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Table 1 Descriptive of the 30 studies aiming to compare at least two interventions in a population of patients with or susceptible to have PC

From: A mini-review of quality of life as an outcome in prostate cancer trials: patient-centered approaches are needed to propose appropriate treatments on behalf of patients

Study Design Inclusion criteria Treatments Primary endpoints Secondary endpoints HRQoL analysis Other results
[26] multicentric, double-blind, phase 3, 2008–2011, follow-up of 48 months adult, chemotherapy-naive, metastatic, castration-resistant PC, adequate organ function dasatinib (n = 762) vs placebo (n = 760) overall survival proportion who achieved an objective response, time to first skeletal-related event, proportion with reduction > 35% in urinary N-telopeptide from baseline, progression-free survival, time to PSA progression, and proportion with reduction > 30% in pain intensity from baseline BPI-SF stratified Cochran-Mantel-Haenszel no
[27] multicentric, double-blind, phase 3, 2009–2010, follow-up of 30 months progressive, metastatic castration-resistant PC, BPI-SF score of zero to three, not previous chemotherapy abiraterone (n = 546) vs placebo (n = 542) time to pain progression (BPI-SF): increase ≥30% from baseline of the mean pain intensity, or increase ≥30% from baseline of the worst pain intensity, or increase ≥50% from baseline of the interference pain intensity time to HRQoL deterioration (FACT-P) from baseline: decrease of the total score > 10%, or decrease of the general function > 9%, or decrease of the trial outcome index > 9%, or decrease of the prostate-specific-subscale > 3%, or decrease of the general function subscales > 3% Kaplan-Meier [47]
[28] multicentric, double-blind, phase 3, 2010–2012, follow-up of 18 months metastases and PSA progression, radiographic progression, or both in bone or soft tissue, despite receiving luteinizing hormone-releasing hormone analogue therapy or undergoing orchiectomy, serum testosterone level < 1·73 nmol/L, ECOG grade 0–1, BPI-SF score 0–3 enzalutamide (n = 872) vs placebo (n = 845) radiographic progression-free survival and overall survival time to initiation of cytotoxic chemotherapy, time to first skeletal-related event, best overall soft-tissue response, time to PSA decline > 50% or more from baseline, time to decline in QoL (FACT-P) Kaplan-Meier no
[29] multicentric, open-label, phase 3, 1989–1999, follow-up of 18 years younger than 75 years of age, life expectancy > 10 years, no other known cancers, localized tumor (T0d, T1, or T2, 1978 criteria of the International Union against Cancer) radical-prostatectomy (n = 347) vs watchful-waiting (n = 348) death from any cause, death from PC, and the risk of metastases initiation of androgen deprivation therapy no no
[30] multicentric, double-blind, phase 3, 1997–2010, follow-up of 24 months radical prostatectomy for clinically localized (T1c or T2) PC less than 4 months before randomization, post-surgery PSA < 0.07 ng/mL confirmed by the assay used in this study, and fulfilled one or more following criteria: preoperative PSA > 20.0 ng/mL, final Gleason score ≥ 8, positive surgical margins, extracapsular extension, seminal vesicle invasion, or micro metastases in any removed pelvic lymph nodes soy protein supplement (n = 86) vs placebo (n = 90) 2-year rate of biochemical cancer recurrence and time to recurrence for those in whom cancer recurred adverse events (gastrointestinal, urinary tract, initiation of cholesterol or hypertension treatments, musculoskeletal pain) no no
[31] multicentric, open-label, phase 3, 1998–2001, follow-up of 10 years adult, histologically confirmed (T1b–T3a, N0, M0), PSA < 50 ng/mL, no contraindications for radical radiotherapy escalated-dose (n = 422) vs control-doses (n = 421) radiotherapy Biochemical progression-free survival and overall survival biochemical failure, initiation of androgen deprivation therapy, progression-free survival, metastases-free survival, time to PC or non-PC death no no
