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Update on Intracavitary Radiation in the Treatment of Bladder Tumors
0022-5347 /81/1263-0323$02.00/0 Vol. 126, September
THE JOURNAL OF UROLOGY
Copyright© 1981 by The Williams & Wilkins Co.
Printed in U.S.A.
UPDATE ON INTRACAVITARY RADIATION IN THE TREATMENT OF BLADDER TUMORS CLARENCE B. HEWITT, JAN F. BABISZEWSKI*
AND
ANTONIO R. ANTUNEZ
From the Departments of Urology and Radiation Therapy, Cleveland Clinic Foundation, Cleveland, Ohio
ABSTRACT
A 15-year experience with intracavitary radiation for the treatment of selected bladder tumors is presented. The age range of these patients was 39 to 91 years, with an average of 65 years. There were 38 men and 17 women with multiple stage A bladder tumors and carcinoma in situ. Some patients were poor risks for treatment by total extirpative surgery. A simplified technique using a 25 mg. radium capsule as a central source is described for administration of 4,000 to 5,000 rad to the surface of the bladder. Most patients tolerate the presence of the radium catheter with little difficulty. No morbidity and no mortality were reported. In this series more than 60 per cent of the patients benefited from the therapy, with no recurrence noted in some cases after up to 8½ years of foHowup. Int:racavitary :radiation is used in few clinics. Use of this modality does not preclude or complicate the subsequent use of other conservative measures or radical therapy if required. It is an effective procedure for treatment of multiple superficial and noninvasive tumors, including pnmary or recurrent carcinoma in situ, that are uncontrolled by other conservative measures. Carcinoma of the bladder affects 21,000 Americans annually. 1 The spectrum of presentation encompasses all degrees ofvesical involvement-slowly growing, recurrent superficial papillary lesions to lethal tumors, which rapidly invade the bladder muscle and metastasize to distant sites. The therapeutic approach to invasion of the bladder wall musculature by tumor usually consists of partial or total extirpation of the bladder, with or without adjuvant external irradiation or with external irradiation alone. Most well circumscribed noninvasive bladder tumors can be treated satisfactorily by transurethral fulguration and resection or by chemotherapeutic instillations. However, a dilemma arises in attempting to manage individuals with well differentiated multiple superficial tumors, either primary or rapidly recurrent, who are not controlled by conservative methods of therapy. Initial radical surgery, although clearly adequate, may be overtreatment in some instances. An additional and effective conservative method of treatment available to most urologists but seldom used is intracavitary radiation. In 1949 and 1958 Friedman and Lewis described the use of intracavitary radiation in the treatment of bladder tumors (all stages and grades) and their experience with 50 patients. 2 • 3 Their elaborate method was termed the Walter Reed technique. In 1972 Hewitt and associates reported on 10 patients treated with a modification of this technique, which was devised to simplify Friedman and Lewis' method for use by urologists in the treatment of special patients. 4 This method of placement of an intracavitary radium source and the 15-year experience emanating from its use in a select group of patients are reported.
1,000 rad to the surface of the bladder. 4 The approximate depth dose in the bladder wall is 90 per cent for 2 mm., 75 per cent for 2 to 5 mm. and 50 per cent for 5 to 13 mm. A standard 24F Foley catheter with a 30 cc balloon was used. The :radium capsule is placed within the lumen of the catheter and positioned in the middle of the balloon portion. It is fixed in position by a special wire basket. Sufficient space remains within the lumen of the catheter for satisfactory urinary drainage. Although it is not difficult to position and to fix the radium capsule in the catheter we have found it more convenient to obtain the radium catheter from a readily available commercial sourcet for a modest rental charge. The radium-containing catheter must be cold-sterilized before use. The usual precau·· tions against radiation hazard must be exercised during catheter preparation and handling. The radium catheter should not be used immediately after t:ransurethral resection, biopsy or fulguration. An interval of 3 to 4 weeks is required to permit complete healing of the bladder and prevent the development of a possible painful radiationinduced ulceration or cystitis. TECHNIQUE
MATERIALS AND METHODS
A 25 mg. radium capsule, filtered with 0.5 mm. platinum and an active length of 1.0 cm. and an external diameter of 2.3 mm., was used in all cases. The radium tissue distance, which is the radius of an inflated 30 cc balloon of a Foley catheter, is 2.2 cm. with the radium centrally placed in the inflated bag. A 25 mg. radium catheter in 24 hours will give an exposure of 600 mg. per hour and a tissue dose of approximately Accepted for publication November 26, 1980. Read at annual meeting of Western Section, American Urological Association, Kona and Honolulu, Hawaii, March 1-8, 1980. * Requests for reprints: Department of Urology, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, Ohio 44106.
