Bladder Cancer: Results of Radical Cystectomy for Invasive and Recurrent Superficial Tumors

0022-5347/ 83/ 1303-0460$02.00/ 0 Vol. 130, September

THE JOURNAL OF UROLOGY

Printed in U.S.A.

Copyright © 1983 by The Williams & Wilkins Co.

BLADDER CANCER: RESULTS OF RADICAL CYSTECTOMY FOR INVASIVE AND RECURRENT SUPERFICIAL TUMORS JOSEPH R. DRAGO

AND

THOMAS J_ ROHNER, JR.

From the Division of Urology, Department of Surgery, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pennsylvania

ABSTRACT

The operative management of bladder carcinoma was reviewed retrospectively in 76 patients: 57 had muscle invasion and 19 had rapidly recurring or extensive superficial tumors requiring aggressive therapy. Of the patients 9 had been managed initially elsewhere with radiation treatment for cure and underwent salvage cystectomy at our institution. The results are discussed comparing patients receiving no radiation (11 of 20 alive) and 4,000 rad given preoperatively (11 of 20 alive), and patients with no muscle invasion but recurrent or extensive superficial tumors (14 of 19 alive). The management of patients with invasive and recurrent or extensive superficial transitional cell bladder carcinoma h as changed in the last 10 to 15 years. In the late 1960s and early 1970s several protocols were evaluated to assess the validity of giving 4,000 rad during 4 weeks with a 4 to 6-week wait before cystectomy. In the mid 1970s and currently 2,000 rad during 1 week followed by immediate cystectomy has been adopted by many centers. i-s We herein evaluate our institutional clinical experience with cystectomy for bladder carcinoma. Morbidity and age of the patient at the time of cystectomy were compared in 3 groups of patients: those receiving no radiation, and those receiving 4,000 or 2,000 rad before cystectomy and urinary diversion. METHODS AND MATERIALS

In this retrospective review 20 early patients did not receive radiation therapy before cystectomy, while 20 received 4,000 rad. Currently, most patients with biopsy-proved invasive disease are receiving 2,000 rad before treatment followed by cystectomy. The operation consisted of a radical cystectomy with removal of the bladder, peritoneum and surrounding fatty areolar tissue, with pelvic lymph node dissection in 37 cases (49 per cent). The most frequent method of urinary diversion was ileal conduit. However, 3 patients underwent ureterosigmoidostomy and 2 underwent cutaneous ureterostomy. Of the 76 patients 9 were selected carefully to undergo partial cystectomy. Of the total bladder cancer population only cystectomy and partial cystectomy patients were studied retrospectively. Patients were treated at our institution from 1971 through September 1981. Followup was available on all patients. There were 57 men and 19 women between 45 and 86 years old. Average patient age was 75.3 years in women and 65.2 years in men. RESULTS

We treated 57 patients with muscle invasion and 19 without muscle invasion but with rapidly recurrent or extensive superficial tumors. Of the patients with muscle invasion 20 did not receive preoperative radiation, 9 have been treated for cure with 7,000 rad, and were referred for recurrent bladder tumors and salvage cystectomy, 20 received 4,000 rad preoperatively and underwent cystectomy with urinary diversion after a 1month rest and 8 received 2,000 rad followed by immediate cystectomy (table 1). None of the 19 patients without muscle invasion received preoperative radiation therapy. Accepted for publication February 11, 1983. Read at annual meeting of American Urological Association, Kansas City, Missouri, May 16- 20, 1982. 460

Survival in the muscle invasion group included 3 of 4 patients (75 per cent) with grade I tumors (2 of the 4 had evidence of carcinoma in situ), 5 of 10 (50 per cent) with grade II tumors, 14 of 30 (47 per cent) with grade III tumors and 8 of 13 (62 per cent) with grade IV tumors (table 2). Of the latter 8 patients 4 have survived >36 months, 2 >24 months and 2 for 15 months. The average number of tumors before cystectomy in patients without muscle invasion was 4, with a range of 3 to > 8. Of these patients 3 had grade I tumors (2 of whom had carcinoma in situ), 8 had grade II tumors, 6 had grade III tumors and 2 had grade IV tumors without muscle invasion. Of the patients with no evidence of muscle invasion all with grades I and IV tumors are alive, compared to 5 of 8 with grade II and 4 of 6 with grade III disease (tables 2 and 3). The patients who fulfilled the criteria for partial cystectomy, including tumor in a position for resection without compromise of either ureteral orifice, at least a 1.5 cm. margin free of tumor TABLE

1. Distribution of various treatment groups and median

survival times

Muscle invasion: Surgery only 2,000 rad plus surgery* 4,000 rad plus surgery• 7,000 rad plus surgery• No muscle invasion

Survival (mos.)

