Screening for Bladder Cancer in Individuals with Spinal Cord Injury IT is more likely for bladder cancer to develop in individuals with spinal cord injury (SCI) and these cancers are more aggressive than those occurring in the general population. In this issue of The Journal, Nahm et al (page 1923) demonstrate that the probability of death from bladder cancer is 6.7-fold higher in the SCI population than in the general population.1 This prompts questions of bladder cancer prevention, screening and treatment for individuals with SCI, and the focus here will be on screening. In the absence of screening, individuals with SCI present with some of the same symptoms as those without SCI, such as hematuria, bladder mass and hydronephrosis. However, individuals with SCI also present with some unique symptoms. Investigation for bladder stones, recurrent urinary tract infections or new incontinence can lead to a diagnosis of bladder cancer. The unique presentation can lead to delayed diagnosis, again raising the question of whether there is a role for screening. In the wake of the controversial recommendations of the U.S. Preventive Services Task Force to limit screening for prostate and breast cancer, many in the medical community are now well aware of the components necessary for an effective screening test. The cancer must be common. Obviously if the cancer is common, then more of the individuals undergoing the screening test stand to benefit and fewer people undergo an unnecessary test. Less obvious is that a high prevalence decreases the false-positive rate, meaning that fewer people undergo unnecessary confirmatory tests. In addition, the test must detect cancers earlier than would be detected through usual care. Finally, early detection should allow for more effective cancer treatment, meaning lower cancer death rates. We must answer whether bladder cancer is sufficiently common in people with SCI to warrant screening. Although some early literature reported the incidence of bladder cancer to be as high as 10% in individuals with SCI,2,3 recent series estimate the incidence to be less than 5% and most estimate it to be less than 2%.4 Because followup varies in many of these studies, a better measure is incidence rate, which is less than 0.1% per person-year in those
0022-5347/15/1936-1880/0 THE JOURNAL OF UROLOGY® © 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
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j
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studies that have reported this measure.5e7 In fact, although an indwelling catheter increased the risk by more than fourfold, the risk was still less than 0.1% per person-year.6 With 20 years of followup, that would be an incidence of 2%. Compared to other cancers for which screening is considered to be of potential benefit, this incidence is relatively low. In addition, we must ask whether the current screening methods are effective at detecting bladder cancer earlier. Screening methods commonly used include urinalysis, cystoscopy and urine cytology. Urinalysis is an ineffective screening test because microhematuria is nearly ubiquitous in SCI cases due to chronic bacteriuria and catheterization. The best available studies suggest that cystoscopy and cytology are not effective screening tools either. Yang and Clowers demonstrated that in 500 individuals with SCI who used an indwelling catheter or intermittent catheterization and were at least 5 to 10 years after injury, no cancers were detected by screening cystoscopy.8 In fact, cancer developed in 1 patient 4 months after a negative cystoscopy and biopsy, and in 2 patients even though they did not meet the inclusion criteria for screening because they did not use a catheter. Similarly Higuchi et al demonstrated that in 65 patients with congenital bladder pathology 10 or more years after bladder augmentation, annual cystoscopy and cytology yielded no bladder tumors during a followup of 15 years.9 However, testing did lead to 26 false-positive cytologies and 4 falsepositive cystoscopies. Other reports of the utility of cytology in patients with SCI yield widely different estimates of sensitivity and specificity. As will be shown, the actual sensitivity and specificity matter little in this setting, mainly because the cancer incidence is so low. It follows from this discussion that if screening does not detect tumors earlier, then it cannot allow for more effective cancer treatment. However, what if we assumed screening did lead to earlier cancer detection and did allow for a better chance of cure with treatment? One group did just that for the question of surveillance cystoscopy and cytology after augmentation cystoplasty in children with
http://dx.doi.org/10.1016/j.juro.2015.03.069 Vol. 193, 1880-1881, June 2015 Printed in U.S.A.
