Combined hyperfractionated radiotherapy and protracted infusion chemotherapy in bladder cancer for organ preservation

Combined hyperfractionated radiotherapy and protracted infusion chemotherapy in bladder cancer for organ preservation

I. J. R a d i a t i o n O n c o l o g y • B i o l o g y • Physics 288 V o l u m e 42, N u m b e r 1 Supplement, 1998 2121 COMBINED HYPERFRACTIONATE...

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I. J. R a d i a t i o n O n c o l o g y • B i o l o g y • Physics


V o l u m e 42, N u m b e r 1 Supplement, 1998

2121 COMBINED HYPERFRACTIONATED RADIOTHERAPY AND PROTRACTED INFUSION CHEMOTHERAPY IN BLADDER CANCER FOR ORGAN PRESERVATION. Saracino B.(1,4), Mecozzi A.(2), Arcangeli G.(I,4), Tirin delli Danesi D.(3), Altavista P.(3), La Vecchia L.(2), Cruciani E.(2), Gio vinazzo

G. (4) Regina Elana Cancer Institute, Rome, Italy (1), San Giovanni Calibita-Fatebenefratelli Hospital - IsolaTiberina (2), Rome, Italy, ENEA Casaccia, Rome, Italy (3), Istituto Medico e di Ricerca Scientifica, Rome, Italy (4). Purpose/Objective: The aim of this study was to define the optimal schedule of chemo-radiotherapy for selective bladder preservation. Materials and Methods:From November 1992, 53 patients with muscle invading bladder tumors after an aggressive TURB were selected to receive 2 MCV chemotherapy cycles and radiotherapy with concomitant protracted venous infusion of CDDP/5-FU (33 pts.) or radiotherapy with concomitant protracted venous infusion of CDDP/5-FU alone (20 pts.). Dose of 5-FU and CDDP ranged from 180 to 220 mg/m2/day and from 4 to 6 mg/m2/day respectively. Radiotherapy, in the first 25 patients, was delivered as three 100 cGy fractions per day, at 4 hours interval, to a dose of 50 Gy to the pelvis plus a boost of 20 Gy to the bladder in 4.5 weeks. Because of the heavy workland of the radiotherapy department, after the completion of the dose-finding study, the fractionation schedule was modified with two 150 cGy fraction per day, at 6 hours interval, to the same total dose. Results: Following grade HI toxicity were observed in MCV and no MCV group respectively: rectal tenesmus in 12/33 and in 0/20 patients, dysuria in 6/33 and in 4/20patients, leukopenia in 3/33 and in 0/20 patients, thrombocytopenia in 7/33 and in 1/20patients. One patient experienced grade IV bone marrow depletion and one patient died for radiation enteritis, both treated with MCV. Of the 28 evalua ble patients treated with MCV, CR was observed in 23 (82%) and PR in 5. Of these latter, 3 deve lopped distant metastases and died at 12, 18 and 24 months from the start of treatment and 2 were submitted to salvage cystectomy but died for distant metastases 6 and 8 months after cystectomy. Of the 19 evaluable patients treated without MCV, CR were observed in 19 (100%). Aider a median follow-up of 43.5 months, 15 of the 23 (65%) CR patients treated with MCV are alive and free of tumor, 8 of these latter had a supea-ficial local failure and were successfully treated with intravescicai therapy. Four patients underwent salvage cystectomy and are alive without evidence of disease. Four patients died, all with ftmetioning tumor-free bladder, 1 for intercorrent disease and 3 for distant metastases. Seventeen (94%) patients treated without MCV are alive and free of lunaor. One patient died for intercurrant disease and one was submitted to a cystectomy for local failure Conclusion: This schedule of bladder - sparing treatment results an acceptable acute toxicity, very similar to those observed with radiotherapy alone. At follow up examination, all patients reported optimal or suboptimal bladder function. Hyperfractionated radiotherapy with concomitant protracted venous infusion of CDDP/5-FU seems to be a succesfully treatment in bladder preservation for patients with infiltrating transitional cell carcinoma. In the group of patients who receive MCV chemotherapy we observed a higher acute toxicity and lower results in terms of complete response, disease free survival and overall survival. However these results deserve further attention and need to be evaluated by a study with larger patient population.

2122 THE ROLE OF ASSOCIATED TIS 1N MUSCLE INVASIVE BLADDER CANCER IN PATIENTS TREATED WITH TURB AND SIMULTANEOUS RADIOCHEMOTHERAPY Birkenhake S. t, Marius p.2, Sauer R. 1 ~Departmentof RadiationOncology,2Departrnentof Biostatistiesof Friedrich-Alexander-UniversitiitErlangen-Nfirnberg,91056Erlangen,Germany. Purpose/Objective: To evaluate the impact of associated superficial transitional cell cancer in muscle invasive tumors on survival, relapse rate and organ preservation. Materials & Methods: From 12/81 to 06/97 362 patients suffering from transitional cell carcinoma of the bladder received radiation with or without concurrent chemotherapy following transurethral resection of the bladder (TURB). In 62 cases TURB was performed in external hospitals. 300 of them (224 male, 76 female) underwent surgery in the University Hospital of Erlangen, in these eases exact histopathological data were available and could be analysed. The median age at the point of diagnosis was 68 (31-89) years, median follow up is 90 (4-176) months. To evaluate the response every patient received another TURB within 6-8 weeks after the end of radiochemotherapy. Results: 30% of those patients with associated Tis in the initial TURB developed either invasive (30%) or non-invasive (13%) relapses. In contrast to this those without Tis relapsed in 13% (invasive) and 4% (non-invasive) significantly less (19=0.01). No impact was seen on initial "response, survival and cystectomy-rate. -Invasive Relapse Non-invasive Relapse ~lnitialResponse (complete remission) iOverall Survival (5 years) i ~CystectomyRate


. = i

Associated Tis [%]

30 13 74 49 30



No Tis [%]

i ~ ] i

18 4 67 45 24


P 0.01 0.01 n.s. n.s. n.s.

. Conclusion: Associated Tis in invasive bladder cancer leads to increased relapse rates after organ preserving therapy, There is no impact on survival, because these relapses can be treated successfully. Therefore the presence of associated Tis is no contraindication for organ preserving therapy of bladder cancer.