Predictors of genitourinary malignancy in patients with asymptomatic microscopic hematuria

doi:10.1016/j.urolonc.2017.09.011

Urologic Oncology: Seminars and Original Investigations

Volume 36, Issue 1, January 2018, Pages 10.e1-10.e6

https://doi.org/10.1016/j.urolonc.2017.09.011 Get rights and content

Highlights

•
12 of 1,049 patients with asymptomatic microscopic hematuria were diagnosed with urologic cancer.
•
Older age, male sex, irritative voiding symptoms, and smoking were associated with urologic cancer.
•
All 12 patients diagnosed with urologic malignancy were older than 50 years of age.

Abstract

Objectives

To report the incidence of genitourinary malignancy and identify associated risk factors in patients undergoing urologic evaluation for asymptomatic microscopic hematuria (AMH) according to the 2012 American Urologic Association guidelines.

Subjects/patients and methods

A retrospective institutional review of patients who underwent evaluation for AMH between 2012 and 2015 was conducted. Covariates analyzed included age, sex, smoking status, history of other malignancy, history of pelvic irradiation, presence of irritative voiding symptoms, use of anticoagulation, number of red blood cells on microscopic urinalysis, and guideline adherence. Univariate analysis was performed to explore the association between these risk factors and the presence of genitourinary malignancy.

Results

Of the 1,049 patients analyzed with AMH, urologic malignancy was diagnosed in 12 patients (1.1%), including 1 upper-tract urothelial cancer, 5 renal tumors, and 6 bladder tumors. All patients with malignancy were over 50 years old. Older age, male sex, smoking history, and irritative voiding symptoms were associated with malignancy on univariate analysis.

Conclusions

Our data adds to the growing evidence that the incidence of malignancy among patients with AMH is low. Risk factors associated with urinary tract cancer are male sex, age>50 years, smoking history, and irritative voiding symptoms. Further prospective, randomized trials would be useful for developing a more tailored screening protocol for low-risk patients.

Introduction

Microscopic hematuria is a relatively common clinical entity that may be a harbinger for significant urinary tract disease. Population-based studies have reported the prevalence of asymptomatic microscopic hematuria (AMH) ranging between 0.19% and 16.1% [1], [2]. Although the etiology of AMH is often benign, the clinician must consider the possibility of urologic malignancy as the culprit. Of patients diagnosed with urothelial carcinoma, up to 23.1% present with microscopic hematuria [3].

While no medical organization recommends routine screening for urinary tract malignancy, guidelines have evolved to evaluate patients with clinically detected AMH [4]. In 2001, the American Urological Association (AUA) issued a best practice policy statement recommending that patients with 3 or more red blood cells per microscopic high-powered field (RBC/HPF) from at least 2 properly collected urine specimens should be evaluated with upper-tract imaging, cystoscopy, and urine cytology [5]. The Canadian Urologic Association published similar guidelines in 2009, suggesting that upper-tract evaluation should start with renal ultrasound [6]. In 2012, the AUA published official guidelines that recommended patients with AMH be evaluated with computed tomography (CT) urography, cystoscopy in those older than 35 years or with certain risk factors, and optional urine cytology only for patients with high risk for carcinoma in situ [7]. Moreover, the threshold to perform a complete urologic evaluation was lowered to include all patients with 1 urinalysis (UA) demonstrating 3 or greater RBC/HPF.

The challenge of investigating AMH lies in appropriate patient selection. This requires thorough risk stratification to identify which patients are more likely to harbor significant disease. Moreover, the decision whether to obtain expensive or invasive tests necessitates balancing the risk of missing significant pathology with that of excess usage of resources and potential harms of testing.

The purpose of our study is to report the incidence of genitourinary (GU) malignancy and to identify associated risk factors in patients undergoing a urologic evaluation for AMH at our institution after the publication of the 2012 AUA guidelines.