BLADDER CANCER SCREENING AND SPINAL CORD INJURY
spina bifida. Although the clinical situation is different from unaugmented adult cases with SCI, the exercise is still instructive. They constructed a decision analysis model that assumed 1) a 0.1% annual incidence rate of bladder cancer, 2) with screening 45% of tumors would be detected at an early stage whereas without screening all would be detected late, 3) a false-positive rate of 25%, and 4) 99% 5-year survival if detected early vs 22% if detected late. All of these assumptions are reasonable for our SCI population too. They predicted that screening would extend life expectancy by 2.5 months (49.7 vs 49.5 years) for a cost-effectiveness ratio of $273,718. This figure exceeds the typical threshold of $100,000, below which medical tests and interventions are deemed to be cost-effective. They varied several of the assumptions to show at what point screening would become cost-effective. This point occurred when the incidence rate was 0.25% per year or when the cost of screening (including the associated costs of tests for false-positives) was less than $327 per year. Interestingly, even if the 5-year survival for
1881
screened tumors was assumed to be 100% and for nonscreened tumors was assumed to be 0%, screening was still not cost-effective. In summary, the general SCI population is at an increased risk of bladder cancer and eventual death from the disease. However, this risk is not high enough to warrant screening. This finding should not stop us from working to identify risk factors that place certain SCI subpopulations at a sufficiently high risk that they would warrant screening. Until then, we should avoid screening the general SCI population, even if they have indwelling catheters, and limit our bladder cancer evaluations to those for signs and symptoms. This practice is cost-effective as well as less burdensome for the patient. Sean P. Elliott* Department of Urology University of Minnesota Minneapolis, Minnesota *Financial interest and/or other relationship with American Medical Systems, GT Urological and PercuVision.
REFERENCES 1. Nahm LS, Chen Y, DeVivo MJ et al: Bladder cancer mortality after spinal cord injury over 4 decades. J Urol 2015; 193: 1923.
4. Welk B, McIntyre A, Teasell R et al: Bladder cancer in individuals with spinal cord injuries. Spinal Cord 2013; 51: 516.
7. Subramonian K, Cartwright RA, Harnden P et al: Bladder cancer in patients with spinal cord injuries. BJU Int 2004; 93: 739.
2. Kaufman JM, Fam B, Jacobs SC et al: Bladder cancer and squamous metaplasia in spinal cord injury patients. J Urol 1977; 118: 967.
5. West DA, Cummings JM, Longo WE et al: Role of chronic catheterization in the development of bladder cancer in patients with spinal cord injury. Urology 1999; 53: 292.
8. Yang CC and Clowers DE: Screening cystoscopy in chronically catheterized spinal cord injury patients. Spinal Cord 1999; 37: 204.
3. Locke JR, Hill DE and Walzer Y: Incidence of squamous cell carcinoma in patients with long-term catheter drainage. J Urol 1985; 133: 1034.
6. Groah SL, Weitzenkamp DA, Lammertse DP et al: Excess risk of bladder cancer in spinal cord injury: evidence for an association between indwelling catheter use and bladder cancer. Arch Phys Med Rehabil 2002; 83: 346.
9. Higuchi TT, Fox JA and Husmann DA: Annual endoscopy and urine cytology for the surveillance of bladder tumors after enterocystoplasty for congenital bladder anomalies. J Urol 2011; 186: 1791.
0022-5347/15/1936-1880/0 THE JOURNAL OF UROLOGY® © 2015 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
1880
j
www.jurology.com
AND
RESEARCH, INC.
studies that have reported this measure.5e7 In fact, although an indwelling catheter increased the risk by more than fourfold, the risk was still less than 0.1% per person-year.6 With 20 years of followup, that would be an incidence of 2%. Compared to other cancers for which screening is considered to be of potential benefit, this incidence is relatively low. In addition, we must ask whether the current screening methods are effective at detecting bladder cancer earlier. Screening methods commonly used include urinalysis, cystoscopy and urine cytology. Urinalysis is an ineffective screening test because microhematuria is nearly ubiquitous in SCI cases due to chronic bacteriuria and catheterization. The best available studies suggest that cystoscopy and cytology are not effective screening tools either. Yang and Clowers demonstrated that in 500 individuals with SCI who used an indwelling catheter or intermittent catheterization and were at least 5 to 10 years after injury, no cancers were detected by screening cystoscopy.8 In fact, cancer developed in 1 patient 4 months after a negative cystoscopy and biopsy, and in 2 patients even though they did not meet the inclusion criteria for screening because they did not use a catheter. Similarly Higuchi et al demonstrated that in 65 patients with congenital bladder pathology 10 or more years after bladder augmentation, annual cystoscopy and cytology yielded no bladder tumors during a followup of 15 years.9 However, testing did lead to 26 false-positive cytologies and 4 falsepositive cystoscopies. Other reports of the utility of cytology in patients with SCI yield widely different estimates of sensitivity and specificity. As will be shown, the actual sensitivity and specificity matter little in this setting, mainly because the cancer incidence is so low. It follows from this discussion that if screening does not detect tumors earlier, then it cannot allow for more effective cancer treatment. However, what if we assumed screening did lead to earlier cancer detection and did allow for a better chance of cure with treatment? One group did just that for the question of surveillance cystoscopy and cytology after augmentation cystoplasty in children with
http://dx.doi.org/10.1016/j.juro.2015.03.069 Vol. 193, 1880-1881, June 2015 Printed in U.S.A.
