Residual Tumor Discovered in Routine Second Transurethral Resection in Patients with Stage T1 Transitional Cell Carcinoma of the Bladder

0022-5347 /91/1462-0316$03.00/0 THE JOURNAL OF UROLOGY Copyright© 1991 by AMERICAN UROLOGICAL ASSOCIATION, INC.

Vol. 146, 316-318, August 1991 Printed in U.S.A.

RESIDUAL TUMOR DISCOVERED IN ROUTINE SECOND TRANSURETHRAL RESECTION IN PATIENTS WITH STAGE Tl TRANSITIONAL CELL CARCINOMA OF THE BLADDER R. KLAN,* V. LOY AND H. HULAND From the Departments of Urology and Pathology, FU Klinikum Steglitz, Free University of Berlin, Berlin, West Germany

ABSTRACT

When a second transurethral resection was routinely performed 8 to 14 days after the initial transurethral resection in 46 patients for stage Tl bladder tumors residual disease was found in 20 despite the surgical report of complete resection in 40. In only 13 patients was residual tumor noted at repeat resection by the senior urologist performing the operation and residual tumor was confirmed histologically in 10 of them. The extent of the lesion is easily misjudged even by experienced surgeons. Early cystoscopy cannot exclude residual tumor. Residual tumor is an important cause of early recurrence and repeat resection of stage Tl lesions is recommended. KEY W ORDS:carcinoma, transitional cell; bladder neoplasms After surgical removal of superficial bladder tumors (stages Ta and Tl) by transurethral resection, tumors seen at endo­ scopic followup are usually considered recurrent tumors, that is newly developed tumors. Tumor recurrence can be expected in 60 to 80% of these patients. 1-4 Such a concept has a profound impact on strategies to prevent recurrence, inasmuch as cys­ toscopy and cytological examination are done every 3 months for many years after transurethral resection and some centers advocate long-term prophylaxis with cytotoxic agents for up to 3 years5 or for the remainder of life.6 Our group collected data suggesting that residual tumor, rather than truly recurrent tumor, is responsible for many new growths after transurethral resection. A 6-month prophylaxis is as good as 3-year prophy­ laxis with mitomycin C.7 Cytological and cystoscopic exami­ nations are positive in some patients as early as 4 weeks after transurethral resection.'5' 8 With an extremely sensitive marker, such as quantitative immunocytology and our monoclonal an­ tibody 486 p 3/12 (which has 90% sensitivity even in grade 1 lesions), 27 of 33 patients (81.8%) who had recurrent tumors remained marker-positive immediately after transurethral re­ section,9 whereas all of those who had no recurrent tumors became marker-negative after transurethral resection. To evaluate the possibility of residual tumor after transure­ thral resection, and because we expected premalignant trans­ formation of the epithelium surrounding the tumor, we per­ formed secondary transurethral resection in 46 of 69 consecu­ tive patients with stage Tl lesions despite the fact that the surgeons had resected all visible tumor at the initial operation.

classification (table 1). We intended to repeat transurethral resection in all 69 patients who had stage pTl lesions but a second resection was possible in only 46. In 23 patients a second transurethral resection was refused by the patient or seemed inadvisable because of patient age or bad performance status. Four patients underwent a third transurethral resection. All initial transurethral resections were supervised by a sen­ ior urologist with the Olympus Vistek Vis-3000 video system. Subsequent operations were always done within 8 to 14 days by a senior urologist. All specimens from the secondary resec­ tions were completely evaluated by a pathologist. RESULTS In 20 of the 46 secondary transurethral resections (43.5%) tumor was found in the histological specimen: 10 of 29 grade 2 (34.5%) and 10 of 17 (58.8%) grade 3 lesions. In 1 patient the residual tumor was of higher grade (grade 3) than at the initial resection, whereas 3 had lower grade (grade 2) lesions. In 7 patients the residual tumor found at repeat resection was a stage Ta tumor. Only 1 patient had upstaging to T2 because of minimal muscle invasion. The rate of tumors at the secondary transurethral resections was lower in patients who had under­ gone fractionated resection initially (11 of 30, or 36.7%) than in those who had had simple resection (9 of 16, or 56.3%). Of the tumor margin and tumor base samples 7 and 0, respectively, were positive for tumor at the initial transurethral resection (table 2). In 6 patients with a negative margin sample residual tumor was found at repeat resection. Smooth muscle had been

MATERIAL AND METHODS From April 1988 to October 1990 a total of 198 consecutive patients with superficial bladder carcinoma (stages Ta, Tl and Tis) underwent transurethral resection at our clinic. In most patients a fractionated resection technique was used: the visible tumor was resected first, tumor margin and tumor base were taken as separate samples, and at least 4 random cold biopsies were done. Fractionated resection was not done in the case of a bad performance status of the patient or anesthesiological problems, or if imminent bladder perforation prevented an extensive transurethral procedure. Fulguration of the base of resection and the surrounding area was not performed system­ atically but more for hemostatic reasons. Specimens were clas­ sified according to the International Union Against Cancer 3 Accepted for publication January 24, 1991. * Current address: Urologische Klinik und Poliklinik, Klinikum Steglitz d. FU Berlin, Hindenburgdamm 30, D-1000, Berlin 45, West Germany.

316

TABLE 1. Histological results in 198 bladder tumor resections (superficial tumors only) between April 1988 and October 1990 Stage pTa pTl pTis Totals TABLE 2.

Grade 1

2

52 1

59 36

53

95

3 10 32 8

50

Totals 121 69 8 198

Results of fractionated resection in 30 patients at initial transurethral operation

No./Total (%) 7 /25 (28.0)* Pos. margin 0/29 (O)t Pos. base * No separate sample from tumor margin in 5 patients. t No separate sample from tumor base in 1 patient.

