title: Radiotherapy or chemotherapy for clinical stage IIA and IIB seminoma: a systematic review and meta-analysis of patient outcomes.
abstract: BACKGROUND
  Outcomes of radiotherapy (RT) compared with chemotherapy (CT) remain poorly defined for clinical stage (CS) IIA and IIB seminoma. We aimed to evaluate the current role of the two treatment modalities in this setting of testicular seminoma.
  
  
  METHODS
  A systematic review and meta-analysis (MA) was carried out to identify all evaluable studies. Search was limited to studies published after 1990 and included the Medline, Embase databases, and abstracts from ASCO (GU), ESMO, AUA, and ASTRO meetings up to April 2014. Sensitivity analyses were applied including the following: CSIIA and CSIIB, paraortic + iliac RT only in both stages, RT dose (≥30 versus <30 Gy), and PEB/EP regimens only.
  
  
  RESULTS
  Thirteen studies have been selected for MA on relapse outcome. No randomized trials compared RT and CT. There were 4 prospective and 9 retrospective studies, with a total of 607 patients receiving RT and 283 patients CT. The pooled relapse rate (RR) was similar between the RT [0.11, 95% confidence interval (CI) 0.08-0.14, P for heterogeneity = 0.096, I(2) = 38%] and CT groups (0.08, 95% CI 0.01-0.15, P for heterogeneity <0.001, I(2) = 82.5%). However, in the sensitivity analysis, the pooled RR for RT in CSIIB was 0.12 (95% CI 0.06-0.17) while it was 0.05 (95% CI 0-0.11) for CT. Long-term side-effects and incidence of second cancers were more frequently reported following RT. The overall incidence of nontesticular second malignancies was 0.04 (95% CI 0.01-0.02) in the RT group and 0.02 (95% CI 0.003-0.04) in the CT group.
  
  
  CONCLUSIONS
  Although RT and CT appeared to be equal options in CSIIA and IIB seminoma, a trend in favor of CT for a lower incidence of side-effects and RR in CSIIB was found. This evidence is limited by the retrospective quality of studies and their small sample size.
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: P
authors.initials: P
authors.lastname: Giannatempo
authors.affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan; Section of Medical Statistics and Biometry 'Giulio A. Maccacaro', University of Milan, Milan.
authors.forename: T
authors.initials: T
authors.lastname: Greco
authors.affiliation: Clinical Epidemiology and Trials Organization Unit.
authors.forename: L
authors.initials: L
authors.lastname: Mariani
authors.affiliation: Department of Surgery, Urology Unit.
authors.forename: N
authors.initials: N
authors.lastname: Nicolai
authors.affiliation: Department of Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: S
authors.initials: S
authors.lastname: Tana
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: E
authors.initials: E
authors.lastname: Farè
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: D
authors.initials: D
authors.lastname: Raggi
authors.affiliation: Department of Surgery, Urology Unit.
authors.forename: L
authors.initials: L
authors.lastname: Piva
authors.affiliation: Department of Surgery, Urology Unit.
authors.forename: M
authors.initials: M
authors.lastname: Catanzaro
authors.affiliation: Department of Surgery, Urology Unit.
authors.forename: D
authors.initials: D
authors.lastname: Biasoni
authors.affiliation: Department of Surgery, Urology Unit.
authors.forename: T
authors.initials: T
authors.lastname: Torelli
authors.affiliation: Department of Surgery, Urology Unit.
authors.forename: S
authors.initials: S
authors.lastname: Stagni
authors.affiliation: Department of Radiotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: B
authors.initials: B
authors.lastname: Avuzzi
authors.affiliation: Department of Surgery, Urology Unit.
authors.forename: M
authors.initials: M
authors.lastname: Maffezzini
authors.affiliation: Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan.
authors.forename: G
authors.initials: G
authors.lastname: Landoni
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: F
authors.initials: F
authors.lastname: De Braud
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Gianni
authors.affiliation: University of Alabama-UAB Comprehensive Cancer Center, Alabama, USA.
authors.forename: G
authors.initials: G
authors.lastname: Sonpavde
authors.affiliation: Department of Surgery, Urology Unit.
authors.forename: R
authors.initials: R
authors.lastname: Salvioni
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. Electronic address: andrea.necchi@istitutotumori.mi.it.
authors.forename: A
authors.initials: A
authors.lastname: Necchi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D011878:Radiotherapy; D018239:Seminoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
keywords: chemotherapy; clinical stage II; radiotherapy; seminoma; systematic review; testicular cancer