Vol. 116, November
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1976 by The Williams & Wilkins Co.
URINE CYTOLOGY IN THE DETECTION OF BLADDER TUMOR RECURRENCE AHMAD ORANDI
From the Departments of Urology and Laboratory, Lake Region Hospital , Fergus Falls , Minnesota
Of 118 patients with primary bladder tumors seen since 1966, 73 have been followed with urine cytology since 1969. Of the 406 tests there have been 85 positive, 296 negative and 25 ambiguous reports. The incidence of falsely positive results is estimated at 4 per cent but the incidence of falsely negative results cannot be assessed in this study. Currently, 51 patients are living, 2 of whom had been seen in 1966. Of the 51 patients 43 are being followed with urine cytology. Bimonthly urine cytology has been found to be a reliable, convenient, safe, less hazardous and less costly method for the detection of bladder tumor recurrence . transurethral resection at a later date. The other patient has had negative cytology for the last 3 years. Therefore , there was a 4 per cent falsely positive incidence. In the remaining instances of positive urine cytology cystoscopy was not done either because the patients failed to return or the language of the report was not strong enough. In such cases a subsequent urine cytology was usually positive. Some patients did not wish to be cystoscoped after each positive urine cytology. Others had stage B 2 or C lesions. In these cases the bimonthly positive urine cytologies were a clear MATERIAL AND METHOD indication of inoperability, incomplete resection and, thereA voided urine specimen was collected in a clean non-sterile fore, not followed with cystoscopy and transurethral resection container and processed within 1 hour. Five ml. urine was every 2 months. There is no way to assess the incidence of falsely negative filtered through 2 filters and 4 slides were made. If the urine was heavily cellular and turbid smears also were made . results since, except for 3, patients with negative urine tests Occasionally, patients mailed a sample of urine in a jar were neither seen nor cystoscoped. The 3 patients with containing 95 per cent alcohol, which was supplied by the negative cytologic reports underwent cystoscopy because of laboratory. Women were advised to shower or to use a bidet hematuria or x-ray findings. All 3 had recurrences proved by before collecting the specimen . The patients had no other transurethral resection . As many as 7 positive urine cytologies have been followed by special preparation prior to collection of the urine specimen. After the filters and smears were fixed they were stained by the cystoscopy and transurethral resections in 1 patient during a period of 5 years (see table). modified Papanicolaou method. The pathologist's impressions of slides and smears were written on a urine cytology form . The original form was kept in CASE REPORTS the laboratory's files. Each new report was added to the original and a copy was then sent to the clinician. Therefore, all Case 1. T, P., a 77-year-old woman, had had 4 resections for previous impressions, remarks and operations were available bladder tumor in 1959, 1961, 1965 and 1966. The patient has for review each time a new cytology was done. There are 51 been followed with 20 negative urine cytologies. There has patients living currently, 43 of whom are being followed with been no resection since 1966 and no cystoscopies since 1971. urine cytology. Comment: Some patients have had persistently negative urine cytologies for many years after several initial transureRESULTS thral resections for recurrent bladder tumor . Case 2. F. G., a 58-year-old man, had had 3 transurethral Of the 406 urine cytologic examinations done on 73 patients 85 tests were interpreted as positive, 296 clearly negative and resections for bladder tumor in 1969, and August and Decem 25 ambiguous reports. At times it was difficult to interpret the ber 1970. Subsequently, there were 14 negative urine cytologies language of the report, for example "rare, slightly altered until April 1973, when recurrence was suspected by a positive cells-a few slightly atypical cells-occasional abnormal test and proved by resection . Since that time 13 urme cells". In 50 instances of positive urine cytology involving 22 cytologies have been negative. Comment: Some patients have had many negative urine patients a subsequent cystoscopy showed possible recurrence. This was followed by transurethral resection revealing positive cytologies with occasional positive tests and proved recurrence tissue in 49 patients and negative tissue in 1. Moreover, of 2 by transurethral resection . Case 3. G. J. , a 56-year-old man, had had a transurethral additional patients with positive urine and negative cystoscopies 1 remained positive and recurrence was proved by resection of a bladder tumor in 1955. Three subsequent resections were done in January and August 1969, and February 1970. Since then the patient had had bouts of hematuria Accepted for publication March 12, 1976. Read at annual meeting of North Central Section, American and a few positive urine cytologies but negative cystoscopies, Urological Association, Phoenix, Arizona, October 5- 12, 1975. until a transitional tumor in the left ureter caused obstruction In this retrospective study we appraise the value of urine cytology in the detection of bladder tumor recurrence. Since December 1969 each patient under oin transurethral resec-"" t"ionof a ladder tumor has been given an a~ointment to the laboratory for bimonthlY urine cytolog_y_ O y patients with positive re orts returned to hos ital for c stoscopy and examination Of 118 patients seen since 1966 wit a primary bladder tumor 73 have been followed with urine cytology in this manner.
