Staged Approach to Invasive Vesical Malignancy

Vol. 108, December Printed in U.S.A.

THE JOURNAL OF UROLOGY

Copyright © 1972 by The Williams & Wilkins Co.

STAGED APPROACH TO INVASIVE VESICAL MALIGNANCY JOHN H. GRIMES, JOHN M. HART, JAMES F. GLENN

AND

E. EVERETT ANDERSON

From the Division of Urology, Duke University Medical Center, Durham, North Carolina

are used as the primary agent, each has less frequent but definite toxicity rates.17 When multiple forms of therapy are used, the complication and mortality figures are increased. It is our purpose herein to report the results of an attempt to reduce therapeutically related complications by varying the order of the therapeutic approach. We reviewed a series of 53 consecutive patients with invasive carcinoma of the bladder treated by radical cystectomy and urinary diversion. Cystectomy as defined herein includes a prostatovesiculectomy in male patients and a hysterosalpingooophorectomy with urethrectomy and subtotal vaginectomy in female patients. Routine urethrectomy was not carried out in the male subjects nor was a radical lymph node dissection performed. In 40 patients ileal conduit was the diversionary method of choice. However, 10 patients in the beginning of this series had ureterosigmoidostomy while 2 patients had a Gersuny diversion and 1 underwent bilateral cutaneous ureterostomy. Initially, cystectomy and urinary diversion were performed as a 1-stage operation. Many of these patients had preoperative radiotherapy. Because of the morbidity and mortality involved in the 1-stage procedure, a 2-stage approach has been employed in some patients since 1968. Some patients received radiation therapy during the interval between urinary diversion and cystectomy. Thus, 39 patients underwent simultaneous diversion and cystectomy and 14 patients underwent cystectomy at a second operation. The interval between surgical procedures ranged from 1 week to 4 months with the majority at 6 weeks post-diversion. This was not a randomized prospective study; however, the age and sex distributions were essentially the same for both groups (table 1).

There has been much discussion about carcinoma of the bladder during the past several decades. Several etiological factors have been recognized. However, in the typical patient the exact cause usually remains unknown. 1 Attempts have been made to classify the disease and to relate prognosis to the histologic grade and clinical stage of the tumor. 2 Various maneuvers and diagnostic studies have been introduced in an attempt to stage the disease more accurately.• Different therapeutic modes and rationales have been advanced in an effort to obtain a cure. These include earlier and more radical forms of surgical extirpation, radiotherapy and chemotherapy in their multiple forms. 4 • 6 Combinations of these have been used in an attempt to improve the survival statistics and each therapeutic modality has been related to the various stages and grades of this malignancy. 5-s With each form of therapy there are complications. Operative mortality rates reported for radical cystectomy vary from 5 to 24 per cent, with most authors reporting about a 15 per cent mortality and complication rates of 60 to 70 per cent have been reported. 9-16 When radiotherapy and chemotherapy Accepted for publication April 14, 1972. Read at annual meeting of Southeastern Section, American Urological Association, Miami Beach, Florida, April 4-8, 1971. 1 Price, J. M., Wear, J. B., Brown, R. R., Satter, E. J. and Olson, C.: Studies on etiology of carcinoma of urinary bladder. J. Ural., 83: 376, 1960. 2 Jewett, H. J., King, L. R. and Shelley, W. M.: A study of 365 cases of infiltrating bladder cancer: relation of certain pathological characteristics to prognosis after extirpation. J. Ural., 92: 668, 1964. 3 Jewett, H.J. and Eversole, S. L., Jr.: Carcinoma of the bladder: characteristic modes of local invasion. J. Ural., 83: 383, 1960. 4 Whitmore, W. F., Jr. and Marshall, V. F.: Radical total cystectomy for cancer of the bladder: 230 consecutive cases five years later. J. Ural., 87: 853, 1962. 6 Bowles, W. T. and Cordonnier, J. J.: Total cystectomy for carcinoma of the bladder. J. Ural., 90: 731, 1963. 6 Hecker, G. N., Hodges, C. V., Moore, R. J. and Higgins, R.: Radical cystectomy after supervoltage radiotherapy. J. Ural., 91: 256, 1964. 7 Laskowski, T. Z., Scott, R., Jr. and Hudgins, P. T.: Combined therapy: radiation and surgery in the treatment of bladder cancer. J. Ural., 99: 733, 1968. 8 DeWeerd, J. H. and Colby, M. Y., Jr.: Combined radiotherapy and surgery for infiltrating carcinoma of the bladder. J. Urol., 99: 593, 1968. 9 Parkhurst, E. C.: Experience with more than 500 ileal conduit diversions in a 12-year period. J. Ural., 99: 434, 1968. 10 Glantz, G. M.: Cystectomy and urinary diversion. J. Urol., 96: 714, 1966. 11 Stone, J. H. and Hodges, C. V.: Radical cys-

