Patient demographics and baseline characteristics
Overall, 516 patients were enrolled in this study at the baseline visit. Following the second visit, 21 (4.1%) patients were excluded. The remaining 495 patients (95.9%) eligible at visit 3 were included in the analyzed patient population (Fig. 1). A total of 361 patients (72.9%) received EBRT and 134 patients (27.1%) received BQT treatment.
Baseline characteristics stratified by EBRT or BQT treatment groups are summarized in Table 2. At baseline, median patient age (range) was 73.0 (48.0–84.0) years and 67.0 (48.0–82.0) years for the for EBRT and BQT groups, respectively. Most patients who received EBRT had a Gleason score of ≥ 7 (73.1%), while most patients who received BQT had a Gleason score of < 7 (84.3%). A higher proportion of patients received neo-adjuvant hormone therapy in the EBRT group (62.0%) than in the BQT group (6.0%) [Table 2].
At baseline, the total EPIC-16 mean (standard deviation [SD]) scores were 11.9 (7.5) and 10.3 (7.7) for the EBRT and BQT groups, respectively (see Supplementary Fig. 1A, Additional file 1) and the UCLA-PCI mean (SD) scores ranged from 27.0 (26.8) to 90.1 (21.5) and 42.2 (30.5) to 90.3 (23.0) across the domains for the EBRT and BQT groups, respectively (see Supplementary Fig. 1B, Additional file 1).
Impact of radiotherapy on quality of life (QoL)
EPIC-16 total scores increased by a mean (SD) of 6.8 (7.6) points at visit 2 and by 2.4 (7.4) points at visit 3 for patients in the EBRT group. For patients who received BQT, the scores increased by a mean (SD) of 4.2 (7.6) and 3.9 (8.2) points at visits 2 and 3, respectively.
Overall, scores increased after radiotherapy, indicating a worsened QoL, across all EPIC-16 domains (Fig. 2). At visit 3 particularly, patients recovered their baseline scores in the urinary incontinence, bowel, vitality/hormonal, and urinary irritation domains, with the exception of the bowel and urinary irritation domains in patients receiving BQT (Fig. 2B and Fig. 2C). The sexual domain scores of patients in both groups worsened at both time points and did not recover at visit 3 compared to other domains. Patients who received concomitant hormone therapy, initiated prior to either EBRT or BQT, showed a higher mean score in the sexual domain between study visits 1 and 2 (mean [SD] visit 1: 6.79 [3.16]; mean [SD] visit 2: 8.39 [2.52]) than patients without hormone therapy (mean [SD] visit 1: 4.84 [3.45]; mean [SD] visit 2: 6.15 [3.29]).
For the overall evolution of urinary problems, e.g., item 1 of EPIC-16 (“Overall, how much of a problem has your function been for you?”), responses were similar at baseline for both EBRT and BQT patients (see Supplementary Fig. 2, Additional file 1). However, more patients treated with EBRT increasingly perceived urinary function as a small-to-big problem at visit 2 (62.0%, n = 221) compared with patients treated with BQT (53.2%, n = 67). At visit 3, patients’ perceptions returned to baseline, i.e., with urinary condition perceived as less of a problem compared with visit 2 (small-to-big problem: 35.5%, n = 126 for EBRT; 48.5%, n = 65 for BQT) [see Supplementary Fig. 2, Additional file 1].
Similarly, for patients who received EBRT, all UCLA-PCI scores showed a decrease at visit 2, indicating worsened QoL, especially in urinary bother, bowel function and bother, and sexual function domains (Fig. 3). At visit 3, scores had recovered QoL in the urinary function, urinary bother, and bowel function domains. For patients who received BQT, UCLA-PCI scores were decreased at visit 2 in the urinary bother, bowel bother, and sexual function domains, none of which recovered at visit 3 (Fig. 3).
Validation of the Spanish version of the EPIC-16 questionnaire
Psychometric validation of the EPIC-16 questionnaire was conducted in 484 patients (EBRT, n = 357; BQT, n = 127).
Reliability of EPIC-16
A strong internal consistency of the Spanish EPIC-16 questionnaire was demonstrated in the vitality/hormonal (Cronbach’s alpha = .729 [95% confidence interval (CI) .68–.77]), urinary incontinence (Cronbach’s alpha = .735 [95% CI .69–.77]), urinary irritation (Cronbach’s alpha = .777 [95% CI .74–.81]), and bowel function domains (Cronbach’s alpha = .879 [95% CI .86–.90]). Only the sexual function domain was < .7 (Cronbach’s alpha = .616 [95% CI .56–.66]).
Test–retest reliability intraclass correlation coefficient (ICC) was analyzed for 226 patients who did not perceive any change in their health status (according to the patient-perceived state of health measure) after radiotherapy. The ICC was moderate in all domains (range, .52–.66), with the exception of the bowel function domain (ICC = .232 [95% CI .10–.36]), indicating that reproducibility in this domain cannot be ensured.
Feasibility of EPIC-16
The floor effect, i.e., worst score of 12 for each domain, was present in < 1% of patients, with the exception of the sexual domain for which 24 (4.9%) patients had a maximum score of 12 at baseline, which increased to 44 (9.1%) and 56 (11.5%) patients at visits 2 and 3, respectively (see Supplementary Fig. 3, Additional file 1).
The ceiling effect, i.e., best score of 0 for each domain, was reached by a high percentage of men in urinary incontinence (n = 364; 65.6%), bowel (n = 345; 70.1%), and vitality/hormonal function (n = 223; 45.5%) domains at baseline (see Supplementary Fig. 3, Additional file 1). Generally, responses were maintained for most items during radiotherapy treatment; while some decreased at study visit 2, they recovered to baseline scores at visit 3. Only items related to sexual domain (7, 8, and 9) showed a greater number of problems and worsened after radiotherapy (see Supplementary Fig. 3, Additional file 1).
Construct validity of EPIC-16
Correlations between different EPIC-16 domains were modest (r < .50 for all Spearman’s correlations at baseline), indicating that the EPIC-16 domains are conceptually distinct and merit independent measure (see Supplementary Table 1, Additional file 1).
EPIC-16 sensitivity to change
Compared to baseline, almost all EPIC-16 mean domain scores worsened at visit 2, regardless of the health-state change as perceived by the patient; similar results were reported at visit 3, with the exception of the urinary irritation/obstruction domain which improved (Fig. 4).
Patients who reported an improved health status at visit 2 compared with baseline generally had smaller effect sizes (i.e., .20 in magnitude) versus those who reported a worsened health status; similar results were also reported at visit 3 (Fig. 4).
Correlation between EPIC-16 and UCLA-PCI
Overall, the EPIC-16 questionnaire scores showed strong correlations with the UCLA-PCI questionnaire domains at study visit 3, with Spearman’s correlations > .4 across all corresponding UCLA-PCI domains (Table 3). The urinary, bowel, and sexual function domains in the EPIC-16 questionnaire were most greatly correlated with respective domains in the UCLA-PCI questionnaire, e.g., the UCLA-PCI urinary function domain had a Spearman’s correlation coefficient with the EPIC-16 urinary incontinence domain of .713, the bowel domains with .579, and the sexual domains with .739.