Microscopic hematuria is a common condition with a prevalence of 9 to 18% of apparently normal individuals.(2
) Mariani et al. evaluated 1000 consecutive patients with hematuria and 9.1% had life-threatening lesions but disease was localized in 92% of cases.(4
) Khadra and colleagues evaluated 1,930 hematuria patients and found bladder cancer in 11.9% including 4.8% and 19.3% of patients with microscopic and gross hematuria, respectively.(10
) Additional findings included urinary tract infections (13%), medical renal disease (9.8%), urolithiasis (3.6%), renal cancers (0.6%), and prostate cancer (0.4%). While significant diseases were less common in patients with microscopic hematuria (31.8%) as opposed to gross hematuria (47.5%), it still represented a considerable disease burden since the absolute number of patients with microscopic hematuria exceeds those with gross hematuria. Due to this risk, the AUA guidelines and clinical practice recommendations both state that patients at high risk for bladder cancer should undergo evaluation with cystoscopy, cytology and upper tract imaging.(5
) It is concerning that 87% of subjects in our study did not undergo appropriate evaluation according to guidelines panels.
Our study identified subjects who were selected for bladder cancer screening based on age over 50 and ≥10 year history of smoking and/or ≥15 year environmental exposure. Similar to other studies, we found microscopic hematuria in 10.9% of our subjects with 73.2% having at least one urinalysis within 3 years prior to inclusion in our screening study. The etiology of most urothelial cancers has been associated with increasing age, tobacco exposure, occupational exposures to aromatic amines and exposures from the chemical and rubber industry.(11
) Cigarette smoking accounts for a large proportion of the disease in men (50–75%) and women (14–35%), while the attributable risk for occupational exposures is only 10%.(12
) Despite the fact that subjects in our population with microscopic hematuria clearly met the criteria for high risk of bladder cancer, only 12.8% were referred to see a urologist for cystoscopic evaluation. Furthermore, only 10.4% had urine cytologic evaluation and 22.6% had imaging. As such, the vast majority of the population with microscopic hematuria at high risk did not have a complete evaluation. Smokers, who are at particularly increased risk for bladder cancer were paradoxically less likely to be referred for guideline-appropriate evaluation than non-smokers. Furthermore, 3 subjects (2%) who were diagnosed with bladder cancer at time of screening study had hematuria that had not been previously evaluated.
Our study confirms prior reports which suggest that many patients with microscopic hematuria do not get referred for evaluation by urologists.(7
) There are no available studies which explore the rationale for referring some patients in favour of others but our study suggests that at 2 separate hospitals, a similar pattern exists with regard to evaluation (or lack thereof) of microscopic hematuria. Future studies will be necessary to evaluate barriers to appropriate evaluation, and to test interventions to improve proper work-up of evaluation. Interventions might include education, or structured, reflexive protocols when hematuria is noted at laboratory testing. Problems with inconsistent referrals have been blamed for delays in diagnosis of bladder cancer.(14
) At this time, 25% of bladder cancers are diagnosed with advanced stage and these patients have a significantly lower survival than patients with non-invasive disease. Of note, a greater proportion of women with bladder cancer die from their disease likely secondary to delay in diagnosis.(15
One possibility for low referral rates is a perceived low yield of cancer in patients with microscopic hematuria. Since over 60% of patients who are evaluated have no explanation for the microscopic hematuria, some clinicians may feel that there is little benefit to referring patients and ordering expensive imaging.(10
) Interestingly, there is significant pressure on clinicians to perform other tests of relatively low yield such as evaluation for colon cancer. As part of Prostate, Lung, Colorectal and Ovarian cancer screening trial, a total of 64,658 subjects underwent screening flexible sigmoidoscopy.(16
) The yields for colorectal cancer per 1000 screened, depending on 5-year age group was 1.1–2.5 in women and 2.4–5.6 in men. This cancer yield is nearly 10 fold less than the likelihood of bladder cancer in patients with microscopic hematuria, yet screening for colorectal cancer is clearly accepted and promoted by primary physicians. Problems with appropriate evaluation of fecal occult blood are common and there are several studies that have attempted to improve physician management approaches, (17
) including education and structured reflexive protocols; these may serve as a model for improvement of management of individuals with hematuria.
This study has several limitations. Data used for this study were originally collected for clinical, not research purposes, leading to the possibility of misclassification of the presence or absence of hematuria, or subsequent work-up. However, the central computerized medical records used for clinical care at both institutions in our study setting make the likelihood of misclassification unlikely. It is a retrospective chart review but performing a prospective study on compliance to guidelines would be self-defeating since clinicians would be biased to conform to guidelines if they knew they were being studied. Also, subjects with microhematuria, without subsequent work up, may have been aware of microhematuria, concerned about the finding, and perhaps more likely to participate in our screening study. This may have lead to an overestimation of the prevalence of subjects with inappropriate work up of hematuria.
Nonetheless, the raw frequency of inappropriate (n=143 of 164 subjects) work up was quite high, emphasizing that even if our prevalence estimates are high, that this is an important clinical problem that deserves further study. Finally, it is not clear why patients were not referred for evaluation and it is possible that some patients were referred but were noncompliant with recommendations to see a urologist.