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Radiocobalt in the Treatment of Bladder Tumors
r The JOURNAL of UROLOGY Vol. 67, No. 6, June 1952 Printed in U.S.A.
RADIOCOBALT IN THE TREATMENT OF BLADDER TUMORS JOHN W. SCHULTE, FRANK HINMAN, JR.
AND
BERTRAM V. A. LOW-BEER
From the Divisions of Urology and Radiology, University of California School of Medicine, San Francisco, Calif.
f
The technique of using radioactive cobalt beads for intracavitary radiation of bladder tumors was first suggested by one of us (BVAL-B) in January 1946. The following reasons argued for a trial of this technique: dissatisfaction with the results of radical surgery and of conventional radium, radon seed, and external x-ray radiation; certain physical advantages of radiocobalt over radium; availability of radiocobalt beads. Dissatisfaction with other methods of treatment of bladder tumors is not limited to this clinic. A recent review of cases of radical cystectomy from the private hospital affiliated with the University of California showed only 3 possible cures among 23 patients. In one of these the neoplasm was shown to have been removed completely by the preliminary transurethral resection. Radon implantation had been tried and abandoned. External high voltage, and low voltage contact x-ray therapy were disappointing in therapeutic effects, and caused contracted bladder, and occasionally ulceration of the rectum. Radiocobalt has certain physical advantages over radium (fig. 1.): 1) The metal cobalt may be made safely into convenient beads of any size and shape before it is activated. 2) Cobalt can be made radioactive to any desirable strength. 3) The undesired beta radiation has the low energy of 0.3 mev and is easily screened by 0.1 mm. thick silver plating. Radium requires more filtration because of higher energy beta radiation. 4) The gamma radiation, upon which the therapeutic effect depends, is almost monochromatic, with a mean energy of 1.2 mev, while radium gives off more heterogeneous gamma rays, with a mean energy of 0.8 mev. 5) For equal dosage units 1 millicurie of Co 60 approximately equals 1.65 milligram of radium. 6) Radiocobalt (21Co 60 ) decays to the stable element nickel (28 Ni 60 ), whereas radium (ssRa226 ) disintegrates through a whole series of radioactive daughter products into the stable element lead ( 32Pb 208 ). 7) The one disadvantage of radiocobalt is its shorter half-life (5.3 years) as compared to radium (1680 years). Radiocobalt was available as it had been developed and used in a series of na.sopharyngeal tumors by Morrison. 1 An inadequate supply of radium had stimulated him to find a radioactive isotope with metallic physical properties, and adequate half-life. Radioactive cobalt met these requirements. Details of metallurgic preparation of the cobalt beads and their activation in the nuclear pile at Oak Ridge are contained in his paper. Read at annual meeting, Western Section, American Urological Association, Sun Valley, Idaho, June 27, 1951. 1 Morrison, L. F.: Arch. Otolaryng., 53: 153-158, 1951. 916
RADIOCODALT IN BLADDER TUMORS
917
RATIONALE OF TECHNIQUE
rrhe rationale for this method of radiation therapy is based on the dose distribution from a centrally located "point source" of radiation. Two factors are here involved: a) inverse square lmv ,vhich governs the distribution of radiation;
FIG. 1. Advantages of rndiocobalt over radium INVERSE
0 1cm \
SQUARI::
J\
~
LAW
75%1oss
Zcm,~\ 66 % ktSi
\
0 cm ' - !177_77rr _..#' \ ~
Comparative percentage 44 % los~
drop in each cm of di<;:,tance
4om~\
cm"'-~~\ \
S
:JG% loss 30 % !OS'S
6cm~
Fm, 2. Example of application of inverse-square law
b) absorption of radiation ,Yhich determines the dose when a gamma ray emitter radioactive substance is used as a "point source" for intracavitary radiation. 2 Intensity of radiation decreases inversely as the square of the distance. vVhen a radioactive substance is in c:ontact with a tumor three fourths of the intensity at I cm. tumor depth is lost at 2 cm. depth per unit area. If the source is 3 cm. from the tumor surface, the loss at 2 cm. depth is then less than one-third of that at l cm. tumor depth (fig. 2). Consequently, ,vith increased distance 2
Friedman, :vr. and Lewis, L. G.: Radio!., 53: :342---361, 1949.
