ROUTINE EXCRETORY UROGRAPHY IN FOLLOW-UP OF SUPERFICIAL TRANSITIONAL CELL CARCINOMA OF BLADDER HOWARD SMITH, M.D. STEPHEN WEINSTEIN, M.D. DANA WEAVER, M.D. GILBERT ROSS, JR., M.D. OLIN BARJENBRUCH, B.A. From the Division of Urology, School of Medicine and the Harry S. Truman Veterans Hospital, Columbia, Missouri ABSTRACT- To determine cost-effective guidelines for the follow-up of patients with superficial transitional cell carcinoma of the bladder (STCCAB), we reviewed clinical histories, pathology report,s. and intravenous pyelography results in 84 patients with Stage Ta or Tl disease. In 4 pa- tients (4.8 %) subsequent upper tract tumors developed with an average interval from initial pres- entation to the development of upper tract disease of 5.4 years. Three of these patients were treated ,succes.sfully. We recommend upper tract surveillance in this group of patients with intravenous pyelography at diagnosis and every twenty-four months thereafter, or .selection of those patients who are at high risk for development of upper tract disease (i.e., ureteral-vesical reflux) with void- ing cystourethrography one month following each resection of tumors near a ureteral orifice. Re- fluxing patients should then either undergo surgical repair of their reflux or yearly pyelography. More than 40,000 new cases of transitional cell carcinoma of the bladder are expected to be diagnosed in the coming year. Seventy percent of these tumors are confined to the mucosa or lamina propria, and are commonly referred to as superficial transitional cell carcinoma of the bladder (STCCAB) .’ Following local treatment, the need for pe- riodic evaluation of the bladder is well docu- mented in such patients. The requirements for the evaluation of the upper collecting system are not well defined. It is known that patients Lvho present with upper tract transitional cell tumors have a high incidence of antecedent or subsequent bladder tumors. However, the inci- dence of patients in whom upper tract disease subsequently develops following a diagnosis of transitional cell carcinoma of the bladder varies in several studies from 0.26 percent to 5.9 per- cent, and similarly recommendations for rou- tine follow-up have varied from biennial in- travenous pyelograms (IVPs) to upper tract evaluation being neither cost-effective nor nec- essary. 2.3 We have reviewed our experience in patients with STCCAB who have been evalu- ated by IVP at the time of diagnosis and pe- riodically thereafter to determine the incidence of subsequent upper tract urothelial tumors and to develop guidelines for the follow-up of these patients. Material and Methods The charts of all patients having the diagno- sis of Stage Ta or Tl STCCAB between January, 1976, and January, 1986, at the University of Missouri Hospital and Clinics and the Harry S. Truman Memorial Veterans Administration Hospital were reviewed. Complete data were available on 84 patients. Patients were excluded in whorn carcinoma in situ developed, or who had progression be- yond Stage Tl during the period of evaluation since they have expected survivals which are shortened and more complex management as compared with those with exclusively superfi- cial disease. At our institution, IVPs are
Transcript
ROUTINE EXCRETORY UROGRAPHY IN FOLLOW-UP OF SUPERFICIAL TRANSITIONAL CELL CARCINOMA OF BLADDER
HOWARD SMITH, M.D. STEPHEN WEINSTEIN, M.D. DANA WEAVER, M.D. GILBERT ROSS, JR., M.D. OLIN BARJENBRUCH, B.A.
From the Division of Urology, School of Medicine and the Harry S. Truman Veterans Hospital, Columbia, Missouri
ABSTRACT- To determine cost-effective guidelines for the follow-up of patients with superficial transitional cell carcinoma of the bladder (STCCAB), we reviewed clinical histories, pathology report,s. and intravenous pyelography results in 84 patients with Stage Ta or Tl disease. In 4 pa- tients (4.8 %) subsequent upper tract tumors developed with an average interval from initial pres- entation to the development of upper tract disease of 5.4 years. Three of these patients were treated ,succes.sfully. We recommend upper tract surveillance in this group of patients with intravenous pyelography at diagnosis and every twenty-four months thereafter, or .selection of those patients who are at high risk for development of upper tract disease (i.e., ureteral-vesical reflux) with void- ing cystourethrography one month following each resection of tumors near a ureteral orifice. Re- fluxing patients should then either undergo surgical repair of their reflux or yearly pyelography.
