British Journal of Urology (1990), 6 6 , 4 M 1 01990 British Journal of Urology

0007-1 33 1/90/006&0040/$10.00

Fractionated Urinary Cytology in the Follow-up of Bladder Cancer K. J. HASTIE, R. AHMAD and C. U. MOISEY Department of Urology. Royal United Hospital, Bath

Summary-Cytological examination of voided urine is an established investigation in urological practice. In a pilot study of 50 patients with histologically proven transitional cell carcinoma of the bladder, urine cytology was undertaken on samples from the initial, mid-stream and terminal parts of the void. Analysis showed that although the cell density varied between the samples in some cases, no part of the void was consistently richer in benign or malignant cells and similar cell types were seen in every sample from any given patient. It was concluded that fractionated cytology did not improve the diagnostic accuracy of urinary cytology and that any sample of urine was suitable for cytological purposes. Cytological examination of voided urine is an established investigation in the diagnosis and follow-up of bladder tumours. Although urine sampling for cytology is simple and non-invasive, false positive and false negative rates approaching 15 and 48% respectively have been reported even when the specimens were examined by experienced cytologists (Loening et al., 1978). Clearly, any modification of the technique which results in greater diagnostic yield would be of value. A pilot study was undertaken to compare the cytology from the initial, mid-stream and terminal sections of the void (fractionated cytology) to assess whether any one part of the urine stream gave more consistent and reliable results.

The cytology samples were examined independently by 1 of 2 experienced cytologists. Those specimens considered highly suggestive of malignancy were, for the purposes of this study, included with those urines which were unequivocallypositive for malignant cells. Subsequently the patients underwent check cystoscopy and the results were compared.

Results Previous histology in the group of patients showed that 25 had grade I lesions, 17 grade I1 and 8 grade 111. On this occasion, 29 patients had a recurrence diagnosed at cystoscopy. More than half of the patients with recurrence (16) had positive cytology and the correlation between positive cytology and recurrence at cytoscopy was closely related to previous histological grade (Table 1). There were 12 false negative cytologies (24%) and 1 false positive. In 3 patients, pus obscured the cellular details and these patients, only 1 of whom had recurrence at cystoscopy, were studied no further. With these exceptions, the overall sensitivity in patients with proven recurrence at cystoscopy was 57%, but all of those with previous grade 111lesions and positive cytology had cystoscopic recurrence. The cytological results were analysed further with regard to fractionation. In all cases, identical cells were observed in all 3 samples from each patient.

Patients and Methods The study group included 50 patients admitted consecutively for check cystoscopy. All had biopsy proven transitional cell carcinoma of the bladder and the mean age was 71.9 years (range 44-90). Pre-operatively, all patients were instructed to provide 3 urine samples from the same void into separate, clearly marked pots, thus sampling the initial, mid-stream and terminal parts of the stream. In all cases a mid-stream sample was collected and cultured to exclude infection. Accepted for publication 10 November 1989

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FRACTIONATEDURINARY CYTOLOGY IN THE FOLLOW-UlP OF BLADDER CANCER Table 1 Comparison between Cytology and Cystoscopy in Relation to Tumour Grade Prior tumour grade

Table 2: Fractionated Cytology Sample with maximal cellularity

No. of patients

Initial Mid-stream Terminal Cellularity equal

2 4 3 8

-

Investigation results

True positive False negative True negative False positive

I (n=22)

2 10

10 0

rr

rir

(n=17)

(n=8)

6 2 8

8 0 0 0

1

True positive =cystoscopic recurrence with positive cytology. False negative = cystoscopic recurrence with negative cytology. True negative = cystoscopy clear with negative cytology. False positive = cystoscopy clear with positive cytology.

In any given case, therefore, if only 1 specimen had been examined, the cytological report would have been the same. In 9 of those with positive cytology, variations in the cellularity were noted between the samples, with 2 patients having proportionally more cells in the initial sample, 4 in the mid-stream sample and 3 in the terminal sample (Table 2). Nevertheless, if malignant cells were detected in one specimen, they were visible in all and all samples examined in the 12 patients with false negative cytology failed to show any malignant cells.

Discussion Cytological examination of urine continues to be of value as it is non-invasive, easily repeated and theoretically examines the entire urothelium. The sensitivity of urinary cytology varies widely between reported series (26-loo%), with a false positive rate of up to 12% (Kern et al., 1968; Harris et al., 1971 ; Lewis et al., 1976). The accuracy of urine cytology is strongly dependent upon histological grade and the positive rate approaches 100% in carcinoma in situ (Koss et al., 1985). A study by the National Bladder Cancer Collaborative Group A (1977) reported that the sensitivity of cytology was 43% for grade I and grade I1 lesions; this is in stark contrast to a sensitivity of 93% in grade 111 disease. False positives may be related to the experience of the cytologist and the criteria used in cytodiagnosis. Similarly, the results may be less reliable in the presence of infection. Positive cytology is known to precede macroscopic disease in some cases (Murphy et al., 1984). A number of techniques have been used to enhance the reliability of urine cytology, including bladder washing with saline or other irrigants, the examination of repeated specimens and even

All cases cytology positive.

vigorous exercise prior to sampling (Lewis et al., 1976). Typically, however, samples for urine cytology are mid-stream specimens, often taken at the same ,time as a urine culture. The possibility that there may be greater or lesser numbers of cells expelled at different points during the urine flow has not, to our knowledge, been previously explored. Thk study has again demonstrated that urine cytology alone is inadequate for follow-up of many patients with previous bladder tumours, as shown by the high false negative rate. It hlas also been shown that the yield is not improved by fractionated sampling and that any part of the voided stream is adequate for cytological purposes.

Acknowledgement The authors are grateful to Drs E. W. Hall and T. McLeod for their assistance with the cytology.

References Harris, M. J., Schwinn, C. P., Morrow, J. W. et al. (1971). Exfoliative cytology of the urinary bladder irrigation specimen. Acta Cytol., 15,385-398. Kern, W. H., Bales, C. E. and Webster, W. W. (1968). Cytologic evaluation of transitional cell carcinoma of the bladder. J . Urol., 100,616-622. Koss, L. G., Deitch, D. R., Ramanathan, R. er uf. (1985). Diagnostic value of cytology of voided urine. Acta Cytol., 29, 8 10-8 16. honing, S., Narayana, A., Yoder, L. et al. (1978). Longitudinal study of bladder cancer with cytology and biopsy. Br. J . Urol., 50,496-501. Lewis, IR. W., Jackson, A. C., Murphy, W. M. et aL (1976). Cytology in the diagnosis and follow up of transitional cell carcinoma of urothelium. J . Urol., 116,4346. Murphy, W. M., Soloway, M. S., Jukkola, A. F. et al. (1984). Urinary cytology and bladder cancer. Cancer, 53, 155551556, Nationall Bladder Cancer CollaberativeGroup A (1977). Cytology and histopathology of bladder cancer cases in a prospective longitudinal study. Cancer Res., 37,291 1-2915.

The Authors K. J. Hastie, MD, FRCS, Registrar. R. Ahmad, FRCS, Honorary Senior House Officer. C. U. Nloisey, FRCS, Consultant Urologist. Requests for reprints to: K. J . Hastie, Department of Urology, Royal Hallamshire Hospital, Sheffield S10 2JF.

Fractionated urinary cytology in the follow-up of bladder cancer.

Cytological examination of voided urine is an established investigation in urological practice. In a pilot study of 50 patients with histologically pr...
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