Randomized phase III trial comparing retroperitoneal lymph node dissection with one course of bleomycin and etoposide plus cisplatin chemotherapy in the adjuvant treatment of clinical stage I Nonseminomatous testicular germ cell tumors: AUO trial AH 01/94 by the German Testicular Cancer Study Group

J Clin Oncol. 2008 Jun 20;26(18):2966-72. doi: 10.1200/JCO.2007.12.0899. Epub 2008 May 5.

Abstract

Purpose: Retroperitoneal lymph node dissection (RPLND) and adjuvant chemotherapy are two adjuvant treatment options for patients with clinical stage I nonseminomatous germ cell tumors of the testis (NSGCT). Aim of this trial was to prove the advantage of one cycle of bleomycin, etoposide, and cisplatin (BEP) chemotherapy compared with RPLND in terms of recurrence.

Patients and methods: Between 1996 and 2005, 382 patients were randomly assigned to receive either RPLND (n = 191) or one course of BEP (n = 191) after orchidectomy. The primary study end point was the rate of recurrence. The trial was powered to detect a 7% reduction (from 10% to 3%) of recurrence with chemotherapy compared with surgery.

Results: After a median follow-up of 4.7 years, two and 15 recurrences were observed in the intention-to-treat population with chemotherapy and surgery, respectively (P = .0011). The difference in the 2-year recurrence-free survival rate between chemotherapy (99.46%; 95% CI, 96.20% to 99.92%) and surgery (91.87%; 95% CI, 86.87% to 95.02%) was 7.59% (95% CI, 3.13% to 12.05%). The hazard ratio to experience a tumor recurrence with surgery as opposed to chemotherapy was 7.937 (95% CI, 1.808 to 34.48).

Conclusion: To our knowledge, this is the largest randomized trial investigating adjuvant treatment strategies in clinical stage I NSGCT, which showed the superiority of one course BEP over RPLND performed according to community standards to prevent recurrence. Although not standard treatment, one course of BEP is active in an unselected group of patients with clinical stage I disease and merits further investigation.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / administration & dosage
  • Bleomycin / adverse effects
  • Chemotherapy, Adjuvant
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Disease-Free Survival
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Humans
  • Lymph Node Excision / adverse effects
  • Lymph Node Excision / methods
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Neoplasms, Germ Cell and Embryonal / drug therapy*
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Neoplasms, Germ Cell and Embryonal / surgery*
  • Orchiectomy
  • Testicular Neoplasms / drug therapy*
  • Testicular Neoplasms / pathology
  • Testicular Neoplasms / surgery*

Substances

  • Bleomycin
  • Etoposide
  • Cisplatin