More than 40,000 new cases of transitional cell carcinoma of the bladder are expected to be diagnosed in the coming year. Seventy percent of these tumors are confined to the mucosa or lamina propria, and are commonly referred to as superficial transitional cell carcinoma of the bladder (STCCAB) .’
Following local treatment, the need for pe- riodic evaluation of the bladder is well docu- mented in such patients. The requirements for the evaluation of the upper collecting system are not well defined. It is known that patients Lvho present with upper tract transitional cell tumors have a high incidence of antecedent or subsequent bladder tumors. However, the inci- dence of patients in whom upper tract disease subsequently develops following a diagnosis of transitional cell carcinoma of the bladder varies in several studies from 0.26 percent to 5.9 per- cent, and similarly recommendations for rou- tine follow-up have varied from biennial in- travenous pyelograms (IVPs) to upper tract evaluation being neither cost-effective nor nec-
essary. 2.3 We have reviewed our experience in patients with STCCAB who have been evalu- ated by IVP at the time of diagnosis and pe- riodically thereafter to determine the incidence of subsequent upper tract urothelial tumors and to develop guidelines for the follow-up of these patients.
Material and Methods
The charts of all patients having the diagno- sis of Stage Ta or Tl STCCAB between January, 1976, and January, 1986, at the University of Missouri Hospital and Clinics and the Harry S. Truman Memorial Veterans Administration Hospital were reviewed. Complete data were available on 84 patients.
Patients were excluded in whorn carcinoma in situ developed, or who had progression be- yond Stage Tl during the period of evaluation since they have expected survivals which are shortened and more complex management as compared with those with exclusively superfi- cial disease. At our institution, IVPs are
TABLE: I. Characteristics of patients followed with superficial transitional cell carcinoma of bladder
Grade Mean Number Mean IVP Associated
Patients Not Follow-up Recurrences Number Interval Upper Tract
(n) ’ * 3 4 Recorded (Mos.1 TCCA IVP (Mos.1 TCCA
Stage TA 62 3 50 8 1 0 44 99 182 15 4
Stage T, 22 1 8 11 1 1 62 84 65 21 0
Total 84 4 58 19 2 1 49 180 243 16 5 4
routinely included in the follow-up of any pa- tient with transitional cell carcinoma of the bladder. IVP results were based on the official reports from the radiology department and our own review of the x-ray films.
The clinical history of each patient was re- viewed in its entirety. The highest grade and stage, duration of evaluation, number of new recurrences, number of IVPs, and positive IVPs were recorded. In patients with upper tract dis- ease, the temporal relationship to the initial diagnosis of STCCAB and previous normal IVPs as well as the clinical course were re- corded.
Results
All bladder tumors were staged according to the TNM system. Of 84 patients, all were histo- logically transitional cell carcinoma. Table I shows the stage, grade, duration of follow-up, and frequency of IVPs in the 84 patients with STCCAB we evaluated. The mean follow-up for Stage Ta patients was forty-four months and for those with Stage Tl, sixty-two months. The mean interval between initial presentation of bladder tumor and the subsequent development of upper tract tumor was 73.8 months. The mean interval between a previously normal IVP and the diagnostic IVP was 35.8 months. In 4 patients (4.8%) upper tract tumors devel- oped during the period of follow-up.
Table II shows the pathologic and clinical characteristics of the patients in our study in whom transitional cell carcinoma of the upper tract developed. Clinical symptoms of upper tract disease were absent in all. Microscopic hematuria was present in 2 patients with con- comitant STCCAB, but absent in the 2 patients with isolated upper tract disease. Urine cytol- ogy was not routinely performed.
Table III tabulates the available literature. The frequency of patients with transitional cell
carcinoma of the bladder in whom upper tract tumors developed ranged from 0.26 percent to 5.9 percent. The mean time from diagnosis to development of upper tract disease was from 4.3 to eleven years, and the frequency of pa- tients with upper tract tumors who had ante- cedent bladder tumors ranged from 10 percent to 22.8 percent.
