UROCHEMOTHERAPY
INTRAVESICAL BACILLUS CALMETTE-GUERIN FOIl PATIENTS WITH HIGH-RISK SUPERFICIAL BLADDER CANCER IRA W. KLIMBERG, M.D. JULIO M. POW-SANG, M.D. CHARLES K. CARTWRIGHT, M.D. ZEV WAJSMAN, M.D. From the Division of Urology, Department of Surgery, University of Florida, and the Division of Urology, Department of Surgery, Veterans Administration Medical Center, Gainesville, Florida
ABSTRACT--Intravesical bacillus Calmette-Gudrin (BCG) was employed in t~ patients with aggressive superficial transitional cell carcinoma of the bladder (c' of the patients had a previous history of recurrent superficial disease, and 41 (75 ~, failures following other intravesical therapy. Thirty-six (66 %) patients responded 19 (34 %) were treatment failures. Twenty-seven (66 %) of 41 patients with c Ta(64 %) of 14 patients with cTis responded, with a mean follow-up period of 30. progression was noted in 8 (15 %) of the patients and muscle invasive disease in history of three or more previous events of tumor recurrence, positive urinary cy centric disease, all fared worse than patients without these characteristics (p < effective agent in controlling superficial transitional cell carcinoma of the bladd risk group of patients who failed previous intravesical therapy. BCG should be group of patients prior to radical surgery.
In 1976 Morales and associates 1 first reported on the use of baeillus Calmette-Gu6rin (BCG) immunotherapy in the treatment of patients with superfieial bladder eaneer. Since that time there have been numerous other reports confirming the effeetiveness of intravesieal BCG, either alone or in eonjunetion with pereutanous administration .2-4 Current data suggest that BCG is the most effective agent available for the treatment of superficial (eTa, eT1, and eTis) carcinoma of the bladder. Prospeetive controlled trials comparing BCG to other intravesieal agents have demonstrated a statistieally signifieant advantage for patients treated with BCG. 5,~
180
Herein we report the resc BCG immunotherapy, in a patients, all of whom exhibi perfieial transitional eell care: der. The results of the treatm, sis of the patterns of failure Material and Me From February 1984 to F patients, all with a previous h superficial transitional c e l l bladder, were enrolled in om col employing intravesieal BCG. There were 46 male
UROLOGY
/
FEBRUARY 1991
/
VOLUI~
patientS ranged in age from forty-two to eightyi,ti~eeyears (mean 63). ':T~e aggressive n a t u r e of the neoplastie iiiathesis was evideneed by the fact that all of i~e ~atients demonstrated reeurrent superfieial " '-'adder prior to aecrual. The recurrences for the group ;h 16 patients (30%) had isodes of tumor reeurrenee. L1from initial bladder eanLo the protocol was three :ients (75 % ) had previously intravesieal chemotherapy ad had suffered subsequent 33 (60 % ) had received one thiotepa, and 26 patients l mitomyein. Eighteen paarolled into the protocol afeeurrent tumor after treat)tepa and mitomycin. nstrated histologie evidence careinoma of the bladder. thorough urologic evaluathe protoeol including exserum ehemistries, liver lplete blood count, urine :e, and ehest roentgenogunderwent eystoscopic extl examination under anesreseetion, selected mueosal tier, and in particular the adder barbotage speeimens ;ie examination. Intermedi~d protein derivative was patients. :e-Gu6rin, either Pasteur Tiee strain (60 mg), was normal saline and instilled lowing a twelve-hour fast. eted to retain the fluid for ~ts were administered once ~nseeutive doses. Monthly tinued thereafter for a total one year. ,py evaluation including }~'[g~Py, bladder biopsy, barbotage cytology, ~q~e~liernatologie testing, and skin testing was ~,~:~ .~, one month following completion of i')v~Neekly installations Subsequent evaluai::!9~!~;~ere conducted every three months. onsidered to be treatment discovered to have either a examination, histologie evimey, or positive cytologic idenee for malignancy was
;d
LIlY 1991
/
discovered at the time of initial post-therapy evaluation, the patient was classified as having persistent disease. If tumor was demonstrable at a later date, after an initial normal evaluation, the patient was classified as having recurrent disease. Tumor progression was defined as histologically confirmed invasive bladder cancer. For patients with eTa or eTis lesions, this included invasion into either the lamina propria or underlying muscle. Patients who had eT1 tumors at the time of enrollment were not considered to have progression unless muscle invasive bladder cancer was demonstrable. Tumor stage at entry was eTa in 26 patients, eT1 in 15 patients, eTis in 14 patients. Tumor grade was as follows: 14 patients (25%) had grade I tumors, and 41 patients (75%) had grade II or grade III tumors. All patients have been observed for a minim u m