The current use of the EORTC QLQ-NMIBC24 and QLQ-BLM30 questionnaires for the assessment of health-related quality of life in bladder cancer patients: a systematic review.

PURPOSE: Investigating the use of the EORTC bladder cancer (BC) modules by evaluating: (a) study contexts/designs; (b) languages/countries in which the modules were administered; (c) their acceptance by patients/investigators; and (d) their psychometric properties. METHODS: A systematic review was performed with studies from 1998 until 20/10/2021 in five databases. Articles/conference abstracts using the EORTC-QLQBLM30 (muscle invasive BC) and the EORTC-QLQNMIBC24 (previously referred to as QLQ-BLS24; non-muscle invasive BC) were included. Two authors independently screened titles/abstracts/full-texts and performed data extraction. RESULTS: A total of 76 eligible studies were identified. Most studies included the BLM30 (n = 53), were in a urological surgery context (n = 41) and were cross-sectional (n = 35) or prospective (n = 30) in design. The BC modules were administered in 14 languages across 19 countries. Missing data were low-moderate for all non-sex related questions (< 1% to 15%). Sex-related questions had higher rates of missing data (ranging from 6.9% to 84%). Most investigators did not use all scales of the questionnaires. One validation study for the original BLS24 led to the development of the NMIBC24, which adopted a new scale structure for which good structural validity was confirmed (n = 3). Good reliability and validity was shown for the NMIBC24 module, except for malaise and bloating/flatulence scales. Psychometric evidence for BLM30 is lacking. CONCLUSION: These results provide insight into how the EORTC BC quality of life modules could be further improved. Current work is ongoing to update the modules and to determine if the two modules can be combined into a single questionnaire that works well in both the NMIBC and MIBC settings.

Occult lymph node metastases in patients without residual muscle-invasive bladder cancer at radical cystectomy with or without neoadjuvant chemotherapy: a nationwide study of 5417 patients.

PURPOSE: Little is known about the prevalence of occult lymph node metastases (LNM) in muscle-invasive bladder cancer (MIBC) patients with pathological downstaging of the primary tumor. We aimed to estimate the prevalence of occult LNM in patients without residual MIBC at radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) or neoadjuvant radiotherapy (NAR), and to assess overall survival (OS). METHODS: Patients with cT2-T4aN0M0 urothelial MIBC who underwent RC plus pelvic lymph node dissection (PLND) with curative intent between January 1995-December 2013 (retrospective Netherlands Cancer Registry (NCR) cohort) and November 2017-October 2019 (prospective NCR-BlaZIB cohort (acronym in Dutch: BlaaskankerZorg In Beeld; in English: Insight into bladder cancer care)) were identified from the nationwide NCR. The prevalence of occult LNM was calculated and OS of patients with <(y)pT2N0 vs. <(y)pT2N+ disease was estimated by the Kaplan-Meier method. RESULTS: In total, 4657 patients from the NCR cohort and 760 patients from the NCR-BlaZIB cohort were included. Of 1374 patients downstaged to <(y)pT2, 4.3% (N = 59) had occult LNM 4.1% (N = 49) of patients with cT2-disease and 5.6% (N = 10) with cT3-4a-disease. This was 4.0% (N = 44) in patients without NAC or NAR, 4.5% (N = 10) in patients with NAC, and 13.5% (N = 5) in patients with NAR but number of patients treated with NAR and downstaged disease was small. The prevalence of <(y)pT2N+ disease was 4.2% (N = 48) in the NCR cohort and 4.6% (N = 11) in the NCR-BlaZIB cohort. For patients with <(y)pT2N+ and <(y)pT2N0, median OS was 3.5 years (95% CI 2.5-8.9) versus 12.9 years (95% CI 11.7-14.0), respectively. CONCLUSION: Occult LNM were found in 4.3% of patients with cT2-4aN0M0 MIBC with (near-) complete downstaging of the primary tumor following RC plus PLND. This was regardless of NAC or clinical T-stage. Patients with occult LNM showed considerable worse survival. These results can help in counseling patients for bladder-sparing treatments.

Validation and reliability of the Dutch version of the EORTC QLQ-BLM30 module for assessing the health-related quality of life of patients with muscle invasive bladder cancer.

