- Email: [email protected]
We Should Screen Smokers for Bladder and Kidney Cancer
EUROPEAN UROLOGY FOCUS 1 (2015) 50–51
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Point of Focus Debate: For
We Should Screen Smokers for Bladder and Kidney Cancer Yair Lotan * Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA
No recommendations currently exist for the screening for either kidney or bladder cancer, and these diseases are diagnosed when patients become symptomatic or after imaging for other causes. This commentary defends the rationale for screening smokers for bladder and kidney cancer. Some important questions on the use of screening in these malignancies need to be answered. 1.
Who should be screened?
The several known risk factors for bladder and kidney cancer include smoking, age, and gender [1,2]. Smoking increases the risk for kidney cancer by 2-fold and >4-fold for bladder cancer [1,2]. To justify screening, there needs to be a sufficient prevalence of disease in a population; otherwise, the cost of testing becomes exorbitant. This is the rationale for using age to determine the timing of screening for breast, colon, and prostate cancers. The same approach can also be applied to bladder cancer. Data extracted from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and the National Lung Screening Trial showed that bladder cancer was identified in 1430 of 154 898 and 439 of 53 173 patients, respectively [3]. Although such numbers may argue against the use of screening, in men aged >70 yr with a smoking exposure 30 pack-years (PYs), incidence rates were >5 per 1000 person-years, similar to the incidence of colon cancer detection on sigmoidoscopy [3]. Men aged >60 yr with a smoking history >30 PYs had incidence rates >2 per 1000 person-years. Therefore, the use of age and smoking history as selection criteria has the potential to identify populations of sufficient risk to justify a screening strategy for bladder and kidney cancer.
2.
Which test?
Issues related to testing involve cost, invasiveness, complications, and, most important, accuracy. False-positive rates are critical to screening. If one were to test 30 million smokers with a test with 99% specificity, 300 000 subjects would have a positive test, which is four times as many subjects as the number of bladder and kidney cancers diagnosed. Nonetheless, testing can be used to detect both bladder and kidney cancer. The most accurate test currently available for bladder cancer is cystoscopy that can be done in the office setting with a minimal risk of bleeding and infection and relatively low cost (<$300), but it is invasive. Noninvasive testing with either hematuria dipstick testing or urine-based tumor markers has been utilized [4]. These tests tend to have a higher sensitivity for high-grade tumors ranging from 60% to 80%, but specificity is lower (50–75%). Because the prevalence of microscopic blood in the urine can be as high as 10–14%, a considerable number of subjects would require cystoscopy, but this would still keep most patients from undergoing invasive testing. There are less data on potential testing for kidney cancer. Cross-sectional imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is the most sensitive way to detect renal masses, but CT and MRI are costly, and CT has the added disadvantage of radiation. Renal ultrasound (US) is a noninvasive low-cost option that can be performed in an office setting. One earlier review of US found that the sensitivity and specificity for diagnosing kidney cancer were 91% and 99%, respectively [5]. In a more recent study of 9959 volunteers, US had an 82% sensitivity with a 99% specificity for kidney cancer [6]. Subjects with
* Corresponding author. Department of Urology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., J1.112, Dallas, TX 75390, USA. Tel. +1 214 648 0389; Fax: +1 214 648 8786. E-mail address: [email protected]. http://dx.doi.org/10.1016/j.euf.2014.12.005 2405-4569/# 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
EUROPEAN UROLOGY FOCUS 1 (2015) 50–51
abnormal US will likely undergo CT scan to confirm because US alone has a predictive value of only 2% for equivocal findings and 50% for positive findings. This approach adds cost, but certainly the very high specificity significantly limits those numbers. Concerns regarding US screening for renal tumors are that small tumors can be missed and that US is operator dependent. 3.
How to deal with overdiagnosis
One of the main concerns with screening is the risk of overdiagnosis. This is a prevalent concern for prostate cancer. Identification of low-risk low-grade disease is one of the main reasons why prostate-specific antigen screening is criticized. However, this may not be an issue in bladder cancer. It is rarely discovered at autopsy, suggesting that most patients become symptomatic during their lifetime. In a large bladder cancer screening trial, Messing et al found that 50% of cancers identified were high grade, and yet only 5% of cancers were muscle invasive [7]. Screening did not diagnose more low-grade cancers than one would expect; it just found the high-grade cancers earlier at a more curable stage. All these data would thus support the benefit of screening in this setting. Kidney cancer screening is a different matter because small renal masses are frequently benign, and many can remain indolent for years [8]. Although clinically insignificant prostate cancers were treated for years, active surveillance is a reasonable and established approach for small renal masses. Even in the case of diagnosis, one can limit the cost and morbidity of incidental small renal masses by surveillance while still treating those that are more aggressive and potentially lethal.