period of two years. Postinduetion followup ranged from twenty-four to forty-eight months (mean 30.5 months) and was terminated at the time of treatment failure. Results Of the total of 55 patients, 36 (66%) responded to treatment and 19 (34 %) were treatment failures. Ten patients had persistent disease at the time of initial evaluation, and of these, disease progression developed in 5. There were 9 patients who were disease-free at the time of their first evaluation who later demonstrated recurrent tumor. Of this group three eventually exhibited progression. Disease progression was manifested by 8 0 5 %) patients. There were no significant differences in the response rate by tumor stage at the time of accession. For patients with eTa disease 18 (69 %) responded to treatment, for cT1 lesions 9 (60 % ) responded, and for cTis 9 (64 %) patients responded to treatment. Progression rates were also similar for all three groups, although lowest for patients with eTa tumors ( l l % ) . The progression rate for patients with cT1 disease was 20 percent, and 14 percent for patients with eTis. None of the 14 patients with grade I tumors had disease progression regardless of their tumor stage. Patients who suffered three or more previous events of tumor reet~rrenee prior to BCG treatment did not fare as well as those patients who had two or less previous recurrences. There were 26 patients with three or more previous recurrences. Of this group 11 (42 % ) were treatment responders, however, 9 patients had either
VOLUME XXXVII, NUMBER 2
181
recurrent or persistent disease, and 6 patients had disease ]progression. In contrast, the response rate for patients with two or less previous recurrences was 86 percent, and only 2 of 29 patients had disease progression (p < 0.005). The presenee of multieentrie disease also correlated with a poorer response rate to therapy. Twenty-seven patients demonstrated multieentrieity and 27 did not. The response rate for the patients with multieentrie disease was 48 percent as compared with 81 pereent for patients without multicentrieity (p < 0.025). In addition 7 of the 8 patients in whom progressive disease developed had multieentric disease. The presence or absenee of positive urinary eytology at the time of accession also eorrelated with treatment outcome. Of the 31 patients with positive cytology at the time of entry, 16 (52 %) responded to treament and in 7 progressive disease developed. Among the 21 patients who had negative urinary cytology at the time of enrollment, 18 (86%) responded to treatment and only 1 patient suffered tumor progression (p < 0.05). Patients who had failed previous treatment with various intravesieal chemotherapeutic agents did not fare as well as patients who reeeived BCG as initial treatment, although in this study, this approaehed but did not reach statistical significance (p < 0.06). Twelve (86 %) of the 14 patients who reeeived BCG as initial treatment responded. Of the 41 patients who were previously treated with other intravesieal chemotherapeutic agents and failed, 24 (59 % ) responded. There was no appreciable difference in the response rates following failure with thiotepa, mitomyein, or both. There was no correlation of response rates or rates of progression when patients were stratified by tumor size. Tumor grade did not eorrelate with response rates, however no patient with grade I tumor exhibited progression of disease. Patients who demonstrated eonversion of their skin tests to purified protein derivative (PPD) from negative to positive following a course of BCG treatment had higher response rates than noneonverters. Of 24 patients whose PPD response converted, 21 (88 %) had no tumor following treatment. There were 17 patients who remained PPD-negative following treatment, and among this group only 6 (35 % ) responded to treatment. The response rate for the 12 patients who were PPD-positive prior to treatment was 58 pereent. 182
Response to therapy at the time of first eys~ toscopy was seen in 45 (82 % ) of the 55 p a t i e n ~ Of the 10 patients who had tumor persistend~ following treatment, 9 had been tre~ previous intravesieal therapy, 9 had more previous events of tumor reeurr, 8 had positive urinary cytology and a trie tumor diathesis. The treatment protoeol was well to] the majority of the patients. Nine (16 % ) demonstrated toxicity from the In 4 patients (7 %), side effects were that they necessitated eessation of Severe hematuria was the cause of tel of treatment in 3 patients. An addil tient had persistently elevated fevers, liver funetion tests, and required t with isoniazid. Five additional patieni nifieant local irritative symptoms toll stillation that resulted in them missin~ ing treatment. Of the 55 patients enrolled, 19 (3~ treatment failures, 8 0 5 % ) had tumo sion, and 11 had either