title: A cast of shadow on adjuvant radiotherapy for prostate cancer: A critical review based on a methodological perspective.
abstract: OBJECTIVE
  To perform a critical review focusing on the applicability in clinical daily practice of data from three randomized controlled trials (RCTs): SWOG 8794, EORTC 22911, and ARO/AUO 96-02.
  
  
  METHODS
  An analytical framework, based on the identified population, interventions, comparators, and outcomes (PICO) was used to refine the search of the evidence from the three large randomized trials regarding the use of radiation therapy after prostatectomy as adjuvant therapy (ART).
  
  
  RESULTS
  With regard to the inclusion criteria: (1) POPULATION: in the time since they were designed, in two among three trial (SWOG 8794 and EORTC 22911) patients had a detectable PSA at the time of randomization, thus representing de facto a substantial proportion of patients who eventually received salvage RT (SRT) at non-normalised PSA levels rather than ART. (2) INTERVENTIONS: although all the trials showed the benefit of postoperative ART compared to a wait-and-see approach, the dose herein employed would be now considered inadequate; (3) COMPARATORS: the comparison arm in all the 3 RCTs was an uncontrolled observation arm, where patients who subsequently developed biochemical failure were treated in various ways, with up to half of them receiving SRT at PSA well above 1 ng/mL, a level that would be now deemed inappropriate; (4) OUTCOMES: only in one trial (SWOG 8794) ART was found to significantly improve overall survival compared to observation, with a ten-year overall survival rate of 74% vs. 66%, although this might be partly the result of imbalanced risk factors due to competing event risk stratification.
  
  
  CONCLUSIONS
  ART has a high level of evidence due to three RCTs with at least 10-year follow-up recording a benefit in biochemical PFS, but its penetrance in present daily clinics should be reconsidered. While the benefit of ART or SRT is eagerly expected from ongoing randomized trials, a dynamic risk-stratified approach should drive the decisions making process.
authors.affiliation: Radiation Oncology, San Camillo and Forlanini Hospital, Rome, Italy. Electronic address: stefano.arcangeli@yahoo.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Arcangeli
authors.affiliation: Radiation Oncology, Campus Biomedico University, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Ramella
authors.affiliation: Radiation Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Berardino
authors.initials: B
authors.lastname: De Bari
authors.affiliation: Department of Oncology, Radiation Oncology, University of Turin School of Medicine, Turin, Italy.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Franco
authors.affiliation: Radiation Oncology Department, Sacro Cuore - Don Calabria Hospital, Negrar, Verona, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Alongi
authors.affiliation: Radiation Oncology, Campus Biomedico University, Rome, Italy.
authors.forename: Rolando M
authors.initials: RM
authors.lastname: D'Angelillo
mesh_terms: D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000532:radiotherapy* / Q000601:surgery; D018714:Radiotherapy, Adjuvant; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate