children decreased by approximately 3 percent-points annually in both countries, but was slightly lower in Belgium in 2004-2009 (SRR = 0.9, 95% CI 0.7-1.0). Despite differences for specific cancer types, overall cancer incidence, survival, and mortality were comparable between Dutch and Belgian children and young adolescents in 2010-2015. Variability in screening, diagnosis, and registration practices probably explains the observed differences in incidence and survival of neuroblastoma and malignant CNS tumors.

Survival of patients with unfavorable prognosis cutaneous melanoma with increased use of immunotherapy agents: a population-based study in Belgium.

BACKGROUND: Although metastatic cutaneous melanoma is associated with an unfavorable prognosis, innovative therapies including immunomodulating agents and targeted therapies have shown survival benefits in clinical trials. We assessed the impact of the introduction of innovative drugs into clinical practice on the survival of patients with metastatic cutaneous melanoma during the period 2004-2017, in Belgium. The evolution of associated expenses was also analyzed. METHODS: This is a retrospective population-based study using data from the national Belgian Cancer Registry, compulsory health insurance, and administrative survival data. The immunomodulating drugs were ipilimumab, nivolumab and pembrolizumab, while targeted therapies included vemurafenib, dabrafenib and trametinib. RESULTS: We did not identify a trend for improvement over time. Median survival (years) was 1.5 (95% CI: 1.1-1.8) in 2004-2008, 1.1 (95% CI: 0.8-1.5) in 2009-2013, and 1.6 (95% CI: 1.3-2.4) in 2014-2017, respectively. In contrast, survival improved in those with unknown primary tumor localization. In this group, median survival time was 2.0 (95% CI: 1.4-2.9) in the most recent period, while it was 1.1 (95% CI: 0.7-1.3) in 2009-2013, and 0.9 (95% CI: 0.6-1.2) in 2004-2008. The uptake of innovative drugs remained modest, with no drug being used by more than 30% of patients. Yearly expenditure was almost non-existent, and gradually increased, reaching several million euros in 2014-2017. CONCLUSION: Patients with metastatic cutaneous melanoma who were diagnosed between 2004 and 2017 showed no apparent improvement in survival. In contrast, increased survival was observed in the subgroup of patients with unknown primary tumor localization.

Surgery of the primary tumor in patients with de novo metastatic breast cancer: a nationwide population-based retrospective cohort study in Belgium.

PURPOSE: We aimed to assess the impact of surgery of primary tumor in overall survival (OS) of women with de novo metastatic breast cancer. METHODS: Nationwide, population-based retrospective cohort study of women diagnosed with de novo metastatic breast cancer in Belgium, between Jan/2010-Dec/2014. Data was obtained from the Belgian Cancer Registry and administrative databases. "Surgery" group was defined by surgery of primary tumor up to nine months after diagnosis. We excluded women who did not receive systemic treatment or did not complete nine months follow-up after diagnosis. All the subsequent analyses reporting on overall survival and the stratified outcome analyses were performed based on this nine-month landmark cohort. OS was estimated using Kaplan-Meier method and compared using adjusted Cox proportional hazards models controlling for confounders with 95% confidence intervals (CI). We performed a stratified analysis according to surgery timing and a propensity score matching analysis. RESULTS: 1985 patients, 534 (26.9%) in the "Surgery" and 1451 (73.1%) in the "No Surgery" group. Patients undergoing surgery were younger (p < 0.001), had better performance status (PS) (p < 0.001), and higher proportion of HER2-positive and triple-negative breast cancer (p = 0.012). Median follow-up was 86.0 months (82.6-88.5). Median OS was 60.1 months (57.1-68.2) in the "Surgery" vs. 41.9 months (39.8-44.2) in the "No Surgery" group (adjusted HR 0.56; 0.49-0.64). OS was similar when surgery was performed upfront or after systemic treatment. Propensity score matching analysis confirmed the same findings. CONCLUSION: Among patients receiving systemic treatment for de novo metastatic breast cancer and surviving nine months or more, those who received surgery of the primary tumor within nine months of diagnosis have longer subsequent survival than those who did not.

Practice patterns, time trends and quality of care of uterine cancer in Belgium: An analysis of the EFFECT database.

