- Email: [email protected]
EARLY INTRAVESICAL EPIRUBICIN INSTILLATION AFTER TRANSURETHRAL RESECTION FOR NON-MUSCLE INVASIVE BLADDER CANCER IS INEFFICIENT FOR RECURRENT TUMOURS
425
426
A SINGLE INSTILLATION OF EPIRUBICIN AFTER TRANSURETHRAL RESECTION OF BLADDER TUMOURS RESULTS IN LESS SMALLSIZED (UP TO 0.5 CM) RECURRENCES ONLY
EARLY INTRAVESICAL EPIRUBICIN INSTILLATION AFTER TRANSURETHRAL RESECTION FOR NON-MUSCLE INVASIVE BLADDER CANCER IS INEFFICIENT FOR RECURRENT TUMOURS
Holmang S.1, Berrum Svennung I.1, Granfors T.2, Jahnson S., Boman H.4
Gudjonsson S.1, Liedberg F.1, Adell L.2, Merdasa F., Hagberg G.2, Olsson R.4, Grabe M.5, 5LFKWRᚎ-6, Larsson B.7, Bendahl P.O.8, Månsson W.1
1
Sahlgrenska University Hospital, Dept. of Urology, Göteborg, Sweden, Central Hospital, Dept. of Urology, Västerås, Sweden, University Hospital, Dept. of Urology, Linköping, Sweden, 4Lasaarettet, Dept. of Urology, Alingsås, Sweden 2
Introduction & Objectives: We studied whether a single instillation of epirubicin after transurethral resection (TUR) of bladder tumours would LQᚐXHQFHWKHLQWHUYDOWRDQGVL]HRIWKHᚏUVWUHFXUUHQFH Material & Methods: $WRWDORISDWLHQWVLQKRVSLWDOVZHUHUDQGRPL]HG to one instillation of 50 mg epirubicin or placebo within 6 hours after TUR of bladder tumours. Results: Seventy-nine (51.0%) out of 155 evaluable patients in the epirubicin group had a recurrence as compared to 95 (62.5%) out of 152 patients in the SODFHER JURXS S 0RVW UHFXUUHQFHV ZHUH VPDOOVL]HG mm.). The tumor size was unknown in 5 patients. Thirty-three (42.9%) out of 79 patients with recurrences in the epirubicin arm compared to 29 patients RXWRI LQWKHSODFHERDUPKDGODUJHU !PP ᚏUVWUHFXUUHQFHV S 5RXJKO\KDOIRIWKHSDWLHQWVZLWKᚏUVWUHFXUUHQFHVZHUHPDQDJHGLQ day surgery and the other half spent a total number of 145 days in hospital, ZLWKQRGLᚎHUHQFHEHWZHHQJURXSV YVGD\V Conclusions: :HFRQᚏUPHGWKHUHVXOWVRISUHYLRXVVWXGLHVVKRZLQJWKDW patients must be treated with a single instillation to prevent one recurrence. Furthermore, our data may indicate that only small-sized recurrences are prevented such that could easily be fulgurated under local anaesthesia at WKHWLPHRIIROORZXSF\VWRVFRS\7KHEHQHᚏWRIVLQJOHLQVWLOODWLRQVFDQEH TXHVWLRQHGLIWKLVᚏQGLQJFDQEHFRQᚏUPHGE\RWKHUV
Lund University Hospital, Dept. of Urology, Lund, Sweden, 2Växjö County Hospital, Dept. of Urology, Växjö, Sweden, Landskrona hospital, Dept. of Urology, Landskrona, Sweden, 4 Trelleborg Hospital, Dept. of Urology, Trelleborg, Sweden, 5Malmö University Hospital, Dept. of Urology, Malmö, Sweden, 6Ljungby Hospital, Dept. of Urology, Ljungby, Sweden, 7 Jönköping County Hospital, Dept. of Urology, Jönköping, Sweden, 8Lund University Hospital, Dept. of Oncology, Lund, Sweden