BLADDER CANCER SCREENING AND SPINAL CORD INJURY
spina bifida. Although the clinical situation is different from unaugmented adult cases with SCI, the exercise is still instructive. They constructed a decision analysis model that assumed 1) a 0.1% annual incidence rate of bladder cancer, 2) with screening 45% of tumors would be detected at an early stage whereas without screening all would be detected late, 3) a false-positive rate of 25%, and 4) 99% 5-year survival if detected early vs 22% if detected late. All of these assumptions are reasonable for our SCI population too. They predicted that screening would extend life expectancy by 2.5 months (49.7 vs 49.5 years) for a cost-effectiveness ratio of $273,718. This figure exceeds the typical threshold of $100,000, below which medical tests and interventions are deemed to be cost-effective. They varied several of the assumptions to show at what point screening would become cost-effective. This point occurred when the incidence rate was 0.25% per year or when the cost of screening (including the associated costs of tests for false-positives) was less than $327 per year. Interestingly, even if the 5-year survival for
1881
screened tumors was assumed to be 100% and for nonscreened tumors was assumed to be 0%, screening was still not cost-effective. In summary, the general SCI population is at an increased risk of bladder cancer and eventual death from the disease. However, this risk is not high enough to warrant screening. This finding should not stop us from working to identify risk factors that place certain SCI subpopulations at a sufficiently high risk that they would warrant screening. Until then, we should avoid screening the general SCI population, even if they have indwelling catheters, and limit our bladder cancer evaluations to those for signs and symptoms. This practice is cost-effective as well as less burdensome for the patient. Sean P. Elliott* Department of Urology University of Minnesota Minneapolis, Minnesota *Financial interest and/or other relationship with American Medical Systems, GT Urological and PercuVision.
REFERENCES 1. Nahm LS, Chen Y, DeVivo MJ et al: Bladder cancer mortality after spinal cord injury over 4 decades. J Urol 2015; 193: 1923.
4. Welk B, McIntyre A, Teasell R et al: Bladder cancer in individuals with spinal cord injuries. Spinal Cord 2013; 51: 516.
7. Subramonian K, Cartwright RA, Harnden P et al: Bladder cancer in patients with spinal cord injuries. BJU Int 2004; 93: 739.
2. Kaufman JM, Fam B, Jacobs SC et al: Bladder cancer and squamous metaplasia in spinal cord injury patients. J Urol 1977; 118: 967.
5. West DA, Cummings JM, Longo WE et al: Role of chronic catheterization in the development of bladder cancer in patients with spinal cord injury. Urology 1999; 53: 292.
8. Yang CC and Clowers DE: Screening cystoscopy in chronically catheterized spinal cord injury patients. Spinal Cord 1999; 37: 204.
3. Locke JR, Hill DE and Walzer Y: Incidence of squamous cell carcinoma in patients with long-term catheter drainage. J Urol 1985; 133: 1034.
6. Groah SL, Weitzenkamp DA, Lammertse DP et al: Excess risk of bladder cancer in spinal cord injury: evidence for an association between indwelling catheter use and bladder cancer. Arch Phys Med Rehabil 2002; 83: 346.
9. Higuchi TT, Fox JA and Husmann DA: Annual endoscopy and urine cytology for the surveillance of bladder tumors after enterocystoplasty for congenital bladder anomalies. J Urol 2011; 186: 1791.