OBJECTIVES: To investigate the practice patterns and quality of care for uterine cancer on a national level in Belgium, including trends in practice over the period 2012-2016. METHODS: Quality indicators were measured using the EFFectiveness of Endometrial Cancer Treatment (EFFECT) database. Multivariable logistic mixed regression was used to test for associations between the quality indicators and year of diagnosis, adjusted for potential confounders and intra-cluster correlations. RESULTS: The EFFECT database includes 4178 patients diagnosed with uterine cancer in the period 2012-2016. Minimally invasive surgery (laparoscopic or robotic-assisted) was applied in 61.6% of patients who had surgery for clinical stage I endometrial carcinoma (EC), increasing from 52.9% in 2012 to 66.4% in 2016. At least pelvic lymph node staging was performed in 69.0% of patients with clinical stage I, high-grade EC; and in 63.9% of patients with clinical stage I-II serous carcinoma, clear cell carcinoma or carcinosarcoma. The latter increased from 48.8% in 2012 to 77.2% in 2016. Adjuvant radiotherapy (external beam and/or brachytherapy) was offered to 33.5% of patients who had surgery without lymph node staging for pathological stage I EC at high-intermediate or high risk of recurrence. Adjuvant chemotherapy was administered to 64.4% of patients with pathological stage III-IVA EC. CONCLUSIONS: Study results indicate an overall good quality of care for patients with uterine cancer in Belgium. Treatment areas with potential room for improvement include the use of minimally invasive surgery, comprehensive surgical staging and adjuvant therapy, which confirms the remaining controversies in uterine cancer treatment and the need for further research.

Correction: Evaluating the health and health economic impact of the COVID-19 pandemic on delayed cancer care in Belgium: A Markov model study protocol.

[This corrects the article DOI: 10.1371/journal.pone.0288777.].

The Upgrade Risk of B3 Lesions to (Pre)Invasive Breast Cancer After Diagnosis on Core Needle or Vacuum Assisted Biopsy. A Belgian National Cohort Study.

INTRODUCTION: Flat epithelial atypia (FEA), lobular neoplasia (LN), papillary lesions (PL), radial scar (RS) and atypical ductal hyperplasia (ADH) are lesions of uncertain malignant potential and classified as B3 lesions by the European guidelines for quality assurance in breast cancer screening and diagnosis. Current management is usually wide local excision (WE), surveillance may be sufficient for some. We investigated the upgrade rate of B3 lesions to breast malignancy in a subsequent resection specimen after diagnosis on core needle-or vacuum assisted biopsy (CNB-VAB) in a national population-based series. METHODS: Using data from the Belgian Cancer Registry (BCR) between January 1, 2013 and December 31, 2016, inclusion criteria were new diagnosis of a B3 lesion on CNB or VAB with subsequent histological assessment on a wider excision specimen. Histological agreement between first- and follow-up investigation was analyzed to determine the upgrade risk to ductal adenocarcinoma in situ (DCIS) or invasive breast cancer (IC) according to the type of B3 lesion. RESULTS: Of 1855 diagnosed B3 lesions, 812 were included in this study: 551 after CNB-261 after VAB. After diagnosis on CNB and VAB, we found 19.0% and 14.9% upgrade to malignancy respectively. Upgrade risks after CNB and VAB were: FEA 39.5% and 17.6%; LN 40.5% and 4.3%; PL 10.4% and 12.5%; RS 25.7%and 0.0%; ADH 29.5% and 20.0%. CONCLUSION: Based on the observed upgrade rate we propose three recommendations: first, resection of ADH, and FEA with WE; second, resection of RS and classical LN with therapeutic VAB and further surveillance when radio-pathological correlation is concordant; third, surveillance of PL.

A Belgian Population-Based Study Reveals Subgroups of Right-sided Colorectal Cancer with a Better Prognosis Compared to Left-sided Cancer.