RESIDUAL TUMOR IN PATIENTS WITH Tl TRANSITIONAl, CELL CARCINOMA

obtained at the initial transurethral resection in 45 of 46 patients in the tumor margin and/or tumor base sample. A total of 22 patients had a single tumor, whereas 24 had 2 or more tumors. The number of tumors did not correlate with the incidence of residual tumor (table 3). In 40 of the 46 patients no tumor was visible to the operating surgeons at the end of the initial transurethral resection and complete resection was reported. However, residual tumor was found at the secondary resection in 16 of the 40 patients (table 4). In 13 of the 46 repeat resections (28.3%) the senior urologist doing the secondary procedure reported residual tumor and residual tumor was confirmed histologically in 10 of them. Of the 10 patients 4 were believed to have had an incomplete initial resection. In 7 other patients residual tumor was sus­ pected at the beginning of the secondary transurethral resection but it was only confirmed in 2. In 8 of 30 patients without visible residual tumor at the secondary transurethral resection tumor was found at histological evaluation of the specimens (table 5). In all patients residual tumor was found at the site of the initial resection except in 2 in whom a small satellite tumor was found at the repeat procedure close to but separate from the resection area. None of the 4 third transurethral resections revealed tumor. DISCUSSION

Among 46 of 69 consecutive patients who underwent trans­ urethral resection for stage Tl bladder carcinoma 20 ( 43.5%) had residual tumor at a secondary resection 8 to 14 days after the initial procedure. Residual tumor was found in nearly every second patient who underwent a repeat procedure and most of them were unexpected. For this study we selected only patients with stage Tl lesions because we did not expect a high rate of residual tumor in patients with stage Ta lesions. However, we currently realize on the basis of our data that residual tumor might be found even in patients with stage Ta tumors. A striking finding of our study was that even experienced surgeons misjudged the true extent of the tumorous lesion at the end of transurethral resection: 16 of 40 tumors judged as TABLE 3. Results of repeat resection correlated with number of tumors

at initial transurethral resection

No. Tumors 2-4 Total No. pts. No. with residual tu­ mors at repeat trans­ urethral resection(%)

Multiple 12

12

22 9(40.9)

6(50.0)

5(41.7)

TABLE 4. Results of secondary transurethral resection compared with

macroscopic finding at end of initial resection

TABLE

Complete Initial Resection ?

Tumor Found at Secondary Transurethral Resection

Yes (40 pts.) No.(%)

Yes No Dysplasia

16(40.0) 20(50.0) 4 (10.0)

No(6 pts.) 4 2

5. Macroscopic finding at 46 second and 4 third transurethral resections

Residual Tumor Visible

Total No.(%) Residual tumor: Confirmed Not confirmed Dysplasia

Yes No.(%)

Suspected No.

No No.(%)

13 (100)

7

30(100)

10 (76.9) 3 (23.1)

2

8(26.7) 18 (60.0) 4(13.3)

2

317

completely resected had been incompletely resected. Mucosa! edema, on one hand, and invisible intraepithelial or submucosal tumor growth, on the other hand, might be the main reason for that finding. The 20 residual tumors found at repeat resection would have contributed 10.0% of the early recurrences in all of our patients with superficial bladder cancer (20 of 198) and 29% of those with stage Tl lesions. The National Bladder Cancer Collaborative Group A reported tumor recurrence at the same site at the initial followup cystoscopy in 16 of 133 patients (12%),10 which is in the same range as in our study. Therefore, we presume that there is a baseline of 10 to 20% of early recurrences that might represent residual tumor. Do our results mean that most early recurrent tumors are residual tumors? We cannot answer this question on the basis of our study. We must distinguish between residual tumors that can be identified by classical morphological criteria, including the presence of clearly malignant tissue at the secondary resec­ tion, and tissue that is premalignant. In the latter case normal­ appearing mucosa around the tumor has histological criteria of either carcinoma in situ, dysplasia or atypia, 8• 11• 12 or even appears benign but it has loss of blood-group antigen or T­ antigen, 13 15 or contains abnormal deoxyribonucleic acid.16• 17 Those findings are known to correlate well with tumor recur­ rence rate.11· 12' 18 In addition, during followup of 55 superficial bladder cancer patients with quantitative immunocytology with the monoclonal antibody 486 p 3/12, an extremely sensitive marker (90% sensitivity in grade l to 3 lesions), 22 became marker-negative immediately after transurethral resection and 20 of them did not have recurrent tumors. Another 27 of the 55 patients remained marker-positive and 14 of them had recurrent tumors. Only 6 patients converted from marker­ negative to marker-positive.9 Underestimating the tumorous lesion is not only a problem concerning depth of infiltration (that is understaging), local mucosa! extent also is easily mis­ judged. Our data indicate that it is advisable to consider a secondary transurethral resection in all patients with stage Tl lesions, even if the surgeons who performed earlier transurethral resec­ tions believed that they removed the tumor completely. Even a second endoscopic look 1 week after transurethral resection will not identify those who have residual tumor. Cytological examinations after transurethral resection, however, might identify some of the patients. We did not address that issue in our study because cytological results are difficult to evaluate as early as 1 week after transurethral resection. Classical standard cytological examinations 3 or 4 weeks later should yield a good marker in high grade lesions. We currently attempt to evaluate cytological and quantitative immunocytological examinations in the early followup of patients with transurethral resection for superficial bladder cancer. REFERENCES

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KLAN, LOY AND HULAND

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