The deflated radium-containing Foley catheter is inserted through the urethra into the bladder with an aseptic technique. It is preferable to use general anesthetic for male patients, since they usually require preliminary urethral dilation to 28 or 30F to facilitate easier insertion of the catheter. Also, adequate lubrication of the catheter is important, especially when it is introduced into the male urethra. Normally, the female patient requires no anesthesia for this procedure. The catheter is han-· dled with long curved forceps to minimize radiation exposure of the hands. When the catheter has been inserted into the bladder the retention balloon is inflated with 30 cc sterile 5 per cent sodium iodide solution colored with a small amount of methylene blue or indigo carmine. During the radium treatment discoloration of the urine by the dye will indicate accidental rupture of the balloon and will require prompt removal of the catheter. Gentle traction is exerted on the catheter to ensure that the balloon is positioned at the bladder outlet. Immediately after insertion of the catheter an x-ray film of the bladder area is taken to confirm that the balloon and the radium are m
t Radium Chemical Co., Inc., New York, New York. 323
324
HEWITT, BABISZEWSKI AND ANTUNEZ
proper position. 4 When this has been determined the catheter is placed on closed gravity drainage and the patient is taken directly to a private room. Most patients tolerate the presence of the radium catheter without great difficulty. Belladonna and opium suppositories control minor bladder spasms, although additional anticholinergic agents or parenteral narcotics may be required when bladder pain is severe. When the patient has received the desired radiation dose the radium catheter is removed in the patient's room, observing the precautions necessary when radium is used. RADIATION PROTECTION
Bedside radiation intensities are typically 20 to 35 mm. per hour, resulting in a permissible total bedside time of 3 to 5 hours per week for any 1 employee. At 6 feet from the source radiation intensities are about 5 mm. per hour and 20 hours per week for personnel attending the patient. Visitors are instructed to remain at least 5 feet away from the patient and an average daily visit of 2 hours per person is permitted during the period of treatment. In addition, the use of a lead shield at the patient's bedside affords additional protection to the visitors. Under no circumstances are visitors who are pregnant or <18 years old permitted in the patient's room. RESULTS
Between August 1965 and January 1979, 55 patients with transitional cell carcinoma were treated with intracavitary radiation at our clinic with the technique described. All patients had previous unsuccessful efforts with transurethral resection or fulguration in controlling tumor recurrence. In addition, 7 patients (5 with grade I lesions and 2 with grade II lesions) received intravesical chemotherapy, which also failed to change the course of urothelial carcinoma recurrence. In most patients with multiple stage A bladder tumors (41) this method of treatment was used as an additional conservative measure and no additional therapy has been necessary to date. In the 15 patients with carcinoma in situ intracavitary irradiation was the only conservative method used after the initial transurethral resection for diagnostic purposes. The historical time span from initial diagnosis to eventual intracavitary radiation was most variable. The interval for patients with stage A tumors ranged from 1 month to 9 years. In patients with carcinoma in situ the interval was markedly shorter, ranging from 1 to 3 months. The age range of these patients was 30 to 91 years, with an average of 65 years. There were 38 men and 17 women. Some of these patients were poor risks for treatment by total extirpative surgery. The total dose of radiation administered to each patient ranged from 3,000 to 7,000 rad. Fifty patients received initial treatment of 4,000 rad and 1 of these patients received an additional 3,000 rad after an interval of 26 months. Three patients received a total of 5,000 rad and 1 individual received only 3,000 rad when the catheter became obstructed and had to be removed prematurely. In 22 patients symptoms of mild to moderate radiation cystitis resolved after 4 to 6 weeks. Two patients had severe symptoms of delayed radiation cystitis approximately 1 to 1½ years after therapy. These patients became asymptomatic after approximately 4 to 5 months, respectively. Two patients had severe symptoms of acute radiation cystitis that resolved. Two patients had hemorrhagic cystitis secondary to the radiation. One of these latter patients had the only serious complication in the series, a contracted bladder with secondary bilateral ureteral obstruction. This patient was the only one in the series who had received external irradiation. He had been treated for a seminoma approximately 23 years before intracavitary radiation therapy.