Section snippets

Patients

A retrospective, Institutional Review Board-approved study of adult patients referred to our urology department for AMH was performed. The electronic medical record was queried to identify all patients seen for an initial visit for microscopic hematuria or hematuria, unspecified (International Classification of Diseases, Ninth Revision diagnosis codes of 599.72 and 599.70). Medical charts were individually reviewed to confirm a documented initial UA demonstrating ≥3 RBC/HPF between July 2012

Results

A final cohort of 1,049 patients with AMH were included for analysis. The study population had a mean age of 57 years (standard deviation = 13.9), and consisted of 620 females (59.1%) and 429 males (40.9%). The remainder of the demographic and baseline clinical data is included in Table 1.

While 621 (59.2%) patients had a negative workup, GU malignancy was diagnosed in 12 patients (1.1%); urolithiasis was incidentally found in 118 (11.2%) patients, although only 19 of these 118 (16.1%) underwent

Discussion

Of the 1,049 patients analyzed, only 12 (1.1%) were found to have urologic cancer. Furthermore, 7 of these patients had low-risk disease—either low-grade Ta bladder cancer or a small renal mass. Our rate of malignancy is lower than the 3.3% rate in the meta-analysis performed by the 2012 AUA guideline panel [7]. Perhaps the higher rate quoted by the guideline panel reflects a biased population, as some studies cited included patients who had gross hematuria and positive urine dipstick without

Conclusion

Our study adds to the growing evidence that the incidence of urologic malignancy among patients with AMH is low. Risk factors associated with the detection of urologic malignancy are older age, male sex, irritative voiding symptoms, and history of smoking. Further prospective studies would be useful for developing a more tailored screening protocol for low-risk patients.

References (26)

I.M. Thompson
The evaluation of microscopic hematuria: a population-based study
J Urol
(1987)
G.D. Grossfeld et al.
Evaluation of asymptomatic microscopic hematuria in adults: the American Urological Association best practice policy—part I: definition, detection, prevalence, and etiology
Urology
(2001)
R. Davis et al.
American Urological Association. Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline
J Urol
(2012)
S. Murakami et al.
Strategies for asymptomatic microscopic hematuria: a prospective study of 1,034 patients
J Urol
(1990)
H. Jung et al.
Association of hematuria on microscopic urinalysis and risk of urinary tract cancer
J Urol
(2011)
R.K. Loo et al.
Stratifying risk of urinary tract malignant tumors in patients with asymptomatic microscopic hematuria
Mayo Clin Proc
(2013)
A.J. Mariani et al.
The significance of adult hematuria: 1,000 hematuria evaluations including a risk-benefit and cost-effectiveness analysis
J Urol.
(1989)
C.W. Commander et al.
Detection of upper tract urothelial malignancies by computed tomography urography in patients referred for hematuria at a large tertiary referral center
Urology
(2017)
W.S. Lai et al.
Assessing the costs of extraurinary findings of computed tomography urogram in the evaluation of asymptomatic microscopic hematuria
Urology
(2016)
A.M. Nieder et al.
Are patients with hematuria appropriately referred to Urology? A multi-institutional questionnaire based survey
Urol Oncol
(2010)

A.B. Shinagare et al.

Evaluating hematuria: impact of guideline adherence on urologic cancer diagnosis

Am J Med

(2014)

A. Buteau et al.

What is evaluation of hematuria by primary care physicians? Use of electronic medical records to assess practice patterns with intermediate follow-up

Urol Oncol

(2014)

R. Madeb et al.

Long-term outcome of patients with a negative work-up for asymptomatic microhematuria

Urology

(2010)

Cited by (18)

