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Home » Bladder Cancer, EU Health, Health

Screening for bladder cancer: rationale and perspectives

Submitted by on 30 Sep 2016 – 17:10

Bladder Cancer screening is currently not recommended in routine practice partly because of low overall incidence. However, Prof Morgan Roupret, Professor, Université Paris, believes that rational screening policies for smaller groups of people based on the presence of risk factors are most likely to benefit from screening

Screening is a strategy used in a population to identify an unrecognized disease in individuals without signs or symptoms. Screening allows for “early detection” of the disease before it has been revealed by any symptoms. An efficient screening program, thus, impacts the specific mortality of the disease, and the benefit risk/cost must be clearly established.
There is one major disease in the field of urologic oncology for which the opportunity of a screening programme could and should be considered: bladder carcinomas (BCa). With the unpleasant clinical outcomes of patients dying from advanced and metastatic BCa, and the recognition that this disease is indeed a public health problem, a logical assumption is that early detection would reduce mortality and morbidity from this disease. (1)From a general health policy perspective, screening for a specific disease in the general population is useful, contingent upon the fact that five conditions are met.

1. The disease must be a threat to the general population due to its epidemiology (incidence and prevalence) and its specific mortality.
2. There is an effective screening test for the disease.
3. This test is acceptable in terms of its cost and morbidity rate.
4. There is an effective treatment for the disease.
5. This treatment is acceptable in terms of its cost and morbidity rate.

Does bladder cancer (BCa) meet these five criteria?
BCa is the sixth most common cancer overall, with an estimated 72,570 new cases and 15,210 deaths in 2013 in the United States [1, 2]. BCa is one of the most diffuse urological malignancies, and it is the most costly in terms of expenditures. BCa screening in the general population has been studied by several investigators [3, 4]; however, partly because of the low overall incidence of BCa (37.5 and 9.3 per 100,000 in men and women, respectively), screening is currently not recommended in routine practice. The United States Preventive Service Task Force (USPSTF) recently concluded that the current evidence is insufficient to assess the risk/benefit ratio of screening for BCa in asymptomatic adults (http://www.uspreventiveservicestaskforce.org/).

“Opportunistic screening” entails the use of diagnostic tests upon the request of an individual. Regarding BCa, the strategy is usually to combine cystoscopy (specific) and a urinary test (sensitive). No study has assessed the diagnostic performance of urinary markers for BCa in the context of screening.

A secondary prevention would be to develop rational screening policies for a smaller group of people based on the presence of risk factors to identify optimal high-risk individuals who are most likely to benefit from screening. Cigarette smoking is the best-established risk factor for BCa, with a relative risk of 1.5 to 3 in past smokers and a RR of 4 to 5 in active smokers [5].

Screening a high-risk group with a history of smoking of ≥ 40 pack-years revealed a significant proportion (3.3%) of individuals with malignancy. In a screening trial in a recent study, the optimal high-risk population most likely to benefit from screening was men older than 60 years, with a smoking history of >30 pack-years; this group had incidence rates of more than 2/1,000 person-years [6]. Thus, a screening strategy for BCa, particularly in smokers, has been previously used, without any convincing data.

It is my personal feeling that the future of screening strategy is hidden in DNA. Cancer is a multifactorial disease that arises from the complex interplay between genetic and environmental factors. Genetic polymorphism is defined as the presence of different allele sequences for a single gene; it is sometimes linked to variations in the expression of constitutive DNA.

Susceptibility means an increased risk conferred by one or more polymorphisms (allele types) of a given gene or genes that expose the individual, family or group of individuals (ethnic/geographic variations) to the genotoxic effects of environmental carcinogens. Differences in the ability to activate carcinogens may contribute to host susceptibility and may be associated with the risk of BCa. The environmental risk factors for developing BCa, such as smoking, are common, although only a fraction of people exposed to these risks will eventually develop these diseases.

Recently, genome-wide association studies (GWAS) have been performed for BCa [7,8]. The GWAS approach allows a search for novel susceptibility loci throughout the genome in a hypothesis-free manner. In recent years, GWAS have emerged as a powerful approach in the discovery of genetics underlying complex traits, such as cancer. Diagnostic tools based on DNA alterations and that can provide high specificity and sensitivity would clearly be of enormous benefit to patients. Screening for BCa in smokers appears to be too broad of a strategy in 2016, and the appropriate method is not to screen only highly exposed patients (tobacco) but to screen only those patients (with DNA susceptibility) who are likely to subsequently develop the disease.

Until these tests are available, in my opinion, smoking avoidance and smoking cessation are the two most important and realistic policies to promote in 2016. Preventing BCa is certainly the most important approach to reduce its incidence and patient mortality. Therefore, the World Urologic Oncology Federation (WUOF) has initiated the Global Bladder Cancer Prevention Program, the goal of which is to integrate smoking cessation into urological practices as a primary prevention.

Whether people are healthy or not, is determined by their circumstances and environment. To a large extent, factors such as where we live, the state of our environment, genetics, our income and education level, all have considerable impacts on health. Thus, smoking avoidance and cessation must remain the main strong messages to send to the population if we want to struggle for a good health policy in Europe.

References:
1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63:11-30.
2. Babjuk M, Burger M, Zigeuner R, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urol 2013;64:639-53.
3. Chou R, Dana T. Screening adults for bladder cancer: a review of the evidence for the U.S. preventive services task force. Ann Intern Med 2010;153:461-8.
4. Larre S, Catto JW, Cookson MS, et al. Screening for bladder cancer: rationale, limitations, whom to target, and perspectives. Eur Urol 2013;63:1049-58.
5. Freedman ND, Silverman DT, Hollenbeck AR, Schatzkin A, Abnet CC. Association between smoking and risk of bladder cancer among men and women. JAMA 2011;306:737-45.
6. Krabbe LM, Svatek RS, Shariat SF, Messing E, Lotan Y. Bladder cancer risk: Use of the PLCO and NLST to identify a suitable screening cohort. Urol Oncol 2014.
7. Fu YP, Kohaar I, Moore LE, et al. The 19q12 Bladder Cancer GWAS Signal: Association with Cyclin E Function and Aggressive Disease. Cancer Res 2014;74:5808-18.
8. Rothman N, Garcia-Closas M, Chatterjee N, et al. A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci. Nat Genet 2010;42:978-84.