Of the 55 patients 22 (40 per cent) had multiple stage A, grade I lesions. Seven patients have had no recurrence for 18 months to 9 years, with a mean of 42 months. Two individuals have had improvement at 1 and 2 years, respectively. Nine patients had no improvement. Four patients were lost to followup (table 1). Seventeen patients (30 per cent) had multiple stage A, grade II lesions. Seven patients have had no recurrence from 1 to 7 years, with a mean of 38 months. Three individuals showed improvement of 1 year. Six patients had no response. One patient was lost to followup. Two individuals (5 per cent) had multiple stage A, grade III lesions. One showed improvement for 26 months. He received another 3,000 rad via intracavitary radiation. He did well with no recurrence for 32 months but then presented with stage B lesions. Another individual was treated with intracavitary radiation but died of an unrelated condition before the initial followup re-examination. Fourteen patients (25 per cent) were diagnosed as having carcinoma in situ. Eight patients have had no recurrence for 1 to 8½ years of followup, with a mean of 33 months and remained asymptomatic. Two individuals showed improvement of 2 years each. Three patients had no improvement. One patient was lost to followup. Urine cytology evaluations were not obtained on a routine basis to establish tumor recurrence. However, in the carcinoma in situ category 7 of 8 patients with no subsequent recurrence consistently had cytological change from positive to negative (table 2). In this series 10 patients underwent cystectomy. Supravesical urinary diversion was performed in the patient with the contracted bladder. Although apparently free of tumor, cystectomy was attempted on this individual but was not technically possible (table 3). In only 2 instances had disease progressed beyond the diagnosed stage at which intracavitary radiation was given. One individual with carcinoma in situ presented with a stage B lesion after 32 months. A third individual with diagnosed carcinoma in situ died of pulmonary metastasis within 6 months of diagnosis. DISCUSSION
The radiation characteristics of the radium catheter merit its consideration in the treatment of multiple low grade superficial tumors and carcinoma in situ, which cannot be controlled by usual means. External irradiation has been found to be ineffective as a curative procedure for this select group of patients in doses that are tolerated by the bladder wall. 5 Intracavitary radiation, administered by the technique described with a dose of 4,000 rad, is within the realm of conservative therapy. Significant morbidity was seen in only 1 individual. He had received external irradiation many years before and a contracted bladder developed after intracavitary radiation. Previous external irradiation may be a contraindication to intracavitary radiation therapy. Use of the latter method does not preclude or complicate the subsequent use of other conservative measures or radical therapy, if required. TABLE
1. Results of treatment Stage/Grade
No recurrence Improved* No improvement No followupt
A/I
A/II
A/III
No. Pts.
No. Pts.
No. Pts.
Ca in Situ No. Pts.
(%)
(%)
(%)
(%)
7 (39) 2 (11) 9 (50)
7 (44)
0 (0) 0 (0) 1 (100) 1-
8 (62) 2 (15) 3 (23) 1-
4-
3 (19) 6 (37) 1-
* Made amenable to transurethral resection and fulguration. t Excluded from evaluation of treatment.
325
INTRACAVITARY RADIATION IN TREATMENT OF BLADDER TUMORS TABLE 2.
Date of Diagnosis
Pt.