1
Introduction & Objectives: Non-muscle invasive bladder cancer is prone to recur after transurethral resection. Several randomised trials as well as one meta-analysis have VKRZQDVLJQLᚏFDQWULVNUHGXFWLRQLQWHUPVRIUHFXUUHQFHZLWKWKHXVHRIHDUO\SRVWRSHUDWLYH single instillation with intravesical chemotherapy. The EAU guidelines state: “it is therefore necessary to treat every patient adjuvantly with intravesical chemotherapy”. Material & Methods: %HWZHHQ DQGSDWLHQWVIURPVHYHQ6ZHGLVKFHQWUHV were randomised to a single intravesical instillation of 80 mg epirubicin during one hour within 24 hours vs. no therapy after transurethral resection of suspected non-muscle invasive bladder tumour (Ta-T1, G1-G2). Patients with primary as well as recurrent tumours were included. Patients were followed for at least 2 years and recurrences registered. Time to recurrence was the primary endpoint. Patients found to have muscle invasive tumour or JUDGHFDQFHUFHOOVRQKLVWRSDWKRORJ\UHSRUWZHUHH[FOXGHGIURPWKHDQDO\VLV7KHHᚎHFW of therapy on primary tumours and recurrences was analysed separately. Results: After exclusions, the results from 219 (72%) patients could be further analysed. 7KH PHGLDQ IROORZXS WLPH ZDV \HDUV SDWLHQWV LQ WKH HSLUXELFLQ DUP had recurrences during follow-up compared to 90/117 (77%) patients in the control arm S ORJUDQNWHVW SDWLHQWVZLWKSULPDU\WXPRXUVWUHDWHGZLWKHSLUXELFLQ ZHUHIUHHIURPUHFXUUHQFHDWODVWIROORZXSFRPSDUHGWR SDWLHQWVLQWKHFRQWURO arm (p=0.007, log-rank test). However, for patients with recurrent tumours treated with HSLUXELFLQ ZHUHIUHHIURPUHFXUUHQFHDWODVWIROORZXSFRPSDUHGWR in the control arm (p=0.42, log-rank test). Conclusions: Early intravesical instillation of epirubicin after TUR-B for primary, low and intermediate risk, non-muscle invasive bladder cancer reduces the risk of recurrence. 3DWLHQWV ZLWK UHFXUUHQW EODGGHU FDQFHU GR QRW EHQHᚏW IURP VXFK WKHUDS\ 2XU UHVXOWV challenge the current EAU guidelines but further studies are warranted.
427
428
IS EARLY SINGLE-DOSE INSTILLATION OF EPIRUBICIN ABLE TO IMPROVE BCG EFFICACY IN NON-MUSCLE INVASIVE HIGH-RISK BLADDER CANCER PATIENTS? RESULTS FROM A PROSPECTIVE, RANDOMISED, DOUBLE-BLIND AND CONTROLLED STUDY
THE EFFECTS OF INTRAVESICAL CHEMO IMMUNOTHERAPY WITH GEMCITABINE AND BACILLUS CALMETTE-GUÉRIN FOR PROPHYLAXIS OF RECURRENCE OF SUPERFICIAL BLADDER CANCER
Bartoletti R.1, Cai T.1, Mondaini N.1, Nesi G.2, Mazzoli S., Boddi V.4
Cho D.Y., Kang S.H., Bae J.H., Park H.S., Moon D.G., Cheon J., Kim J.J., Yoon D.K.
