title: Neoadjuvant androgen deprivation therapy for prostate volume reduction, lower urinary tract symptom relief and quality of life improvement in men with intermediate- to high-risk prostate cancer: a randomised non-inferiority trial of degarelix versus goserelin plus bicalutamide.
abstract: OBJECTIVE
  The treatment of intermediate- to high-risk prostate cancer with radical radiotherapy is usually in combination with neoadjuvant androgen deprivation therapy. The aim of the present trial was to investigate whether degarelix achieves comparable efficacy with that of goserelin plus bicalutamide as neoadjuvant therapy before radiotherapy.
  
  
  METHODS
  The study was a randomised, parallel-arm, active-controlled, open-label trial in 244 men with a UICC prostate cancer TNM category T2b-T4, N0, M0, Gleason score ≥7, or prostate-specific antigen ≥10 ng/ml and a total prostate volume >30 ml, who were scheduled to undergo radical radiotherapy and in whom neoadjuvant androgen deprivation therapy was indicated. Eligible patients received treatment with either monthly degarelix (240/80 mg) or goserelin (3.6 mg) for 12 weeks, the latter patients also receiving bicalutamide (50 mg) for 17 days initially. The primary efficacy measure was the mean percentage reduction in total prostate volume from baseline at week 12 measured by transrectal ultrasound. The severity and relief of lower urinary tract symptoms were assessed by the International Prostate Symptom Score questionnaire. Quality of life was assessed by the eighth question of the International Prostate Symptom Score. About 50% of the patients had moderate to severe lower urinary tract symptoms at baseline.
  
  
  RESULTS
  The total prostate volume decreased significantly from baseline to week 12 in both treatment groups, reaching -36.0 ± 14.5% in degarelix-treated patients and -35.3 ± 16.7% in goserelin-treated patients (adjusted difference: -0.3%; 95% confidence interval: -4.74; 4.14%). At the end of the therapy, more degarelix- than goserelin-treated patients reported International Prostate Symptom Score decreases of ≥3 points (37% versus 27%, P = 0.21). In addition, in patients with a baseline International Prostate Symptom Score of ≥13, the magnitude of the decrease was larger in degarelix- (n = 53) versus goserelin-treated patients (n = 17) (6.04 versus 3.41, P = 0.06).
  
  
  CONCLUSIONS
  The efficacy of degarelix in terms of prostate shrinkage is non-inferior to that of goserelin plus bicalutamide. The added benefits of degarelix in terms of more pronounced lower urinary tract symptom relief in symptomatic patients could be the reflection of differences in the direct effects on extra-pituitary receptors in the lower urinary tract [Clinicaltrials.gov ID: NCT00833248].
authors.affiliation: Cardiff University, Section of Oncology & Palliative Medicine, Velindre Hospital, Cardiff, UK. MasonMD@cf.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Mason
authors.forename: X
authors.initials: X
authors.lastname: Maldonado Pijoan
authors.forename: C
authors.initials: C
authors.lastname: Steidle
authors.forename: S
authors.initials: S
authors.lastname: Guerif
authors.forename: T
authors.initials: T
authors.lastname: Wiegel
authors.forename: E
authors.initials: E
authors.lastname: van der Meulen
authors.forename: P B F
authors.initials: PB
authors.lastname: Bergqvist
authors.forename: V
authors.initials: V
authors.lastname: Khoo
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D000813:Anilides / Q000008:administration & dosage / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017273:Goserelin / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011788:Quality of Life; D012307:Risk Factors; D013739:Testosterone / Q000097:blood; D014105:Tosyl Compounds / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; 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; D013739:Testosterone; C053541:bicalutamide; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen