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Hematuria and Urologic Malignancies

  • Yeong-Hau H. Lien
    Correspondence
    Requests for reprints should be addressed to Yeong-Hau H. Lien, MD, PhD, Arizona Kidney Disease and Hypertension Center, Tucson, AZ 85718.
    Affiliations
    Department of Medicine, College of Medicine, University of Arizona, Tucson

    Arizona Kidney Disease and Hypertension Center, Tucson
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      SEE RELATED ARTICLES pp. 625 and 633
      In the developed countries, prostate, bladder, and kidney cancers are the first, fourth, and sixth most common cancers, respectively, in men. These urologic malignancies account for 33.3% of total malignancies and 15.6% of malignancy-related mortality in men. In women, kidney and bladder cancers are the 11th and 15th most common cancers and together account for 4.6% of total malignancies and 3.7% of malignancy-related mortality.

      Available at: http://globocan.iar.fr. Accessed April 20, 2014.

      Asymptomatic microscopic hematuria is the most common presenting sign of urologic malignancies that may lead to early diagnosis and cure of these cancers.
      • Grossfeld G.D.
      • Litwin M.S.
      • Wolf Jr., J.S.
      • et al.
      Evaluation of asymptomatic microscopic hematuria in adults: the American Urological Association best practice policy–part II: patient evaluation, cytology, voided markers, imaging, cystoscopy, nephrology evaluation, and follow-up.
      In 2001, the American Urology Association reported guidelines for the evaluation of asymptomatic microscopic hematuria. Urologic image studies, cystoscopy, and urine cytology were recommended for hematuria without benign causes.
      • Grossfeld G.D.
      • Litwin M.S.
      • Wolf Jr., J.S.
      • et al.
      Evaluation of asymptomatic microscopic hematuria in adults: the American Urological Association best practice policy–part II: patient evaluation, cytology, voided markers, imaging, cystoscopy, nephrology evaluation, and follow-up.
      With the improvement of imaging technology, the guidelines have been revised recently. Computed tomography (CT) and magnetic resonance urographies are recommended as the first and second choices of urologic image study, respectively, whereas urine cytology is recommended as an optional test for patients with high-risk factors for urologic malignancies, but negative urologic image studies.
      • Davis R.
      • Jones J.S.
      • Barocas D.A.
      • et al.
      Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline.
      Although we have had hematuria guidelines for more than a decade, little information is available regarding physicians' adherence to and utilities of those guidelines. In this issue of the Journal, there are 2 retrospective cohort studies addressing these issues.
      • Friedlander D.F.
      • Resnick M.J.
      • You C.
      • et al.
      Variation in the intensity of hematuria evaluation: a target for primary care quality improvement.
      • Shinagare A.B.
      • Silverman S.G.
      • Gershanik E.F.
      • Chang S.L.
      • Khorasani R.
      Evaluating hematuria: impact of guideline adherence on urologic cancer diagnosis.
      The first study is from the Vanderbilt University Medical Center with 2455 primary care patients aged 40 years or more who were diagnosed with hematuria between 2004 and 2012 in the absence of other explanatory diagnosis.
      • Friedlander D.F.
      • Resnick M.J.
      • You C.
      • et al.
      Variation in the intensity of hematuria evaluation: a target for primary care quality improvement.
      The second study is from the Brigham and Women's Hospital. A total of 100 patients were randomly selected from a pool of 1771 ambulatory and inpatients aged 18 years or more with hematuria not due to menstruation or exercise. Detailed clinical information was obtained via chart reviews.
      • Shinagare A.B.
      • Silverman S.G.
      • Gershanik E.F.
      • Chang S.L.
      • Khorasani R.
      Evaluating hematuria: impact of guideline adherence on urologic cancer diagnosis.
      The settings of these 2 studies are different, but they complement each other. The findings are alarming: The nonadherence rate is 94% and 64% in these 2 studies,
      • Friedlander D.F.
      • Resnick M.J.
      • You C.
      • et al.
      Variation in the intensity of hematuria evaluation: a target for primary care quality improvement.