BACKGROUND: Patients with left-sided colorectal cancer (L-CRC) are known to have a significantly better prognosis than those with right-sided CRC (R-CRC). It has been hypothesized that RAS, BRAF mutations, or deficient mismatch repair status (MMR) might be responsible for the prognostic effect of primary tumor location (PTL). This study aims to evaluate the prognostic effect of PTL in the Belgian population and to determine the role of biomarkers (MMR, BRAF, and RAS status) in this effect. PATIENTS AND METHODS: We performed a retrospective analysis of Belgian Cancer Registry data. First, we studied the prognostic effect of PTL on 5-year relative survival of 91,946 patients diagnosed with CRC (all stages) from 2004-2015. Second, we investigated the interaction between biomarkers and the prognostic effect of PTL in 1818 patients diagnosed with stage IV CRC in 2014-2015. RESULTS: L-CRC was associated with a significantly better 5-year relative survival compared to R-CRC in all stages and ages combined (68.4%, 95% CI, 67.7-69.1% vs 65.6%, 95% CI, 64.7-66.4%). Also, when stratified by age, sex, and stage, the prognosis of L-CRC was better compared to R-CRC in most subgroups. Only in stage II and certain subgroups of elderly patients, the opposite was observed. Furthermore, our data showed that none of the biomarkers had a significant interaction with the effect of PTL on survival. CONCLUSION: This population-based study confirms that L-CRC is associated with significantly better relative survival compared to R-CRC, in all stages and ages combined. Furthermore, in stage IV L-CRC is associated with a longer survival than R-CRC, regardless of MMR, RAS, and BRAF status.

Belgian observational survival data (incidence years 2004-2017) and expenditure for innovative oncology drugs in twelve cancer indications.

BACKGROUND: The Food and Drug Administration and European Medicines Agency typically approve market access for cancer drugs based on surrogate end-points, which do not always translate into substantiated improvements in outcomes that matter the most to patients, i.e. survival and quality of life. These drugs often, also, have a high price tag. We assessed whether there was an increase in cancer drug expenditure for a broad selection of indications, and whether this correlates with increased overall survival. METHODS: This cohort study used Belgian Cancer Registry data from 125,692 patients (12 cancer indications, incidence period 2004-2017), which was linked to reimbursement and survival data. This reliably represents the Belgian situation. One-to-five year observed survival probability, median survival time, oncology drug expenditure and mean oncology drug cost per patient were reviewed. FINDINGS: In almost all indications, total expenditure and average treatment cost for oncology drugs increased over the years (2004-2017). In contrast, mixed findings are observed for the evolution in overall survival probability and median survival time. While an absolute improvement in the 3-year survival probability of about 10% is noticed in non-small-cell lung cancer and chronic myeloid leukaemia, improvements in about half of the other indications are limited or even absent. INTERPRETATION: The Belgian observational data indicate that assuming 'innovative' oncology drugs always add value in terms of improved survival is often unjustified. The literature also highlights the problem of using surrogate end-points, and the lack of comparative evidence showing an added value of oncology drugs for both survival and quality of life at market approval or during the post-marketing phase. Comparative studies should be conducted in the pre-marketing phase that are suitable for registration purposes, aid reimbursement decisions and support physicians and patients when making treatment decisions.

Survival in stage IV ovarian cancer with increased use of debulking surgery and bevacizumab.

OBJECTIVES: Advanced ovarian cancer has a poor prognosis, with a 5 year survival probability of <30%. Attempts to improve survival have focused on debulking surgery and systemic therapy. We assessed the evolution of treatment patterns and survival of patients with advanced epithelial ovarian cancer with specific attention to changes in survival after introducing bevacizumab. METHODS: Population based data from the Belgian Cancer Registry were coupled with administrative reimbursement data from the compulsory health insurance organizations and the national database where date of death is registered, based on the patient's unique national number. Patients with epithelial ovarian cancer stage IV diagnosed in 2004-17 were included. The proportion of patients who underwent debulking surgery and received bevacizumab was calculated per incidence year. Survival was compared for the three incidence periods (2004-08, 2009-13, 2014-17) and before and after the introduction of bevacizumab. RESULTS: 2034 patients with stage IV epitheial ovarian cancer were included. From 2012 onwards, uptake of bevacizumab increased, with 50% of patients with stage IV ovarian cancer diagnosed in 2017 receiving bevacizumab. The proportion of stage IV patients who underwent debulking surgery also increased over time, from 21.1% in 2004-08 to 50.4% and 45.4% in 2009-13 and 2014-17, respectively. The 3 year observed survival probability fluctuated between 27% and 42% without a trend over time. The increase in debulking surgery was associated with improved survival (hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.79 to 0.98) but the introduction of bevacizumab was not (HR 0.94, 95% CI 0.85 to 1.03). For patients diagnosed in 2004, the mean cost per patient treated with oncological drugs was about €12 500, which doubled to about €25 000 for patients diagnosed in 2014 or later. CONCLUSIONS: Despite a rise in the use of debulking surgery and the introduction of bevacizumab into clinical practice, no improvement in 3 year survival probability was observed for patients with advanced ovarian cancer in Belgium.