tectomy for invasive bladder cancer. J. Ural., 96: 207, 1966. 12 Marsh, R. J. and Ceccarelli, F. E.: Ten-year analysis of primary bladder tumors at Brooke General Hospital. J. Ural., 91: 530, 1964. 13 Parkhurst, E. C. and Leadbetter, W. F.: A report on 93 ileal loop urinary diversions. J. Ural., 83:.398, 1960. 14 Burnham, J. P. and Farrer, J.: A group experience with uretero-ileal-cutaneous anastomosis for urinary diversion: results and complications of the isolated ileal conduit (Bricker procedure) in 96 patients. J. Ural., 83: 622, 1960. 15 Cordonnier, J. J.: Cystectomy for carcinoma of the bladder. J. Ural., 99: 172, 1968. 16 Brown, H. M. and Elliot, J. S.: Bladder cancer: an evaluation of diagnosis and treatment of 93 patients. J. Ural., 102: 63, 1969. 17 Frank, H. G.: The radiological assessment of bladder tumors. Part 2. Radiotherapy. J. Ural., 92: 484, 1964.

872

873

INVASIVE VESICAL MALIGNANCY TABLE

1

No. Male Total Pts. One procedure Staged procedure

39 14

T_rnLE

30 11

Age (yrs.)

No. Female Pts.

Age (yrs.)

40-80 53-73

3

32-72 7--05

2. Mortality

TABLE

Single Procedure Staged Procedure (39 patients) (14 patients) No. (%) No. (%) Hospital deaths Late deaths Lost to followup Over-all mortality

TABLE

7 18 5 30

(18) (46) (13) (77)

0 3 (21)

2 (14) 5 (35)

3. Mortality rates reported in the literature % Mortality 14.0 21.8 13.0 17. 9 8. 8 4.6 13.0 13.0 24.0 13.5 14.0

Parkhurst & Leadbetter" Burnham & Farrer14 Brown & Elliot16 Parkhurst• Laskowski & associates' Cordonnier15 DeWeerd and Colby• Sakati & Marshall" Glantz10 Stone & Hodges" Whitmore & Marshall•

TABLE

5. Severe complications in the early postoperative period

U reteroileal anastomotic leak Gastrointestinal hemorrhage Wound infection Wound hemorrhage Wound dehiscence Ileoileal anastomotic leak Necrosis of loop Pelvic abscess Hepatic failure Cardiac arrest Respiratory arrest Pulmonary edema Bowel obstruction

TABLE

6. Mild complications in the early postoperative period One Procedure

Staged Procedure

2 3

lieus Wound infection Pyelonephritis Partial small bowel obstruction Pelvic abscess U retero-ileal anastomotic leak

4. Complications

2

Late

Early

One procedure Staged procedure

while 71 per cent of the patients in the staged group were free of complications. Among the 39 patients in the 1-stage surgical group there were 37 complications. Most of these occurred in the early postoperative period and were of a severe nature (tables 4 and 5). All late complications involved the gastrointestinal tract. In

Mild

Severe

7 5

20 0

Mild

Severe

0

3 0

TABLE CompIi cation

7

Radiated

Non-Irradiated

1-stage operation

RESULTS

The complications related to therapy were analyzed and divided into early (within 1 month of operation) and late. They were subdivided into mild and severe. Mild complications may be classified as those that added some discomfort or minimal delay to the convalescent period. All complications that led to further operation, intensive medical therapy and/or caused significant delay in discharge from the hospital were termed severe. In the group undergoing a 1-stage operation, there were 7 hospital deaths, an 18 per cent mortality rate (table 2). This is comparable to mortality rates reported by Parkhurst and Leadbetter, 13 DeWeerd and Colby,8 Whitmore and Marshall,4 and Stone and Hodges11 (table 3). In the staged group there were no hospital deaths. In the group having a 1-stage operation only 33 per cent had no complications 18 Sakati, I. A. and Marshall, V. F.: Postoperative fatalities in urology. J. Urol., 96: 412, 1966.

