The 1642 men with localised prostate cancer included in this study were 37 to 69 years of age (mean 61.2 years) when diagnosed (table 1). A total of 981 cases (60%) had radical prostatectomy, and most of the remainder had external beam radiotherapy, with or without androgen deprivation therapy (289/1636 (18%)) or active surveillance (200/1636 (12%)). Just over half of the radical prostatectomies were nerve sparing in intent (494/981). Four men who had orchidectomy as primary therapy and two with unknown primary therapy were excluded from further analysis.
Table 1 Baseline demographic and clinical characteristics of cases of prostate cancer and baseline demographic characteristics of controls
There was significant heterogeneity within treatment types of all demographic characteristics—except country of birth and comorbidity—and all disease characteristics (all P<0.001). Cases who had radical prostatectomy or low dose rate brachytherapy tended to be younger and have earlier stage disease, lower prostate specific antigen levels, and lower Gleason score than cases in other treatment groups, and tended to have higher incomes and better education. Cases who had nerve sparing prostatectomy were younger and more likely to have higher baseline sexual function than those who did not have it. Cases who had external beam radiotherapy or androgen deprivation therapy, or the two combined, were older, had later stage disease, and had more comorbidity than those who received other treatments. There were no substantial differences in the demographic profiles of the controls and the cases (pooled across treatments).
A total of 1493 (91%) patients with prostate cancer interviewed at baseline were also interviewed at three years; 1530 (93%) cases and 433 (87%) controls completed the two year interview. Completion rates differed across treatment groups and ranged from 97% (low dose rate brachytherapy) to 77% (androgen deprivation therapy (fig 2). The smallest number of cases remaining at three years in any group was 43 in the group who had been treated with high dose rate brachytherapy. When all variables in table 1 were included in a logistic regression model, only being born overseas (odds ratio (OR) 1.52, 95% confidence interval (CI) 1.02 to 2.27) and not having private health insurance (OR 1.85, 95% CI 1.21 to 2.83) increased the likelihood of withdrawal from the study.
Fig 2 Percentage of quality of life interviews completed annually by each group. Abbreviations: ADT, androgen deprivation therapy; EBRT, external beam radiation therapy; HDR, high dose rate; LDR, low dose rate
At the three year interview, 99 cases (6.6%) reported that they had been diagnosed with “recurrent disease or disease that had spread after diagnosis.” None of the men who had received low dose rate brachytherapy reported this outcome, whereas two (2%) who had undergone external beam radiotherapy, five (3%) on active surveillance, 64 (7%) who had been treated with radical prostatectomy, and four (30%) who had received androgen deprivation therapy alone reported recurrent disease or disease spread. Of the variables in table 1, only Gleason score (OR 1.87, 95% CI 1.47 to 2.38) and the log of prostate specific antigen level (OR 1.96, 95% CI 1.42 to 2.72) were independent, statistically significant predictors of recurrence or spread.
General quality of life
Table 2 presents the mean scores for each quality of life domain and treatment group at baseline and at year three. Given that these scores are not adjusted for clinical and demographic characteristics, they reflect the combined impact of disease, treatment, and age on long term quality of life. Mental component scores of cases at baseline were similar to those of controls for all groups, except those having non-nerve sparing radical prostatectomy (table 2). Overall, men with localised prostate cancer had higher baseline physical scores than controls, in particular men who had nerve sparing radical prostatectomy (OR 1.85, 95% CI 1.48 to 2.32) or low dose rate brachytherapy (OR 2.36, 95% CI 1.43 to 3.89). Men who had androgen deprivation therapy, however, had lower scores than controls.
Table 2 Mean unadjusted physical, mental, urinary, bowel, and sexual domain scores at baseline and three years after diagnosis for patients with prostate cancer and for controls
After adjustment for baseline physical component score, age, income, area of residence, and comorbidity, men who had androgen deprivation therapy alone were least likely to have better physical scores than controls at three years after diagnosis (fig 3).
Fig 3 Adjusted odds ratios and 95% confidence intervals for the likelihood of having higher physical or mental component scores than controls at one to three years after diagnosis. *Adjusted for age, baseline physical score, region of residence, income, (more ...)
Cases who had radical prostatectomy or high dose rate brachytherapy were unlikely to have a higher mental component score than controls in the first year (fig 3). However, mental component scores for cases in all treatments groups were similar to those of controls at three years.
Urinary function and bother
At baseline, few cases (33/1636 (2.0%)) reported urinary incontinence—that is, few agreed that they experienced “urinary leakage that required one or more pads per day to control.” This single measure of incontinence, which does not include all forms of incontinence, was most prevalent at baseline in men who subsequently had androgen deprivation therapy (4/61 (6.6%)) or active surveillance (12/200 (6.0%); table 3). After diagnosis, the highest rate of incontinence was in the group who had radical prostatectomy: 156 men (16.3%) reported incontinence at one year and 111 (12.3%) at three years.