reeu ent (5) disease without prog: patients who demonstrated had musele invasion, and 2 t propria invasion and earei~ patients had tumor persistei at the time of first eystoseopJ patients had tumor progressJ a mean observation period o: ing induetion therapy. Fi~ group underwent radical eystoprostateeto~ and 3 who were poor surgical eandidates W ~ treated with external beam irradiation an d ;I t~mi~rant eispl2tin. There were two d e a t ~ • g up, on from metastatic bladder e a i i ~ and one from intereurrent disease• Eleven patients had either reeurrer sistent disease without progression: treated with radieal eystoprostateetom fuse eareinoma in situ, 4 were treated ditional intravesieal therapy, and managed by transurethral resection fulguration. All 11 of these patient', alive. Comment Intravesieal BCG has been studied e~ sively since Morales and assoeiates 1 first ported on its effieaey in the treatment of su~i ' fielal transitional cell earcinoma of the blad~ ~ Several reports testify to the e f f e c t i v e l a ~
UROLOGY
/
FEBRUARY 199I
/
VOLUME XXXVII, N I J M ~
,
_Lu a. . . . . ,?hylaxis and treatment of t eTis carcinoma of the erall combined response :ve approximated 67 pereTa and eT1 tumors, and ~ith eTis lesions. Prospeeaomparing BCG to other ce demonstrated a signifiLose patients treated with 7, 27 (66 % ) of 41 patients md 9 (64 % ) of 14 patients to BCG immunotherapy Lp period of 30.5 months. d response rate in patients th BCG as the initial inas compared with patients t with other intravesical rots (59 %) before receivm e t approached, but did 1 significance in this small :ory of three or more premr recurrence, positive he time of accession, and all fared worse than the hour these characteristics. ;st reactivity to PPD also ood of experiencing susCG immunotherapy. verall response rates were ize or grade of the initial thy that no patient with ~rogressive disease during ty. ~atients were t r e a t m e n t istent or recurrent tumor ression, and 8 (15%) had ;ix patients demonstrated er, and 1 patient had sysand died. Radical cysto~rformed in 9 patients. st be kept in mind when tment results. This group highly selected group of [ve superficial transitional median number of preevents was three, and 30 !s had more than five pretdition, three quarters of .atment failures following ents, and 33 percent had thiotepa and mitomycin. tpy should be employed in arrent superficial bladder
Y 1991
/
cancer prior to radical surgical treatment. Our experience and that of other investigators indicate that approximately 60 percent of patients who were treatment failures following other forms of intravesical treatment will respond to BCG treatment. The use of BCG as a secondline salvage therapy in this group may allow many of these patients to preserve their bladders. The treatment regimen used in this study used a single induction course of six weekly instillations followed by monthly maintenance for one year. Haaff and associates 9 have recently reported that retreatment with a second induction course of BCG is warranted for patients failing the initial treatment course. In their report 68 percent of initial BCG failures were observed to respond to a second course of treatment. Badalament and associates 1° have d e a r l y demonstrated in a prospective randomized trial that there was no additional benefit bestowed on patients who were treated with monthly maintenance therapy following their six-week induction course of BCG. Maintenanee bacillus Calmette-Gu6rin was associated with increased local toxicity and dosage reduction was required in nearly half of the patients so treated. We are 15resently p e r f o r m i n g i n d u c t i o n therapy with six weekly instillations of intravesieal BCG. These patients are then observed closely w i t h eystoseopy, selected mueosal biopsy, and barbotage urinary cytology. For patients with persistent or recurrent disease at the time of initial eystoseopy we repeat a second course of induction. In addition patients whose PPD skin test does not convert from negative to positive following induction are candidates for reinduetion. These nonconverters are at high risk for treatment failure and require diligent and thorough observation. Maintenance B e G therapy is no longer employed at our institution. Failures following the second course of intravesieal BCC are considered for definitive therapy. Although effective intravesieal therapy has been shown to reduce the rate of tumor recurrence and disease progression, there is no evidence that it changes the aggressive biologic potential of tumors in patients who fail to respond. Patients who are treatment failures following two courses of intravesieal BCO remain at high risk of invasive or disseminated disease developing, and the employment of definitive therapy should not be postponed.