URINE CYTOLOGY IN DETECTION OF BLADDER TUMOR RECURREN CE
Seven positive cy tologies followed by transurethral resection in patient C. 0.* Date
Clinica l Informat ion and Urine Cytology Reports
ll-26-69 3-25-70 7-7-70
Transurethral resection, extensive bladder tumor Transurethral resection, recurrence Cytology: many atypical cells present, strongly suggestive of Ca of bla dder Trans urethral ,resection, recurrence Cytology: only few superfi cial epithelial cells present Cytology: more epit helia l cells t han average; no other elements s uch as pus cells p resent Cytology : atypical cells present, some artifact; should be studied further to rule out malignancy Transurethral resection, recurrence Cytology: few pus cells and occasional epit helial cells present Cytology: marked pleomorphism of cells; not sure of malignancy; occasional cells resemble cytomegalic inclusion bodies; suggest further evaluation and repeat Cytology: abnormal cells suggestive of malignancy are present Transurethral resection, recurrence Cytology: no malignant cells present Cytology: occasional abnormal cells are seen; recurrence may be suspected Cytology: occasional abnormal cells present Cytology: abnormal cells suspicious of malignancy are present Transurethral resection, recurrence Cytology: negative; few neut rophils present Cytology: negative Cytology: atypical cells present; t hey are suggestive of malignancy Cytology: occasional abnormal cells present; recurrence suspected Cytology: small number of atypical cells, few neutrophils and few bacteria are present Transurethral resection, recurrence Cytology: few slightly atypical cells are present; recurrence should be ruled out Cytology: about \12 dozen slightly atypical cells are seen in t his relatively acellular urine; may be early recurrence; you m ay follow him Cytology: few epithelial cells, few neutrophils and rare altered cells present; suspect early recurrence; you may follow him Transurethral resection, recurrence Cytology: no malignant cells ident ified; few pus cells seen Cytology: many abnormal cells present; recurrence is suspected Cytology: many abnormal cells and few neutrophils are present Transurethral resection, recurrence Cytology: class III; a few clumps of abnorm a l cells are seen Cytology: rare, slight ly a ltered cells seen; should be considered negative Cytology: class Ill; a few abnormal cells seen; suspicious for malignancy
7-15-70 9-1-70 10-9-70 11-12-70 12-1-70 12-31-70 2-10-71 3-26-71 5-7-71 9-17-71 11-17-71 2-3-72 4-13-72 4-24-72 6-7-72 8-10-72 10-17-72 1-9-73 3-30-73 4-12-73 7-17-73 10-12-73
12-28-73 3-21-74 6-3-74 8-15-74 9-27-74 10-15-74 1-24-75 4-7-75 7-15-75
Note gradual appearance of malignant cells. Positive tests indicated recurrence each time. * Birth date- 11-5-17, hospital No. - 103,305.
to the left kidney, demonstrated on the excretory urogram and followed by excision. Comment: An invisible primary tumor may confuse the value of urine cytology in the detection of tumor recurrence. In such cases the urine tumor cells may originate from either or both the primary and recurrent lesions.
vations, since the latter depends on the size, locat ion and the condition of the bladder at t he t ime of examination. Furthermore, the patient who is cystoscoped 6 months after transurethral resection could have been harborin g a growing cancer for 3 or 4 months. If our primary objective in the mana gement of a bladder tumor is early detection and eradication t hen cystoscopy every 3 to 6 months is an arbit rary and certainly a non-scientific met hod . The incidence of falsely ne ative resu lts in this stud could not e determme and it is probable that some recurr o undet_filj;ed . However, if a recurrent a er lesion does not produce malignant cells in the urine, does not cause gross or microscopic hematuria and would not create any subjective symptoms for the patient during a long period the lesion may not be considered a true malignancy. Furthermore, since these patients are quite willing to have a bimonthly or a quarterly urine cytology malignant transformation of such lesions would be discovered in their earliest stages. If a recurrent lesion is missed during routine cystoscopy because of its size or location, or if a transurethral resection has been inadequate a subsequent urine cytology within a few days or weeks would most probably be positive. Therefore, urine cytology is a good monitor for the accuracy of the endoscopic observation and the effectiveness of the surgical management. It is beyond question that for patients it is much easier, safer, less painful and much less hazardous to void a urine sample in a specimen jar than to have a cystoscope in their bladder. Therefore, urine cytology can be done as often as once a month if indicated. In this era of cost consciousness the difference between the 2 methods of followup management cannot be ignored. Based on an average survival of 31 months for each patient in t his group of 118 patients with primary bladder tumors since 1966 it is estimated that the cost difference between cystoscopy every 3 months and bimonthly urine cytology at our hospital would have amounted to approximately $83,000 for the last 9 years. Presently, there are 43 patients being followed with bimonthly urine cytologies. The difference between the cost of the present method of followup as compared to the cystoscopy method at our hospital would amount to $14,000 per year. CONCLUSIONS
Urine cytology may be a reliable test for the detection of recurrent bladder tumor and may be positive as early as 2 months after resection and even before the lesion is easily visible endoscopically. A persistent posit ive cytology may indicate inadequate resection, an aggressive tumor or an invisible lesion. For the patient it is more convenient, less costly and much less hazardous than cystoscopy. A routine second look biopsy every 2 months, as suggested by Mahoney and associates, is in support of these cytologic observations. 1
DISCUSSION Ms. Mavis Cucci and Ruby Haagenson helped accumulate A careful analysis of all cytologic reports proves that the the data. bladder tumor does not recur suddenly at a 3 or 6-month REFERENCE interval and that the malignant cells do not appear in the urine all at once. Rather, the malignant transformation is a gradual 1. Mahoney, E. M., Kearney, G. P . and Harrison, J. H.: Results of and continuous process. It is possible to detect the onset of routine second look biopsy in transurethrally treated carcinoma what we call recurrence as early as 2 months postoperatively. of the bladder. Read at annual meeting of New England Section, Although they are diagnostic cytologic manifestations of American Urological Association, Southampton, Bermuda, Septhese recurrences may not be confirmed by cystoscopic obsertember 29-0ctober 5, 1974.