Mason 2013 (CS30).

Study characteristics
Methods	Study design: parallel‐group randomized controlled clinical trial Study dates: 2009 to 2011 Setting: multicenter, outpatient, international Country: France, Germany, Greece, Netherlands, Spain, United Kingdom, United States Official title: a randomized, parallel‐arm, open‐label trial comparing degarelix with goserelin plus antiandrogen flare protection (bicalutamide), in terms of prostate size reduction in prostate cancer patients of intermediate‐to‐high risk, who require neoadjuvant hormone therapy prior to radiotherapy (curative intent) Follow‐up: 12 weeks
Participants	Inclusion criteria: UICC prostate cancer TNM category T2b to T4, N0, M0, Gleason score ≥ 7, or PSA ≥ 10 ng/mL and prostate volume > 30 mL; scheduled to undergo radical radiotherapy treatment and in whom neoadjuvant androgen suppression therapy was indicated Patient has given written informed consent before any trial‐related activity is performed Exclusion criteria: Previous treatment for prostate cancer Previous trans‐urethral resection of the prostate Patients who are lymph node positive or have other metastatic disease Use of urethral catheter Current treatment with a 5‐alpha reductase inhibitor or α‐adrenoceptor antagonist History of severe untreated asthma, anaphylactic reactions, or severe urticaria and/or angioedema Hypersensitivity towards any component of the investigational product Other previous cancers within the last 5 years with the exception of prostate cancer and some types of skin cancer Certain risk factors for abnormal heart rhythms/QT prolongation (corrected QT interval over 450 ms, torsades de pointes, or use of certain medications with potential risk) Clinical disorders other than prostate cancer including but not limited to renal, hematological, gastrointestinal, endocrine, cardiac, neurological, psychiatric disease, alcohol or drug abuse, or other conditions as judged by the Investigator Sample size: 246 (randomized)/244 (treated) Stage of disease, n (%): localized 152 (62%); advanced 83 (34%); not classifiable 9 (4%)
Interventions	Group 1 (n = 180): degarelix 240 mg/80 mg administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL s.c. injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively. Group 2 (n = 64): goserelin (3.6 mg) + bicalutamide (50 mg); on Day 0, men began once‐daily oral treatment with bicalutamide as antiandrogen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.
Outcomes	Primary outcomes: Change from baseline in prostate size based on trans‐rectal ultrasound (TRUS) at Week 12 Secondary outcomes: Change from baseline in total IPSS at Weeks 4, 8, and 12 Change from baseline in serum testosterone levels during the study Change from baseline in serum PSA levels during the study Change from baseline in serum estradiol levels during the study Change from baseline in QoL related to urinary symptoms at each visit. The IPSS questionnaire included an additional single question to assess the participant's QoL in relation to his urinary symptoms. The question was: 'If you were to spend the rest of your life with your urinary condition the way it is now, how would you feel about that?' The possible answers to this question ranged from 'delighted' (a score of '0') to 'terrible' (a score of '6'). Number of participants with markedly abnormal values in vital signs and body weight Number of participants with markedly abnormal values in safety laboratory variables
Funding sources	Ferring Pharmaceuticals
Declarations of interest	Authors had industry relationships.
Notes	Trial ID: NCT00833248, EUCTR2008‐005232‐33‐NL
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote from publication: “patients were randomised in a 3:1 ratio” Comment: insufficient information to permit judgment.
Allocation concealment (selection bias)	Unclear risk	Quote from publication: “patients were randomised in a 3:1 ratio” Comment: insufficient information to permit judgment.
Blinding of participants and personnel (performance bias) Subjective outcomes	High risk	Quote from publication: “open‐label trial”; there was no blinding (or it was not reported) Comment: we judge that subjective outcomes are influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Subjective outcomes	Unclear risk	Quote from publication: “open‐label trial”; there was no blinding of outcome assessment (or it was not reported) Comment: insufficient information to permit judgment.
Incomplete outcome data (attrition bias) Biochemical progression	Unclear risk	Comment: the study did not address this outcome.
Incomplete outcome data (attrition bias) Adverse events	Low risk	Comment: no missing outcome data.
Incomplete outcome data (attrition bias) Quality of life	Unclear risk	Comment: quality of life assessment was not included because data were not relevant to this review (scale used: IPSS).
Selective reporting (reporting bias)	Low risk	Comment: the study protocol is available, and all outcomes of interest have been reported.
Other bias	Low risk	Comment: we did not identify other sources of bias.