VOLUME XXXVII, NUMBER 2
183
University of Florida Box J-247, JHM Health Center Department of Surgery Division of Urology Gainesville, Florida 32610-0247 (DR. KLIMBERG)
References 1. Morales A, Eidinger D, and Bruce AW: Intracavitary bacillus Calmette-Gu6rin in the treatment of superficial bladder tumors, J Urol 116:180 (1976). 2. Lamm DL, et ah Bacillus Calmette-Gu6rin immunotherapy of superficial bladder cancer, J Urol 124:38 (1980). 3. DeKernion JB, et ah The management of superficial bladder tumors and carcinoma in situ with intravesical bacillus Calmette-Gu6rin, J Urol 133:598 (1985).
184
4. Lamm DL: Bacillus Calmette-Gu bladder cancer, J Urol 134:40 (1985). 5. Brosman SA: Experience with ba( patients with superficial bladder car( (1982). 6. Netto NR Jr, and Lemos GC: A methods for the prophylaxis of recurrel mors, J Urol 129:33 (1983). 7. Brosman SA: The use of bacillus therapy of bladder carcinoma in situ, J 8. Herr HW, et ah Long term effel Calmette-Gu6rin on flat carcinoma in 135:265 (1986). 9. Haaff EO, Dresner SM, Ratliff T] courses of intravesical bacillus Calmer cell carcinoma of the bladder, J Urol 1 10. Badalament RA, et aI: A prosp~ maintenance versus non-maintenan Calmette-Gu6rin therapy of supcrfici~ Oncol 5:441 (1987).
UROLOGY
/
FEBRUARY 1991
/
VOLUME XXXVII, N U ~
INTRAVESICAL BACILLUS CALMETTE-GUERIN FOIl PATIENTS WITH HIGH-RISK SUPERFICIAL BLADDER CANCER IRA W. KLIMBERG, M.D. JULIO M. POW-SANG, M.D. CHARLES K. CARTWRIGHT, M.D. ZEV WAJSMAN, M.D. From the Division of Urology, Department of Surgery, University of Florida, and the Division of Urology, Department of Surgery, Veterans Administration Medical Center, Gainesville, Florida
ABSTRACT--Intravesical bacillus Calmette-Gudrin (BCG) was employed in t~ patients with aggressive superficial transitional cell carcinoma of the bladder (c' of the patients had a previous history of recurrent superficial disease, and 41 (75 ~, failures following other intravesical therapy. Thirty-six (66 %) patients responded 19 (34 %) were treatment failures. Twenty-seven (66 %) of 41 patients with c Ta(64 %) of 14 patients with cTis responded, with a mean follow-up period of 30. progression was noted in 8 (15 %) of the patients and muscle invasive disease in history of three or more previous events of tumor recurrence, positive urinary cy centric disease, all fared worse than patients without these characteristics (p < effective agent in controlling superficial transitional cell carcinoma of the bladd risk group of patients who failed previous intravesical therapy. BCG should be group of patients prior to radical surgery.