918
J. W. SCHULTE, F. HINMAN, JR. AND
. V. A. LOW-BEER
between source and tumor, greater relative depth doses can be attained. This facilitates the delivery of high doses to deep seated tissues without producing necrosis of tissue surface. The effective tissue dose is due to absorption of the radiation by the tissues. Since the energy absorption in air closely parallels that in tissues for the high energy cobalt gamma rays, in clinical practice there is very little difference in the dose at a given point in tissue and in a corresponding point in air within a radiation source-tissue distance not exceeding 4 cm. A balloon distended to 50 cc. has a diameter a little over 4 cm. Figure 3 shows the millicurie hours necessary to produce 1000 roentgen 'Y at various cobalt-tissue distances. TECHNIQUE OF APPLICATION
Originally the radioactive cobalt bead (0.3-0.5 mm. in diameter) was placed in the central channel of a Foley or Foley-Alcock type catheter in such a position 28
Milhcurie-Hours necessary to produce. 1000,r;-at various Cobalt-tissue distan<:.es. Cobalt 60 head 3-5.Smm in diameter -.with a filter of .01:rnm Aq.
26
Sc::
24
§ •• ~
20
t
18
~
14
i4cm "~
..
Cobalt-Tissue Millicurie
~3:o ~
f!;
di.stance i.n ceot1meter
e
..
1
6
2
o
hours for 1000 t" I
76.4
2
306
3 4 5
688 1220 1910
200 +oo 600 eoo 1000 1200 .1400 1600 1eoo Co 60 n::iillicurie-hour,9 per 1000 qamma-roer,t'lens
2000
Fm. 3. Graph of dose-distance relationshipss
that when the Foley bag was inflated the bead was in its center. Such a catheter is used to insure uniform distribution of radiation. However, not all catheter bags are symmetrical, so that the symmetry of the bag must be ascertained by inflation prior to use. Subsequently a home-made, then a manufactured* special catheter has been used to hold the bead and still permit the outflow of urine. This eliminated the cystostomy or large three-way catheter. Details, including a spherical 50 cc bag, built-in barrier for use of a stilet, and drainage holes at the base of the balloon, are shown in figure 4. The catheter is cold- or hot-sterilized after insertion of the bead through a distal opening. The balloon is tested for sphericity and leaks. The procedure begins by inserting the catheter through the urethra, with or * By the American Cystoscope Makers, Inc. 3 Low-Beer, B. V. A.: The clinical use of radioactive isotopes, American Lecture Series, No. 54; American Lectures in Radiation Therapy, Springfield, Ill., Charles C Thomas, 1950.
RADIOCOBALT IN BLADDER TUMORS
919
without the use of a stilet. The balloon is filled with 50 cc of a mixture of dilute sodium iodide ( < 1 per cent) to ,vhich 1-2 drops of methylene blue has been
Fm. 4. Modified balloon catheter for radiocobalt administration, to eliminate use of cystostomy.
Ii'rn. 5. AP roentgenogram ,Yith iodide-filled balloon, showing position of bead.
added. AP, lateral, and oblique roentgenograms are made, first, to measure the distance from bead to tumor, and, second, to ascertain symmetry of the bag (fig. 5).
920
J. W. SCHULTE, F. HINMAN, JR. AND B. V. A. LOW-BEER
Dosage is calculated from the measured distance of tumor to bead, taking into account radiographic distortion. Our practice has been to give 6000 gamma roentgens at each insertion to the surface of the bladder, usually at a distance of 2 to 2.5 cm. from the radiocobalt bead. Each exposure lasts about 100 hours. If one application is not sufficient (infiltrating tumor or lack of resolution after initial dose), a second application is given after an interval of from four to six weeks. TABLE AGE
PT.