No. Alive/Total

Mean

Range

30/57 11/20 7/8 11/20 1/9 14/ 19

63.2 13 46.3 12 57.3

32-119 5- 26 6- 92 10-111

Average number of tumors preoperatively was 2 for muscle invasion group and 4 for no muscle invasion group. • Cystectomy and diversion.

and negative random biopsies for carcinoma in situ, dysplasia or atypia, have had a high survival rate. Of the 9 patients 8 (89 per cent) are alive for > 40 months. All 8 patients except 1 had muscle invading tumors and 7 are alive. Complications. The average hospital stay was 18 days, with several days being required for preoperative bowel preparation or preoperative radiation in some patients. Wound infection occurred in 5 patients, prolonged ileus in 6, acute renal failure that responded to appropriate fluid and electrolyte replacement in 1, and a pulmonary embolus in 1 (table 4). Only 1 patient died 62 days postoperatively of a pelvic abscess and septicemia. The morbidity compares favorably to that of other series, and the mortality rate of 1 of 76 patients (1.2 per cent) compares favorably to many series.'-3 • 5 • 6 Preoperative radiation treatment of either 2,000 or 4,000 rad did not increase significantly the morbidity or complications. Noteworthy is the fact that none of the 29 patients >70 years old who were treated with cystec-

461

BLADDER CANCER TABLE

2. Data on survival and grade of tumor in patients with and

without muscle invasion Grade (No. alive/total) Totals Muscle invasion No muscle invasion

TABLE

3/4 3/3

II

III

IV

5/10 5/8

14/30

8/13 2/2

4/6

30/57 14/19

3. Tumor, nodes and metastasis staging classification of

bladder cancer Tumor, Nodes and Metastasis

Jewett Classification

CIS, TIS Tl T2 T3a T3b T3bn

0 A Bl B2 C D

TABLE 4.

No. Pts. 7 14 8 17 19 11

Complications No. Pts.

Phlebitis Prolapsed loop of bowel Obstruction of distal ileum Ileus (prolonged > 7 days) Transient hyponatremia Pelvic cellulitis Partial bowel obstruction Bleeding from penile artery Wound infection Sepsis Pulmonary emboli Femoral vein injury Pelvic abscess (radiated area) Congestive heart failure Urinary extravasation Urinary leakage (partial cystectomy) Endocardial ischemia Sacral decubitis ulcer Gastric dilatation Active duodenal ulcer Pneumonia Acute renal failure

1 1 1 6

1 1 2

1 5

1 1

1 1 1 1 1 1 1 1 1 1 1

Average hospital stay was 18 days.

lymph node dissection 27 had negative nodes. However, 4 of the 10 patients with microscopically positive nodes are alive and free of disease >18 months postoperatively (table 5). It is known that once a transitional cell tumor invades the muscularis 50 per cent of the patients will be dead of the disease in ~18 months and a smaller percentage will survive 5 years. 8- 10 Nine patients underwent partial cystectomy for treatment of bladder cancer. Strict criteria applied to these patients included negative random biopsies, solitary tumors and tumors located in a position to assure an adequate margin of at least 1.5 to 2 cm. free of tumor. Of these 9 patients 8 have survived. One patient had received preoperative radiation (2,000 rad). This retrospective review poses certain questions that are unanswerable to date. Why is there no difference between the preoperative radiation group receiving 4,000 rad and the group treated earlier in the series with no radiation? Cystectomy and ileal diversion, even in the elderly patients (average patient age in our series was 75.3 years for women and 65.2 years for men, with 29 patients >70 years old) can be accomplished with low morbidity and low mortality (fig. 2). None of the patients ~70 years old died in the perioperative period. The over-all mortality rate of 1 per cent in our series compares favorably to that reported previously. 5' 6 Our patient died 62 days postoperatively of pelvic abscess and septicemia. All patients were volumeloaded with a large intravenous line placed 24 hours preoperatively. Digitalis was not given routinely nor has it been our policy to treat patients with heparin or sodium warfarin in the perioperative period, as have other investigators. 11 A case can be made for cystectomy and diversion in patients with muscle invading tumors, as well as early cystectomy in patients with high grade superficial recurrent or extensive tumors. Perhaps with early cystectomy increases in survival may be forthcoming. Survival statistics in patients with bladder carcinoma have not changed considerably in the last 30 years, perhaps with the exception of patients who were downstaged after 4,000 rad given preoperatively. However, there are no predictors to determine