BACKGROUND: Quality of Life (QoL) of bladder cancer patients has been largely neglected. This is partly due to the lack of well-validated QoL questionnaires. The aim of this study is to examine the structural validity, reliability (i.e., internal consistency and test-retest reliability), construct validity (i.e., divergent validity and known group validity) and responsiveness of the Dutch version of the European Organisation for Research and Treatment of Cancer QoL questionnaire for muscle invasive bladder cancer (EORTC-QLQ-BLM30). METHODS: Patients with newly diagnosed muscle invasive bladder cancer (MIBC) participating in the population-based 'Blaaskankerzorg In Beeld' (BlaZIB) study who completed the EORTC-QLQ-BLM30 at baseline were included. BlaZIB is a Dutch nationwide population-based prospective cohort study collecting clinical data and QoL data of bladder cancer patients. QoL is assessed with a self-administered questionnaire at four points in time: 6 weeks (baseline), 6 months, 12 months and 24 months after diagnosis. Confirmatory factor analysis and multitrait scaling analysis were used to investigate and adapt the scale structure. Reliability, construct validity and responsiveness of the revised scales were evaluated. RESULTS: Of the 1542 patients invited to participate, 650 patients (42.2%) completed the QLQ-BLM30 at baseline. The questionnaire's scale structure was revised into seven scales and eight single items. Internal consistency and test-reliability were adequate for most scales (Cronbach's α ≥0.70 and intraclass correlation coefficient ≥ 0.70, respectively), with the exception of the revised urostomy problem scale and abdominal bloating and flatulence scale. The questionnaire exhibited little overlap with the EORTC-QLQ-C30: all correlations were < 0.40, except for the correlation between emotional function (QLQ-C30) and future worries (QLQ-BLM30). The questionnaire was able to distinguish between patient subgroups formed on the basis of physical function, but not - as hypothesized- based on stage. Changes in health due to treatment were captured by the questionnaire, indicating that the questionnaire is responsive to change. CONCLUSIONS: This study shows that the adapted scale structure of the EORTC-QLQ-BLM30 generally exhibits good measurement properties in Dutch patients, but needs to be validated in other languages and settings. TRIAL REGISTRATION: BlaZIB, NL8106, www.trialregister.nl.

Insight into bladder cancer care: study protocol of a large nationwide prospective cohort study (BlaZIB).

BACKGROUND: Despite the embedding of bladder cancer management in European guidelines, large variation in clinical practice exists for applied diagnostics and treatments. This variation may affect patients' outcomes including complications, disease recurrence, progression, survival, and health-related quality of life (HRQL). Lack of detailed clinical data and HRQL data hampers a comprehensive evaluation of bladder cancer care. Through prospective data registration, this study aims to provide insight in bladder cancer care in the Netherlands and to identify barriers and modulators of optimal bladder cancer care. METHODS: This study is a nationwide prospective cohort study including all patients who were newly diagnosed with high-risk non-muscle invasive bladder cancer (HR-NMIBC; Tis and/or T1, N0, M0/x) or non-metastatic muscle invasive bladder cancer (MIBC; ≥T2, N0/x-3, M0/x) in the Netherlands between November 1st 2017 and October 31st 2019. Extensive data on patient- and tumor characteristics, diagnostics, treatment and follow-up up to 2 years after diagnosis will be collected prospectively from electronic health records in the participating hospitals by data managers of the Netherlands Cancer Registry (NCR). Additionally, patients will be requested to participate in a HRQL survey shortly after diagnosis and subsequently at 6, 12 and 24 months. The HRQL survey includes six standardized questionnaires, e.g. SCQ Comorbidity score, EQ-5D-5 L, EORTC-QLQ-C30, EORTC-QLQ-BLM30, EORTC-QLQ-NMIBC24 and BCI. Variation in care and deviation from the European guidelines will be assessed through descriptive analyses and multivariable multilevel analyses. Survival analyses will be used to assess the association between variation in care and relevant outcomes such as survival. DISCUSSION: The results of this observational study will guide modifications of clinical practice and/or adaptation of guidelines and may set the agenda for new specific research questions in the management of bladder cancer. TRIAL REGISTRATION: Retrospectively registered in the Netherlands Trial Register. Trial identification number: NL8106. Registered on October 22nd 2019.

Overdiagnosis by mammographic screening for breast cancer studied in birth cohorts in The Netherlands.