1 FOLLOW-UP
TYPE OF TUMOR
SEX
REMARKS
Papillomatosis
A.M.
66
I
F
I
Multiple benign?
Improved, small re-1 Severe radiation cyscurrence resected. titis.
Multiple benign
No improvement.
--------
M.O.
70
I F
I No demonstrable effect on tumor. J
Localized tumors
~--_l_:J_:__I 74
G. S.
F
No subsequent recurrence.
Malignant papillomal Recurrence.
I Malignant papillomal Lesions are healed.
Moderate radiation cystitis. Good resuit.
I
II F. V.
I 59 I F
I
Malignant papilloma Recurred.
----
I
H. 0.
69
60
Papillary carcinoma! Healed, no recur"Grade I" I rence.
I M
-I I1
-J.-A-.
Ureteral transplantation.
I
I
M
I
Good result.
Papillary carcinoma I Developed 1 small "Grade I" recurrence.
Some improvement.
INDICATIONS FOR TREATMENT
On theoretical grounds, multiple papillomas ·without infiltration are ideal for treatment by intracavitary radiation, since fulguration and resection are often impractical and cystectomy too radical. We have also used cobalt therapy for single, superficially infiltrating tumors (Jewett's 4 group 2A), as well as on advanced lesions. IMMEDIATE REACTIONS
Reactions of the bladder wall to cobalt radiation appear to be somewhat less severe than with similar doses of radium or externally-administered x-radiation. Doses of 6000 roentgens produce erythema as seen by cystoscopy; the patient usually complains only of some burning and frequency of urination. The second exposure, for a total of 12,000 roentgens, however, gives a more severe reaction 4
Jewett, H.J.: J. Urol., 67: 672, 1952
921
RADIOCOBALT IN BLADDER TUMORS
with edema and intense erythema, which takes about two months to subside, leaving a bladder of smaller capacity. TABLE PT.
I
AGE
I
SEX
I
TYPE OF TUMOR
2 REMARKS
FOLLOW-UP
Infiltrative tumors R. C.
I
78
I F
I Papillary carcinoma Too recent to deter- I Previous deep x-ray "Grade III"
mine result.
_C ___s___ ,__ 75--F--1-T-r-an_s_i-t1-.o-n_a_l_ _ce_l_l_, __ N_o_im_p_ro_v_e_m-en_t___ carcinoma.
therapy elsewhere.
l Dying
of matosis.
carcino-
E.R.
58
F
Transitional carcinoma.
cell
Developed "pyo bladder" 1 month later.
Right ureteral transplantation.
M.H.
64
M
"Anaplastic" cinoma
car-
No Improvement.
Bladder tumor extended in spite of bilateral ureteral transplantation and deep x-ray therapy.
C.M.
56
M
"Ana plastic" cinoma
car-
Recent case. No apparent improvement.
Ureteral transplantation.
F. S.
66
F
"Anaplastic" cinoma
car-
No improvement.
Ureteral transplantation. Died in 2 months of carcinomatosis.
Fm. 6. A. M. (female, aged 66). A, multiple, ? benign papillomas, with two exposures to cobalt, 3 months apart. B, 5 months after initial treatment. Well 2 years later except for small bladder capacity. (Subsequently developed recurrence.) RESULTS OF THERAPY
Papillomatosis and localized tumors responded more often (table 1) than infiltrative tumors (table 2) in which even palliation was not seen. Of the 13 patients followed long enough for evaluation of immediate results, 6 received some benefit, but among these, only one has remained free of recurrence. We can draw no conclusions, however, from such a small series and so short a follow-up.