University of Florence, Dept. of Urology, Florence, Italy, 2University of Florence, Dept. of Pathology and Oncology, Florence, Italy, Santa Maria Annunziata Hospital, STDs Centre, Florence, Italy, 4University of Florence, Dept. of Public Health and Epidemiology, Florence, Italy 1
Introduction & Objectives: The European Association of Urology Guidelines on Bladder Cancer advocates a single immediate chemotherapeutic instillation in all cases of NMIBC. Is early single-dose instillation advisable in all NMIBC? In order to answer to the question we have designed a prospective, randomized, FRQWUROOHGDQGGRXEOHEOLQGVWXG\ZLWKWKHDLPRIHYDOXDWLQJHᚑFDF\RISHULRSHUDWLYHLQVWLOODWLRQRIHSLUXELFLQ IRULPSURYLQJVXEVHTXHQW%&*LQVWLOODWLRQHᚑFDF\LQKLJKULVN10,%&SDWLHQWV Material & Methods: %HWZHHQ-DQXDU\DQG-XQHSDWLHQWVDᚎHFWHGE\KLJKULVN10,%&ZHUH HQUROOHGLQWKLVVWXG\SDWLHQWVZHUHDVVLJQHGWR*URXS$>SHULRSHUDWLYHHSLUXELFLQ PJPOQRUPDO saline) plus delayed BCG instillations (5 x 108 colony-forming units in 50 ml of saline)] and 81 to Group B GHOD\HG%&*DORQH 7KHPDLQRXWFRPHPHDVXUHVZHUHWLPHWRᚏUVWUHFXUUHQFHDQGUHFXUUHQFHUDWH$OOGDWD REWDLQHGIURPDPHGLDQIROORZXSRIPRQWKVLQJURXS$DQGPRQWKVLQJURXS%ZHUHDQDO\]HG Results: At the end of follow-up, 46 out of 80 patients in group A (57.5%) had no evidence of disease, MXVWOLNHRXWRILQJURXS% 1RVWDWLVWLFDOGLᚎHUHQFHZDVREVHUYHGEHWZHHQWKHWZRJURXSVLQ WHUPVRIUHFXUUHQFHUDWH S RUWLPHWRᚏUVWUHFXUUHQFH S .DSODQ0HLHUDQDO\VLVRIUHFXUUHQFH VKRZHGQRVLJQLᚏFDQWGLᚎHUHQFHVEHWZHHQJURXS$DQGJURXS% S $WPXOWLYDULDWHDQDO\VLVWKHHDUO\ VLQJOHGRVHLQVWLOODWLRQRIHSLUXELFLQZDVQRWLQGLFDWHGDVDQLQGHSHQGHQWSURJQRVWLFIDFWRU>+5 &, @ Conclusions: 7KHSUHVHQWVWXG\VKRZHGWKDWQRVWDWLVWLFDOO\VLJQLᚏFDQWGLᚎHUHQFHVZHUHUHSRUWHGLQWHUPV of recurrence-rate between high-risk NMIBC patients who had undergone perioperative epirubicin instillation plus delayed BCG and those who had undergone BCG alone.
Korea University Hospital, Dept. of Urology, Seoul, South Korea Introduction & Objectives: ZH SURVSHFWLYHO\ VWXGLHG WKH HᚎHFWV DQG WKH safety of intravesical chemo immunotherapy with gemcitabine and Bacillus &DOPHWWH*XHULQ %&* IRU SURSK\OD[LV RI UHFXUUHQFH RI VXSHUᚏFLDO EODGGHU cancer (pTa, pT1) and compared with those of BCG monotherapy. Material & Methods: %HWZHHQ0D\DQG$SULOVXSHUᚏFLDOEODGGHU cancer patients were enrolled in this study and treated by chemo immunotherapy DQG%&* Q RUFRQYHQWLRQDOZHHNV%&*PRQRWKHUDS\ Q )RUWKH chemo immunotherapy, gemcitabine(1000 mg) was instilled immediately after trans-urethral resection(TUR) and one week later (2000 mg). At 2 week after TUR, Tice-strain BCG was instilled into the bladder once a week for 6 weeks. Complications, recurrence rates, progression rates and recurrence-free period (RFP) were analyzed in both groups. Results: 7KH UHFXUUHQFH UDWH ZDV LQ SDWLHQWV ZLWK FKHPR immunotherapy and 26.7%(12/45) in BCG