title: Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial.
abstract: BACKGROUND
  Adjuvant radiotherapy is effective treatment for stage I seminoma, but is associated with a risk of late non-germ-cell cancer and cardiovascular events. After good results in initial studies with one injection of carboplatin, we undertook a large randomised trial to compare the approaches of radiotherapy with chemotherapy in seminoma treatment.
  
  
  METHODS
  Between 1996 and 2001, 1477 patients from 70 hospitals in 14 countries were randomly assigned to receive radiotherapy (para-aortic strip or dog-leg field; n=904) or one injection of carboplatin (n=573; dose based on the formula 7x[glomerular filtration rate+25] mg), at two trial centres in the UK and Belgium. The primary outcome measure was the relapse-free rate, with the trial powered to exclude absolute differences in 2-year rates of more than 3%. Analysis was by intention to treat and per protocol. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN27163214.
  
  
  RESULTS
  885 and 560 patients received radiotherapy and carboplatin, respectively. With a median follow-up of 4 years (IQR 3.0-4.9), relapse-free survival rates for radiotherapy and carboplatin were similar (96.7% [95% CI 95.3-97.7] vs 97.7% [96.0-98.6] at 2 years; 95.9% [94.4-97.1] vs 94.8% [92.5-96.4] at 3 years, respectively; hazard ratio 1.28 [90% CI 0.85-1.93], p=0.32). At 2 years' follow-up, the absolute differences in relapse-free rates (radiotherapy-chemotherapy) were -1.0% (90% CI -2.5 to 0.5) by direct comparison of proportions, and 0.9% (-0.5 to 3.0) by a hazard-ratio-based approach. Patients given carboplatin were less lethargic and less likely to take time off work than those given radiotherapy. New, second primary testicular germ-cell tumours were reported in ten patients allocated irradiation (all after para-aortic strip field) and two allocated carboplatin (5-year event rate 1.96% [95% CI 1.0-3.8] vs 0.54% [0.1-2.1], p=0.04). One seminoma-related death occurred after radiotherapy and none after carboplatin.
  
  
  CONCLUSIONS
  This trial has shown the non-inferiority of carboplatin to radiotherapy in the treatment of stage I seminoma. Although the absence of disease-related deaths and preliminary data indicating fewer second primary testicular germ-cell tumours favour carboplatin use, these findings need to be confirmed beyond 4 years' follow-up.
authors.affiliation: Department of Medical Oncology, St Bart's and the London Hospital, London EC1A 7BE, UK. r.t.oliver@qmul.ac.uk
authors.forename: R T D
authors.initials: RT
authors.lastname: Oliver
authors.forename: M D
authors.initials: MD
authors.lastname: Mason
authors.forename: G M
authors.initials: GM
authors.lastname: Mead
authors.forename: H
authors.initials: H
authors.lastname: von der Maase
authors.forename: G J S
authors.initials: GJ
authors.lastname: Rustin
authors.forename: J K
authors.initials: JK
authors.lastname: Joffe
authors.forename: R
authors.initials: R
authors.lastname: de Wit
authors.forename: N
authors.initials: N
authors.lastname: Aass
authors.forename: J D
authors.initials: JD
authors.lastname: Graham
authors.forename: R
authors.initials: R
authors.lastname: Coleman
authors.forename: S J
authors.initials: SJ
authors.lastname: Kirk
authors.forename: S P
authors.initials: SP
authors.lastname: Stenning
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009364:Neoplasm Recurrence, Local; D009919:Orchiectomy; D018714:Radiotherapy, Adjuvant; D018239:Seminoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D015996:Survival Rate; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin