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Point of Focus Debate: Against

Smoking Status Is Not Sufficient to Accurately Target Patients Who Would Benefit from Screening for Bladder and Kidney Cancer

By: Morgan Rouprêt

EU Focus, Volume 1 Issue 1, November 2015, Pages 52-53

Published online: 13 November 2015

Abstract Full Text Full Text PDF (162 KB)

Take Home Message

Until tests become available, smoking avoidance and smoking cessation are the two most critical and realistic policies to promote nonsmoking in 2014. Preventing bladder cancer and renal cell carcinoma is certainly the most important approach to reduce their incidences and patient mortality.

Screening is a strategy used to detect disease within an asymptomatic population. The underlying hypothesis is that asymptomatic disease detection leads to earlier staged disease (stage migration) and better outcomes from treatment. However, the disease needs to be common or severe enough to warrant detection, must have a known natural history for which earlier treatment improves outcomes, and the detection method (test) must be accurate, safe, reliable, and cost effective. Screening programmes have yet to be implemented for two major diseases in the field of urologic oncology and should be considered: bladder cancer (BCa) and renal cell carcinoma (RCC). Both cancers have a poor outcome when advanced, are extremely expensive to manage, and many patients present with metastatic disease [1]. However, the background prevalence rates for both cancers is low; 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] and [2]. RCC represents 2–3% of all cancers, with an age-standardised rate incidence of 5.8 and mortality of 1.4 per 100 000 in Western nations [1] and [3].

BCa screening in the general population has been evaluated (reviewed by Chou and Dana [4] and Larre et al. [5]). However, partly because of the low overall incidence of BCa, screening is currently not recommended in routine practice. For RCC, >50% of tumours are detected incidentally when noninvasive imaging is used to investigate nonspecific symptoms or other diseases. Because advanced disease at diagnosis is now rare [1] and [3], there are no published data or screening recommendations for RCC in the general population.

Although general population-based screening for BCa and RCC seems illogical, targeted screening of high-risk populations makes clinical and economic sense. However, as often the case, the devil is in the details. How do we define these high-risk populations (beyond familial syndromes [3]), and what test do we screen with? The answer may be smokers.

Cigarette smoking is the best established risk factor for BCa, with a relative risk of 1.5–3 in past smokers and a relative risk (RR) of 4–5 in active smokers [6]. Cigarette smoking is also the best established risk factor for RCC (RR: 1.25–1.55) [7]. In a previous report, the most efficient screening tool for BCa was the combination of UroVysion (Abbott Molecular, Des Plaines, IL, USA), cytology, and urinary dipstick testing [8]. Screening a high-risk group with a history of smoking of ≥40 pack-years revealed a significant proportion (3.3%) of individuals with malignancy. Lotan et al. used the NMP22 BladderChek (Alere, Waltham, MA, USA) to screen an asymptomatic high-risk population. BladderChek can detect noninvasive cancers, but the low prevalence of BCa in this population did not permit the assessment of intervention efficacy (ie, the incidence of BCa was 0.13%) [9]. In a recent screening trial, the optimal high-risk population most likely to benefit from screening was men aged >60 yr with a smoking history of >30 pack-years; this group had incidence rates >2 in 1000 person-years [10]. Consequently, a screening strategy for BCa, particularly in smokers, has been previously used without any convincing data. No such data are available for RCC.

I believe 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 persons (ethnic or 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 and RCC. The environmental risk factors for developing BCa and RCC, such as smoking, are common, although only a fraction of people exposed to these risks eventually develop these diseases.

Genomewide association studies (GWASs) were recently performed for RCC and BCa [11], [12], [13], [14], and [15]. The GWAS approach allows a search for novel susceptibility loci throughout the genome in a hypothesis-free manner. In recent years, GWASs 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 RCC and BCa in smokers appears to be too broad of a strategy in 2014, 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 subsequently to develop the disease.

Until these tests are available, smoking avoidance and smoking cessation are the two most critical and realistic policies to promote in 2014. Preventing BCa and RCC is certainly the most important approach to reduce their incidences and patient mortality. Therefore, the World Urologic Oncology Federation has initiated the Global Bladder Cancer Prevention Program with the goal of integrating smoking cessation into urologic practices as a primary prevention.

Conflicts of interest

The author has nothing to disclose.

References

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Footnotes

Academic Urology Department, Pitié-Salpétrière Hospital, Assistance Publique - Hopitaux de Paris, Universiy Pierre and Marie Curie, Paris, France

Corresponding author. Academic Urology Department, Hôpital Pitié, 47-83 blvd de l’Hôpital, 75013 Paris, France.

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