[32] multicentric, open-label, phase 3, 2003–2007, follow-up of 7 years locally advanced PC (either T2a N0 M0, PSA ≥10 μg/L, Gleason score of ≥7) or T2b–4 N0 M0 tumors regardless of PSA and Gleason score androgen suppression + leuprorelin (n = 268) or zoledronic acid (n = 268) or both (n = 267) vs standard (n = 268) PC-specific mortality PSA progression, local progression, distant progression, bone progression, time to secondary therapeutic intervention, all-cause mortality no no
[33] multicentric, double-blind, phase 3, 2008–2011, follow-up of 38 months adult, histologically or cytologically confirmed PC, surgically castrated or continuously medically castrated, serum testosterone levels ≤ 2·4 nmol/L oral zibotentan (524) vs placebo (528) overall survival time to pain and PSA progression, progression-free survival, safety, time to deterioration of symptoms (FACT-P Symptom Index-8), time to deterioration of HRQoL (FACT-P total scores) Log-rank no
[34] multicentric, open-label, phase 2, 2011–2013, 108 weeks progressive metastatic castration-resistant PC, castrate concentrations of testosterone, ECOG grade 0–1 1400 (n = 35) or 400 (n = 37) mg daily doses of ODM-201 vs standard (n = 38) PSA response at week 12, defined as a decrease of 50% or more in serum PSA from baseline objective disease response (RECIST for soft tissue and PCWG2 criteria for bone), time to PSA progression analyzed (PCWG2 criteria), and time to radiographic disease progression (RECIST and PCWG2 criteria) no no
[35] multicentric, double-blind, phase 3, 2009–2010, follow-up of 24 months histologically or cytologically confirmed PC, undergone orchiectomy or received gonadotropin-releasing hormone agonist therapy, castrate testosterone levels, ECOG grade 0–2, previously received docetaxel, progressive disease (PCWG2 criteria) enzalutamide (n = 800) vs placebo (n = 399) overall survival time to first skeletal-related event, change in pain severity and interference from baseline to week 13, pain palliation at week 13, pain progression at week 13, time to pain progression, overall improvement in HRQoL, improvements in individual HRQoL domains, time to HRQoL deterioration (FACT-P) Kaplan-Meier, Log-Rank, stratified Cochran-Mantel-Haenszel no
[54] multicentric, double-blind, phase 3, follow-up of 30 months adult, histologically or cytologically confirmed PC, radiographically documented metastatic disease with evidence of disease progression after receiving docetaxel orteronel (n = 734) vs placebo (n = 365) overall survival radiographic progression-free survival, PSA decrease > 50% at 12 weeks, pain response at 12 weeks, response by RECIST 1·1, time to PSA progression, duration of pain response, time to pain progression, safety no no
[36] simulation-based study, follow-up of 11 years between the ages of 55 and 75 years screening vs non-screening incremental cost-effectiveness ratio life-years gained, costs, gained in quality-adjusted life-years no no
[37] multicentric, double-blind, phase 3, 2008–2011, follow-up of 36 months histologically confirmed, progressive castration-resistant PC, two or more bone metastases detected on skeletal scintigraphy and no known visceral metastases, baseline PSA level ≥ 5 ng/mL, evidence of progressively increasing PSA values, ECOG grade 0–2, life expectancy ≥ 6 months, adequate hematologic, renal, and liver function radium-223 (n = 614) vs placebo (n = 307) overall survival time to first symptomatic skeletal event, time to increase in PSA concentration, time to increase in total alkaline phosphatase concentration, confirmed reduction of at least 30% in total alkaline phosphataseponse, normalization of total alkaline phosphatase concentration no [42, 48]
[38] multicentric, open-label, phase 3, 1996–1999, follow-up of 12 years born between 1929 and 1944 (aged 55, 59, 63, or 67 years at entry), identified from the Finnish population Registry, no previous PC diagnosis screening (n = 31,866) vs non-screening (n = 48,278) overall mortality and prostate-specific mortality no no no