A drawback of early detection of breast cancer through mammographic screening is the diagnosis of breast cancers that would never have become clinically detected. This phenomenon, called overdiagnosis, is ideally quantified from the breast cancer incidence of screened and unscreened cohorts of women with follow-up until death. Such cohorts do not exist, requiring other methods to estimate overdiagnosis. We are the first to quantify overdiagnosis from invasive breast cancer and ductal carcinoma in situ (DCIS) in birth cohorts using an age-period-cohort -model (APC-model) including variables for the initial and subsequent screening rounds and a 5-year period after leaving screening. Data on the female population and breast cancer incidence were obtained from Statistics Netherlands, "Stichting Medische registratie" and the Dutch Cancer Registry for women aged 0-99 years. Data on screening participation was obtained from the five regional screening organizations. Overdiagnosis was calculated from the excess breast cancer incidence in the screened group divided by the breast cancer incidence in presence of screening for women aged 20-99 years (population perspective) and for women in the screened-age range (individual perspective). Overdiagnosis of invasive breast cancer was 11% from the population perspective and 17% from the invited women perspective in birth cohorts screened from age 49 to 74. For invasive breast cancer and DCIS together, overdiagnosis was 14% from population perspective and 22% from invited women perspective. A major strength of an APC-model including the different phases of screening is that it allows to estimate overdiagnosis in birth cohorts, thereby preventing overestimation.

Immediate and delayed effects of mammographic screening on breast cancer mortality and incidence in birth cohorts.

BACKGROUND: Trend studies investigating the impact of mammographic screening usually display age-specific mortality and incidence rates over time, resulting in an underestimate of the benefit of screening, that is, mortality reduction, and an overestimate of its major harmful effect, that is, overdiagnosis. This study proposes a more appropriate way of analysing trends. METHODS: Breast cancer mortality (1950-2009) and incidence data (1975-2009) were obtained from Statistics Netherlands, 'Stg. Medische registratie' and the National Cancer Registry in the Netherlands for women aged 25-85 years. Data were visualised in age-birth cohort and age-period figures. RESULTS: Birth cohorts invited to participate in the mammographic screening programme showed a deflection in the breast cancer mortality rates within the first 5 years after invitation. Thereafter, the mortality rate increased, although less rapidly than in uninvited birth cohorts. Furthermore, invited birth cohorts showed a sharp increase in invasive breast cancer incidence rate during the first 5 years of invitation, followed by a moderate increase during the following screening years and a decline after passing the upper age limit. CONCLUSION: When applying a trend study to estimate the impact of mammographic screening, we recommend using a birth cohort approach.

Extrapolation of pre-screening trends: Impact of assumptions on overdiagnosis estimates by mammographic screening.

BACKGROUND: Overdiagnosis by mammographic screening is defined as the excess in breast cancer incidence in the presence of screening compared to the incidence in the absence of screening. The latter is often estimated by extrapolating the pre-screening incidence trend. The aim of this theoretical study is to investigate the impact of assumptions in extrapolating the pre-screening incidence trend of invasive breast cancer on the estimated percentage of overdiagnosis. METHODS: We extracted data on invasive breast cancer incidence and person-years by calendar year (1975-2009) and 5-year age groups (0-85 years) from Dutch databases. Different combinations of assumptions for extrapolating the pre-screening period were investigated, such as variations in the type of regression model, end of the pre-screening period, screened age range, post-screening age range and adjustment for a trend in women <45. This resulted in 69,120 estimates of the percentage of overdiagnosis, i.e. excess cancer incidence in the presence of screening as a proportion of the number of screen-detected and interval cancers. RESULTS: Most overdiagnosis percentages are overestimated because of inadequate adjustment for lead time. The overdiagnosis estimates range between -7.1% and 65.1%, with a median of 33.6%. The choice of pre-screening period has the largest influence on the estimated percentage of overdiagnosis: the median estimate is 17.1% for extrapolations using 1975-1986 as the pre-screening period and 44.7% for extrapolations using 1975-1988 as the pre-screening period. CONCLUSION: The results of this theoretical study most likely cover the true overdiagnosis estimate, which is unknown, and may not necessarily represent the median overdiagnosis estimate. This study shows that overdiagnosis estimates heavily depend on the assumptions made in extrapolating the incidence in the pre-screening period, especially on the choice of the pre-screening period. These limitations should be acknowledged when adopting this approach to estimate overdiagnosis.