SP HP
Before Radium Cystoscopy/ Cytology
+/+ +/+ +/+ +/+
Feb. 1970 Dec. 1972 Feb. 1974 Feb. 1975 Jan. 1975 July 1975 Nov. 1975 Feb. 1970
AH RU JS OL LF NS
+!+ +/+ +/+ +/+
Response to treatment of Ca in situ
-----·------·-----.--
Mos. After Radium (Cystoscopy/Cytology) Date of Radium Catheter Feb. 1970 Jan. 1973 Sept. 1974 Mar. 1974 Jan. 1976 Aug. 1975 Dec. 1975 Mar. 1970
6
3
-/-
-/-/+ -/-
-/-/-/-
-/-
9
12
18
-/-/-/+ -/-/+ -/-
-/-/+ -/+ -/-/+ -/-
-/-
-/+ -/+ -/-/-/-
+/+* -/-/+ -/-/-/-
-/-
-/-
-/-
-/-
-/-
-/-
-/-
-/-
24
36
48
-/-
-/-
-/-
-/-/-
-/-
-/-
-/-
-/-
-/-
60
>60
-/-
-/-
* Cystectomy and ilea! conduit.
TABLE 3.
Stage at Radiation Therapy
Patients undergoing cystectomy No. Pts.
Stage at Cystectomy
No. Pts.
A-I
4
2
A-II
3
Ca in situ
3
A-I A-II Ca in situ A-II Ca in situ A-II Ca in situ
1 2 1
2
In this series 59 per cent of the patients benefited from this therapeutic method. In 44 per cent of the cases improvement of ~l years was noted and the patients became amenable to transurethral resection and fulguration. Gratifying results were seen in the group of patients with diffuse carcinoma in situ. Recurrence has not been noted in 60 per cent of these individuals for ~2 years. Indeed, irradiation of the entire bladder may also be a prophylactic measure in preventing future development of new tumors. It is also noteworthy that only 2 patients who had disease recurrence presented with higher stage lesions. Both of these were amenable to radical surgery. Intracavitary radiation is used in few centers. We encourage its consideration as an additional conservative measure for the treatment of selected cases of multiple superficial and noninvasive tumors, including carcinoma in situ, primary or recurrent, which are uncontrolled by other conservative procedures in an attempt to preserve the integrity of the bladder. REFERENCES
1. Morrison, A. S. and Cole, P.: Epidemiology of bladder cancer. Urol.
Clin. N. Amer., 3: 13, 1976.
2. Friedman, M. and Lewis, L. G.: A new technic for radium treatment of carcinoma of the bladder. Radiology, 53: 342, 1949. 3. Friedman, M. and Lewis, L. G.: Irradiation of carcinoma of the bladder by a central intracavitary radium or cobalt source (the Walter Reed technique). Amer. J. Roentgen., 79: 6, 1958. 4. Hewitt, C. B., Kiser, W. S., Antunez, A. R. and Shernak, E. S.: Intracavitary radiation in the treatment of bladder tumors. J. Urol., 107: 603, 1972. 5. Buschke, F.: Supervoltage irradiation. Prophylactic vs therapeutic use for transitional cell carcinoma of the bladder, group L J.A.M.A., 206: 2724, 1968. EDITORIAL COMMENT The authors present a 15-year experience with intracavitary radiation for superficial bladder cancer. Approximately a third of the patients with grade 1 or 2, stage A tumors remain free of tumor for an average of 3 years after intracavitary radiation. Of 14 patients with carcinoma in situ 8 were free of tumor for an average of 33 months. Importantly, only 2 of 55 patients had tumors progress in stage subsequent to therapy. Experience with external radiation therapy in patients with superficial bladder cancer has taught us that although it may control the initial lesion(s) subsequent tumor development is likely and monitoring the urothelium for these new occurrences may be hampered. In addition, a subsequent extirpative operation often is more difficult. These may be some of the reasons why intracavitary radiation has not been used widely, despite its ability to control the immediate problem. Despite this, however, it offers an appealing alternative in patients failing intravesical chemotherapy and not candidates for cystectomy.