Comment
A small, but significant fraction (4.8%) of patients in this study with STCCAB later had development of upper tract urothelial tumors. Other investigators have reported anywhere from a very low frequency to worrisome per- centages of patients in whom upper tract dis- ease develops following the diagnosis of bladder carcinoma. Walter and Soloway reported no upper tract tumors in 184 patients followed for Stage 0 or Stage A bladder tumors. Mechali and Correa4 reported on 382 patients with bladder tumors. One patient presented with simulta- neous upper tract and bladder tumors and in 1 patient an upper tract tumor later developed. On the other hand, Grabstald, Whitmore, and Melamed reported on 70 patients with renal transitional cell carcinoma, 16 (22.8%) of whom had prior bladder or ureteral tumors with a patient follow-up of three to thirty-nine months. Likewise, Smart6 reviewed 25 cases of upper tract transitional cell carcinoma finding 4 (16%) of their patients to have had prior bladder tumors. Mateos et aZ.3 found 5.9 per- cent of 288 patients with STCCAB to have up- per tract disease.
Risk factors for the development of upper tract urothelial tumors in patients who present with bladder tumors are not readily available. However, two authors, Amar and Mateos and colleagues have looked at the influence of re- flux. Amar and Sakit7 found upper tract transi- tional cell carcinoma to follow the diagnosis of
194 UROLOGY / OCTOBER 1989 / VOLUME XXXIV,SUMBER 4
TABLE III. Compilation of avdahle series’: I6
Study *pts having Bpts-subsequent time-Initial UT w’hx of tumor total Ox to UT
prior BT followed (mean)
Soloway 0.261337 not g,ven
Amar 0.45%1222 no reflux 11 yr. 6.4/44 reflux 10.2 yr
Overall 1.5%/266
MateOS
Werth
Smart
England
Batata
10%/35
16%/25
10
0.9%/2 13 no rt:flu i(
20%/75 reflux
overall 5.9%/288
1.5%/332
8.0 yr 4.3 yr
4.5 yr
not gwzn
7.8 yr
7H yr
not gwen
ran(le 1-8 yr
Grabstald 22.8%/70 7.:‘ yr
Sherwood 10 9.(, yr
Mechall 0.26%1382 not given
bladder transitional cell carcinoma in 0.45 per- cent of 22 patients without reflux and in 6.4 percent of 44 patients with knowrn reflux; Mateos et ~1.~ similarly found upper tract dis- ease in 0.9 percent of 213 patients without re- flux and 20 percent of 75 patients with reflux. The increased occurrence in these patients was believed to be secondary to seeding of the upper tract. Recommendations include follow-up cys- tograms and even ureteral reimplantation. In- terestingly, Schmidt, Jacobo, and Weinstein8 found reflux to occur in 9 consecutively studied patients who had been followed with recurrent transitional cell carcinoma of the bladder.
In our study, no signs or sym!ptoms specifi- cally attributable to upper tract disease were present at the time of diagnosis. Microscopic hematuria did not appear to have predictive \ralue since it was present in those patients with simultaneous STCCAB and upper tract disease, and absent when only an upper tract neoplasm w’as present. Urine cytologies were not routinely performed. Blute, Gittes, and Gittes” and McCarron, Chasko, and Gra!.‘O have found, in a review of 100 histologically proved renal pelvis tumors, a high correlation between tumor stage, grade, and cytology findings. There were 80 percent false-negatit,e studies in low-grade, low-stage lesions as compared with 60 percent positive results with high-grade le- sions. Of the 4 patients in our study w.ith upper
P
Y
i i
i d
J no routine f/u
for upper tract disease unless resection of BT
is near an orifice then: VCUG
IVP q 1 yr. x 2 then q 2 yrs.
Pas ne9
/< ’ no further
upper tract repair IVP f/U
reflux yearly
FIGURE 1. Initial diagnosis of superficial transi- tional cell carcinoma of bladder and intravenous pyelogram.
tract involvement, all had low-grade, low-stage disease. Overall an accuracy of 35 to 60 percent can be expected with a voided urine sample. Passive catheter collection can improve this to the order of 60-70 percent.“,12
If there are few physical findings and cytolo- gies are unreliable, what is the best method to follow patients with superficial transitional cell carcinoma of the bladder taking into account the known risks? It is apparent from our study that there is a subset of these patients who are at an increased risk of upper tract disease develop- ing and who will benefit from early diagnosis (3 of 4 in our study are long-term survivors).