Systematic Review of the Incidence of and Risk Factors for Urothelial Cancers and Renal Cell Carcinoma Among Patients with Haematuria
2022, European Urology
Citation Excerpt :
The weighted pooled incidence of UTUC was 0.75% (95% CI 0.4–1.2%; Supplementary Fig. 1E). Data were available for analysis of bladder cancer incidence in 25 studies overall [2,12,16,17,21,23,25–29,34,37,39–41,43–47,49,50,52,54], for which the cumulative number of participants was 201 158. The weighted pooled incidence of bladder cancer was 2.3% (95% CI 1.57–3.1%; Supplementary Fig. 2).
The current impact of haematuria investigations on health care organisations is significant. There is currently no consensus on how to investigate patients with haematuria.
To evaluate the incidence of bladder cancer, upper tract urothelial carcinoma (UTUC), and renal cell carcinoma (RCC) among patients undergoing investigation for haematuria and identify any risk factors for bladder cancer, UTUC, and RCC (BUR).
Medline, Embase, and Cochrane controlled trials databases and ClinicalTrials.gov were searched for all relevant publications from January 1, 2000 to June 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Prospective, retrospective, and cross-sectional studies with a minimum population of 50 patients with haematuria were considered for the review.
A total of 44 studies were included. The total number of participants was 229 701. The pooled incidence rate for urothelial bladder cancer was 17% (95% confidence interval [CI] 14–20%) for visible haematuria (VH) and 3.3% (95% CI 2.45–4.3%) for nonvisible haematuria (NVH). The pooled incidence rate for RCC was 2% (95% CI 1–2%) for VH and 0.58% (95% CI 0.42–0.77%) for NVH. The pooled incidence rate for UTUC was 0.75% (95% CI 0.4–1.2%) for VH and 0.17% (95% CI 0.081–0.299%) for NVH. On sensitivity analysis, the proportions of males (risk ratio [RR] 1.14, 95% CI 1.10–1.17 for VH; 1.54, 95% CI 1.34–1.78 for NVH; p < 0.00001; moderate certainty evidence) and individuals with a smoking history (RR 1.41, 95% CI 1.24–1.61 for VH; 1.53, 95% CI 1.36–1.72 for NVH; p < 0.00001; moderate certainty evidence) appeared to be higher in BUR than in non-BUR groups.
Male gender and smoking history are risk factors for BUR cancer in haematuria, with bladder cancer being the commonest cancer. The incidence of RCC and UTUC in NVH is low. The review serves as a reference standard for future policy-making on investigation of haematuria by global organisations.
Our review shows that male gender and smoking history are risk factors for cancers of the bladder, kidney, and ureter. The review also provides information on the proportion of patients who have cancer when they have blood in their urine (haematuria) and will allow policy-makers to decide on the most appropriate method for investigating haematuria in patients.
Comparison of Microscopic Hematuria Guidelines as Applied in 1018 Patients With Microscopic Hematuria
2021, Urology
Citation Excerpt :
We found that the use of the updated guidelines may decrease the number of invasive and costly diagnostic procedures conducted without compromising the diagnosis of malignancies. The urinary malignancy rate for the patients in our study was 3.3%, similar to that in the other studies in the literature.3,5,10 Gonzales et al. evaluated 2118 patients for asymptomatic MH and found that 25 patients (1.2%) had been diagnosed with bladder cancer.11
To compare the 2012 American Urological Association (AUA) and 2020 AUA/Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU) microscopic hematuria (MH) guidelines as applied in 1,018 patients with MH, to confirm of risk groups and to investigate the natural history of patients with MH.
Patients who had undergone a complete urological evaluation for MH according to the 2012 AUA MH guidelines were identified retrospectively. All the patients were then classified into low-, intermediate-, or high-risk for urinary tract malignancy according to the updated 2020 AUA/SUFU MH guidelines, for a second evaluation. The results of the first and second evaluations using the previous 2012 AUA and updated 2020 AUA/SUFU MH guidelines, respectively, were then compared.
A total of 1018 patients with MH were identified. The urinary tract malignancy rate was 3.3% (34 of the 1,018 patients). According to the 2020 AUA/SUFU MH guidelines, there were 218 patients (21.4%) in the low-risk group, 447 patients (43.9%) in the intermediate-risk group, and 353 patients (34.6%) in the high-risk group. All the 34 patients with malignancy were from the intermediate- or high-risk group who require further urological evaluation. There was no patient with newly developed urinary tract malignancy at the median follow-up time of 28 months (12-58).