Mark S. Soloway Department of Urology University of Tennessee Center for the Health Sciences Memphis, Tennessee
THE JOURNAL OF UROLOGY
Copyright© 1981 by The Williams & Wilkins Co.
Printed in U.S.A.
UPDATE ON INTRACAVITARY RADIATION IN THE TREATMENT OF BLADDER TUMORS CLARENCE B. HEWITT, JAN F. BABISZEWSKI*
AND
ANTONIO R. ANTUNEZ
From the Departments of Urology and Radiation Therapy, Cleveland Clinic Foundation, Cleveland, Ohio
ABSTRACT
A 15-year experience with intracavitary radiation for the treatment of selected bladder tumors is presented. The age range of these patients was 39 to 91 years, with an average of 65 years. There were 38 men and 17 women with multiple stage A bladder tumors and carcinoma in situ. Some patients were poor risks for treatment by total extirpative surgery. A simplified technique using a 25 mg. radium capsule as a central source is described for administration of 4,000 to 5,000 rad to the surface of the bladder. Most patients tolerate the presence of the radium catheter with little difficulty. No morbidity and no mortality were reported. In this series more than 60 per cent of the patients benefited from the therapy, with no recurrence noted in some cases after up to 8½ years of foHowup. Int:racavitary :radiation is used in few clinics. Use of this modality does not preclude or complicate the subsequent use of other conservative measures or radical therapy if required. It is an effective procedure for treatment of multiple superficial and noninvasive tumors, including pnmary or recurrent carcinoma in situ, that are uncontrolled by other conservative measures. Carcinoma of the bladder affects 21,000 Americans annually. 1 The spectrum of presentation encompasses all degrees ofvesical involvement-slowly growing, recurrent superficial papillary lesions to lethal tumors, which rapidly invade the bladder muscle and metastasize to distant sites. The therapeutic approach to invasion of the bladder wall musculature by tumor usually consists of partial or total extirpation of the bladder, with or without adjuvant external irradiation or with external irradiation alone. Most well circumscribed noninvasive bladder tumors can be treated satisfactorily by transurethral fulguration and resection or by chemotherapeutic instillations. However, a dilemma arises in attempting to manage individuals with well differentiated multiple superficial tumors, either primary or rapidly recurrent, who are not controlled by conservative methods of therapy. Initial radical surgery, although clearly adequate, may be overtreatment in some instances. An additional and effective conservative method of treatment available to most urologists but seldom used is intracavitary radiation. In 1949 and 1958 Friedman and Lewis described the use of intracavitary radiation in the treatment of bladder tumors (all stages and grades) and their experience with 50 patients. 2 • 3 Their elaborate method was termed the Walter Reed technique. In 1972 Hewitt and associates reported on 10 patients treated with a modification of this technique, which was devised to simplify Friedman and Lewis' method for use by urologists in the treatment of special patients. 4 This method of placement of an intracavitary radium source and the 15-year experience emanating from its use in a select group of patients are reported.
1,000 rad to the surface of the bladder. 4 The approximate depth dose in the bladder wall is 90 per cent for 2 mm., 75 per cent for 2 to 5 mm. and 50 per cent for 5 to 13 mm. A standard 24F Foley catheter with a 30 cc balloon was used. The :radium capsule is placed within the lumen of the catheter and positioned in the middle of the balloon portion. It is fixed in position by a special wire basket. Sufficient space remains within the lumen of the catheter for satisfactory urinary drainage. Although it is not difficult to position and to fix the radium capsule in the catheter we have found it more convenient to obtain the radium catheter from a readily available commercial sourcet for a modest rental charge. The radium-containing catheter must be cold-sterilized before use. The usual precau·· tions against radiation hazard must be exercised during catheter preparation and handling. The radium catheter should not be used immediately after t:ransurethral resection, biopsy or fulguration. An interval of 3 to 4 weeks is required to permit complete healing of the bladder and prevent the development of a possible painful radiationinduced ulceration or cystitis. TECHNIQUE
MATERIALS AND METHODS
A 25 mg. radium capsule, filtered with 0.5 mm. platinum and an active length of 1.0 cm. and an external diameter of 2.3 mm., was used in all cases. The radium tissue distance, which is the radius of an inflated 30 cc balloon of a Foley catheter, is 2.2 cm. with the radium centrally placed in the inflated bag. A 25 mg. radium catheter in 24 hours will give an exposure of 600 mg. per hour and a tissue dose of approximately Accepted for publication November 26, 1980. Read at annual meeting of Western Section, American Urological Association, Kona and Honolulu, Hawaii, March 1-8, 1980. * Requests for reprints: Department of Urology, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, Ohio 44106.
