Microscopic hematuria is a common finding in patients presenting to both primary care doctors as well as urologists. Sources of microscopic hematuria include infection, stones, inflammatory disorders as well as cancer of the genitourinary tract, particularly urothelial cancer. A primary focus in the urologic workup of hematuria is to rule out cancer. This is done using radiographic studies as well as procedures such as cystoscopy and bladder biopsy. As the authors state in their article titled "The utility of serial urinary cytology in the initial evaluation of the patient with microscopic hematuria", cytologic analysis of voided urine, though attractive due to its noninvasive nature, has been found to have the neither the sensitivity, cost-effectiveness, nor the ease of administration necessary to replace more invasive diagnostics in the evaluation of microscopic hematuria

A Kumar

CA Hofland

Deep Trivedi

Edward M Messing

EM Messing

F Brown

G Castro

GD Grossfeld

HB Grossman

K Nakamura

MP Raitanen

N Nese

R Madeb

RA Badalament

English

PubMed

Abstract Microscopic hematuria is a common finding in patients presenting to both primary care doctors as well as urologists. Sources of microscopic hematuria include infection, stones, inflammatory disorders as well as cancer of the genitourinary tract, particularly urothelial cancer. A primary focus in the urologic workup of hematuria is to rule out cancer. This is done using radiographic studies as well as procedures such as cystoscopy and bladder biopsy. As the authors state in their article titled "The utility of serial urinary cytology in the initial evaluation of the patient with microscopic hematuria", cytologic analysis of voided urine, though attractive due to its noninvasive nature, has been found to have the neither the sensitivity, cost-effectiveness, nor the ease of administration necessary to replace more invasive diagnostics in the evaluation of microscopic hematuria.</p

Messing Edward M

Trivedi Deep

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BMC Urology

Commentary: the role of cytologic analysis of voided urine in the work-up of asymptomatic microhematuria