922
J. W. SCHULTE, F. HINMAN, JR. AND B. V. A. LOW-BEER
Three cases are reviewed in more detail because they are representative of of the group as a whole. 1. Multiple papillomatosis. Mrs. A. M., aged 66, had known recurrent papillomas of the bladder for 15 years. These had been treated elsewhere by electrodesiccation as they recurred. When first cystoscoped here 18 months ago, her bladder mucosa was so studded with minute papillomas that no field could be found that didn't demonstrate 15 or 20. In addition, her bladder presented numerous scared areas where the lesions had been previously fulgurated (fig. 6, A). Accordingly, after study, she was given 6000 roentgens of radiation with radiocobalt. She was followed at bimonthly intervals for the next 3 months. She developed a rather severe radiation reaction characterized by an intensely red and edematous bladder mucous membrane, which, huwever, had largely subsided at the end of two months. At that time, it was noted that she still had a few
Fm. 7. Malignant papilloma. G. S. (female, aged 74). A, grade 1 malignant papillomawith tumors on right and previous resection on left. B, good results 3 months later.
tiny papillomas about the right orifice, and she was given a second 5200 roentgen radiation. The second exposure produced again a rather severe reaction, but within 2 months, no trace of papillomas could be seen (fig. 6, B). She has been cystoscoped at 2 to 3 monthly intervals since. Probably as a result of a combination of radiation and previous fulguration, her bladder capacity is now only 100 cc and the epithelium is very sensitive and bleeds almost at the touch. In addition, 6 months ago she was found to have a small tumor near the right orifice, which on biopsy proved to be a malignant papilloma, and again two months ago, was found to have multiple recurrences. These were destroyed by fulguration since it is doubtful that her bladder could stand further radiation. 2. Localized tumor. Mrs. G. S., aged 74, was first seen almost 2 years ago, at which time she was found to have a single papilloma above and to the left of the left orifice. This was resected and the base fulgurated. The tissue diagnosis ,vas "malignant papilloma." She was observed at regular intervals for one year
RADIOCOBALT IN BLADDER TUMORS
923
without evidence of recurrence. However, after about 14 months she was cystoscoped and found to have a fairly large new papilloma surrounded by myriads of small seedlings on the posterior bladder wall (fig. 7, A). A biopsy again showed malignant papilloma, and she was given a total of 6200 roentgens radiation with radiocobalt at one treatment. After 6 weeks, although she still had a rather severe radiation cystitis, the papillomas had disappeared. At 3 months, her bladder mucosa appeared normal, and no evidence of papillomas could be seen (fig. 7, B). She is still being observed at 3 month intervals, and so far has had no recurrence. 3. Infiltrative tumor. Mr. M. H., aged 64, was found to have anaplastic infiltrating carcinoma (fig. 8, A). He was given radiocobalt therapy, bilateral ureteral transplantation and deep x-ray therapy without significant effect, either curative or palliative (fig. 8, B).
Fm. 8. Infiltrating tumor. M. H. (male, aged 64). A, anaplastic, infiltrating carcinoma treated with radioactive cobalt, bilateral ureteral transplantation, and deep x-ray therapy B, poor final result 4 months later. DISCUSSION
We had hoped that this new modality of radiation therapy would help us in the treatment of the two groups of patients who are least satisfactorily treated by present methods. The first, multiple papillomas, are very hard to treat by resection or fulguration and are not considered sufficiently malignant in potentiality to warrant radical cystectomy and ureteral transplantation with its attendant discomfort and morbidity. The second, infiltrative lesions which are into or through the muscle, are beyond cure by resection or radical operation. The lesions between these extremes are best treated in our hands by thorough transurethral resection or by cystectomy, without radiation therapy. Our experience, while limited, leads us to feel that multiple papillomas may respond to intracavitary radiation, but if not, surgical treatment, including cystectomy if necessary, should be used. Advanced, infiltrative lesions, at the other extreme have received no curative benefit, and it has become increasingly
924
J. W. SCHULTE, F. HINMAN, JR. AND B. V. A. LOW-BEER
doubtful that they obtain even palliative improvement. We shall continue to use radiocobalt therapy in these two types of lesions in an effort to improve the radiation dosage and so gain more experience as to the limitations of this method of radiation therapy. Experience so far indicates that the method will be of some avail in a limited group of lesions only. A combination of intracavitary radiocobalt therapy with external x-ray therapy to the paravesical tissues is under consideration at present. Such a method would have much in common with the well known and effective treatment of cancer of the uterine cervix with radium and x-ray.