monotherapy patients(p=0.915). But the recurrence-free period (RFP) of chemo immunotherapy group (10.1 PRQWKV ZDV VLJQLᚏFDQWO\ ORQJHU WKDQ WKDW RI %&* PRQRWKHUDS\ JURXS months, p=0.021). Progression rates of two groups were 2.6% and 6.7%, respectively (p=0.594). Treatment was well tolerated and most of complications were self-limiting in both group patients. Conclusions: Intravesical chemo immunotherapy with gemcitabine and BCG VHHPHGWREHHᚎHFWLYHIRUSURORQJDWLRQRIWKHUHFXUUHQFHIUHHSHULRGWKDQ%&* PRQRWKHUDS\LQVXSHUᚏFLDOEODGGHUFDQFHUSDWLHQWVEXWFDQFHUUHFXUUHQFHUDWH ZDVQRWVLJQLᚏFDQWO\GLᚎHUHQWEHWZHHQWZRJURXSV
Eur Urol Suppl 2008;7(3):177
426
A SINGLE INSTILLATION OF EPIRUBICIN AFTER TRANSURETHRAL RESECTION OF BLADDER TUMOURS RESULTS IN LESS SMALLSIZED (UP TO 0.5 CM) RECURRENCES ONLY
EARLY INTRAVESICAL EPIRUBICIN INSTILLATION AFTER TRANSURETHRAL RESECTION FOR NON-MUSCLE INVASIVE BLADDER CANCER IS INEFFICIENT FOR RECURRENT TUMOURS
Holmang S.1, Berrum Svennung I.1, Granfors T.2, Jahnson S., Boman H.4
Gudjonsson S.1, Liedberg F.1, Adell L.2, Merdasa F., Hagberg G.2, Olsson R.4, Grabe M.5, 5LFKWRᚎ-6, Larsson B.7, Bendahl P.O.8, Månsson W.1
1
Sahlgrenska University Hospital, Dept. of Urology, Göteborg, Sweden, Central Hospital, Dept. of Urology, Västerås, Sweden, University Hospital, Dept. of Urology, Linköping, Sweden, 4Lasaarettet, Dept. of Urology, Alingsås, Sweden 2
Introduction & Objectives: We studied whether a single instillation of epirubicin after transurethral resection (TUR) of bladder tumours would LQᚐXHQFHWKHLQWHUYDOWRDQGVL]HRIWKHᚏUVWUHFXUUHQFH Material & Methods: $WRWDORISDWLHQWVLQKRVSLWDOVZHUHUDQGRPL]HG to one instillation of 50 mg epirubicin or placebo within 6 hours after TUR of bladder tumours. Results: Seventy-nine (51.0%) out of 155 evaluable patients in the epirubicin group had a recurrence as compared to 95 (62.5%) out of 152 patients in the SODFHER JURXS S 0RVW UHFXUUHQFHV ZHUH VPDOOVL]HG mm.). The tumor size was unknown in 5 patients. Thirty-three (42.9%) out of 79 patients with recurrences in the epirubicin arm compared to 29 patients RXWRI LQWKHSODFHERDUPKDGODUJHU !PP ᚏUVWUHFXUUHQFHV S 5RXJKO\KDOIRIWKHSDWLHQWVZLWKᚏUVWUHFXUUHQFHVZHUHPDQDJHGLQ day surgery and the other half spent a total number of 145 days in hospital, ZLWKQRGLᚎHUHQFHEHWZHHQJURXSV YVGD\V Conclusions: :HFRQᚏUPHGWKHUHVXOWVRISUHYLRXVVWXGLHVVKRZLQJWKDW patients must be treated with a single instillation to prevent one recurrence. Furthermore, our data may indicate that only small-sized recurrences are prevented such that could easily be fulgurated under local anaesthesia at WKHWLPHRIIROORZXSF\VWRVFRS\7KHEHQHᚏWRIVLQJOHLQVWLOODWLRQVFDQEH TXHVWLRQHGLIWKLVᚏQGLQJFDQEHFRQᚏUPHGE\RWKHUV
