Platinum Priority – Bladder CancerEditorial by Brant A. Inman and Michael R. Abern on pp. 48–50 of this issueOutcomes of a Bladder Cancer Screening Program Using Home Hematuria Testing and Molecular Markers
Introduction
In 2012 bladder cancer (BCa) accounted for 7% of new cancer diagnoses and 3% of cancer deaths in US men [1]. Due to the high costs of monitoring and treatment, it was among the most expensive cancers in the United States and accounted for approximately $3.7 billion in 2001 [2]. BCa is also a major problem worldwide. According to data from GLOBOCAN 2008, there were 133 696 new BCa cases and 51 056 deaths in Europe [3].
Approximately one-fourth of BCas are muscle invasive at the time of diagnosis, with high rates of treatment-related morbidity as well as metastatic progression. Accordingly, there has been investigation into BCa screening, with the goal of identifying the disease at an earlier stage.
Initial studies of home dipstick testing for microhematuria found lower cancer-specific mortality among screen-detected cases compared to registry data [4], [5]. However, the positive predictive value (PPV) of home microhematuria testing as a trigger for further evaluation was 8% for urothelial carcinoma and 12.3% for any genitourinary malignancy. Traditional screening tools (eg, cystoscopy) are not adequate for population-based screening because they are invasive and are not cost-efficient [2]. In addition, the procedure may be associated with some pain or discomfort in a third of cases [6]. To reduce the number of unnecessary cystoscopies required to diagnose a single cancer, the authors suggested future studies to evaluate a sequential screening approach with dipstick testing and molecular markers [7].
Such a study, called the Bladder Cancer Urine Marker Project [BLU-P], was initiated in the Netherlands [8]. This study analyzed the feasibility and performance characteristics of BCa screening with newly developed molecular tools in an asymptomatic Dutch population. The purpose of this report is to present the final results of the BLU-P study, which has been completed.
Section snippets
Subjects, recruitment, and underlying risk factors
BLU-P was designed as a feasibility study to assess the feasibility of population-based screening for BCa on the basis of consecutive (14-d) home-based hematuria testing.
In addition, we aimed to assess the performance characteristics and feasibility of applying four urine-based molecular tests with the goal of reducing unnecessary cystoscopies; Messing et al. [4] found that up to 92% were unnecessary if positive hematuria was the only indication for cystoscopy.
At the beginning in February 2008,
Outcomes of the screening program
From a total of 6500 men invited to the study up to December 2009, 1984 (30.5%) responded that they would participate in the study and 536 responded that they would not participate. An additional 23 invitations were returned because the addressee had moved away from the area and 19 had died. An additional 50 responded that they were ineligible to participate due to a prior history of BCa (n = 40) or because they were too old (n = 10).
Of the 1984 men who agreed to participate, 1747 (88.1%) actually
Discussion
BCa screening has been studied as a possible way to decrease the frequency, morbidity, and mortality of advanced disease. Our results from the BLU-P screening study suggest that sequential screening for BCa using home dipstick testing and molecular markers is feasible but has a low diagnostic yield in an asymptomatic European population. Although the use of molecular markers reduced the number of cystoscopies performed for microhematuria evaluation, very few urothelial tumors were diagnosed in
Conclusions
A sequential BCa screening protocol of home dipstick testing followed by molecular markers substantially reduced the number of cystoscopy recommendations compared with dipstick testing alone and had very few missed cancers. However, this mass screening program was not useful in an unselected asymptomatic European male population. This finding might be explained in part by a lower frequency of risk factors in our population. Additional study is warranted to evaluate the performance of a two-tier
References (23)
- et al.
Considerations on implementing diagnostic markers into clinical decision making in bladder cancer
Urol Oncol
(2010) - et al.
Feasibility study of screening for bladder cancer with urinary molecular markers (the BLU-P project)
Urol Oncol
(2010) - et al.
A community study of bladder cancer screening by the detection of occult urinary bleeding
J Urol
(1992) - et al.
Select screening in a specific high-risk population of patients suggests a stage migration toward detection of non–muscle-invasive bladder cancer
Eur Urol
(2011) - et al.
Economic impact of screening for bladder cancer using bladder tumor markers: a decision analysis
Urol Oncol
(2006) - et al.
Cancer treatment and survivorship statistics, 2012
CA Cancer J Clin
(2012) - et al.
The health economics of bladder cancer: a comprehensive review of the published literature
PharmacoEconomics
(2003) - GLOBOCAN 2008. International Agency for Research on Cancer Web site. http://globocan.iarc.fr/. Accessed October 23,...
- et al.
Comparison of bladder cancer outcome in men undergoing hematuria home screening versus those with standard clinical presentations
Urology
(1995) - et al.
Long-term outcome of hematuria home screening for bladder cancer in men
Cancer
(2006)
Patients’ perceived burden of cystoscopic and urinary surveillance of bladder cancer: a randomized comparison
BJU Int
Cited by (46)
Systematic Review of the Incidence of and Risk Factors for Urothelial Cancers and Renal Cell Carcinoma Among Patients with Haematuria
2022, European UrologyCitation Excerpt :The total number of participants in the studies included was 229 701. Fourteen studies [2,12,15,16,21–23,28,29,31,34,38,51,54] had a prospective design, of which five studies had a published protocol [2,21,23,25,54]. Five studies were primary care studies [23,28,32,42,48] and 39 were secondary care studies.
Management of Patients with Normal Cystoscopy but Positive Cytology or Urine Markers
2020, European Urology OncologyCancer molecular markers: A guide to cancer detection and management
2018, Seminars in Cancer BiologyBladder cancer
2016, The LancetCitation Excerpt :In the general adult population, non-visible haematuria is found in 2–7% of men and 3–15% of women.69 Non-visible haematuria is often intermittent and varies in intensity over time; as such, the diagnostic yield of screening with dipstick urine testing is too small to make screening cost-effective,70 even in selected high-risk groups, such as heavy smokers and individuals with environmental exposure to bladder carcinogens.71,72 A Cochrane analysis73 published in 2015 concluded that the quality of the screening studies was too low to support any recommendation.
Microhematuria assessment an IBCN consensus—Based upon a critical review of current guidelines
2016, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :It appears reasonable not to initiate further testing before confirmation. Definition of an erythrocyte cut-off value to initiate urologic assessment is certainly required to confirm the presence of aMh, but it remains unclear if this would be helpful in discriminating between high-risk and low-risk patients regarding bladder cancer detection [43]. Amazingly, information concerning underlying conditions beyond bladder cancer is poor and controversial.