Conservative treatment with transurethral resection, neoadjuvant chemotherapy followed by radiochemotherapy in stage T2-3 transitional bladder cancer

Clin Transl Oncol. 2006 Dec;8(12):903-11. doi: 10.1007/s12094-006-0154-1.

Abstract

Purpose: Organ preservation has been investigated in patients (p) with infiltrating transitional cell carcinoma (TCC) of the bladder over the past decade as an alternative to radical cystectomy. This is a trimodal schedule study, including transurethral resection of bladder tumor (TURB), neoadjuvant chemotherapy and concomitant radiochemotherapy (RTC).

Patients and methods: From April 1996 until August 2005, 29 evaluable patients (p) with T2-T3NXM0 bladder cancer were enrolled. After a transurethral resection of bladder tumor (TURB), we administered 2 cycles of induction chemotherapy with CMV (15 p) or Gemcitabine-Cisplatin (14 p) followed by radiotherapy 45 Gy 1.8 Gy/fraction and two cycles of concomitant cisplatin 70 mg/m(2). 2-3 weeks later, a cystoscopy with tumor-site biopsy was performed. If complete histological response, p were treated with consolidation radiotherapy until 64.8 Gy. For p with residual or recurrent tumor, cystectomy was performed.

Results: We included 28 men and 1 women (median age 63, range 39-72 years) with PS (ECOG) 0-1. The stage was: 21 p T2; 6 p T3a; and 2 p T3b. Toxicity was higher in CMV compared with Gem- Cis: grade (3/4) neutropenia 4/15 (26%) vs 1/14 (7%); febrile neutropenia 3/15 (20%) vs 1/14 (7%); grade (3/4) trombocytopenia 2/15 (13%) vs 1/14 (7%). Toxicities with concomitant RCT were low-moderate: urocystitis (26%) and enteritis (18%).

Response: microscopically complete TURB was obtained in 20 p (69%), but not in 9 p (31%) (7 microscopic, and 2 macroscopic residual tumor). We found a complete histologic response after induction RCT in 25 p (86%). After a median follow-up of 69.4 months (m) (range: 8-97.7), there were 8 deaths, with a overall survival of 72%. Furthermore 14 of 29 p (48%) were alive with intact bladder, and median survival time with intact bladder was 63.6 m (50.1-77.2); were predictive of best outcome T2 stage vs T3 (p < 0.0001), and complete histologic resection in initial TURB vs residual tumor (p = 0.0004).

Conclusions: Combined treatment provide high response rates and can be offered as an alternative option to radical cystectomy in selected patients with TCC. Patients with T2 stage and complete histologic resection in initial TURB had the best outcome.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents* / administration & dosage
  • Antineoplastic Agents* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Carcinoma, Transitional Cell / mortality
  • Carcinoma, Transitional Cell / therapy*
  • Cisplatin / administration & dosage
  • Combined Modality Therapy
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Female
  • Gemcitabine
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Neoadjuvant Therapy* / adverse effects
  • Neoadjuvant Therapy* / methods
  • Neoplasm Staging
  • Radiotherapy* / adverse effects
  • Radiotherapy* / methods
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / therapy*
  • Urologic Surgical Procedures* / methods
  • Vinblastine / administration & dosage

Substances

  • Antineoplastic Agents
  • Deoxycytidine
  • Vinblastine
  • Cisplatin
  • Methotrexate
  • Gemcitabine

Supplementary concepts

  • MEC protocol 1