In 1976 Morales and associates 1 first reported on the use of baeillus Calmette-Gu6rin (BCG) immunotherapy in the treatment of patients with superfieial bladder eaneer. Since that time there have been numerous other reports confirming the effeetiveness of intravesieal BCG, either alone or in eonjunetion with pereutanous administration .2-4 Current data suggest that BCG is the most effective agent available for the treatment of superficial (eTa, eT1, and eTis) carcinoma of the bladder. Prospeetive controlled trials comparing BCG to other intravesieal agents have demonstrated a statistieally signifieant advantage for patients treated with BCG. 5,~
180
Herein we report the resc BCG immunotherapy, in a patients, all of whom exhibi perfieial transitional eell care: der. The results of the treatm, sis of the patterns of failure Material and Me From February 1984 to F patients, all with a previous h superficial transitional c e l l bladder, were enrolled in om col employing intravesieal BCG. There were 46 male
UROLOGY
/
FEBRUARY 1991
/
VOLUI~
patientS ranged in age from forty-two to eightyi,ti~eeyears (mean 63). ':T~e aggressive n a t u r e of the neoplastie iiiathesis was evideneed by the fact that all of i~e ~atients demonstrated reeurrent superfieial " '-'adder prior to aecrual. The recurrences for the group ;h 16 patients (30%) had isodes of tumor reeurrenee. L1from initial bladder eanLo the protocol was three :ients (75 % ) had previously intravesieal chemotherapy ad had suffered subsequent 33 (60 % ) had received one thiotepa, and 26 patients l mitomyein. Eighteen paarolled into the protocol afeeurrent tumor after treat)tepa and mitomycin. nstrated histologie evidence careinoma of the bladder. thorough urologic evaluathe protoeol including exserum ehemistries, liver lplete blood count, urine :e, and ehest roentgenogunderwent eystoscopic extl examination under anesreseetion, selected mueosal tier, and in particular the adder barbotage speeimens ;ie examination. Intermedi~d protein derivative was patients. :e-Gu6rin, either Pasteur Tiee strain (60 mg), was normal saline and instilled lowing a twelve-hour fast. eted to retain the fluid for ~ts were administered once ~nseeutive doses. Monthly tinued thereafter for a total one year. ,py evaluation including }~'[g~Py, bladder biopsy, barbotage cytology, ~q~e~liernatologie testing, and skin testing was ~,~:~ .~, one month following completion of i')v~Neekly installations Subsequent evaluai::!9~!~;~ere conducted every three months. onsidered to be treatment discovered to have either a examination, histologie evimey, or positive cytologic idenee for malignancy was
;d
LIlY 1991
/
discovered at the time of initial post-therapy evaluation, the patient was classified as having persistent disease. If tumor was demonstrable at a later date, after an initial normal evaluation, the patient was classified as having recurrent disease. Tumor progression was defined as histologically confirmed invasive bladder cancer. For patients with eTa or eTis lesions, this included invasion into either the lamina propria or underlying muscle. Patients who had eT1 tumors at the time of enrollment were not considered to have progression unless muscle invasive bladder cancer was demonstrable. Tumor stage at entry was eTa in 26 patients, eT1 in 15 patients, eTis in 14 patients. Tumor grade was as follows: 14 patients (25%) had grade I tumors, and 41 patients (75%) had grade II or grade III tumors. All patients have been observed for a minim u m period of two years. Postinduetion followup ranged from twenty-four to forty-eight months (mean 30.5 months) and was terminated at the time of treatment failure. Results Of the total of 55 patients, 36 (66%) responded to treatment and 19 (34 %) were treatment failures. Ten patients had persistent disease at the time of initial evaluation, and of these, disease progression developed in 5. There were 9 patients who were disease-free at the time of their first evaluation who later demonstrated recurrent tumor. Of this group three eventually exhibited progression. Disease progression was manifested by 8 0 5 %) patients. There were no significant differences in the response rate by tumor stage at the time of accession. For patients with eTa disease 18 (69 %) responded to treatment, for cT1 lesions 9 (60 % ) responded, and for cTis 9 (64 %) patients responded to treatment. Progression rates were also similar for all three groups, although lowest for patients with eTa tumors ( l l % ) . The progression rate for patients with cT1 disease was 20 percent, and 14 percent for patients with eTis. None of the 14 patients with grade I tumors had disease progression regardless of their tumor stage. Patients who suffered three or more previous events of tumor reet~rrenee prior to BCG treatment did not fare as well as those patients who had two or less previous recurrences. There were 26 patients with three or more previous recurrences. Of this group 11 (42 % ) were treatment responders, however, 9 patients had either