RADIOCOBALT IN THE TREATMENT OF BLADDER TUMORS JOHN W. SCHULTE, FRANK HINMAN, JR.
AND
BERTRAM V. A. LOW-BEER
From the Divisions of Urology and Radiology, University of California School of Medicine, San Francisco, Calif.
f
The technique of using radioactive cobalt beads for intracavitary radiation of bladder tumors was first suggested by one of us (BVAL-B) in January 1946. The following reasons argued for a trial of this technique: dissatisfaction with the results of radical surgery and of conventional radium, radon seed, and external x-ray radiation; certain physical advantages of radiocobalt over radium; availability of radiocobalt beads. Dissatisfaction with other methods of treatment of bladder tumors is not limited to this clinic. A recent review of cases of radical cystectomy from the private hospital affiliated with the University of California showed only 3 possible cures among 23 patients. In one of these the neoplasm was shown to have been removed completely by the preliminary transurethral resection. Radon implantation had been tried and abandoned. External high voltage, and low voltage contact x-ray therapy were disappointing in therapeutic effects, and caused contracted bladder, and occasionally ulceration of the rectum. Radiocobalt has certain physical advantages over radium (fig. 1.): 1) The metal cobalt may be made safely into convenient beads of any size and shape before it is activated. 2) Cobalt can be made radioactive to any desirable strength. 3) The undesired beta radiation has the low energy of 0.3 mev and is easily screened by 0.1 mm. thick silver plating. Radium requires more filtration because of higher energy beta radiation. 4) The gamma radiation, upon which the therapeutic effect depends, is almost monochromatic, with a mean energy of 1.2 mev, while radium gives off more heterogeneous gamma rays, with a mean energy of 0.8 mev. 5) For equal dosage units 1 millicurie of Co 60 approximately equals 1.65 milligram of radium. 6) Radiocobalt (21Co 60 ) decays to the stable element nickel (28 Ni 60 ), whereas radium (ssRa226 ) disintegrates through a whole series of radioactive daughter products into the stable element lead ( 32Pb 208 ). 7) The one disadvantage of radiocobalt is its shorter half-life (5.3 years) as compared to radium (1680 years). Radiocobalt was available as it had been developed and used in a series of na.sopharyngeal tumors by Morrison. 1 An inadequate supply of radium had stimulated him to find a radioactive isotope with metallic physical properties, and adequate half-life. Radioactive cobalt met these requirements. Details of metallurgic preparation of the cobalt beads and their activation in the nuclear pile at Oak Ridge are contained in his paper. Read at annual meeting, Western Section, American Urological Association, Sun Valley, Idaho, June 27, 1951. 1 Morrison, L. F.: Arch. Otolaryng., 53: 153-158, 1951. 916
RADIOCODALT IN BLADDER TUMORS
917
RATIONALE OF TECHNIQUE
rrhe rationale for this method of radiation therapy is based on the dose distribution from a centrally located "point source" of radiation. Two factors are here involved: a) inverse square lmv ,vhich governs the distribution of radiation;
FIG. 1. Advantages of rndiocobalt over radium INVERSE
0 1cm \
SQUARI::
J\
~
LAW
75%1oss
Zcm,~\ 66 % ktSi
\
0 cm ' - !177_77rr _..#' \ ~
Comparative percentage 44 % los~
drop in each cm of di<;:,tance
4om~\
cm"'-~~\ \
S
:JG% loss 30 % !OS'S
6cm~
Fm, 2. Example of application of inverse-square law
b) absorption of radiation ,Yhich determines the dose when a gamma ray emitter radioactive substance is used as a "point source" for intracavitary radiation. 2 Intensity of radiation decreases inversely as the square of the distance. vVhen a radioactive substance is in c:ontact with a tumor three fourths of the intensity at I cm. tumor depth is lost at 2 cm. depth per unit area. If the source is 3 cm. from the tumor surface, the loss at 2 cm. depth is then less than one-third of that at l cm. tumor depth (fig. 2). Consequently, ,vith increased distance 2
Friedman, :vr. and Lewis, L. G.: Radio!., 53: :342---361, 1949.