Overall and stage-specific survival of patients with screen-detected colorectal cancer in European countries: A population-based study in 9 countries.

Background: An increasing proportion of colorectal cancers (CRCs) are detected through screening due to the availability of organised population-based programmes. We aimed to analyse survival probabilities of patients with screen-detected CRC in European countries. Methods: Data from CRC patients were obtained from 16 population-based cancer registries in nine European countries. We included patients with cancer diagnosed from the year organised CRC screening programmes were introduced until the most recent year with available data at the time of analysis, whose ages at diagnosis fell into the age groups targeted by screening. Patients were followed up with regards to vital status until 2016-2020 across the various countries. Overall and CRC-specific survival were analysed by mode of detection and stage at diagnosis for all countries combined and for each country separately using the Kaplan-Meier method. Findings: We included data from 228 134 patients, of whom 134 597 (aged 60-69 years at diagnosis targeted by screening in all countries) were considered in analyses for all countries combined. 22·3% (38 080/134 597) of patients had cancer detected through screening. Most screen-detected cancers were found at stages I-II (65·6% [12 772/19 469 included in stage-specific analyses]), while the majority of non-screen-detected cancers were found at stages III-IV (56·4% [31 882/56 543 included in stage-specific analyses]). Five-year overall and CRC-specific survival rates for patients with screen-detected cancer were 83·4% (95% CI 82·9-83·9) and 89·2% (88·8-89·7), respectively; for patients with non-screen-detected cancer, they were much lower (57·5% [57·2-57·8] and 65·7% [65·4-66·1], respectively). The favourable survival of patients with screen-detected cancer was also seen within each stage - five-year overall survival rates for patients with screen-detected stage I, II, III, and IV cancers were 92.4% (95% CI 91·6-93·1), 87·9% (86·6-89·1), 80·7% (79·3-82·0), and 32·3 (29·4-35·2), respectively. These patterns were also consistently seen for each individual country. Interpretation: Patients with cancer diagnosed at screening have a very favourable prognosis. In the rare case of detection of advanced stage cancer, survival probabilities are still much higher than those commonly reported for all patients regardless of mode of detection. Although these results cannot be taken to quantify screening effects, they provide useful and encouraging information for patients with screen-detected CRC and their physicians. Funding: This study was supported in part by grants from the German Federal Ministry of Education and Research and the German Cancer Aid.

Completeness and selection bias of a Belgian multidisciplinary, registration-based study on the EFFectiveness and quality of Endometrial Cancer Treatment (EFFECT).