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BMC UrologyOpen AcceCommentary
Commentary: the role of cytologic analysis of voided urine 
in the work-up of asymptomatic microhematuria
Deep Trivedi and Edward M Messing*
Address: Department of Urology, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642, USA
Email: Deep Trivedi - deep_trivedi@urmc.rochester.edu; Edward M Messing* - edward_messing@urmc.rochester.edu
* Corresponding author    
Abstract
Microscopic hematuria is a common finding in patients presenting to both primary care doctors as
well as urologists. Sources of microscopic hematuria include infection, stones, inflammatory
disorders as well as cancer of the genitourinary tract, particularly urothelial cancer. A primary focus
in the urologic workup of hematuria is to rule out cancer. This is done using radiographic studies
as well as procedures such as cystoscopy and bladder biopsy. As the authors state in their article
titled "The utility of serial urinary cytology in the initial evaluation of the patient with microscopic
hematuria", cytologic analysis of voided urine, though attractive due to its noninvasive nature, has
been found to have the neither the sensitivity, cost-effectiveness, nor the ease of administration
necessary to replace more invasive diagnostics in the evaluation of microscopic hematuria.
Commentary
The use of urine cytology to detect bladder cancer in
patients who present with microhematuria has been fre-
quently reported. This is, in no small part, due to the intu-
itive attractiveness of a non-invasive, relatively
inexpensive screening test for a lethal disease that can be
obtained in the office or clinic setting without exposing
the patient to the risks of invasive procedures, surgery,
radiation or contrast exposure. Another theoretical advan-
tage of urine cytology screening is the ability to rule out
malignancy, not only reducing patient concern, but also
promoting cost savings through the avoidance of invasive
and radiological procedures.
Unfortunately, the diagnostic capabilities of voided urine
cytology are rather disappointing. Although the test has a
high overall specificity (reported as up to 98%,)[1] its util-
ity as a primary detection tool is quite marginal, because
of its low overall sensitivity in detecting urothelial cancer
(ranging from 40% to 76%)[2] as compared to over 91%
for cystoscopy [3]. This disparity is especially pronounced
in the detection of low grade tumors, with the sensitivity
of voided cytology dropping to 11.1%[4]. The low sensi-
tivity of this test is why most new urine marker studies
(BTA, NMP22, Bladderchek, FISH, etc) compare their per-
formance to that of voided urine cytology instead of cys-
toscopy---they will always appear more effective.
In their paper, "Utility of Serial Urinary Cytology in the
Initial Evaluation of the Patient with Microscopic Hema-
turia" published recently in BMC Urology [5], Rosser and
colleagues confirm the low sensitivity of urinary cytology
at 33% (88% if atypia is considered positive) and the high
specificity of urine cytology ranging from 67% (47/
47+23) if atypia is considered positive to 100% (if atypia
if considered negative)[5]. Furthermore, the high sensitiv-
ity of cystoscopy for the detection of bladder tumors is
confirmed at 100% in this study.
Published: 10 September 2009
BMC Urology 2009, 9:13 doi:10.1186/1471-2490-9-13
Received: 16 July 2009
Accepted: 10 September 2009
This article is available from: http://www.biomedcentral.com/1471-2490/9/13
© 2009 Trivedi and Messing; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 3
(page number not for citation purposes)
BMC Urology 2009, 9:13 http://www.biomedcentral.com/1471-2490/9/13Although urine cytology is relatively sensitive in detecting
high grade cancer and carcinoma in situ (sensitivity 80-
90%)[6], 60% of urothelial tumors at presentation are
low grade and stage lesions[7]. Because of its low sensitiv-
ity for the latter cancers, voided urine cytology cannot be
used to decide which patient with microhematuria can
safely forgo cystoscopy. The incremental benefit of voided
urine cytology to the sensitivity of cystoscopy is minimal,
with the majority of its value derived from being able to
detect occult carcinoma-in-situ (CIS), which represents de
novo disease in only 3% of UC cases [8]. Although the
authors acknowledge that no cases of urothelial CIS were
present in their sample, they make no mention of the sizes
or grades of the cancers detected in the 17 patients in
whom biopsy-proven bladder cancer was diagnosed. If
high-grade cancers were largely missed by voided urine
cytology, the value of this test would be further dimin-
ished.
But perhaps the greatest problem with urine cytology not
discussed in the paper is that results are quite operator
dependent with the skill of the cytologist and cytologic
technician being very important [9]. Also, the authors fail
to elaborate on the technical aspects of cytopathologic
evaluation of the urine specimens in their study (includ-
ing fixation methods and time between collection and fix-
ation/preparation) as well as the experience and number
of cytopathologists who participated.
Even from an economic perspective, previously published
reports suggest that voided urinary cytology is not a cost-
effective test. In a series by Hofland and Mariani of 1000
consecutive patients presenting with either documented
gross or microhematuria, 660 patients underwent cyto-
logic analysis of voided urine samples as part of a work-up
involving cystoscopy +/-biopsy, urography (excretory or
retrograde pyelography, but excluding CT), renal ultra-
sound, and urine culture. Seventy-one patients in this
series were diagnosed with UC. Voided urine cytology was
found to be positive in 25 of the 660 patients (3.8%).
Using 2002 Medicare data, the authors noted the unit cost
for testing a voided urine cytology sample of $50.71 to be
significantly less than that of cystoscopy ($216.54) or IVP
(Intravenous Pyelogram) ($93.02). Consequently, they
calculated the total cost of voided urine cytology to be
$33,467 (660 × $50.71) compared to $206,442 (956 ×
$216.54) for cystoscopy and $89, 836 (966 × 93.02) for
IVP. Urine cytology, however, was diagnostic for a life
threatening condition (genitourinary malignancy, DIC,
glomerulopathy) in only 21 cases (3.3%), as compared to
68 cases (7.1%) and 53 cases (5.5%) for cystoscopy and
excretory urography, respectively. Furthermore, only in 4
cases (0.6%) did urine cytology provide unique informa-
tion, not obtained from any other diagnostic procedure
that resulted in a diagnosis of UC as compared to 64 cases
and 16 cases for cystoscopy and IVP, respectively. Accord-
ingly, the authors found the cost to produce unique, diag-
nostically relevant information from voided urine
cytology to be $33,467/4 ($8367.00), almost double that
of IVP at $5616.00 ($89,836/16) and more than double
that of cystoscopy at $3235.00 ($206,442/64) [10].
Hence, despite being relatively inexpensive on a per-test
basis, voided urine cytology does not appear to be a cost-
effective test.
Additionally, in the workup of hematuria, microscopic or
otherwise, the urologist's job goes beyond ruling out the
presence or absence of urinary tract malignancy. Stones,
vascular malformations, inflammatory as well as infec-
tious lesions detectable by cystoscopy, may all result in
blood in the urine. Furthermore, bladder wash cytology,
which has increased sensitivity compared to cytology on
voided urine specimens [11], may be obtained during cys-
toscopy, serving to add diagnostic value over voided urine
cytology even in the face of CIS missed cystoscopically or
radiologically. In sum, voided urine cytology does not
obviate the need for cystoscopy. For similar reasons,
voided urine cytology cannot replace radiographic stud-
ies, which can detect not only benign lesions but neo-
plasms outside the collecting system, for example, in the
renal parenchyma.
Voided urine cytology does not appear to have a primary
role in the evaluation of asymptomatic microhematuria
but may have a role as a supplement to cystoscopy and
excretory urography in a minority of cases (for example
when "invisible" diseases such as CIS are suspected.)
However, hematuria is a "late" detector of bladder cancer
and almost never is voided urine cytology the single test
during a hematuria workup that detects urothelial cancer
[12].
One may argue that in the above series by Hofland and
Mariani, for the 4 patients in whom malignancy was
solely detected by urine cytology that this test proved to be
very valuable. But the question arises, "for a disease with
a rather low prevalence (urothelial CIS), is a test with a
very small unique diagnostic yield justified?" If one
extrapolates the cost analysis by Hofland and Mariani to
the general population, the magnitude of inefficiency
becomes glaringly obvious. Asymptomatic microhematu-
ria is prevalent in up to 21% of the US population [13] or
roughly 60 million Americans. If each individual was only
tested once, cytology alone would cost over $3 billion.
Furthermore, if a similar yield of diagnostically unique
information of 0.6% was applied to this population, over
$2.98 billion would be spent on a relatively insensitive
and redundant test. In today's political environment
where increased pressure is being placed on the health
care system to reign in costs, the elimination of voidedPage 2 of 3
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urinary cytology in the workup of asymptomatic microhe-
maturia has the potential to effect significant savings.
Perhaps with its high documented positive predictive
value (assuming atypia is not considered positive), posi-
tive urine cytology can be used to direct high risk patients
to operating room procedures, obviating the need for
office cystoscopy since a biopsy and/or ureteroscopy
would be needed as a supplement to surveillance cystos-
copy. Furthermore, there may be a role in using voided
urine cytology in patients with a history of bladder cancer
who are at risk for recurrence and disease progression.
With the availability of numerous other more sensitive
urine based assays to detect urothelial cancer, the role for
voided urine cytology in the diagnosis of urinary tract
malignancy (other than CIS) appears to be diminishing.
The search for a sensitive, non-invasive, inexpensive, read-
ily available test for urothelial cancer must go on.
Competing interests
The authors declare that they have no competing interests.
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Pre-publication history
The pre-publication history for this paper can be accessed
here:
http://www.biomedcentral.com/1471-2490/9/13/prepubPage 3 of 3
(page number not for citation purposes)


