Transcript The Role of Urine cytology in the investigation of Haematuria?

The Role of Urine cytology in
the investigation of Haematuria?
B Barrass
Audit Meeting 17th May 2006
Overview

Urine Cytology

The Role of cytology in haematuria assessment

Audit Standards

Aims

Methods

Results

Comparison with Audit stanards

Discussion

Recommendations
Atypical
Malignant
Urine Cytology
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1864 -Exfoliated urothelial cells first described
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1945 -First used to diagnose urothelial malignancy
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Graded I-V
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

I-II
III
IV-V
(Papanicolaou & Marshal 1945)
normal
suspicious
malignant
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Sensitivity 42% - 66%
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Specificity up to 97%
Problems with Urine Cytology
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Low grade malignancy less likely shed cells
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Patients with suspicious cytology faced with:



Anxiety over undiagnosed cancer
Several invasive investigations and F/U
False positive common




Stones
UTI
Radiotherapy
Urinary Instrumentation
Only 50% with positive cytology have cancer – who should
be investigated?
How Should Suspicious Cytology be
Followed-up?
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2005 Nabi et al followed up 70 patients with haematuria & C3-C5
cytology & normal investigations
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25 had normal repeat cytology
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4 had persistent suspicious cytology
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41 developed cancer in mean 5.6 months
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37 had positive repeat cytology
8 had recurrent haematuria
4 had prostate cancer
Recommends investigate:
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
Persistent positive cytology
Symptoms
Audit Standards
1.
Was cytology repeated?
2.
Was repeat abnormal cytology investigated?
3.
Were investigations thorough

Lower tract:
-GA cystoscopy

Upper tract:
-IVU
-Retrograde & washing
-Ureteroscopy retrograde abnormal
Aims
1.
Review the investigations & diagnosis for positive
cytology
2.
Review additional Investigations to investigate for
positive cytology
3.
Review if these investigations generated additional
diagnosis
4.
What was the cost & morbidity of additional tests?
5.
How did the results compare with the audit standards?
6.
Recommend use and follow-up of cytology in the
investigation of haematuria
Methods
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All urine cytology was reviewed between 01/10/2001 and
31/06/2004
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Patients were identified who had C3-5 cytology either


No histological diagnosis
No repeat cytology
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Notes were obtained and reviewed
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Data was recorded regarding
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
Investigations & associated morbidity
Diagnosis
Follow-up and survival
Results: Patient identification
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1829 urine samples analysed
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9% were atypical
11% were inadequate
80% were benign.
Of the 164 (9%) atypical samples
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53 (32%) had urothelial neoplasia
33 (20%) had repeat cytology
14 (8.5%) had other urological / gynaecological malignancy
61 (42.7%) had no further sample or biopsy
3 had missing records
65 (40%) had either no biopsy, no repeated cytology or
persistently abnormal cytology
Results: Positive Cytology & Cancer
INADEQUATE


187 biopsy following
urine cytology
53 TCC with benign cytology
BENIGN
ATYPICAL
BENIGN
2
68
11
CIS/TCC
11
53
42
sensitivity
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Specificity
Atypical cytology identified
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42 TCC
1 breast met (bladder)
11 prostate cancer
1 endometrial cancer
1 penile cancer
This study
47%
93%
Keir&Womak 2002
28%
72%
Beyer Boon 1978
70%
92%
57% primary
34% recurrent
90%
72%
99%
Raitanen 2002
Amberson & Laino
1993
Results – reason for checking cytology
Reason for investigating
Number
%
Unknown
8
12.3
microscopic haematuria
16
24.6
irritative LUTS
3
4.6
to investigate mets
1
1.5
to investiagte haematuria non specified
5
7.7
to investigate frank haematuria
23
35.4
f/u TCC
7
10.8
to investigate haemospermia
1
1.5
to investigate vaginal discharge
1
1.5
Results – Initial Investigation
Lower tract
Upper tract
INVESTIGATION
No.
%
INVESTIGATION
No.
%
unknown
7
10.8
unknown
8
12.3
Nil
3
4.6
Nil
5
7.7
Cystoscopy
2
3.1
IVU
4
6.2
flexible cystoscopy
48
73.8
USS / KUB
34
52.3
GA cyst
2
3.1
CT
2
3.1
USS
2
3.1
KUB
1
1.5
CT
1
1.5
USS
11
16.9
Results – Initial Diagnosis
C5
10.80%
DIAGNOSIS
%
Diagnosis
21
32.3
Normal
28
43.1
Unknown
16
24.6
C3/4
89.20%
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NUMBER
Of those with a diagnosis:
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7 (33%) had a tumour
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14 (66.7%) had a benign diagnosis
Results – Additional Lower Tract
Investigation & diagnosis
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11 patients (16.9%) had further investigation
1 (10%) aspirated after GA cystoscopy
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The remaining 54 (83.1%) had either
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no further imaging of the lower urinary tract (47)
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or were unknown (7)
Initial Diagnosis
Additional Investigation
Finding
No.
cystitis
GA cystoscopy
normal
2
normal
GA cystoscopy
normal
3
Other Diagnosis
GA cystoscopy
Confirmed
5
v-v Fistula
MRI / USS
Normal
1
Normal
CT
Normal
1
Results – Additional Upper Tract
Investigation & Diagnosis
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9 (13.8%) underwent further
upper tract investigations
Additional Investigation
No.
%
Unknown
7
10.8
Ureteroscopy, retrograde,
biopsy, washing
1
1.5
2 (22.2%)
had a diagnosis (ureteric stones)
causing stones positive cytology
Retrograde
2
3.1

