title: Comparative efficacy, tolerability, and survival outcomes of various radiopharmaceuticals in castration-resistant prostate cancer with bone metastasis: a meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  A meta-analysis was conducted to assess the impact of radiopharmaceuticals (RPs) in castration-resistant prostate cancer (CRPC) on pain control, symptomatic skeletal events (SSEs), toxicity profile, quality of life (QoL), and overall survival (OS).
  
  
  METHODS
  The PubMed/MEDLINE, CANCERLIT, EMBASE, Cochrane Library database, and other search engines were searched to identify randomized controlled trials (RCTs) comparing RPs with control (placebo or radiation therapy) in metastatic CRPC. Data were extracted and assessed for the risk of bias (Cochrane's risk of bias tool). Pooled data were expressed as odds ratio (OR), with 95% confidence intervals (CIs; Mantel-Haenszel fixed-effects model).
  
  
  RESULTS
  Eight RCTs with a total patient population of 1,877 patients were identified. The use of RP was associated with significant reduction in pain intensity and SSE (OR: 0.63, 95% CI: 0.51-0.78, I(2)=27%, P,0.0001), improved QoL (OR: 0.71, 95% CI: 0.55-0.91, I(2)=65%, three trials, 1,178 patients, P=0.006), and a minimal improved OS (OR: 0.84, 95% CI: 0.64-1.04, I(2)=47%, seven trials, 1,845 patients, P=0.11). A subgroup analysis suggested an improved OS with radium-223 (OR: 0.68, 95% CI: 0.51-0.90, one trial, 921 patients) and strontium-89 (OR: 0.21, 95% CI: 0.05-0.91, one trial, 49 patients). Strontium-89 (five trials) was associated with increased rates of grade 3 and 4 thrombocytopenia (OR: 4.26, 95% CI: 2.22-8.18, P=0.01), leucopenia (OR: 7.98, 95% CI: 1.82-34.95, P=0.02), pain flare (OR: 6.82, 95% CI: 3.42-13.55, P=0.04), and emesis (OR: 3.61, 95% CI: 1.76-7.40, P=0.02).
  
  
  CONCLUSIONS
  The use of RPs was associated with significant reduction in SSEs and improved QoL, while the radium-223-related OS benefit warrants further large, RCTs in docetaxel naive metastatic CRPC patients.
authors.affiliation: Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia.
authors.forename: Mutahir
authors.initials: M
authors.lastname: Tunio
authors.affiliation: Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia.
authors.forename: Mushabbab
authors.initials: M
authors.lastname: Al Asiri
authors.affiliation: Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia.
authors.forename: Abdulrehman
authors.initials: A
authors.lastname: Al Hadab
authors.affiliation: Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt.
authors.forename: Yasser
authors.initials: Y
authors.lastname: Bayoumi
mesh_terms: D001859:Bone Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D016009:Chi-Square Distribution; D006801:Humans; D008297:Male; D016017:Odds Ratio; D064129:Prostatic Neoplasms, Castration-Resistant / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011788:Quality of Life; D011832:Radiation Injuries / Q000209:etiology; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D019275:Radiopharmaceuticals
keywords: castration-resistant prostate cancer; meta-analysis; overall survival; pain control; quality of life; radiopharmaceuticals; symptomatic skeletal events