      • Shinagare A.B.
      • Silverman S.G.
      • Gershanik E.F.
      • Chang S.L.
      • Khorasani R.
      Evaluating hematuria: impact of guideline adherence on urologic cancer diagnosis.
      respectively. Of note, in the second study, a small portion of patients were evaluated by urologists whose nonadherence rate is only 6%. When urologists are excluded, the nonadherence rate increases to 81%.
      • Shinagare A.B.
      • Silverman S.G.
      • Gershanik E.F.
      • Chang S.L.
      • Khorasani R.
      Evaluating hematuria: impact of guideline adherence on urologic cancer diagnosis.
      In the Vanderbilt study, women are significantly less likely to undergo cystoscopy, image study, or both; only 3.8% of female patients had recommended cystoscopy and images, whereas 10.4% of male patients had a complete workup.
      • Friedlander D.F.
      • Resnick M.J.
      • You C.
      • et al.
      Variation in the intensity of hematuria evaluation: a target for primary care quality improvement.
      In other studies, women with hematuria are reported less likely to be referred to urologists, to have urological image studies, or to have an earlier diagnosis of bladder cancer.
      • Buteau A.
      • Seideman C.A.
      • Svatek R.S.
      • et al.
      What is evaluation of hematuria by primary care physicians? Use of electronic medical records to assess practice patterns with intermediate follow-up.
      • Cohn J.A.
      • Vekhter B.
      • Lyttle C.
      • Steinberg G.D.
      • Large M.C.
      Sex disparities in diagnosis of bladder cancer after initial presentation with hematuria: a nationwide claims-based investigation.
      It seems that sex disparities exist in the hematuria workup, which may explain why women have disproportionately higher mortality rates relative to the incidence of bladder cancer.
      • Cohn J.A.
      • Vekhter B.
      • Lyttle C.
      • Steinberg G.D.
      • Large M.C.
      Sex disparities in diagnosis of bladder cancer after initial presentation with hematuria: a nationwide claims-based investigation.
      How do we improve hematuria guideline adherence? Other than ignorance, there are many factors associated with nonadherence. CT urography is a sensitive image study for both the upper and lower urinary tract, but it has a relatively high radiation exposure and requires contrast media. It is possible that patients or insurance companies decline these studies because of high cost or risks. Ideally, CT urography and cystoscopy should be reserved for patients at high risk for urologic malignancies. We need to look for benign causes of microscopic hematuria before subjecting patients to those tests. We should also look for risk factors for urologic malignancies. Strong family history, smoking, and occupational exposure, mainly in industrial areas processing paint, dye, metal, and petroleum products, are known risk factors for urologic malignancies.
      • Burger M.
      • Catto J.W.
      • Dalbagni G.
      • et al.
      Epidemiology and risk factors of urothelial bladder cancer.
      A new carcinogen, aristolochic acid, has been confirmed recently as a culprit for transitional cell carcinoma of the urinary tract
      • Grollman A.P.
      • Shibutani S.
      • Moriya M.
      • et al.
      Aristolochic acid and the etiology of endemic (Balkan) nephropathy.
      • Chen C.H.
      • Dickman K.G.
      • Moriya M.
      • et al.
      Aristolochic acid-associated urothelial cancer in Taiwan.
      and recognized as one of the most potent carcinogens known to humans.
      • Clyne M.
      Bladder cancer: aristolochic acid–one of the most potent carcinogens known to man.
      Aristolochic acid is found in Chinese herbal medicine and contaminated flour in the Balkan region and should be included as a major risk factor for urologic malignancies.
      • Grollman A.P.
      • Shibutani S.
      • Moriya M.
      • et al.
      Aristolochic acid and the etiology of endemic (Balkan) nephropathy.
      • Chen C.H.
      • Dickman K.G.
      • Moriya M.
      • et al.
      Aristolochic acid-associated urothelial cancer in Taiwan.
      By eliminating benign causes of microscopic hematuria and recognizing high-risk individuals, we can then justify urologic image studies and cystoscopy as lifesaving procedures for our patients.

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