918
J. W. SCHULTE, F. HINMAN, JR. AND
. V. A. LOW-BEER
between source and tumor, greater relative depth doses can be attained. This facilitates the delivery of high doses to deep seated tissues without producing necrosis of tissue surface. The effective tissue dose is due to absorption of the radiation by the tissues. Since the energy absorption in air closely parallels that in tissues for the high energy cobalt gamma rays, in clinical practice there is very little difference in the dose at a given point in tissue and in a corresponding point in air within a radiation source-tissue distance not exceeding 4 cm. A balloon distended to 50 cc. has a diameter a little over 4 cm. Figure 3 shows the millicurie hours necessary to produce 1000 roentgen 'Y at various cobalt-tissue distances. TECHNIQUE OF APPLICATION
Originally the radioactive cobalt bead (0.3-0.5 mm. in diameter) was placed in the central channel of a Foley or Foley-Alcock type catheter in such a position 28
Milhcurie-Hours necessary to produce. 1000,r;-at various Cobalt-tissue distan<:.es. Cobalt 60 head 3-5.Smm in diameter -.with a filter of .01:rnm Aq.
26
Sc::
24
§ •• ~
20
t
18
~
14
i4cm "~
..
Cobalt-Tissue Millicurie
~3:o ~
f!;
di.stance i.n ceot1meter
e
..
1
6
2
o
hours for 1000 t" I
76.4
2
306
3 4 5
688 1220 1910
200 +oo 600 eoo 1000 1200 .1400 1600 1eoo Co 60 n::iillicurie-hour,9 per 1000 qamma-roer,t'lens
2000
Fm. 3. Graph of dose-distance relationshipss
that when the Foley bag was inflated the bead was in its center. Such a catheter is used to insure uniform distribution of radiation. However, not all catheter bags are symmetrical, so that the symmetry of the bag must be ascertained by inflation prior to use. Subsequently a home-made, then a manufactured* special catheter has been used to hold the bead and still permit the outflow of urine. This eliminated the cystostomy or large three-way catheter. Details, including a spherical 50 cc bag, built-in barrier for use of a stilet, and drainage holes at the base of the balloon, are shown in figure 4. The catheter is cold- or hot-sterilized after insertion of the bead through a distal opening. The balloon is tested for sphericity and leaks. The procedure begins by inserting the catheter through the urethra, with or * By the American Cystoscope Makers, Inc. 3 Low-Beer, B. V. A.: The clinical use of radioactive isotopes, American Lecture Series, No. 54; American Lectures in Radiation Therapy, Springfield, Ill., Charles C Thomas, 1950.
RADIOCOBALT IN BLADDER TUMORS
919
without the use of a stilet. The balloon is filled with 50 cc of a mixture of dilute sodium iodide ( < 1 per cent) to ,vhich 1-2 drops of methylene blue has been
Fm. 4. Modified balloon catheter for radiocobalt administration, to eliminate use of cystostomy.
Ii'rn. 5. AP roentgenogram ,Yith iodide-filled balloon, showing position of bead.
added. AP, lateral, and oblique roentgenograms are made, first, to measure the distance from bead to tumor, and, second, to ascertain symmetry of the bag (fig. 5).
920
J. W. SCHULTE, F. HINMAN, JR. AND B. V. A. LOW-BEER
Dosage is calculated from the measured distance of tumor to bead, taking into account radiographic distortion. Our practice has been to give 6000 gamma roentgens at each insertion to the surface of the bladder, usually at a distance of 2 to 2.5 cm. from the radiocobalt bead. Each exposure lasts about 100 hours. If one application is not sufficient (infiltrating tumor or lack of resolution after initial dose), a second application is given after an interval of from four to six weeks. TABLE AGE
PT.
1 FOLLOW-UP
TYPE OF TUMOR
SEX
REMARKS
Papillomatosis
A.M.