BACKGROUND: With the aim of obtaining more uniformity and quality in the treatment of corpus uteri cancer in Belgium, the EFFECT project has prospectively collected detailed information on the real-world clinical care offered to 4063 Belgian women with primary corpus uteri cancer. However, as data was collected on a voluntary basis, data may be incomplete and biased. Therefore, this study aimed to assess the completeness and potential selection bias of the EFFECT database. METHODS: Five databases were deterministically coupled by use of the patient's national social security number. Participation bias was assessed by identifying characteristics associated with hospital participation in EFFECT, if any. Registration bias was assessed by identifying patient, tumor and treatment characteristics associated with patient registration by participating hospitals, if any. Uni- and multivariable logistic regression were applied. RESULTS: EFFECT covers 56% of all Belgian women diagnosed with primary corpus uteri cancer between 2012 and 2016. These women were registered by 54% of hospitals, which submitted a median of 86% of their patients. Participation of hospitals was found to be biased: low-volume and Walloon-region centers were less likely to participate. Registration of patients by participating hospitals was found to be biased: patients with a less favorable risk profile, with missing data for several clinical-pathological risk factors, that did not undergo curative surgery, and were not discussed in a multidisciplinary tumor board were less likely to be registered. CONCLUSIONS: Due to its voluntary nature, the EFFECT database suffers from a selection bias, both in terms of the hospitals choosing to participate and the patients being included by participating institutions. This study, therefore, highlights the importance of assessing the selection bias that may be present in any study that voluntarily collects clinical data not otherwise routinely collected. Nevertheless, the EFFECT database covers detailed information on the real-world clinical care offered to 56% of all Belgian women diagnosed with corpus uteri cancer between 2012 and 2016, and may therefore act as a powerful tool for measuring and improving the quality of corpus uteri cancer care in Belgium.

Proportion and stage distribution of screen-detected and non-screen-detected colorectal cancer in nine European countries: an international, population-based study.

BACKGROUND: The effects of recently implemented colorectal cancer screening programmes in Europe on colorectal cancer mortality will take several years to be fully known. We aimed to analyse the characteristics and parameters of screening programmes, proportions of colorectal cancers detected through screening, and stage distribution in screen-detected and non-screen-detected colorectal cancers to provide a timely assessment of the potential effects of screening programmes in several European countries. METHODS: We conducted this population-based study in nine European countries for which data on mode of detection were available (Belgium, Denmark, England, France, Italy, Ireland, the Netherlands, Slovenia, and Spain). Data from 16 population-based cancer registries were included. Patients were included if they were diagnosed with colorectal cancer from the year that organised colorectal cancer screening programmes were implemented in each country until the latest year with available data at the time of analysis, and if their age at diagnosis fell within the age groups targeted by the programmes. Data collected included sex, age at diagnosis, date of diagnosis, topography, morphology, clinical and pathological TNM information based on the edition in place at time of diagnosis, and mode of detection (ie, screen detected or non-screen detected). If stage information was not available, patients were not included in stage-specific analyses. The primary outcome was proportion and stage distribution of screen-detected versus non-screen detected colorectal cancers. FINDINGS: 228 667 colorectal cancer cases were included in the analyses. Proportions of screen-detected cancers varied widely across countries and regions. The highest proportions (40-60%) were found in Slovenia and the Basque Country in Spain, where FIT-based programmes were fully rolled out, and participation rates were higher than 50%. A similar proportion of screen-detected cancers was also found for the Netherlands in 2015, where participation was over 70%, even though the programme had not yet been fully rolled out to all age groups. In most other countries and regions, proportions of screen-detected cancers were below 30%. Compared with non-screen-detected cancers, screen-detected cancers were much more often found in the distal colon (range 34·5-51·1% screen detected vs 26·4-35·7% non-screen detected) and less often in the proximal colon (19·5-29·9% screen detected vs 24·9-32·8% non-screen detected) p≤0·02 for each country, more often at stage I (35·7-52·7% screen detected vs 13·2-24·9% non-screen detected), and less often at stage IV (5·8-12·5% screen detected vs 22·5-31·9% non-screen detected) p<0·0001 for each country. INTERPRETATION: The proportion of colorectal cancer cases detected by screening varied widely between countries. However, in all countries, screen-detected cancers had a more favourable stage distribution than cancers detected otherwise. There is still much need and scope for improving early detection of cancer across all segments of the colorectum, and particularly in the proximal colon and rectum. FUNDING: Deutsche Krebshilfe.

Tumour characteristics of screen-detected and interval cancers in the Flemish Breast Cancer Screening Programme: A mammographic breast density study.