[39] multicentric, double-blind, phase 3, 2009–2012, follow-up of 36 months at least one bone metastasis from castration-resistant PC, progression after docetaxel treatment ipilimumab (n = 399) vs placebo (n = 400) overall survival progression-free survival, pain response, safety profile no no
[40] multicentric, double-blind, phase 3, 2008–2010, follow-up of 36 months histologically or cytologically confirmed PC, metastatic and castration-resistant (refractory to androgen ablation), surgical or ongoing chemical castration, baseline testosterone level < 50 ng/dL sunitinib (n = 584) vs placebo (n = 289) overall survival progression-free survival, objective response rate, safety no no
[41] open-label, pilot study, follow-up of 3 months localized PC (T1c-T3,N0/NX), Gleason score > 6, risk of nodal involvement > 10%, no prior therapy for PC, no history of thrombosis, no unstable angina, no heart failure, serum testosterone > 280 ng/dL, normal blood counts, creatinine, and transaminases goserelin (n = 12) or bicalutamide (n = 10) + dutasteride vs bicalutamide, dutasteride, and ketoconazole (n = 13) Prostate tissue androgen levels serum androgen levels, prostate androgen receptor program activity, PSA nadir, pathologic outcomes no no
[42] multicentric, double-blind, phase 3, 2008–2011, follow-up of 38 months histologically confirmed, progressive castration-resistant PC, two or more bone metastases detected on skeletal scintigraphy and no known visceral metastases, baseline PSA level ≥ 5 ng/mL, evidence of progressively increasing PSA values, ECOG grade 0–2, life expectancy ≥ 6 months, adequate hematologic, renal, and liver function radium-223 (n = 614) vs placebo (n = 307) overall survival time to the first symptomatic skeletal event, clinically evaluated symptomatic skeletal events, total alkaline phosphatase and PSA concentrations, adverse events, mean change in the FACT-P total score at week 16 Student [37, 48]
[43] multicentric, double-blind, phase 3, 2009–2012, follow-up of 52 weeks adult, clinical stage II (T1b-T2bN0M0) PC, with i) Gleason score < seven and the serum PSA level < 20 ng/mL, or ii) Gleason score ≥ seven and PSA < 15 ng/mL, ability to achieve erection at least half the time (International Index of Erectile Function question one response 3–5), Zubrod Performance Status score < 2, serum testosterone within normal limits, and no prior bilateral orchiectomy, chemotherapy, external radiotherapy, brachytherapy, surgical, or other ablative therapy for PC tadalafil (n = 121) vs placebo (n = 31) maintaining spontaneous erections between weeks 28 and 30 after the start of radiotherapy overall sexual function, sexual satisfaction, marital adjustment and their partners’ sexual satisfaction, adverse events (NCI Common Terminology Criteria for Adverse Events, version 4) Fisher, Student, Wilcoxon, generalized estimation equation, logistic, Spearman no
[44] multicentric, open-label, phase 3, 2000–2004, follow-up of 10 years adult, PC with one of the following criteria: clinical classification T1b-4 (American Joint Committee on Cancer staging system, 5th edition), Gleason grade 2–6 and PSA > 10 but < 100 ng/mL, T1b-4 Gleason grade seven and PSA < 20 ng/mL, or T1b-1c Gleason score 8–10 and PSA < 20 ng/mL 28 weeks (n = 737) vs 8 weeks (n = 752) of androgen suppression PC-specific mortality overall and disease-free survival, time to loco regional progression or distant metastatic progression, time to biochemical failure and to biochemical failure on secondary androgen suppression, adverse events no no
[45] phase 3, 2002–2006, follow-up of 7 years favorable- to high-risk PC hypofractionated external-beam radiotiony (n = 151) vs conventional fractionation intensity-modulated radiation (n = 152) cumulative incidence of biochemical and/or clinical disease failure toxicity (modified LENT and RTOG) criteria, PC mortality, overall survival no no