The use of the updated 2020 AUA/SUFU MH guidelines may reduce the number of diagnostic procedures without compromising the diagnosis of life-threatening malignant lesions.
Diagnostic yield of repeat evaluation for asymptomatic microscopic hematuria after negative initial workup
2021, Urologic Oncology: Seminars and Original Investigations
The American Urological Association guideline for asymptomatic microhematuria recommends in patients with a negative initial workup, repeat workup should be considered for those with persistent/recurrent microhematuria. However, there is little data on the yield of repeat evaluation. Our hypothesis was that repeat workup yields a low detection rate of urologic malignancy.
We retrospectively reviewed all patients at our institution who underwent microhematuria workup with cystoscopy and upper tract imaging from May 2010 to June 2016. Microhematuria was defined as ≥3 RBCs/HPF on a properly collected specimen in the absence of a benign cause. Demographics, age, smoking history, history of radiation, and findings on repeat cystoscopy and imaging were collected. Our primary endpoint was a new diagnosis of urologic malignancy.
Our initial cohort included 1,332 patients, of whom 21 were diagnosed with urothelial carcinoma and 7 with suspicious renal masses on initial workup. A total of 637 patients with negative initial workup had persistent/recurrent microhematuria. Repeat cystoscopy was performed in 161 (25%) patients at a median of 39 months, and repeat upper tract imaging was performed in 317 (50%) patients at a median of 39 months. Overall, repeat cystoscopy revealed new bladder cancer in 2 (1.2%) patients and repeat imaging revealed new suspicious renal mass in 4 (1.3%) patients.
We observed a low number of newly diagnosed malignancies among patients with persistent/recurrent asymptomatic microhematuria who had a prior negative workup. Additional research is required to determine the utility of a repeat AMH workup.
Use of a Risk Stratification Tool to Guide Evaluation of Patients With Asymptomatic Microscopic Hematuria
2020, Urology
Citation Excerpt :
A retrospective review of all patients who underwent AMH evaluation from 2012 to 2015 in the Smith Institute of Urology was conducted. This cohort and the specific data collection have been previously characterized.18,19 The total number of patients was 1049, though 55 of these patients received no evaluation at all and were not included in the analysis.
To determine if use of the hematuria risk index can reduce testing and cost, while maintaining equivalent lesion detection in patients with asymptomatic microscopic hematuria.
Retrospective cohort study of 1049 patients at single institution. Hematuria risk index score was calculated based on clinical factors including age, sex, smoking history, and degree of hematuria for each patient along with evaluation studies performed and total number of tumors discovered. Cost benefit analysis was performed based on published Medicare averages.
Tumor detection rate in overall, low-risk, and moderate-risk groups were 1.2%, 0%, and 2.96% at a total cost of $408,376. When low-risk group is not screened cost decreases to $166,252 with no lesions missed. The cost to discover one lesion/cancer in the overall group was $34,031.3, the cost to find one high-grade clinically significant lesion/cancer was $136,125.3 for the overall group. When the low-risk group was removed, the cost to find a high-grade clinically significant lesion/cancer decreased to $55,417.3 without missing any significant lesions. Ultrasound may be utilized instead of computed tomography with minimal loss of lesion detection in select moderate risk patients.
None of the low-risk hematuria risk patients were diagnosed with any lesions, as such these patients may not need an evaluation. Furthermore, by utilizing a risk-stratified approach to the assessment of asymptomatic microscopic hematuria health care costs can be significantly decreased with limited negative consequences in terms of lesion detection.
Evaluation of Asymptomatic Microscopic Hematuria by Renal Ultrasound to Detect Upper Tract Malignancy: A 20-Year Experience in a Community Hospital
2019, Urology
Citation Excerpt :