66
I
F
I
Multiple benign?
Improved, small re-1 Severe radiation cyscurrence resected. titis.
Multiple benign
No improvement.
--------
M.O.
70
I F
I No demonstrable effect on tumor. J
Localized tumors
~--_l_:J_:__I 74
G. S.
F
No subsequent recurrence.
Malignant papillomal Recurrence.
I Malignant papillomal Lesions are healed.
Moderate radiation cystitis. Good resuit.
I
II F. V.
I 59 I F
I
Malignant papilloma Recurred.
----
I
H. 0.
69
60
Papillary carcinoma! Healed, no recur"Grade I" I rence.
I M
-I I1
-J.-A-.
Ureteral transplantation.
I
I
M
I
Good result.
Papillary carcinoma I Developed 1 small "Grade I" recurrence.
Some improvement.
INDICATIONS FOR TREATMENT
On theoretical grounds, multiple papillomas ·without infiltration are ideal for treatment by intracavitary radiation, since fulguration and resection are often impractical and cystectomy too radical. We have also used cobalt therapy for single, superficially infiltrating tumors (Jewett's 4 group 2A), as well as on advanced lesions. IMMEDIATE REACTIONS
Reactions of the bladder wall to cobalt radiation appear to be somewhat less severe than with similar doses of radium or externally-administered x-radiation. Doses of 6000 roentgens produce erythema as seen by cystoscopy; the patient usually complains only of some burning and frequency of urination. The second exposure, for a total of 12,000 roentgens, however, gives a more severe reaction 4
Jewett, H.J.: J. Urol., 67: 672, 1952
921
RADIOCOBALT IN BLADDER TUMORS
with edema and intense erythema, which takes about two months to subside, leaving a bladder of smaller capacity. TABLE PT.
I
AGE
I
SEX
I
TYPE OF TUMOR
2 REMARKS
FOLLOW-UP
Infiltrative tumors R. C.
I
78
I F
I Papillary carcinoma Too recent to deter- I Previous deep x-ray "Grade III"
mine result.
_C ___s___ ,__ 75--F--1-T-r-an_s_i-t1-.o-n_a_l_ _ce_l_l_, __ N_o_im_p_ro_v_e_m-en_t___ carcinoma.
therapy elsewhere.
l Dying
of matosis.
carcino-
E.R.
58
F
Transitional carcinoma.
cell
Developed "pyo bladder" 1 month later.
Right ureteral transplantation.
M.H.
64
M
"Anaplastic" cinoma
car-
No Improvement.
Bladder tumor extended in spite of bilateral ureteral transplantation and deep x-ray therapy.
C.M.
56
M
"Ana plastic" cinoma
car-
Recent case. No apparent improvement.
Ureteral transplantation.
F. S.
66
F
"Anaplastic" cinoma
car-
No improvement.
Ureteral transplantation. Died in 2 months of carcinomatosis.
Fm. 6. A. M. (female, aged 66). A, multiple, ? benign papillomas, with two exposures to cobalt, 3 months apart. B, 5 months after initial treatment. Well 2 years later except for small bladder capacity. (Subsequently developed recurrence.) RESULTS OF THERAPY
Papillomatosis and localized tumors responded more often (table 1) than infiltrative tumors (table 2) in which even palliation was not seen. Of the 13 patients followed long enough for evaluation of immediate results, 6 received some benefit, but among these, only one has remained free of recurrence. We can draw no conclusions, however, from such a small series and so short a follow-up.