Table 3 Unadjusted proportion of men with localised prostate cancer who reported incontinence, moderate or severe bowel problems, or impotence at baseline and three years after diagnosis
All men except those who had undergone nerve sparing radical prostatectomy or low dose rate brachytherapy had lower urinary function scores than controls at baseline (table 2). Urinary function scores fell significantly below control scores in all groups between baseline and year one, except for in cases on active surveillance, androgen deprivation therapy, or high dose rate brachytherapy (fig 4). The odds ratio was lowest in those who had radical prostatectomy (OR 0.17, 95% CI 0.13 to 0.22). For all groups except those on androgen deprivation therapy or high dose rate brachytherapy, the adjusted odds ratio increased or stabilised between year one and year three. All treatment groups had worse urinary bother at baseline than did controls (table 2), and this persisted up to three years in most groups (fig 4).
Fig 4 Adjusted odds ratios and 95% confidence intervals for urinary, bowel, and sexual function and bother scores higher than those in control group—that is, better function and less bother than controls—by primary treatment group one (more ...)
Urinary bother at baseline in all men was highly correlated with their international prostate symptom score (R2=0.56; P<0.001), more so than with the University of California, Los Angeles prostate cancer index urinary function score (R2=0.21; P<0.001). Of the men who reported less urinary bother than controls three years after diagnosis, 68 men (64%) on active surveillance and 22 men (34%) on androgen deprivation therapy had a transurethral resection of the prostate. The fact that these men underwent this procedure might explain the reduction in bother.
Bowel function and bother
Bowel problems were defined as responding to the question “Overall, how big a problem have your bowel habits been?” with either “moderate” or “big.” Although bowel function of cases at baseline was generally similar to that of controls (table 2), men who had external beam radiotherapy, both with and without androgen deprivation therapy, had worse bowel function than controls at one year (OR 0.51, 95% CI 0.34 to 0.74) and at three years (OR 0.58, 95% CI 0.39 to 0.86) after diagnosis (fig 4). Bowel bother was persistently worse in all treatment groups relative to controls, with the greatest impact in the groups who received treatment that included external beam radiotherapy either alone at one year (OR 0.24, 95% CI 0.15 to 0.36) and three years (OR 0.22, 95% CI 0.14 to 0.34) or in combination with androgen deprivation therapy at one year (OR 0.24, 95% CI 0.16 to 0.35) and three years (OR 0.19 95% CI 0.13 to 0.28).
Sexual function and bother
Sexual function at baseline differed between groups (tables 2 and 3)—15.6% (76/494) of men who subsequently had nerve sparing radical prostatectomy were impotent at baseline compared with 42.1% (24/61) of those who had androgen deprivation therapy. On the other hand, 109 controls (22.3%) and 128 men (27.6%) who had non-nerve sparing radical prostatectomy stated at baseline that they were unable to obtain an erection firm enough for sexual intercourse (table 3). At three years, 67.9% (307/494) of men who had nerve sparing radical prostatectomy, 86.7% (379/476) of men who had non-nerve sparing radical prostatectomy, 67.9% (72/123) of men who had external beam radiotherapy, and 36.4% (20/58) of men who had low dose rate brachytherapy were impotent.
After adjusting for age, baseline function, income, area of residence, and comorbidity score, all treatment groups had worse sexual function than controls at one, two, and three years (fig 4), although in all groups there was some improvement between the score at one year and that at three years. The treatment with greatest adverse impact on sexual function was androgen deprivation therapy (OR 0.02, 95% CI 0.01 to 0.07). Cases who had nerve sparing radical prostatectomy had a better outcome at three years (adjusted OR 0.10, 95% CI 0.08 to 0.13) than those who had non-nerve sparing surgery (adjusted OR 0.05, 95% CI 0.04 to 0.07; P<0.001).
All treatment groups, with the exception of men on androgen deprivation therapy (who had poor baseline function), persistently reported more sexual bother than controls (fig 4). At three years, 494 men (33% of cases) reported that they had used some form of treatment to achieve an erection. Use of such treatments was highest in cases with good baseline sexual function and, therefore, considerable motivation to return to baseline function. Of the men who reported seeking assistance for erectile function, 383 (77.5%) stated that they used a phosphodiesterase type 5 inhibitor (for example, sildenafil, tadalafil, or vardenafil (Viagra, Cialis, and Levitra, respectively)), although 168 (43.9%) of these individuals stated that such agents were of “little or no use.” After adjusting for age, baseline potency, and treatment type, use of a phosphodiesterase type 5 inhibitor appeared to have no effect on potency at three years.