In Table III is compiled the available se- ries.13m1” The mean time from diagnosis of STC- CAB to development of upper tract tumors ranged from 4.3 to eleven years. The shortest time interval in which upper tract tumors were found to develop was one year and the longest twenty-two years. In our study, the mean time to development of upper tract disease was 6.2 years.
It is apparent from the data that patients re- quire long-term surveillance and continue many years later to be at risk for development of upper tract disease. In fact, it is probably the length of follow-up that has led to the variabil- ity of upper tract tumor occurrence rates in the literature. In our study the time to development of upper tract disease from initial diagnosis of bladder tumors is 6.2 vears and our mean fol- i low-up is four years. With further we expect to see upper tract tumors an increasing number of patients.
follow-up, develop in
1. Droller MJ: Transitional cell carcinoma: upper tracts and bladder, in Walsh PC, et OZ. (Eds): Campbell’s Urology, Philadel- phia, Saunders, 1986, ~012, pp 1343-1369.
2. Walzer Y, and Soloway MS: Should the followup of patients with bladder include routine excretory urography, J Urol 130: 672 (1983).
3. Mateos JAD,Gassol JMB, Redorta J& and Robles JM: Vesi- corenal reflux and upper urinary tract transitional cell carcinoma after transurethral resection of recurrent superficial bladder car- cinoma, J Urol 128: 49 (1987).
4. Mechali P, and Correa RJ: The risk of upper urinary tract tumors in patients with bladder carcinoma, Abstr. 515, presented at the American Urologic Association, Kansas City, MO, 1982.
6. Smart JG: Renal and ureteric tumors in association with bladder tumors, Br J Urol 36: 380 (1964).
7. Amar AD, and Sakit D: Upper urinary tract transitional cell carcinoma in patients with bladder carcinoma and associated ve- sicoureteral reflux, J Urol 133: 468 (1985).
8. Schmidt JD, Jacob0 EC, and Weinstein SH: Vesicoureteral reflux in recurrent carcinoma of the bladder-implications for treatment and prognosis, J Urol 116: 734 (1976).
9. Blute R, Gittes R, and Gittes RF: Renal brush biopsy: sur- vey of indications, technique, and results, J Urol 126: 146 (1981).
10. McCarron JP Jr, Chasko SB, and Gray GF Jr: Systematic mapping of nephroureterectomy specimens removed for urothe- lial cancer. Pathological findings and clinical correlations. J Ural 128: 243 (1982).
11. Leistenschneider IV, and Nagel R: Lavage cytolou of the renal pelvis and ureter with special reference to tumors, J Ural 124: 587 (1980).
12. Zincke II, et al: Significance of urinary cytologli in the early detection of transitional cell cancer of the upper urinary tract, J Urol 116: 781 (1976).
13. Werth DD, Weigel J\;v and Mebust WK: Primary neo- plasms of the ureter, J Ural 125: 628 (1981).
14. England HR, Paris AMI, and Bland! JP: The correlation of Tl bladder tumour history with prognosis and follow-up require- ments, Br J Urol 53: 593 (1981).
15. Batata MA, et al: Primary carcinoma of the ureter: a prog- nostic study, Cancer 35: 1626 (1975).
16. Sherwood ST: Upper urinary tract tumor following blad- der carcinoma: natural history of urethral neoplastic disease, Br J Radio1 44: 137 (1971).
196 UROLOGY / OCTOBER 1089 i \‘OI.UME XXX\‘, KtihlBER .j
What then is the most cost-effective surveil- lance method? In our institution an IVP costs $207 and a VCUG $204. With this in mind, we recommend one of either follow-up regimens in Figure 1. They each have their advantages. No. 1 will select out the population at risk and, if the reflux is repaired, possibly reduce the pa- tient’s likelihood of development of upper tract disease. However, it increases the number of of- fice visits, and fails to pick up the small number of occurrences in patients without reflux. No. 2 has simplicity and sensitivity in its favor. Both methods, using our data, are comparable in cost. Regardless of the method employed, we recommend upper tract observation in patients who present with STCCAB.
Univ. of Missouri School of Medicine 510 N Division of Urology Columbia, Missouri 65212