Lean patients: None Early mild Early severe Late mild Late severe Obese patients: None Early mild Early severe Late mild Late severe

4 2

7

2 2

2 2

1 4 0 0

3 0 0

2-stage operation

Lean patients: None Early mild Early severe

Late mild Late severe Obese patients: None Early mild Early severe Late mild Late severe

2 0 0 0

2 0 0 0

3 1 0 0 0

2 0 0 0 0

874

GRIMES AND ASSOCIATES

the group having 2-stage procedures, 4 patients had a total of 5 complications, all of which were mild and all of which were in the early postoperative period (table 6). In some of these patients the followup is only a year or slightly more and additional delayed complications might be anticipated. Other factors that may have contributed to the difference were reviewed. Most of the operations were accomplished by 2 senior staff surgeons and this was not considered to have any effect on the difference in morbidity. We attempted to determine whether obesity or radiation therapy could provide an explanation for the decreased morbidity in the staged procedure. The percentage of patients having complications was low with the staged procedure in both the obese and the irradiated group and was high in both groups when the procedure was done at one time (table 7). This indicates that the lengthy procedure rather than obesity or radiation per se was the etiologic factor in the development of complications. Since most of the bladder cancers were stage B2 with only a few stage C lesions, the stage of the tumor did not seem to be responsible for the difference in morbidity. Long-term followup necessarily relates to the disease process as well as the therapeutic modalities and the mortality statistics reflect this. The cause of death in almost every instance was metastatic carcinoma. Any patient not seen in the last 6 months is considered lost to followup and for statistical purposes dead. Thus, we find 77 per cent (30 of 39) of the 1-stage group dead while 35 per cent (5 of 14) of the 2-stage group are dead, reflecting the still dismal results in treatment of vesical malignancy. DISCUSSION

In a retrospective study such as this involving many complex therapeutic regimens for a debilitating lethal disease, there are many variables to account for the differences seen. The effect of presurgical radiotherapy is noticed in the poor healing properties of radiated tissue, especially the terminal ileum and ureters. Such problems as delayed wound healing, wound infections, wound dehiscence, ureteroileal anastomotic leaks, ileoileal leaks and even necrosis of the ileal conduit are usually attributable to radiation effect. Another factor is the increased operative and anesthetic time required for the 1stage procedure, with its inherent pulmonary and cardiovascular risks. Although it has not been proved in a prospective study, the stress of a lengthy operation does seem at times to be related to such complications as congestive heart failure, pulmonary edema, pulmonary embolism and respiratory and cardiac arrest. The problems of postoperative renal and hepatic failure in massive postoperative gastrointestinal hemorrhage may be related to prolonged anesthetic periods. It is indeed unfortunate that many of the patients who have fared the poorest from a metabolic viewpoint are precisely those who must undergo a second surgical insult

because of a complication. The stormy and sometimes disastrous course followed by patients who have undergone prolonged operation is all too familiar to most of us. The staged surgical approach seems to offer several advantages, the first of which is that it allows the surgeon an opportunity for accurately determining the clinical stage of the malignancy. Direct exploration of the abdomen, examination of the deep pelvic, iliac and para-aortic nodes with biopsies for frozen section when necessary and general determination of operability enhance an intelligent approach to individual therapy. The patient found to have disease outside the pelvis-stage D2-is usually closed without a diversion and is referred for radiotherapy. The relative absence of complications involving either ureteral or bowel anastomosis in the staged group of patients demonstrates the advantage of performing the diversion prior to the institution of radiotherapy. At this point, healthy ureters and bowel are still available. Decreased operative time involved with a diversion alone is reflected by the lack of cardiovascular, pulmonary and renal problems in this group. The difference in severe complication rates is striking. The disadvantages of staging the operative approach must also be considered. The most important one is that it delays removing the bladder with its invasive cancer. However, radiotherapy to the bladder may be instituted within a week after the diversionary procedure so that the patient is being treated. The important point is that the conduit is now out of the pelvis and the field of radiation. It has been claimed that this only combines several debilitating courses of therapy, leaving the patient in negative nitrogen balance and at his weakest point at the time of the cystectomy. 6 We have not found this to be true and indeed have practically no complications following the second-stage procedure. This approach does subject the patient to the risks and hazards inherent in 2 anesthetics but most patients can tolerate 2 reasonably timed anesthetic periods quite satisfactorily. The cystectomy may be more difficult because of adhesions and fibrosis secondary to the intervening radiotherapy. The over-all cost to the patient required by 2 hospitalizations may be greater. SUMMARY

A recent series of 53 patients having cystectomy and urinary diversion for carcinoma of the bladder were evaluated for complication and mortality rates. Complications and mortality were compared between those who had a 1-stage operation and those having a 2-stage procedure. With the 2-staged surgical approach, operative mortality rates were markedly reduced, complications were more reasonable in number and degree, accurate clinical staging of disease permitted more rational therapy and the minimal delay in accomplishing cystectomy has not caused an untoward reduction of survival.