Conservative treatment of invasive bladder carcinoma by transurethral resection, protracted intravenous infusion chemotherapy, and hyperfractionated radiotherapy: long term results.
BACKGROUND
Organ preservation has been investigated in patients with muscle-invasive bladder carcinoma over the past decades as an alternative to radical cystectomy. The majority of studies reported that trimodal schedules, including transurethral resection of bladder tumor (TURB), radiotherapy (RT), and chemotherapy, are a feasible and safe organ-sparing approach without deferring the survival probability. However, to the authors' knowledge the best combination of RT and chemotherapy has yet to be well defined. The current study evaluated the long-term results of a schedule of concurrent cisplatin and 5-fluorouracil (5-FU) administered as protracted intravenous infusions (PVI) during hyperfractionated radiotherapy (HFRT) with organ-sparing intent in patients with infiltrating transitional cell carcinoma of the bladder (TCCB).


METHODS
Seventy-seven patients with a classification of T2-T4aN0M0 TCCB were enrolled in the current study. After a complete TURB and bladder mapping, 42 of 77 patients underwent 2 cycles of induction chemotherapy. All 77 patients underwent HFRT and a schedule of cisplatin (4-6 mg/m(2) per day) and 5-FU (180-220 mg/m(2) per day) as concomitant PVI (radiochemotherapy [RCT]). Six to 8 weeks after RCT, patient response was evaluated by computed tomography scan, urine cytology, and TURB. Patients who achieved a complete response (CR) were followed at regular intervals. For patients with residual or recurrent invasive tumor, salvage cystectomy was recommended.


RESULTS
Seventy-two patients were evaluable for response: 65 achieved a CR (90.3%) and 7 (9.7%) achieved a partial response. No significant difference was observed for the different prognostic factors with the exception of stage of disease (T2 [95.7%] vs. T3-T4a [80.0%]; P = 0.04). The observed toxicity, mainly hematologic, was higher among the patients who received induction chemotherapy compared with the patients who did not receive induction chemotherapy, even though the difference was not statistically significant. After a median follow-up of 82.2 months (range, 30-138 months), 44 of 65 (57.1%) patients who achieved a CR were alive. Of these 44 patients, 33 had tumor-free bladders. The 5-year overall, bladder-intact, tumor-specific, disease-free, and cystectomy-free survival rates for all 77 patients were 58.5%, 46.6%, 75.0%, 53.5%, and 76.1%, respectively. No associations were observed in overall and tumor-specific survival with different prognostic factors.


CONCLUSIONS
Combined treatment appeared to provide high response rates and can be offered as an alternative option to radical cystectomy in selected patients who refuse or are unsuitable for surgery.
Department of Biotechnologies, Health and Ecosystems Protection, Section of Toxicology and Biomedical Sciences, ENEA Casaccia, Rome, Italy.
Donatella Tirindelli
DT
Danesi
Giorgio
G
Arcangeli
Enrico
E
Cruciani
Pierluigi
P
Altavista
Antonella
A
Mecozzi
Bianca
B
Saracino
Filina
F
Orefici
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D015653:Cystectomy; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D018714:Radiotherapy, Adjuvant; D016896:Treatment Outcome; D014521:Urethra / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery*
D002945:Cisplatin; D005472:Fluorouracil