Lund University Hospital, Dept. of Urology, Lund, Sweden, 2Växjö County Hospital, Dept. of Urology, Växjö, Sweden, Landskrona hospital, Dept. of Urology, Landskrona, Sweden, 4 Trelleborg Hospital, Dept. of Urology, Trelleborg, Sweden, 5Malmö University Hospital, Dept. of Urology, Malmö, Sweden, 6Ljungby Hospital, Dept. of Urology, Ljungby, Sweden, 7 Jönköping County Hospital, Dept. of Urology, Jönköping, Sweden, 8Lund University Hospital, Dept. of Oncology, Lund, Sweden
1
Introduction & Objectives: Non-muscle invasive bladder cancer is prone to recur after transurethral resection. Several randomised trials as well as one meta-analysis have VKRZQDVLJQLᚏFDQWULVNUHGXFWLRQLQWHUPVRIUHFXUUHQFHZLWKWKHXVHRIHDUO\SRVWRSHUDWLYH single instillation with intravesical chemotherapy. The EAU guidelines state: “it is therefore necessary to treat every patient adjuvantly with intravesical chemotherapy”. Material & Methods: %HWZHHQ DQGSDWLHQWVIURPVHYHQ6ZHGLVKFHQWUHV were randomised to a single intravesical instillation of 80 mg epirubicin during one hour within 24 hours vs. no therapy after transurethral resection of suspected non-muscle invasive bladder tumour (Ta-T1, G1-G2). Patients with primary as well as recurrent tumours were included. Patients were followed for at least 2 years and recurrences registered. Time to recurrence was the primary endpoint. Patients found to have muscle invasive tumour or JUDGHFDQFHUFHOOVRQKLVWRSDWKRORJ\UHSRUWZHUHH[FOXGHGIURPWKHDQDO\VLV7KHHᚎHFW of therapy on primary tumours and recurrences was analysed separately. Results: After exclusions, the results from 219 (72%) patients could be further analysed. 7KH PHGLDQ IROORZXS WLPH ZDV \HDUV SDWLHQWV LQ WKH HSLUXELFLQ DUP had recurrences during follow-up compared to 90/117 (77%) patients in the control arm S ORJUDQNWHVW SDWLHQWVZLWKSULPDU\WXPRXUVWUHDWHGZLWKHSLUXELFLQ ZHUHIUHHIURPUHFXUUHQFHDWODVWIROORZXSFRPSDUHGWR SDWLHQWVLQWKHFRQWURO arm (p=0.007, log-rank test). However, for patients with recurrent tumours treated with HSLUXELFLQ ZHUHIUHHIURPUHFXUUHQFHDWODVWIROORZXSFRPSDUHGWR in the control arm (p=0.42, log-rank test). Conclusions: Early intravesical instillation of epirubicin after TUR-B for primary, low and intermediate risk, non-muscle invasive bladder cancer reduces the risk of recurrence. 3DWLHQWV ZLWK UHFXUUHQW EODGGHU FDQFHU GR QRW EHQHᚏW IURP VXFK WKHUDS\ 2XU UHVXOWV challenge the current EAU guidelines but further studies are warranted.
427
428
IS EARLY SINGLE-DOSE INSTILLATION OF EPIRUBICIN ABLE TO IMPROVE BCG EFFICACY IN NON-MUSCLE INVASIVE HIGH-RISK BLADDER CANCER PATIENTS? RESULTS FROM A PROSPECTIVE, RANDOMISED, DOUBLE-BLIND AND CONTROLLED STUDY
THE EFFECTS OF INTRAVESICAL CHEMO IMMUNOTHERAPY WITH GEMCITABINE AND BACILLUS CALMETTE-GUÉRIN FOR PROPHYLAXIS OF RECURRENCE OF SUPERFICIAL BLADDER CANCER
Bartoletti R.1, Cai T.1, Mondaini N.1, Nesi G.2, Mazzoli S., Boddi V.4
Cho D.Y., Kang S.H., Bae J.H., Park H.S., Moon D.G., Cheon J., Kim J.J., Yoon D.K.