OBJECTIVE: The objective is to investigate tumour prognostic factors versus breast density in screen-detected cancers and interval cancers. The results may highlight the need for more personalised screening protocols based on breast density in organized screening programmes. STUDY DESIGN: A retrospective study was performed of tumour characteristics of screen-detected cancers (n=468) and interval cancers (n=515) of 983 women who participated in the Flemish Breast Cancer Screening Programme in 2009-2010. Breast density was obtained from the screening programme data. Information on nodal invasion and histological grading was taken from the Belgian Cancer Registry. Tumour size and proliferation and receptor expression status were retrieved from pathology reports. The differences in tumour characteristics between screen-detected and interval cancers as well as the variation in these variables with breast density in both groups were studied by logistic regression. RESULTS: A comparison of tumour characteristics between screen-detected cancers and interval cancers systematically showed features of more aggressive tumours in interval cancers: larger tumour size, nodal invasion, grade 3 tumours, and hormone receptor negative phenotype (p<0.05). The analysis of tumour characteristics versus breast density in screen-detected cancers showed higher numbers of aggressive grade 3 tumours in low-density breasts and of the luminal A subtype with good prognosis in high-density breasts (p<0.05). This analysis for interval cancers highlights a high proportion of the difficult-to-treat triple-negative subtype in low-density breasts compared with high-density breasts. In conclusion, the study data support arguments against changes in breast cancer screening programmes with prolongation of screening intervals in low-density breasts.

Quality of pathology reporting and adherence to guidelines in rectal neuroendocrine neoplasms: a Belgian national study.

The incidence of neuroendocrine neoplasms (NEN) in the rectum is rising since the introduction of colonoscopy screening programs. Guidelines, such as the European NeuroEndocrine Tumor Society (ENETS) algorithm, are mainly based on expert opinion. The goal of this nationwide study is to gain a better insight into the evolution in pathology reporting and adherence to the ENETS guidelines in Belgium. In Belgium, all NENs have to be reported to the Belgian Cancer Registry. We thoroughly reviewed all available pathology reports, coded as rectal NEN between 2004 and 2015, and reclassified according to World Health Organisation (WHO) classification 2019. To evaluate the adherence to the ENETS guidelines, population-based cancer registry data were linked with the medical procedures of the Belgian Health Insurance database. A total of 670 rectal NEN were retained and 16% of the cases needed reclassification. Annual incidence between 2004 and 2015 tripled from 0,20 to 0,61 per 100.000 inhabitants. Reporting of Ki67 proliferation index ameliorated most, while reporting of tumor size, lymphovascular and perineural invasion remained disappointing. Endoscopic ultrasound was performed in only 36.6% of the cases, while the mostly recommended mode of treatment (endoscopic/surgical/no resection) was followed in the majority of the cases. Incidence of rectal NEN in Belgium increased throughout the years and quality of pathology reporting improved especially after the WHO classification update in 2010. The growing awareness and knowledge among clinicians and pathologists in the community counters the need for centralization.

Gastric cancer incidence and mortality trends 2007-2016 in three European countries.

BACKGROUND : Increased awareness of gastric cancer risk, easy access to upper endoscopy, and high definition endoscopes with virtual chromoendoscopy may have led to the increase in early diagnosis of gastric cancer observed in recent years in Europe, which may be associated with improved survival. Currently, no data exist on the impact of early diagnosis on survival at a populational level in Europe. Our aim was to assess gastric cancer incidence, early diagnosis, and survival in northwestern and southern European countries with a low-to-moderate incidence of gastric cancer. METHODS : Data on 41 138 gastric cancers diagnosed in 2007-2016 were retrieved from national cancer registries of Belgium, the Netherlands, and northern Portugal. Age-standardized incidence and mortality rates were assessed and expressed per 100 000 person-years. Early diagnosis was defined as T1 tumors. Net survival estimates for 2007-2011 vs. 2012-2016 were compared. RESULTS : Age-standardized incidence and mortality decreased over time in Belgium, northern Portugal, and the Netherlands (relative incidence decrease 8.6 %, 4.5 %, and 46.8 %, respectively; relative mortality decrease 22.0 %, 30.9 %, and 50.0 %, respectively). Early gastric cancer diagnosis increased over time for all countries. Net 1-year survival improved significantly between the two time periods in all countries, and at 5 years in Belgium and Portugal. CONCLUSIONS : This is the first study comparing trends (2007-2016) in gastric cancer incidence and mortality in some European countries. We found an increasing proportion of T1 gastric cancers and a decrease in age-standardized mortality over time, supporting the use of secondary prevention strategies.