Lai et al found CTU led to increased costs of $694.50 per initial patient screened to evaluate extraurinary findings.25 Although CTU is highly sensitive, its benefit should outweigh the expense10,18,25,26 and the risks of contrast-induced nephropathy, contrast reactions, and radiation exposure.8 Future development of CTU techniques to reduce radiation exposure27 and contrast28 may decrease these burdens and enable its widespread use.
To evaluate the sensitivity of ultrasound imaging in detecting upper urinary tract malignancy in patients with asymptomatic microscopic hematuria (AMH) in an outpatient community setting.
A list of all patients who received renal ultrasound for hematuria in our health care system between January 1, 1997 and July 1, 2015 was obtained, and electronic health records were retrospectively reviewed. Patients were excluded for age (<18 years), <3 years follow-up, prior upper tract malignancy, recent urinary tract catheterization, inpatient status, pregnancy, insufficient data, or gross hematuria. The initial ultrasound was considered positive if suspicious findings led to a subsequent diagnosis of an upper tract malignancy. False negatives were determined by electronic medical record follow-up for at least 3 years.
Of the 2138 patients with AMH who met inclusion criteria, ultrasound imaging detected suspicious findings in 9 of 9 patients with renal cell carcinoma and 3 of 3 patients with upper tract urothelial cancer, indicating a sensitivity of 100% and 100%, respectively. Four additional malignancies were diagnosed more than 3 years after the initial evaluation for an incidence rate of 1.6 cases of upper tract malignancy per 10,000 person-years.
The prevalence of upper urinary tract malignancy was low in patients with AMH. Ultrasonography is an appropriate modality for upper tract imaging in the initial evaluation of patients with AMH. Practice guidelines should be updated to reflect the high sensitivity of ultrasound and low risk of upper tract malignancy in patients with AMH.
The Prevalence of Bladder Cancer During Cystoscopy for Asymptomatic Microscopic Hematuria
2019, Urology
Citation Excerpt :
While the more restrictive NICE guidelines have been critiqued by others who show that they would fail to diagnose some urologic malignancies, they highlight the challenges in reaching a consensus on managing AMH.15 The number of red blood cells on urine microscopy has also been proposed as a threshold for initiating the AMH work-up, although the association between bladder cancer and degree of microscopic hematuria is highly variable.3,13,14 Jung et al have previously proposed a cutoff of ≥25 RBCs/HPF for initiating the AMH work-up based on their findings that bladder cancer was positively associated with this more restrictive threshold.3
To investigate the rate of bladder cancer in patients undergoing cystoscopic evaluation for asymptomatic microscopic hematuria (AMH) in order to identify groups at sufficiently low-risk for bladder cancer in whom invasive testing may be avoided.
We performed a retrospective review of patients who underwent cystoscopic evaluation for AMH between 2010 and 2018. Age, gender, smoking status, history of pelvic radiation, and number of red blood cells per high-power field on urine microscopy were recorded. We used logistic regression to explore the association between specific risk factors and a diagnosis of bladder cancer on cystoscopy.
Among the 2118 patients who underwent cystoscopy for AMH, 25 patients (1.2%) were diagnosed with a bladder cancer, all of which were nonmuscle invasive urothelial carcinoma. There were no bladder cancers detected in patients under the age of 50. Older age and positive smoking history were significantly associated with bladder cancer.
Bladder cancer was an uncommon finding on cystoscopy among patients being evaluated for AMH, especially in younger patients. We confirmed several known risk factors for bladder cancer, including older age and smoking history. Further studies are required to evaluate the utility of cystoscopy for identifying latent bladder cancers in low-risk patients.

View all citing articles on Scopus

View full text

Original articlePredictors of genitourinary malignancy in patients with asymptomatic microscopic hematuria

Highlights

Abstract

Objectives

Subjects/patients and methods

Results

Conclusions

Introduction

Section snippets

Patients

Results

Discussion

Conclusion

J Urol

Urology

J Urol

J Urol

J Urol

Mayo Clin Proc

J Urol.

Urology

Urology

Urol Oncol

Am J Med

Urol Oncol

Urology

Original article
Predictors of genitourinary malignancy in patients with asymptomatic microscopic hematuria