The deflated radium-containing Foley catheter is inserted through the urethra into the bladder with an aseptic technique. It is preferable to use general anesthetic for male patients, since they usually require preliminary urethral dilation to 28 or 30F to facilitate easier insertion of the catheter. Also, adequate lubrication of the catheter is important, especially when it is introduced into the male urethra. Normally, the female patient requires no anesthesia for this procedure. The catheter is han-· dled with long curved forceps to minimize radiation exposure of the hands. When the catheter has been inserted into the bladder the retention balloon is inflated with 30 cc sterile 5 per cent sodium iodide solution colored with a small amount of methylene blue or indigo carmine. During the radium treatment discoloration of the urine by the dye will indicate accidental rupture of the balloon and will require prompt removal of the catheter. Gentle traction is exerted on the catheter to ensure that the balloon is positioned at the bladder outlet. Immediately after insertion of the catheter an x-ray film of the bladder area is taken to confirm that the balloon and the radium are m
t Radium Chemical Co., Inc., New York, New York. 323
324
HEWITT, BABISZEWSKI AND ANTUNEZ
proper position. 4 When this has been determined the catheter is placed on closed gravity drainage and the patient is taken directly to a private room. Most patients tolerate the presence of the radium catheter without great difficulty. Belladonna and opium suppositories control minor bladder spasms, although additional anticholinergic agents or parenteral narcotics may be required when bladder pain is severe. When the patient has received the desired radiation dose the radium catheter is removed in the patient's room, observing the precautions necessary when radium is used. RADIATION PROTECTION
Bedside radiation intensities are typically 20 to 35 mm. per hour, resulting in a permissible total bedside time of 3 to 5 hours per week for any 1 employee. At 6 feet from the source radiation intensities are about 5 mm. per hour and 20 hours per week for personnel attending the patient. Visitors are instructed to remain at least 5 feet away from the patient and an average daily visit of 2 hours per person is permitted during the period of treatment. In addition, the use of a lead shield at the patient's bedside affords additional protection to the visitors. Under no circumstances are visitors who are pregnant or <18 years old permitted in the patient's room. RESULTS
Between August 1965 and January 1979, 55 patients with transitional cell carcinoma were treated with intracavitary radiation at our clinic with the technique described. All patients had previous unsuccessful efforts with transurethral resection or fulguration in controlling tumor recurrence. In addition, 7 patients (5 with grade I lesions and 2 with grade II lesions) received intravesical chemotherapy, which also failed to change the course of urothelial carcinoma recurrence. In most patients with multiple stage A bladder tumors (41) this method of treatment was used as an additional conservative measure and no additional therapy has been necessary to date. In the 15 patients with carcinoma in situ intracavitary irradiation was the only conservative method used after the initial transurethral resection for diagnostic purposes. The historical time span from initial diagnosis to eventual intracavitary radiation was most variable. The interval for patients with stage A tumors ranged from 1 month to 9 years. In patients with carcinoma in situ the interval was markedly shorter, ranging from 1 to 3 months. The age range of these patients was 30 to 91 years, with an average of 65 years. There were 38 men and 17 women. Some of these patients were poor risks for treatment by total extirpative surgery. The total dose of radiation administered to each patient ranged from 3,000 to 7,000 rad. Fifty patients received initial treatment of 4,000 rad and 1 of these patients received an additional 3,000 rad after an interval of 26 months. Three patients received a total of 5,000 rad and 1 individual received only 3,000 rad when the catheter became obstructed and had to be removed prematurely. In 22 patients symptoms of mild to moderate radiation cystitis resolved after 4 to 6 weeks. Two patients had severe symptoms of delayed radiation cystitis approximately 1 to 1½ years after therapy. These patients became asymptomatic after approximately 4 to 5 months, respectively. Two patients had severe symptoms of acute radiation cystitis that resolved. Two patients had hemorrhagic cystitis secondary to the radiation. One of these latter patients had the only serious complication in the series, a contracted bladder with secondary bilateral ureteral obstruction. This patient was the only one in the series who had received external irradiation. He had been treated for a seminoma approximately 23 years before intracavitary radiation therapy.
