Summary of outcomes from higher quality PRO studies in non-metastatic/local disease
| References* | Disease | Age of patients (years) | Patients enrolled (n)† | Treatments being compared | Primary endpoint | Results of the primary clinical endpoint‡ | OS difference | Main PRO findings |
| Prescott et al 2007 Williams et al 2011 | Breast | Mean: 72.6 | 255 | The standard treatment of postoperative breast irradiation versus the omission of radiotherapy | PRO | The 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 applicable | Breast radiotherapy is tolerated well by most older patients with breast cancer without impairing their overall HRQoL. |
| Van Hooft et al 2011 | Colorectal | Mean (SD): 71 (10.8) | 98 | Colonic stenting versus emergency surgery | PRO | No difference was recorded between treatment groups in mortality, morbidity and stoma rates. | Not applicable | No 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 | Colorectal | Median (range): 71 (54–83) | 1248 | Laparoscopic versus open surgery | Disease-free survival | The 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 arms | The 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 | Lung | Median (range): 71 (49–87) | 222 | Sublobar resection plus adjuvant intraoperative brachytherapy versus sublobar resection alone | Time to local recurrence | There 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 arms | There 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 2010 | Prostate | Mean (SD): group A 71.3 (8.1), group B 73.0 (6.7), group C 73.6 (7.3) | 311 | Venlafaxine versus medroxyprogesterone acetate versus cyproterone acetate | PRO | Serious 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 applicable | The 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 2007 | Prostate | Mean (range): 75 (47–94) | 282 | Oral tamoxifen (1.0, 2.5, 5.0, 10.0 or 20.0 mg/day) versus placebo | PRO§ 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 applicable | At 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 | Prostate | Median (range): group A 71 (50–88), group B 71 (54–83), group C 71 (51–88), group D 72 (54–82) | 1532 | Conventional-dose (70.2 Gy) radiation therapy versus dose-escalated (79.2 Gy) conformal radiation therapy | OS | There 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 arms | There 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 2013 | Prostate | Median: 71 | 305 | Degarelix versus goserelin plus bicalutamide | Total prostate volume reduction | Total 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 applicable | At 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 2012 | Prostate | Mean: 72.5 | 201 | Monthly degarelix (240/80 mg) or goserelin (3.6 mg) for 12 weeks | Total prostate volume reduction | At 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 applicable | Decreases 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 | Prostate | Median (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) | 293 | Immediate androgen-deprivation therapy versus delayed therapy | OS | 5-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 arm | Sexual 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 | Prostate | Median (range): 74 (48–97) | 1207 | Apalutamide plus androgen-deprivation therapy versus placebo plus androgen-deprivation therapy | Metastasis-free survival | Median 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 arms | Group 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.