51
found that in a population with >1.6% cancer incidence, screening with the NMP22 Bladderchek urine-based tumor marker (Alere, Waltham, MA, USA) would result in both improved overall survival and cost savings [9]. Patients diagnosed with muscle-invasive bladder cancer require very expensive treatments including cystectomy and chemotherapy, and many still succumb to their disease. Although there are no similar studies in kidney cancer, it is possible that renal US testing may be reasonable in some populations. What is the alternative? Cost is rarely discussed as a reason to avoid treating patients with metastatic disease even when the treatment is not curative. In conclusion, until we can find a cure for metastatic disease, screening high-risk populations is a better investment than spending money on end-of-life care with noncurative treatments. Conflicts of interest: The author has nothing to disclose.
References [1] Navai N, Wood CG. Environmental and modifiable risk factors in renal cell carcinoma. Urol Oncol 2012;30:220–4. [2] Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 2013;63:234–41. [3] 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. In press. http://dx.doi.org/10.1016/j.urolonc.2014.06.009 [4] Xylinas E, Kluth LA, Rieken M, Karakiewicz PI, Lotan Y, Shariat SF. Urine markers for detection and surveillance of bladder cancer. Urol Oncol 2014;32:222–9. [5] Aslaksen A, Halvorsen OJ, Gothlin JH. Detection of renal and renal pelvic tumours with urography and ultrasonography. Eur J Radiol 1990;11:54–8. [6] Filipas D, Spix C, Schulz-Lampel D, et al. Screening for renal cell
4.
Can we justify costs?
carcinoma using ultrasonography: a feasibility study. BJU Int 2003; 91:5959.
The cost of screening is always cited as the reason why it should not be done. As stated earlier, we can identify populations at increased risk, have tests that can identify cancers noninvasively, and improve stage at detection with likely survival benefits. A Markov model created to estimate cumulative cancer-related costs and the efficacy of screening (vs no screening) of a high-risk population for bladder cancer using a urine-based tumor marker over a 5-yr period
[7] Messing EM, Madeb R, Young T, et al. Long-term outcome of hematuria home screening for bladder cancer in men. Cancer 2006;107: 2173–9. [8] Smaldone MC, Kutikov A, Egleston BL, et al. Small renal masses progressing to metastases under active surveillance: a systematic review and pooled analysis. Cancer 2012;118:997–1006. [9] Lotan Y, Svatek RS, Sagalowsky AI. Should we screen for bladder cancer in a high-risk population?: A cost per life-year saved analysis. Cancer 2006;107:982–90.
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Point of Focus Debate: For
We Should Screen Smokers for Bladder and Kidney Cancer Yair Lotan * Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA
No recommendations currently exist for the screening for either kidney or bladder cancer, and these diseases are diagnosed when patients become symptomatic or after imaging for other causes. This commentary defends the rationale for screening smokers for bladder and kidney cancer. Some important questions on the use of screening in these malignancies need to be answered. 1.
Who should be screened?
The several known risk factors for bladder and kidney cancer include smoking, age, and gender [1,2]. Smoking increases the risk for kidney cancer by 2-fold and >4-fold for bladder cancer [1,2]. To justify screening, there needs to be a sufficient prevalence of disease in a population; otherwise, the cost of testing becomes exorbitant. This is the rationale for using age to determine the timing of screening for breast, colon, and prostate cancers. The same approach can also be applied to bladder cancer. Data extracted from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and the National Lung Screening Trial showed that bladder cancer was identified in 1430 of 154 898 and 439 of 53 173 patients, respectively [3]. Although such numbers may argue against the use of screening, in men aged >70 yr with a smoking exposure 30 pack-years (PYs), incidence rates were >5 per 1000 person-years, similar to the incidence of colon cancer detection on sigmoidoscopy [3]. Men aged >60 yr with a smoking history >30 PYs had incidence rates >2 per 1000 person-years. Therefore, the use of age and smoking history as selection criteria has the potential to identify populations of sufficient risk to justify a screening strategy for bladder and kidney cancer.
2.
Which test?