[46] multicentric, double-blind, phase3, 2006–2010, follow-up of 60 months pathologically confirmed PC with evidence of bone metastases on a bone scan, judged to be unresponsive or refractory to hormone treatment atrasentan (n = 498) vs placebo (n = 496) progression-free survival and overall survival toxicities no (results will be reported separately) no
[47] multicentric, double-blind, phase 3, 2009–2010, follow-up of 60 months PSA progression (PCWG2 criteria) or radiographic progression in soft tissue or bone, ongoing androgen deprivation therapy with a serum testosterone level < 50 ng/dL, ECOG grade 0–1, BPI-SF score 0–3 abiraterone acetate (n = 546) vs placebo (n = 542) radiographic progression-free survival and overall survival time to opiate use for cancer-related pain, long-term safety no [27]
[48] multicentric, double-blind, phase 3, 2008–2011, follow-up of 32 months histologically confirmed, progressive castration-resistant PC, two or more bone metastases detected on skeletal scintigraphy and no known visceral metastases, baseline PSA level ≥ 5 ng/mL, evidence of progressively increasing PSA values, ECOG grade 0–2, life expectancy ≥ 6 months, adequate hematologic, renal, and liver function radium-223 (n = 614) vs placebo (n = 307) overall survival time to first symptomatic skeletal event, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture, occurrence of spinal cord compression, occurrence of tumor-related orthopedic surgical intervention no [37, 42]
[1] multicentric, open-label, phase 3, 1994–2013, follow-up of 13 years aged 50–74 years from population registries and randomly assigned by computer generated random numbers PSA screening (n = 7408) vs no intervention (n = 6107) PC-specific mortality no no no
[49] multicentric, double-blind, phase 3, 2006–2008, follow-up of 42 months adult, histologically confirmed, non-metastatic castration-resistant PC at high risk for developing bone metastasis, as characterized by PSA ≥ 8.0 ng/mL within 3 months before random assignment, PSA doubling time ≤ 10 months at baseline, or both denosumab (n = 716) vs placebo (n = 716) time to first occurrence of bone metastasis or death resulting from any cause time to first bone metastasis excluding deaths, overall survival no no
[50] phase 3, blind, 2004–2012, follow-up of 36 months adult, histologically confirmed PC, at least one bone metastasis by radiographic imaging, with ECOG grade 0–2, creatinine clearance (Cockroft-Gault) > 30 mL/min zoledronic acid (n = 323) vs placebo (n = 322) time to first skeletal-related event overall survival, progression-free survival, safety no no
[51] multicentric, double-blind, phase 3, 2007–2010, follow-up of 54 months metastatic castrate-resistant PC, adequate organ function, no prior chemotherapy aflibercept (n = 612) vs placebo (n = 612) overall survival PSA response, time to skeletal-related event, progression-free survival no (results will be reported separately) no
[52] multicentric, open-label, phase 2, 2009–2011, follow-up of 24 weeks intermediate- and high-risk patients had histologically confirmed localized PC (> three positive biopsies) and one of the following criteria: PSA > 10 ng/mL, PSA velocity > 2 ng/mL per year, Gleason score > 7 24-week (n = 30) vs 12-week (n = 28) abiraterone acetate 12-week prostate tissue testosterone and dihydrotestosterone levels 12- and 24-week intra prostatic hormones, serum hormones, monthly serum PSA, and prostate pathologic assessment no no
[53] multicentric, double-blind, phase 3, 2007–2010, follow-up of 12 weeks moderate to severe hot flashes ≥ four per day, life expectancy > 9 months, no history of hepatic dysfunction, no allergies to soy or dairy, no uncontrolled hypertension, no history of seizures, no history of intolerance to venlafaxine venlafaxine + milk powder or placebo + soy powder or venlafaxine + soy powder vs placebo + milk powder number of hot flashes times severity 12-week QoL level (FACT-P), adverse events ANalysis Of VAriances no