VOLUME XXXVII, NUMBER 2
181
recurrent or persistent disease, and 6 patients had disease ]progression. In contrast, the response rate for patients with two or less previous recurrences was 86 percent, and only 2 of 29 patients had disease progression (p < 0.005). The presenee of multieentrie disease also correlated with a poorer response rate to therapy. Twenty-seven patients demonstrated multieentrieity and 27 did not. The response rate for the patients with multieentrie disease was 48 percent as compared with 81 pereent for patients without multicentrieity (p < 0.025). In addition 7 of the 8 patients in whom progressive disease developed had multieentric disease. The presence or absenee of positive urinary eytology at the time of accession also eorrelated with treatment outcome. Of the 31 patients with positive cytology at the time of entry, 16 (52 %) responded to treament and in 7 progressive disease developed. Among the 21 patients who had negative urinary cytology at the time of enrollment, 18 (86%) responded to treatment and only 1 patient suffered tumor progression (p < 0.05). Patients who had failed previous treatment with various intravesieal chemotherapeutic agents did not fare as well as patients who reeeived BCG as initial treatment, although in this study, this approaehed but did not reach statistical significance (p < 0.06). Twelve (86 %) of the 14 patients who reeeived BCG as initial treatment responded. Of the 41 patients who were previously treated with other intravesieal chemotherapeutic agents and failed, 24 (59 % ) responded. There was no appreciable difference in the response rates following failure with thiotepa, mitomyein, or both. There was no correlation of response rates or rates of progression when patients were stratified by tumor size. Tumor grade did not eorrelate with response rates, however no patient with grade I tumor exhibited progression of disease. Patients who demonstrated eonversion of their skin tests to purified protein derivative (PPD) from negative to positive following a course of BCG treatment had higher response rates than noneonverters. Of 24 patients whose PPD response converted, 21 (88 %) had no tumor following treatment. There were 17 patients who remained PPD-negative following treatment, and among this group only 6 (35 % ) responded to treatment. The response rate for the 12 patients who were PPD-positive prior to treatment was 58 pereent. 182
Response to therapy at the time of first eys~ toscopy was seen in 45 (82 % ) of the 55 p a t i e n ~ Of the 10 patients who had tumor persistend~ following treatment, 9 had been tre~ previous intravesieal therapy, 9 had more previous events of tumor reeurr, 8 had positive urinary cytology and a trie tumor diathesis. The treatment protoeol was well to] the majority of the patients. Nine (16 % ) demonstrated toxicity from the In 4 patients (7 %), side effects were that they necessitated eessation of Severe hematuria was the cause of tel of treatment in 3 patients. An addil tient had persistently elevated fevers, liver funetion tests, and required t with isoniazid. Five additional patieni nifieant local irritative symptoms toll stillation that resulted in them missin~ ing treatment. Of the 55 patients enrolled, 19 (3~ treatment failures, 8 0 5 % ) had tumo sion, and 11 had either reeu ent (5) disease without prog: patients who demonstrated had musele invasion, and 2 t propria invasion and earei~ patients had tumor persistei at the time of first eystoseopJ patients had tumor progressJ a mean observation period o: ing induetion therapy. Fi~ group underwent radical eystoprostateeto~ and 3 who were poor surgical eandidates W ~ treated with external beam irradiation an d ;I t~mi~rant eispl2tin. There were two d e a t ~ • g up, on from metastatic bladder e a i i ~ and one from intereurrent disease• Eleven patients had either reeurrer sistent disease without progression: treated with radieal eystoprostateetom fuse eareinoma in situ, 4 were treated ditional intravesieal therapy, and managed by transurethral resection fulguration. All 11 of these patient', alive. Comment Intravesieal BCG has been studied e~ sively since Morales and assoeiates 1 first ported on its effieaey in the treatment of su~i ' fielal transitional cell earcinoma of the blad~ ~ Several reports testify to the e f f e c t i v e l a ~
UROLOGY
/
FEBRUARY 199I
/
VOLUME XXXVII, N I J M ~
,