Issues related to testing involve cost, invasiveness, complications, and, most important, accuracy. False-positive rates are critical to screening. If one were to test 30 million smokers with a test with 99% specificity, 300 000 subjects would have a positive test, which is four times as many subjects as the number of bladder and kidney cancers diagnosed. Nonetheless, testing can be used to detect both bladder and kidney cancer. The most accurate test currently available for bladder cancer is cystoscopy that can be done in the office setting with a minimal risk of bleeding and infection and relatively low cost (<$300), but it is invasive. Noninvasive testing with either hematuria dipstick testing or urine-based tumor markers has been utilized [4]. These tests tend to have a higher sensitivity for high-grade tumors ranging from 60% to 80%, but specificity is lower (50–75%). Because the prevalence of microscopic blood in the urine can be as high as 10–14%, a considerable number of subjects would require cystoscopy, but this would still keep most patients from undergoing invasive testing. There are less data on potential testing for kidney cancer. Cross-sectional imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is the most sensitive way to detect renal masses, but CT and MRI are costly, and CT has the added disadvantage of radiation. Renal ultrasound (US) is a noninvasive low-cost option that can be performed in an office setting. One earlier review of US found that the sensitivity and specificity for diagnosing kidney cancer were 91% and 99%, respectively [5]. In a more recent study of 9959 volunteers, US had an 82% sensitivity with a 99% specificity for kidney cancer [6]. Subjects with
* Corresponding author. Department of Urology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., J1.112, Dallas, TX 75390, USA. Tel. +1 214 648 0389; Fax: +1 214 648 8786. E-mail address: [email protected]. http://dx.doi.org/10.1016/j.euf.2014.12.005 2405-4569/# 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
EUROPEAN UROLOGY FOCUS 1 (2015) 50–51
abnormal US will likely undergo CT scan to confirm because US alone has a predictive value of only 2% for equivocal findings and 50% for positive findings. This approach adds cost, but certainly the very high specificity significantly limits those numbers. Concerns regarding US screening for renal tumors are that small tumors can be missed and that US is operator dependent. 3.
How to deal with overdiagnosis
One of the main concerns with screening is the risk of overdiagnosis. This is a prevalent concern for prostate cancer. Identification of low-risk low-grade disease is one of the main reasons why prostate-specific antigen screening is criticized. However, this may not be an issue in bladder cancer. It is rarely discovered at autopsy, suggesting that most patients become symptomatic during their lifetime. In a large bladder cancer screening trial, Messing et al found that 50% of cancers identified were high grade, and yet only 5% of cancers were muscle invasive [7]. Screening did not diagnose more low-grade cancers than one would expect; it just found the high-grade cancers earlier at a more curable stage. All these data would thus support the benefit of screening in this setting. Kidney cancer screening is a different matter because small renal masses are frequently benign, and many can remain indolent for years [8]. Although clinically insignificant prostate cancers were treated for years, active surveillance is a reasonable and established approach for small renal masses. Even in the case of diagnosis, one can limit the cost and morbidity of incidental small renal masses by surveillance while still treating those that are more aggressive and potentially lethal.
51
found that in a population with >1.6% cancer incidence, screening with the NMP22 Bladderchek urine-based tumor marker (Alere, Waltham, MA, USA) would result in both improved overall survival and cost savings [9]. Patients diagnosed with muscle-invasive bladder cancer require very expensive treatments including cystectomy and chemotherapy, and many still succumb to their disease. Although there are no similar studies in kidney cancer, it is possible that renal US testing may be reasonable in some populations. What is the alternative? Cost is rarely discussed as a reason to avoid treating patients with metastatic disease even when the treatment is not curative. In conclusion, until we can find a cure for metastatic disease, screening high-risk populations is a better investment than spending money on end-of-life care with noncurative treatments. Conflicts of interest: The author has nothing to disclose.
References [1] Navai N, Wood CG. Environmental and modifiable risk factors in renal cell carcinoma. Urol Oncol 2012;30:220–4. [2] Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 2013;63:234–41. [3] 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. In press. http://dx.doi.org/10.1016/j.urolonc.2014.06.009 [4] Xylinas E, Kluth LA, Rieken M, Karakiewicz PI, Lotan Y, Shariat SF. Urine markers for detection and surveillance of bladder cancer. Urol Oncol 2014;32:222–9. [5] Aslaksen A, Halvorsen OJ, Gothlin JH. Detection of renal and renal pelvic tumours with urography and ultrasonography. Eur J Radiol 1990;11:54–8. [6] Filipas D, Spix C, Schulz-Lampel D, et al. Screening for renal cell
4.
Can we justify costs?
carcinoma using ultrasonography: a feasibility study. BJU Int 2003; 91:5959.
The cost of screening is always cited as the reason why it should not be done. As stated earlier, we can identify populations at increased risk, have tests that can identify cancers noninvasively, and improve stage at detection with likely survival benefits. A Markov model created to estimate cumulative cancer-related costs and the efficacy of screening (vs no screening) of a high-risk population for bladder cancer using a urine-based tumor marker over a 5-yr period
[7] Messing EM, Madeb R, Young T, et al. Long-term outcome of hematuria home screening for bladder cancer in men. Cancer 2006;107: 2173–9. [8] Smaldone MC, Kutikov A, Egleston BL, et al. Small renal masses progressing to metastases under active surveillance: a systematic review and pooled analysis. Cancer 2012;118:997–1006. [9] Lotan Y, Svatek RS, Sagalowsky AI. Should we screen for bladder cancer in a high-risk population?: A cost per life-year saved analysis. Cancer 2006;107:982–90.