title: High dose versus conventional dose in external beam radiotherapy of prostate cancer: a meta-analysis of long-term follow-up.
abstract: OBJECTIVE
  To assess the efficacy and toxicity between high-dose radiotherapy (HDRT) and conventional-dose radiotherapy (CDRT) by collecting randomized controlled trials of long-term follow-ups.
  
  
  METHODS
  Unrestricted by language, we searched Ovid MEDLINE, Ovid EMBASE, Cochrane Library, Science Citation Index (Web of Science) and ClinicalTrials.gov for the following end points: biochemical failure (BF), overall survival (OS), prostate cancer-specific survival (PCSS) and side effects. The meta-analysis was performed by using Review Manager 5.2 and Stata version 12.0 software packages. Results were expressed as the odds ratio (OR) with the corresponding 95 % confidence interval (CI).
  
  
  RESULTS
  Six randomized controlled trials, with a total population of 2,822, were eligible. In terms of 10-year efficacy relative to CDRT, the HDRT was associated with almost an equivalent OS (73.4 vs. 74.3 %, OR 1.05, 95 % CI 0.86-1.28; p = 0.64) and PCSS (90.7 vs. 91.6 %, OR 1.11, 95 % CI 0.83-1.49; p = 0.47), but a significant decrease in the BF (34.0 vs. 24.7 %, OR 0.61, 95 % CI 0.51-0.74; p < 0.00001). In terms of toxicity, HDRT significantly increased the late Grade 2 or higher (G ≥ 2) gastrointestinal toxicity (28.0 vs. 18.6 %, OR 1.72, 95 % CI 1.42-2.08; p < 0.00001) and late G ≥ 2 genitourinary (GU) toxicity (22.6 vs. 19.5 %, OR 1.24, 95 % CI 1.01-1.52; p = 0.04). In the subgroup analysis, trials with or without androgen deprivation therapy both had a significant decrease in the BF at 10 years. With regard to quality of life, there was no significant difference between HDRT and CDRT (p > 0.05).
  
  
  CONCLUSIONS
  This was the first meta-analysis of trials with long-term follow-up to indicate that HDRT is superior to CDRT in terms of preventing BF in localized prostate cancer patients. However, this advantage did not translate into an improvement in OS and PCSS. This was also the first meta-analysis to suggest that the HDRT in three-dimensional conformal radiotherapy (3D-CRT) significantly increases the late G ≥ 2 GU toxicity. Thus, the dose escalation in 3D-CRT should be discreetly used in the treatment of prostate cancer due to the increase in late toxicities.
authors.affiliation: West China Hospital Cancer Center, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Zan
authors.initials: Z
authors.lastname: Hou
authors.forename: Guangjun
authors.initials: G
authors.lastname: Li
authors.forename: Sen
authors.initials: S
authors.lastname: Bai
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D004307:Dose-Response Relationship, Radiation; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000209:etiology; D041981:Gastrointestinal Tract / Q000528:radiation effects; D006801:Humans; D008297:Male; D052801:Male Urogenital Diseases / Q000209:etiology; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011788:Quality of Life; D011832:Radiation Injuries / Q000453:epidemiology / Q000209:etiology*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D017211:Treatment Failure; D016896:Treatment Outcome; D014566:Urogenital System / Q000528:radiation effects
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen