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The Role of Urine cytology in the investigation of Haematuria?. B Barrass Audit Meeting 17 th May 2006. Overview. Urine Cytology The Role of cytology in haematuria assessment Audit Standards Aims Methods Results Comparison with Audit stanards Discussion Recommendations.
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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 • 1864 -Exfoliated urothelial cells first described • 1945 -First used to diagnose urothelial malignancy • Graded I-V(Papanicolaou & Marshal 1945) • I-II normal • III suspicious • IV-V malignant • Sensitivity 42% - 66% • Specificity up to 97%
Problems with Urine Cytology • Low grade malignancy less likely shed cells • 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? • 2005 Nabi et al followed up 70 patients with haematuria & C3-C5 cytology & normal investigations • 25 had normal repeat cytology • 4 had persistent suspicious cytology • 41 developed cancer in mean 5.6 months • 37 had positive repeat cytology • 8 had recurrent haematuria • 4 had prostate cancer • Recommends investigate: • Persistent positive cytology • Symptoms
Audit Standards • Was cytology repeated? • Was repeat abnormal cytology investigated? • Were investigations thorough • Lower tract: -GA cystoscopy • Upper tract: -IVU -Retrograde & washing -Ureteroscopy retrograde abnormal
Aims • Review the investigations & diagnosis for positive cytology • Review additional Investigations to investigate for positive cytology • Review if these investigations generated additional diagnosis • What was the cost & morbidity of additional tests? • How did the results compare with the audit standards? • Recommend use and follow-up of cytology in the investigation of haematuria
Methods • All urine cytology was reviewed between 01/10/2001 and 31/06/2004 • Patients were identified who had C3-5 cytology either • No histological diagnosis • No repeat cytology • Notes were obtained and reviewed • Data was recorded regarding • Investigations & associated morbidity • Diagnosis • Follow-up and survival
Results: Patient identification • 1829 urine samples analysed • 9% were atypical • 11% were inadequate • 80% were benign. • Of the 164 (9%) atypical samples • 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 • 187 biopsy following urine cytology • 53 TCC with benign cytology • Atypical cytology identified • 42 TCC • 1 breast met (bladder) • 11 prostate cancer • 1 endometrial cancer • 1 penile cancer
Results – Initial Investigation Lower tractUpper tract
Results – Initial Diagnosis • Of those with a diagnosis: • 7 (33%) had a tumour • 14 (66.7%) had a benign diagnosis
Results – Additional Lower Tract Investigation & diagnosis • 11 patients (16.9%) had further investigation • 1 (10%) aspirated after GA cystoscopy • The remaining 54 (83.1%) had either • no further imaging of the lower urinary tract (47) • or were unknown (7)
Results – Additional Upper Tract Investigation & Diagnosis • 9 (13.8%) underwent further upper tract investigations • 2 (22.2%) had a diagnosis (ureteric stones) causing stones positive cytology • 1 (11.%) had diagnosis (duplex) that did not cause abnormal cytology • 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
Results: Overall Additional Diagnostic Yield of Investigating Cytology • Lower tract diagnosis • Nil • Upper tract diagnosis • 2 upper ureteric stones 3.1% of total, 22.2% of those investigated (found on retrogrades) • No additional malignancies were detected • one patient had a serious complication (aspiration) • There were four false positives (6.2%) detected on re-investigation • 3 found on lower tract imaging and 1 found on cytology
Results: Final Diagnosis after all Investigations • 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 (100% frank haematuria, non-specified or known cancer)
Follow-up and Outcome • The median follow-up • 30 months (1 - 54 months). • Mortality • 13.8% (9 patients) • Disease specific mortality • 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 • (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.
Discussion • The results were below the standard in terms of • repeating positive cytology • Investigating positive cytology • The investigation of positive cytology was variable • Investigation of cytology • 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 • The presence of frank haematuria seemed to correlate with malignancy • C3-4 cytology does not rule out finding tumour • The recurrence rate was low and there were no new cancers during follow-up, suggesting most patients were unlikely to have significant cancer • Most diagnoses were benign (70% C5 and 93.1 C3/4)
Recommendations • 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 • Atypical cytology should be repeated and investigated only if persistently abnormal • A prospective study of the long-term follow-up of atypical cytology is needed • Do patients with benign diagnosis or cytology that normalises on F/U have any increase in risk? • What is the diagnostic yield of full investigation for positive cytology –does it add to the haematuria assessment? • Are there any reliable clinical markers that can be used to identify those who should be investigated e.g. frank bleeding?