922
J. W. SCHULTE, F. HINMAN, JR. AND B. V. A. LOW-BEER
Three cases are reviewed in more detail because they are representative of of the group as a whole. 1. Multiple papillomatosis. Mrs. A. M., aged 66, had known recurrent papillomas of the bladder for 15 years. These had been treated elsewhere by electrodesiccation as they recurred. When first cystoscoped here 18 months ago, her bladder mucosa was so studded with minute papillomas that no field could be found that didn't demonstrate 15 or 20. In addition, her bladder presented numerous scared areas where the lesions had been previously fulgurated (fig. 6, A). Accordingly, after study, she was given 6000 roentgens of radiation with radiocobalt. She was followed at bimonthly intervals for the next 3 months. She developed a rather severe radiation reaction characterized by an intensely red and edematous bladder mucous membrane, which, huwever, had largely subsided at the end of two months. At that time, it was noted that she still had a few
Fm. 7. Malignant papilloma. G. S. (female, aged 74). A, grade 1 malignant papillomawith tumors on right and previous resection on left. B, good results 3 months later.
tiny papillomas about the right orifice, and she was given a second 5200 roentgen radiation. The second exposure produced again a rather severe reaction, but within 2 months, no trace of papillomas could be seen (fig. 6, B). She has been cystoscoped at 2 to 3 monthly intervals since. Probably as a result of a combination of radiation and previous fulguration, her bladder capacity is now only 100 cc and the epithelium is very sensitive and bleeds almost at the touch. In addition, 6 months ago she was found to have a small tumor near the right orifice, which on biopsy proved to be a malignant papilloma, and again two months ago, was found to have multiple recurrences. These were destroyed by fulguration since it is doubtful that her bladder could stand further radiation. 2. Localized tumor. Mrs. G. S., aged 74, was first seen almost 2 years ago, at which time she was found to have a single papilloma above and to the left of the left orifice. This was resected and the base fulgurated. The tissue diagnosis ,vas "malignant papilloma." She was observed at regular intervals for one year
RADIOCOBALT IN BLADDER TUMORS
923
without evidence of recurrence. However, after about 14 months she was cystoscoped and found to have a fairly large new papilloma surrounded by myriads of small seedlings on the posterior bladder wall (fig. 7, A). A biopsy again showed malignant papilloma, and she was given a total of 6200 roentgens radiation with radiocobalt at one treatment. After 6 weeks, although she still had a rather severe radiation cystitis, the papillomas had disappeared. At 3 months, her bladder mucosa appeared normal, and no evidence of papillomas could be seen (fig. 7, B). She is still being observed at 3 month intervals, and so far has had no recurrence. 3. Infiltrative tumor. Mr. M. H., aged 64, was found to have anaplastic infiltrating carcinoma (fig. 8, A). He was given radiocobalt therapy, bilateral ureteral transplantation and deep x-ray therapy without significant effect, either curative or palliative (fig. 8, B).
Fm. 8. Infiltrating tumor. M. H. (male, aged 64). A, anaplastic, infiltrating carcinoma treated with radioactive cobalt, bilateral ureteral transplantation, and deep x-ray therapy B, poor final result 4 months later. DISCUSSION
We had hoped that this new modality of radiation therapy would help us in the treatment of the two groups of patients who are least satisfactorily treated by present methods. The first, multiple papillomas, are very hard to treat by resection or fulguration and are not considered sufficiently malignant in potentiality to warrant radical cystectomy and ureteral transplantation with its attendant discomfort and morbidity. The second, infiltrative lesions which are into or through the muscle, are beyond cure by resection or radical operation. The lesions between these extremes are best treated in our hands by thorough transurethral resection or by cystectomy, without radiation therapy. Our experience, while limited, leads us to feel that multiple papillomas may respond to intracavitary radiation, but if not, surgical treatment, including cystectomy if necessary, should be used. Advanced, infiltrative lesions, at the other extreme have received no curative benefit, and it has become increasingly
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J. W. SCHULTE, F. HINMAN, JR. AND B. V. A. LOW-BEER
doubtful that they obtain even palliative improvement. We shall continue to use radiocobalt therapy in these two types of lesions in an effort to improve the radiation dosage and so gain more experience as to the limitations of this method of radiation therapy. Experience so far indicates that the method will be of some avail in a limited group of lesions only. A combination of intracavitary radiocobalt therapy with external x-ray therapy to the paravesical tissues is under consideration at present. Such a method would have much in common with the well known and effective treatment of cancer of the uterine cervix with radium and x-ray.