University of Florence, Dept. of Urology, Florence, Italy, 2University of Florence, Dept. of Pathology and Oncology, Florence, Italy, Santa Maria Annunziata Hospital, STDs Centre, Florence, Italy, 4University of Florence, Dept. of Public Health and Epidemiology, Florence, Italy 1
Introduction & Objectives: The European Association of Urology Guidelines on Bladder Cancer advocates a single immediate chemotherapeutic instillation in all cases of NMIBC. Is early single-dose instillation advisable in all NMIBC? In order to answer to the question we have designed a prospective, randomized, FRQWUROOHGDQGGRXEOHEOLQGVWXG\ZLWKWKHDLPRIHYDOXDWLQJHᚑFDF\RISHULRSHUDWLYHLQVWLOODWLRQRIHSLUXELFLQ IRULPSURYLQJVXEVHTXHQW%&*LQVWLOODWLRQHᚑFDF\LQKLJKULVN10,%&SDWLHQWV Material & Methods: %HWZHHQ-DQXDU\DQG-XQHSDWLHQWVDᚎHFWHGE\KLJKULVN10,%&ZHUH HQUROOHGLQWKLVVWXG\SDWLHQWVZHUHDVVLJQHGWR*URXS$>SHULRSHUDWLYHHSLUXELFLQ PJPOQRUPDO saline) plus delayed BCG instillations (5 x 108 colony-forming units in 50 ml of saline)] and 81 to Group B GHOD\HG%&*DORQH 7KHPDLQRXWFRPHPHDVXUHVZHUHWLPHWRᚏUVWUHFXUUHQFHDQGUHFXUUHQFHUDWH$OOGDWD REWDLQHGIURPDPHGLDQIROORZXSRIPRQWKVLQJURXS$DQGPRQWKVLQJURXS%ZHUHDQDO\]HG Results: At the end of follow-up, 46 out of 80 patients in group A (57.5%) had no evidence of disease, MXVWOLNHRXWRILQJURXS% 1RVWDWLVWLFDOGLᚎHUHQFHZDVREVHUYHGEHWZHHQWKHWZRJURXSVLQ WHUPVRIUHFXUUHQFHUDWH S RUWLPHWRᚏUVWUHFXUUHQFH S .DSODQ0HLHUDQDO\VLVRIUHFXUUHQFH VKRZHGQRVLJQLᚏFDQWGLᚎHUHQFHVEHWZHHQJURXS$DQGJURXS% S $WPXOWLYDULDWHDQDO\VLVWKHHDUO\ VLQJOHGRVHLQVWLOODWLRQRIHSLUXELFLQZDVQRWLQGLFDWHGDVDQLQGHSHQGHQWSURJQRVWLFIDFWRU>+5 &, @ Conclusions: 7KHSUHVHQWVWXG\VKRZHGWKDWQRVWDWLVWLFDOO\VLJQLᚏFDQWGLᚎHUHQFHVZHUHUHSRUWHGLQWHUPV of recurrence-rate between high-risk NMIBC patients who had undergone perioperative epirubicin instillation plus delayed BCG and those who had undergone BCG alone.
Korea University Hospital, Dept. of Urology, Seoul, South Korea Introduction & Objectives: ZH SURVSHFWLYHO\ VWXGLHG WKH HᚎHFWV DQG WKH safety of intravesical chemo immunotherapy with gemcitabine and Bacillus &DOPHWWH*XHULQ %&* IRU SURSK\OD[LV RI UHFXUUHQFH RI VXSHUᚏFLDO EODGGHU cancer (pTa, pT1) and compared with those of BCG monotherapy. Material & Methods: %HWZHHQ0D\DQG$SULOVXSHUᚏFLDOEODGGHU cancer patients were enrolled in this study and treated by chemo immunotherapy DQG%&* Q RUFRQYHQWLRQDOZHHNV%&*PRQRWKHUDS\ Q )RUWKH chemo immunotherapy, gemcitabine(1000 mg) was instilled immediately after trans-urethral resection(TUR) and one week later (2000 mg). At 2 week after TUR, Tice-strain BCG was instilled into the bladder once a week for 6 weeks. Complications, recurrence rates, progression rates and recurrence-free period (RFP) were analyzed in both groups. Results: 7KH UHFXUUHQFH UDWH ZDV LQ SDWLHQWV ZLWK FKHPR immunotherapy and 26.7%(12/45) in BCG monotherapy patients(p=0.915). But the recurrence-free period (RFP) of chemo immunotherapy group (10.1 PRQWKV ZDV VLJQLᚏFDQWO\ ORQJHU WKDQ WKDW RI %&* PRQRWKHUDS\ JURXS months, p=0.021). Progression rates of two groups were 2.6% and 6.7%, respectively (p=0.594). Treatment was well tolerated and most of complications were self-limiting in both group patients. Conclusions: Intravesical chemo immunotherapy with gemcitabine and BCG VHHPHGWREHHᚎHFWLYHIRUSURORQJDWLRQRIWKHUHFXUUHQFHIUHHSHULRGWKDQ%&* PRQRWKHUDS\LQVXSHUᚏFLDOEODGGHUFDQFHUSDWLHQWVEXWFDQFHUUHFXUUHQFHUDWH ZDVQRWVLJQLᚏFDQWO\GLᚎHUHQWEHWZHHQWZRJURXSV
Eur Urol Suppl 2008;7(3):177