title: Androgen deprivation therapy for volume reduction, lower urinary tract symptom relief and quality of life improvement in patients with prostate cancer: degarelix vs goserelin plus bicalutamide.
abstract: Study Type--Therapy (RCT) Level of Evidence 1b. What's known on the subject? and What does the study add? Androgen deprivation therapy (ADT) is commonly used as a primary treatment for patients with prostate cancer (PCa) who are not eligible for radical treatment options. ADT is also used in patients with PCa as neo-adjuvant hormone therapy to reduce prostate volume and down-stage the disease before radiotherapy with curative intent. The present study showed that ADT with the gonadotropin hormone-releasing hormone (GhRH) antagonist degarelix is non-inferior to combined treatment with the LHRH agonist goserelin and bicalutamide in terms of reducing prostate volume during the treatment period of 3 months. Degarelix treatment evokes, however, significantly better relief of lower urinary tract symptoms in patients having moderate and severe voiding problems.
  
  
  OBJECTIVE
  • To assess the efficacy of monthly degarelix treatment for reduction of total prostate volume (TPV), relief of lower urinary tract symptoms (LUTS) and improvement of quality of life (QoL) in patients with prostate cancer (PCa) using monthly goserelin as active control.
  
  
  METHODS
  • This was a randomized, parallel-arm, active-controlled, open-label, multicentre trial on 182 patients treated with either monthly degarelix (240/80 mg) or goserelin (3.6 mg) for 12 weeks. • For flare protection, goserelin-treated patients also received daily bicalutamide (50 mg) during the initial 28 days. • Key trial variables monitored monthly were TPV (primary endpoint), serum testosterone, prostate-specific antigen (PSA), the International Prostate Symptom Score (IPSS) and the Benign Prostate Hyperplasia Impact Index.
  
  
  RESULTS
  • In all, 175 patients completed the trial (96.1%). • At week 12, changes in TPV for degarelix and goserelin were similar (-37.2% vs -39.0%) and met the predefined non-inferiority criterion. • Decreases in IPSS were greater in degarelix than in goserelin-treated patients, differences being statistically significant in patients with baseline IPSS > 13 (-6.7 ± 1.8 vs -4.0 ± 1.0; P = 0.02). • The number of patients with an IPSS change of ≥ 3 over baseline was also significantly higher in patients treated with degarelix (61.0 vs 44.3%, P = 0.02). • Both treatments were safe and well tolerated.
  
  
  CONCLUSIONS
  • Medical castration reduces TPV and could also improve LUTS in patients with PCa. • While the short-term efficacy of degarelix and goserelin + bicalutamide was the same in terms of TPV reduction, degarelix showed superiority in LUTS relief in symptomatic patients, which could highlight the different actions of these drugs on extrapituitary gonadotrophin-releasing hormone (GnRH) receptors in the bladder and/or the prostate.
authors.affiliation: Department of Urology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. karol. axcrona@radiumhospitalet.no
authors.forename: Karol
authors.initials: K
authors.lastname: Axcrona
authors.forename: Sirpa
authors.initials: S
authors.lastname: Aaltomaa
authors.forename: Carlos Martins
authors.initials: CM
authors.lastname: da Silva
authors.forename: Haluk
authors.initials: H
authors.lastname: Ozen
authors.forename: Jan-Erik
authors.initials: JE
authors.lastname: Damber
authors.forename: László B
authors.initials: LB
authors.lastname: Tankó
authors.forename: Enrico
authors.initials: E
authors.lastname: Colli
authors.forename: Peter
authors.initials: P
authors.lastname: Klarskov
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D059411:Lower Urinary Tract Symptoms / Q000209:etiology / Q000517:prevention & control; D008297:Male; D009570:Nitriles / Q000008:administration & dosage; D009842:Oligopeptides / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011788:Quality of Life; D014105:Tosyl Compounds / Q000008:administration & dosage; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D003692:Delayed-Action Preparations; D009570:Nitriles; D009842:Oligopeptides; D014105:Tosyl Compounds; C431566:acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; C053541:bicalutamide