Of the 55 patients 22 (40 per cent) had multiple stage A, grade I lesions. Seven patients have had no recurrence for 18 months to 9 years, with a mean of 42 months. Two individuals have had improvement at 1 and 2 years, respectively. Nine patients had no improvement. Four patients were lost to followup (table 1). Seventeen patients (30 per cent) had multiple stage A, grade II lesions. Seven patients have had no recurrence from 1 to 7 years, with a mean of 38 months. Three individuals showed improvement of 1 year. Six patients had no response. One patient was lost to followup. Two individuals (5 per cent) had multiple stage A, grade III lesions. One showed improvement for 26 months. He received another 3,000 rad via intracavitary radiation. He did well with no recurrence for 32 months but then presented with stage B lesions. Another individual was treated with intracavitary radiation but died of an unrelated condition before the initial followup re-examination. Fourteen patients (25 per cent) were diagnosed as having carcinoma in situ. Eight patients have had no recurrence for 1 to 8½ years of followup, with a mean of 33 months and remained asymptomatic. Two individuals showed improvement of 2 years each. Three patients had no improvement. One patient was lost to followup. Urine cytology evaluations were not obtained on a routine basis to establish tumor recurrence. However, in the carcinoma in situ category 7 of 8 patients with no subsequent recurrence consistently had cytological change from positive to negative (table 2). In this series 10 patients underwent cystectomy. Supravesical urinary diversion was performed in the patient with the contracted bladder. Although apparently free of tumor, cystectomy was attempted on this individual but was not technically possible (table 3). In only 2 instances had disease progressed beyond the diagnosed stage at which intracavitary radiation was given. One individual with carcinoma in situ presented with a stage B lesion after 32 months. A third individual with diagnosed carcinoma in situ died of pulmonary metastasis within 6 months of diagnosis. DISCUSSION
The radiation characteristics of the radium catheter merit its consideration in the treatment of multiple low grade superficial tumors and carcinoma in situ, which cannot be controlled by usual means. External irradiation has been found to be ineffective as a curative procedure for this select group of patients in doses that are tolerated by the bladder wall. 5 Intracavitary radiation, administered by the technique described with a dose of 4,000 rad, is within the realm of conservative therapy. Significant morbidity was seen in only 1 individual. He had received external irradiation many years before and a contracted bladder developed after intracavitary radiation. Previous external irradiation may be a contraindication to intracavitary radiation therapy. Use of the latter method does not preclude or complicate the subsequent use of other conservative measures or radical therapy, if required. TABLE
1. Results of treatment Stage/Grade
No recurrence Improved* No improvement No followupt
A/I
A/II
A/III
No. Pts.
No. Pts.
No. Pts.
Ca in Situ No. Pts.
(%)
(%)
(%)
(%)
7 (39) 2 (11) 9 (50)
7 (44)
0 (0) 0 (0) 1 (100) 1-
8 (62) 2 (15) 3 (23) 1-
4-
3 (19) 6 (37) 1-
* Made amenable to transurethral resection and fulguration. t Excluded from evaluation of treatment.
325
INTRACAVITARY RADIATION IN TREATMENT OF BLADDER TUMORS TABLE 2.
Date of Diagnosis
Pt.