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DISCUSSION

The over-all survival rates are 30 of 57 patients (52.6 per cent) with muscle invasion, 11 of 20 (55 per cent) treated with surgery alone (median survival 63.2 months, range 32 to 119 months, the majority being treated from 1971 through 1975), 11 of 20 (55 per cent) treated with 4,000 rad preoperatively (median survival 46.3 months, range 6 to 92 months, the majority being treated from 1975 through 1978) and, more recently, 7 of 8 (88 per cent) treated with 2,000 rad preoperatively (median survival 13 months) (tables 1 and 2). If we exclude the group that received 7,000 rad for cure of the bladder cancer the survival rate for patients with muscle invasion is 29 of 48 (60.4 per cent). The survival for patients with and without muscle invasion, who received 7,000 rad is 43 of 67 patients (64.2 per cent). One notes the fact that not all patients have survived 18 months to date but the average length of survival is > 18 months, which is an interval most common for metastatic disease to have presented. Graphically, the survivals are depicted using the BerksonGage calculations (fig. 1). 7 It is of interest that 11 of our 20 early patients who received no radiation therapy are alive, with a mean survival of 63 months (table 2). The survival rate for patients who received 4,000 rad preoperatively followed by cystectomy 1 month later was the same (11 of 20, with a mean survival of 46 months). Of the 37 patients who underwent pelvic

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Fm. 1. Graph of survival using Berkson-Gage calculations TABLE

5. Pathological findings in 37 patients who underwent pelvic

lymph node dissection Nodal Metastasis Radiation for cure, 6 pts. 4,000 rad, 15 pts. 2,000 rad, 8 pts. No radiation, 8 pts.

Pos., 3 Neg.,3 Pos., 2 Neg., 13 Pos., 2 Neg., 6 Pos., 3 Neg.,5

Status Dead 1 alive, 1 alive, 7 alive, Alive 5 alive, 1 alive, 4 alive,

2 dead 1 dead 6 dead 1 dead 2 dead 1 dead

462

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REFERENCES

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therapeutic adjunctive therapy: 3 have survived >24 months and 1 is 18 months postoperative. In summary, we believe that cystectomy and urinary diversion can be accomplished with a low mortality and morbidity rate even in elderly patients when proper attention is given to preoperative management and postoperative care. Survival rates in this series were similar whether patients received 4,000 rad preoperatively or no radiation therapy, with the same number of patients surviving for similar intervals (survival rate 55 per cent). Only with early aggressive surgical management will survival statistics for patients with bladder carcinoma be improved.

8 6

4 2 40-49 50-59 60-69 70-79 80-89

AGE RANGE Fm. 2. Age and sex distribution

which patient would be downstaged. 5 In our review no firm conclusions regarding 4,000 or 2,000 rad, or no radiation preoperatively can be made because of the number of patients and because this was not a randomized prospective study. Finally, in addition to early cystectomy, patients with positive lymph nodes perhaps may benefit from 1 or 2 cycles of chemotherapy in the perioperative period. However, of our 10 patients with positive lymph nodes 4 are alive without any systemic chemo-

1. Reid, E. C., Oliver, J. A. and Fishman, I. J.: Preoperative irradiation and cystectomy in 135 cases of bladder cancer. Urology, 8: 247, 1976. 2. Van der Werf-Messing, B.: Carcinoma of the bladder treated by preoperative irradiation followed by cystectomy. Cancer, 32: 1084, 1973. 3. Whitmore, W. F., Jr., Batata, M. A., Ghoneim, M. A., Grabstald, H~ and Unal, A.: Radical cystectomy with or without prior irradiation in the treatment of bladder cancer. J. Urol., 118: 184, 1977. 4. Heney, N. M. and Prout, G. R., Jr.: Preoperative irradiation as an adjuvant in the surgical management of patients with invasive bladder cancer. Urol. Clin. N. Amer., 7: 543, 1980. 5. Batata, M.A., Chu, F. C., Hilaris, B. S., Whitmore, W. F., Kim, Y. S. and Lee, M. Z.: Bladder cancer in men and women treated by radiation therapy and/or radical cystectomy. Urology, 18: 15, 1981. 6. Brannan, W., Ochsner, M. G., Whitehead, C. M., Jr. and Rosencrantz, D.: Cystectomy and segmental resection for primary carcinoma of the bladder: experience at Ochsner Clinic. South. Med. J., 66: 241, 1973. 7. Expectation of life in the United States at new high. Metropolitan Life Insurance Co., Stat. Bull., 61: 15, October-December 1980. 8. Caldwell, W. L.: Carcinoma of the urinary bladder. J.A.M.A., 229: 1643, 1974. 9. Richie, J.P., Skinner, D. G. and Kaufman, J. J.: Radical cystectomy for carcinoma of the bladder: 16 years of experience. J. Urol., 113: 186, 1975. 10. Whitmore, W. F.: Integrated irradiation and cystectomy for bladder cancer. Brit. J. Urol., 52: 1, 1980. 11. Skinner, D. G.: Complications of lymph node dissection: In: Complications of Urologic Surgery: Prevention and Management. Edited by R. B. Smith and D. G. Skinner. Philadelphia: W. B. Saunders Co., chapt. 22, p. 422, 1976.