Table 3

Summary of outcomes from higher quality PRO studies in non-metastatic/local disease

References*DiseaseAge of patients
(years)
Patients enrolled (n)†Treatments being comparedPrimary endpointResults of the primary clinical endpoint‡OS differenceMain PRO findings
Prescott et al 2007
Williams et al 2011
BreastMean: 72.6255The standard treatment of postoperative breast irradiation versus the omission of radiotherapyPROThe acute morbidity recorded by clinicians showed that breast erythema was significantly more common in the radiotherapy arm, at 2 weeks from completion of treatment (p<0.0001). At 8 and 12 months after surgery, breast oedema and telangiectasia were observed significantly more in women who had radiotherapy. At 12 months, breast retraction scores were significantly higher in the radiotherapy group (p=0.003).Not applicableBreast radiotherapy is tolerated well by most older patients with breast cancer without impairing their overall HRQoL.
Van Hooft et al 2011ColorectalMean (SD): 71 (10.8)98Colonic stenting versus emergency surgeryPRONo difference was recorded between treatment groups in mortality, morbidity and stoma rates.Not applicableNo differences between arms were found.
Janson et al 2004
Kuhry et al 2005
Janson et al 2007
Janson et al 2009
Buunen et al 2009
ColorectalMedian (range): 71 (54–83)1248Laparoscopic versus open surgeryDisease-free survivalThe combined 3year disease-free survival for all stages was 74.2% (95% CI 70.4% to 78.0%) in the laparoscopic group and 76.2% (95% CI 72.6% to 79.8%) in the open surgery group (p=0.70).No difference between treatment armsThe HRQOL, as measured by the EORTC QLQ-C30, demonstrated no difference at baseline. In social function, there was a statistically significant benefit of laparoscopic at the assessments at 2 and 4 weeks (p=0.046 and 0.031, respectively). At the 12-week assessment, a borderline significance was found (p=0.050). In role function, there was a significant benefit of laparoscopic at the 2-week assessment (p=0.006).
Fernando et al 2014
Fernando et al 2015
LungMedian (range): 71 (49–87)222Sublobar resection plus adjuvant intraoperative brachytherapy versus sublobar resection aloneTime to local recurrenceThere was no difference in time to local recurrence (HR 1.01, 95% CI 0.51 to 1.98; log-rank p=0.98) or in the types of local recurrence.No difference between treatment armsThere were no significant differences between the study arms in baseline QOL scores and in percentage change of QOL scores from baseline to 3, 12 or 24 months.
Irani et al 2010ProstateMean (SD): group A 71.3 (8.1), group B 73.0 (6.7), group C 73.6 (7.3)311Venlafaxine versus medroxyprogesterone acetate versus cyproterone acetatePROSerious side effects occurred in four, seven and five patients in the venlafaxine, cyproterone and medroxyprogesterone groups, respectively, of which none, one (dyspnoea) and one (urticaria) were considered related to the drug, respectively (p not reported).Not applicableThe change in median daily hot-flush score between randomisation and 1 month was −47.2% (IQR −74.3 to −2.5) in the venlafaxine group, −94.5% (−100.0 to −74.5) in the cyproterone group and −83.7% (−98.9 to −64.3) in the medroxyprogesterone group. The decrease from baseline was significant for all three groups (p<0.0001). Pairwise comparison of treatment groups adjusted by the Bonferroni method confirmed that the decreases in hot-flush score were significantly larger in the cyproterone and medroxyprogesterone groups than in the venlafaxine group, regardless of the interval considered (p<0.0001 in all cases).
Fradet et al 2007ProstateMean (range): 75 (47–94)282Oral tamoxifen (1.0, 2.5, 5.0, 10.0 or 20.0 mg/day) versus placeboPRO§
PSA inhibition (ie, baseline level minus PSA level at protocol visit expressed as a percentage of the baseline value)
There was no evidence of a negative effect on PSA inhibition at any assessment.Not applicableAt 6 and 12 months, tamoxifen decreased the incidence of breast events in a dose-dependent manner, with breast events observed in 86.2%, 60.0%, 55.3%, 23.5% and 8.8% of patients receiving tamoxifen 1.0, 2.5, 5.0, 10.0 and 20.0 mg, respectively, compared with 96.7% of patients receiving placebo at 6 months (p≤0.0002 for doses of >1 mg, p=0.0891 for tamoxifen 1 mg)