SP HP
Before Radium Cystoscopy/ Cytology
+/+ +/+ +/+ +/+
Feb. 1970 Dec. 1972 Feb. 1974 Feb. 1975 Jan. 1975 July 1975 Nov. 1975 Feb. 1970
AH RU JS OL LF NS
+!+ +/+ +/+ +/+
Response to treatment of Ca in situ
-----·------·-----.--
Mos. After Radium (Cystoscopy/Cytology) Date of Radium Catheter Feb. 1970 Jan. 1973 Sept. 1974 Mar. 1974 Jan. 1976 Aug. 1975 Dec. 1975 Mar. 1970
6
3
-/-
-/-/+ -/-
-/-/-/-
-/-
9
12
18
-/-/-/+ -/-/+ -/-
-/-/+ -/+ -/-/+ -/-
-/-
-/+ -/+ -/-/-/-
+/+* -/-/+ -/-/-/-
-/-
-/-
-/-
-/-
-/-
-/-
-/-
-/-
24
36
48
-/-
-/-
-/-
-/-/-
-/-
-/-
-/-
-/-
-/-
60
>60
-/-
-/-
* Cystectomy and ilea! conduit.
TABLE 3.
Stage at Radiation Therapy
Patients undergoing cystectomy No. Pts.
Stage at Cystectomy
No. Pts.
A-I
4
2
A-II
3
Ca in situ
3
A-I A-II Ca in situ A-II Ca in situ A-II Ca in situ
1 2 1
2
In this series 59 per cent of the patients benefited from this therapeutic method. In 44 per cent of the cases improvement of ~l years was noted and the patients became amenable to transurethral resection and fulguration. Gratifying results were seen in the group of patients with diffuse carcinoma in situ. Recurrence has not been noted in 60 per cent of these individuals for ~2 years. Indeed, irradiation of the entire bladder may also be a prophylactic measure in preventing future development of new tumors. It is also noteworthy that only 2 patients who had disease recurrence presented with higher stage lesions. Both of these were amenable to radical surgery. Intracavitary radiation is used in few centers. We encourage its consideration as an additional conservative measure for the treatment of selected cases of multiple superficial and noninvasive tumors, including carcinoma in situ, primary or recurrent, which are uncontrolled by other conservative procedures in an attempt to preserve the integrity of the bladder. REFERENCES
1. Morrison, A. S. and Cole, P.: Epidemiology of bladder cancer. Urol.
Clin. N. Amer., 3: 13, 1976.
2. Friedman, M. and Lewis, L. G.: A new technic for radium treatment of carcinoma of the bladder. Radiology, 53: 342, 1949. 3. Friedman, M. and Lewis, L. G.: Irradiation of carcinoma of the bladder by a central intracavitary radium or cobalt source (the Walter Reed technique). Amer. J. Roentgen., 79: 6, 1958. 4. Hewitt, C. B., Kiser, W. S., Antunez, A. R. and Shernak, E. S.: Intracavitary radiation in the treatment of bladder tumors. J. Urol., 107: 603, 1972. 5. Buschke, F.: Supervoltage irradiation. Prophylactic vs therapeutic use for transitional cell carcinoma of the bladder, group L J.A.M.A., 206: 2724, 1968. EDITORIAL COMMENT The authors present a 15-year experience with intracavitary radiation for superficial bladder cancer. Approximately a third of the patients with grade 1 or 2, stage A tumors remain free of tumor for an average of 3 years after intracavitary radiation. Of 14 patients with carcinoma in situ 8 were free of tumor for an average of 33 months. Importantly, only 2 of 55 patients had tumors progress in stage subsequent to therapy. Experience with external radiation therapy in patients with superficial bladder cancer has taught us that although it may control the initial lesion(s) subsequent tumor development is likely and monitoring the urothelium for these new occurrences may be hampered. In addition, a subsequent extirpative operation often is more difficult. These may be some of the reasons why intracavitary radiation has not been used widely, despite its ability to control the immediate problem. Despite this, however, it offers an appealing alternative in patients failing intravesical chemotherapy and not candidates for cystectomy.
Mark S. Soloway Department of Urology University of Tennessee Center for the Health Sciences Memphis, Tennessee