_Lu a. . . . . ,?hylaxis and treatment of t eTis carcinoma of the erall combined response :ve approximated 67 pereTa and eT1 tumors, and ~ith eTis lesions. Prospeeaomparing BCG to other ce demonstrated a signifiLose patients treated with 7, 27 (66 % ) of 41 patients md 9 (64 % ) of 14 patients to BCG immunotherapy Lp period of 30.5 months. d response rate in patients th BCG as the initial inas compared with patients t with other intravesical rots (59 %) before receivm e t approached, but did 1 significance in this small :ory of three or more premr recurrence, positive he time of accession, and all fared worse than the hour these characteristics. ;st reactivity to PPD also ood of experiencing susCG immunotherapy. verall response rates were ize or grade of the initial thy that no patient with ~rogressive disease during ty. ~atients were t r e a t m e n t istent or recurrent tumor ression, and 8 (15%) had ;ix patients demonstrated er, and 1 patient had sysand died. Radical cysto~rformed in 9 patients. st be kept in mind when tment results. This group highly selected group of [ve superficial transitional median number of preevents was three, and 30 !s had more than five pretdition, three quarters of .atment failures following ents, and 33 percent had thiotepa and mitomycin. tpy should be employed in arrent superficial bladder
Y 1991
/
cancer prior to radical surgical treatment. Our experience and that of other investigators indicate that approximately 60 percent of patients who were treatment failures following other forms of intravesical treatment will respond to BCG treatment. The use of BCG as a secondline salvage therapy in this group may allow many of these patients to preserve their bladders. The treatment regimen used in this study used a single induction course of six weekly instillations followed by monthly maintenance for one year. Haaff and associates 9 have recently reported that retreatment with a second induction course of BCG is warranted for patients failing the initial treatment course. In their report 68 percent of initial BCG failures were observed to respond to a second course of treatment. Badalament and associates 1° have d e a r l y demonstrated in a prospective randomized trial that there was no additional benefit bestowed on patients who were treated with monthly maintenance therapy following their six-week induction course of BCG. Maintenanee bacillus Calmette-Gu6rin was associated with increased local toxicity and dosage reduction was required in nearly half of the patients so treated. We are 15resently p e r f o r m i n g i n d u c t i o n therapy with six weekly instillations of intravesieal BCG. These patients are then observed closely w i t h eystoseopy, selected mueosal biopsy, and barbotage urinary cytology. For patients with persistent or recurrent disease at the time of initial eystoseopy we repeat a second course of induction. In addition patients whose PPD skin test does not convert from negative to positive following induction are candidates for reinduetion. These nonconverters are at high risk for treatment failure and require diligent and thorough observation. Maintenance B e G therapy is no longer employed at our institution. Failures following the second course of intravesieal BCC are considered for definitive therapy. Although effective intravesieal therapy has been shown to reduce the rate of tumor recurrence and disease progression, there is no evidence that it changes the aggressive biologic potential of tumors in patients who fail to respond. Patients who are treatment failures following two courses of intravesieal BCO remain at high risk of invasive or disseminated disease developing, and the employment of definitive therapy should not be postponed.
VOLUME XXXVII, NUMBER 2
183
University of Florida Box J-247, JHM Health Center Department of Surgery Division of Urology Gainesville, Florida 32610-0247 (DR. KLIMBERG)
References 1. Morales A, Eidinger D, and Bruce AW: Intracavitary bacillus Calmette-Gu6rin in the treatment of superficial bladder tumors, J Urol 116:180 (1976). 2. Lamm DL, et ah Bacillus Calmette-Gu6rin immunotherapy of superficial bladder cancer, J Urol 124:38 (1980). 3. DeKernion JB, et ah The management of superficial bladder tumors and carcinoma in situ with intravesical bacillus Calmette-Gu6rin, J Urol 133:598 (1985).
184
4. Lamm DL: Bacillus Calmette-Gu bladder cancer, J Urol 134:40 (1985). 5. Brosman SA: Experience with ba( patients with superficial bladder car( (1982). 6. Netto NR Jr, and Lemos GC: A methods for the prophylaxis of recurrel mors, J Urol 129:33 (1983). 7. Brosman SA: The use of bacillus therapy of bladder carcinoma in situ, J 8. Herr HW, et ah Long term effel Calmette-Gu6rin on flat carcinoma in 135:265 (1986). 9. Haaff EO, Dresner SM, Ratliff T] courses of intravesical bacillus Calmer cell carcinoma of the bladder, J Urol 1 10. Badalament RA, et aI: A prosp~ maintenance versus non-maintenan Calmette-Gu6rin therapy of supcrfici~ Oncol 5:441 (1987).
UROLOGY
/
FEBRUARY 1991
/
VOLUME XXXVII, N U ~