IVU
4
6.2
1 (11.%)
had diagnosis (duplex) that did
not cause abnormal cytology
IVU & retrogrades
1
1.5

IVU RGP ureteroscopy
1
1.5
Nil
49
75.4

6 (66.7%)
either had a diagnosis confirmed
or were confirmed to be normal.
Results: Follow-up Cytology
Six patients (9.2%) also had repeat cytology
Finding on
cytology
Number
Investigation
normal
1
Not investigated
1
Fully investigated (no
diagnosis)
abnormal
1
Fully investigated
(diagnosis)
abnormal
2
Not investigated
inadequate
1
Fully investigated
abnormal
Results: Overall Additional Diagnostic
Yield of Investigating Cytology
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Lower tract diagnosis
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Nil
Upper tract diagnosis
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2 upper ureteric stones
3.1% of total, 22.2% of those investigated
(found on retrogrades)
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No additional malignancies were detected
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one patient had a serious complication (aspiration)
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There were four false positives (6.2%) detected on reinvestigation
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3 found on lower tract imaging and 1 found on cytology
Results: Final Diagnosis after all
Investigations
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Diagnosis
Number
%
Diagnosis
20
30.1
Normal
29
44.6
Unknown
16
24.6
3 patients have unexplained positive cytology of which
only one underwent further investigations
54 (83.1%) had no further lower tract imaging
and 49 (75.4%) had no further upper tract imaging.
Results: Significance of Frank
Haematuria
Diagnosis
% with frank
haematuria
Normal
35.4
Any diagnosis
52.4
Cancer
71.4
(100% frank haematuria, non-specified or known cancer)
Follow-up and Outcome
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The median follow-up
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Mortality
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13.8% (9 patients)
Disease specific mortality
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30 months (1 - 54 months).
6.2% (4 patients)
All disease specific deaths occurred in patients diagnosed with
TCC on initial assessment
2 (50%) had C3-4 cytology and 2 (50%) had C5 cytology
1 recurrence during follow-up
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(2.3% of those found to be normal or benign on initial assessment)
Previous TCC with C5 cytology.
An initial flexible cytoscopy was normal
Disease free interval 40 months
Grade & stage G1Pta TCC
This patient did not contribute to the mortality.
Comparison with Audit Standard
Standard
Result
Was cytology repeated?
36 (37%) of 97 with no diagnosis had
repeat cytology
Was abnormal cytology
investigated
2 (50%) of 4 with persistently
abnormal cytology were investigated
Were additional lower tract
investigations sufficient
10 (15.4%) had a GA cystoscopy
Were additional upper tract
investigations sufficient
9 (13.8%) had upper tract
investigation and 5 (7.7%) had
retrograde or ureteroscopy
Discussion

The results were below the standard in terms of


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repeating positive cytology
Investigating positive cytology
The investigation of positive cytology was variable
Investigation of cytology
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didn't yield many additional diagnosis over all (3.1%)
Did not yield any additional cancers
Did yield a high number of diagnosis among those investigated (22.2%)
Retrograde yielded all additional diagnosis
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The presence of frank haematuria seemed to correlate with malignancy
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C3-4 cytology does not rule out finding tumour
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The recurrence rate was low and there were no new cancers during followup, suggesting most patients were unlikely to have significant cancer
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Most diagnoses were benign (70% C5 and 93.1 C3/4)
Recommendations
1.
Cytology does not seem to increase the diagnosis of malignancy
through the haematuria clinic but…


Few were investigated
Low rate of malignancy during F/U
2.
Atypical cytology should be repeated and investigated only if
persistently abnormal
3.
A prospective study of the long-term follow-up of atypical
cytology is needed
1.
Do patients with benign diagnosis or cytology that
normalises on F/U have any increase in risk?
2.
What is the diagnostic yield of full investigation for positive
cytology –does it add to the haematuria assessment?
3.
Are there any reliable clinical markers that can be used to
identify those who should be investigated e.g. frank bleeding?