Michalski et al 2018
Bruner et al 2015
Michalski et al 2013
ProstateMedian (range): group A 71 (50–88), group B 71 (54–83), group C 71 (51–88), group D 72 (54–82)1532Conventional-dose (70.2 Gy) radiation therapy versus dose-escalated (79.2 Gy) conformal radiation therapyOSThere was no difference in OS between the 751 men in the 79.2 Gy arm and the 748 men in the 70.2 Gy arm. The 8-year rates of OS were 76% with 79.2 Gy and 75% with 70.2 Gy (HR 1.00, 95% CI 0.83 to 1.20; p= 0.98).No difference between treatment armsThere were no significant differences between treatment modalities for any of the FACE or IIEF subscale scores or total scores at any time point.
Mason et al 2013ProstateMedian: 71305Degarelix versus goserelin plus bicalutamideTotal prostate volume reductionTotal prostate volume decreased significantly from baseline to week 12 in both treatment groups (adjusted difference: −0.3%; 95% CI −4.74% to 4.14%; non-inferiority established).Not applicableAt the end of the therapy, more degarelix-treated than goserelin-treated patients reported IPSS decreases of >3 points (37% vs 27%, p=0.21). In addition, in patients with a baseline IPSS of >13, the magnitude of the decrease was larger in degarelix-treated (n=53) than in goserelin-treated patients (n=17) (6.04 vs 3.41, p=0.06).
Axcrona et al 2012ProstateMean: 72.5201Monthly degarelix (240/80 mg) or goserelin (3.6 mg) for 12 weeksTotal prostate volume reductionAt week 12, changes in total prostate volume for degarelix and goserelin were similar (−37.2% vs − 39.0%) and met the predefined non-inferiority criterion.Not applicableDecreases in IPSS were greater in degarelix-treated than in goserelin-treated patients, with differences being statistically significant in patients with baseline IPSS of >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).
Duchesne et al 2017
Duchesne et al 2016
ProstateMedian (IQR): group A 70.0 (50.7–85.0), group B 71.1 (54.0–88.0), group C 80.0 (76.4–84.9), group D 78.8 (59.4–88.9)293Immediate androgen-deprivation therapy versus delayed therapyOS5-year OS was 86.4% (95% CI 78.5% to 91.5%) in the delayed therapy arm vs 91.2% (95% CI 84.2% to 95.2%) in the immediate therapy arm (log-rank p=0.047).Improved in the experimental armSexual activity was lower in the immediate therapy group than in the delayed group at 6 and 12 months (p<0.0001), with the differences exceeding the clinically significant threshold of 10 points until beyond 2 years. The immediate therapy group also had more hormone treatment-related symptoms at 6 and 12 months (p<0.0001), but with differences below the threshold of clinical significance. For the individual symptoms, hot flushes were clinically significantly higher in the immediate group over the 5-year period (p<0.0001), as were nipple or breast symptoms (p=0.00013).
Smith et al 2018
Saad et al 2018
ProstateMedian (range): 74 (48–97)1207Apalutamide plus androgen-deprivation therapy versus placebo plus androgen-deprivation therapyMetastasis-free survivalMedian metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (HR for metastasis or death 0.28, 95% CI 0.23 to 0.35; p<0.001).No difference between treatment armsGroup mean PRO scores over time show that HRQOL was maintained from baseline after initiation of apalutamide treatment and was similar over time among patients receiving apalutamide versus placebo. Least-squares mean change from baseline shows that HRQOL deterioration was more apparent in the placebo group.
  • *The full list of references are reported in the online supplementary appendix C .

  • †Overall number of patients recruited in the study regardless of those with a baseline PRO assessment.

  • ‡When an RCT had no primary clinical endpoint, we reported the results of the main secondary clinical endpoint.

  • §In this study, PRO and PSA inhibition were co-primary endpoints.

  • EORTC, European Organisation for Research and Treatment of Cancer; FACE, functional alterations due to changes in elimination; HRQOL, health-related quality of life; IIEF, International Index of Erectile Function; IPSS, International Prostate Symptom Score; OS, overall survival; PRO, patient-reported outcome; PSA, prostate-specific antigen; QOL, quality of life;RCT, randomised controlled trial.