Asymptomatic microscopic hematuria in adults: summary of the AUA best practice policy recommendations. Am Fam Physician

Comparison of bladder cancer outcome in men undergoing hematuria home screening versus those with standard clinical presentations. Urology

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 followup.&quot;. Urology

FinnBladder Group: &quot;Differences between local and review urinary cytology in diagnosis of bladder cancer. An interobserver multicenter analysis.&quot;. Eur Urol

Marianai AJ: &quot;Is urine cytology required for a hematuria evaluation.&quot;.

MB: &quot;Carcinoma in situ of the urinary bladder: review of clinicopathologic characteristics with an emphasis on aspects related to molecular diagnostic techniques and prognosis.&quot;.

Melamed MR: &quot;The sensitivity of bladder wash flow cytometry, bladder wash cytology, and voided cytology in the detection of bladder carcinoma.&quot;.

Messing EM: &quot;Long-term outcome of home dipstick testing for hematuria.&quot;.

NP: &quot;Comparison of NMP22 BladderChek test and urine cytology for the detection of bladder cancer.&quot;.

Rosser CJ: &quot;Utility of Serial Urinary Cytology in the Initial Evaluation of the Patient with Microscopic Hematuria.&quot;.

Surveillance for recurrent bladder cancer using a point-of-care proteomic assay&quot;.

Urine Cytology-Is it still the Gold Standard for Screening?&quot;. Urol Clinics of North America

Usefulness of urine cytology in the diagnosis of bladder cancer: relationship with pathologic findings&quot;. Acas Urol Esp

http://doaj.org/search?source=%7B%22query%22%3A%7B%22bool%22%3A%7B%22must%22%3A%5B%7B%22term%22%3A%7B%22id%22%3A%22fa232742be7346fbaf2634e79c13ec7b%22%7D%7D%5D%7D%7D%7D

Commentary: the role of cytologic analysis of voided urine in the work-up of asymptomatic microhematuria

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