ProtecT clinical, patient-reported outcomes revealed
medwireNews: Two articles published in The New England Journal of Medicine report on the clinical and patient-reported outcomes of the ProtecT trial’s assessment of three approaches for the management of localised prostate cancer detected by prostate-specific antigen (PSA) testing.
The primary outcome of prostate cancer-specific mortality after a median 10 years of follow-up was comparable irrespective of whether participants underwent active surveillance, radical surgery or radiotherapy, with 1.5, 0.9 and 0.7 deaths per 1000 person–years.
The treatment groups also did not differ significantly with respect to the number of deaths from any cause.
However, patients assigned to the active monitoring versus the surgery or radiotherapy groups were significantly more likely to experience disease progression, defined as evidence of metastatic or clinical T3 or T4 disease, use of long-term androgen-deprivation therapy or presence of obstructive disease or rectal fistula. The corresponding rates of progression were 22.9, 8.9 and 9.0 events per 1000 person–years.
The incidence of metastases was also significantly higher for men assigned to the active surveillance arm than the radical prostatectomy or radiotherapy arms, at 6.3 versus 2.4 and 3.0 events per 1000 person–years.
“These differences show the effectiveness of immediate radical therapy over active monitoring, but they have not translated into significant differences — nor have they ruled out equivalence — in disease-specific or all-cause mortality; thus, longer-term follow-up is necessary”, write Freddie Hamdy (University of Oxford, UK) and colleagues.
The ProtecT (Prostate Testing for Cancer and Treatment) trial included 1643 men aged 50–69 years, of whom 545 were randomly assigned to undergo active surveillance, which involved serum PSA measurements every 3 months for the first year and every 6–12 months subsequently, with a review conducted if levels rose by at least 50%. The other treatment arms comprised 553 men treated with radical prostatectomy and 545 given radiotherapy with short-term neoadjuvant androgen-deprivation therapy.
Study participants also completed questionnaires evaluating health-related quality of life measures at baseline (ie, at the time of biopsy), at 6 and 12 months post-randomisation and every year thereafter for 6 years. These patient-reported outcomes were assessed by Jenny Donovan (University of Bristol, UK) and fellow researchers.
They found that “patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups.”
For instance, men who underwent radical prostatectomy were more likely to experience urinary incontinence and have worse sexual function, especially erectile function, than those in the radiotherapy or active monitoring groups at 6 months. And although urinary and sexual function recovered somewhat during the course of the study, radical prostatectomy-treated patients consistently reported poorer outcomes.
By contrast, radical prostatectomy did not adversely affect bowel function, whereas the scores for this outcome were worse in the radiotherapy arm, especially at 6 months. Thereafter, bowel function, with the exception of bloody stools, improved among radiotherapy-treated men.
In the active surveillance group, urinary and sexual function was initially less affected than the radical-treatment arms, but declined over time, “as increasing numbers of men received radical treatments and age-related changes occurred”, say Donovan et al. Bowel function did not change over time.
They note that there were no differences between treatment arms “in measures of anxiety, depression, or general health-related or cancer-related quality of life.”
Donovan and team believe that these data together with the clinical findings “can be used by policymakers who are developing guidelines and by patients and clinicians who are making decisions about treatments for newly diagnosed localized prostate cancer or who are contemplating PSA testing.”
But they add that “follow-up for an additional 5 to 10 years is required to fully inform decisions involving the tradeoff between the shorter-term effects of the management strategies shown here and the longer course of progression and treatment of prostate cancer in the context of the onset of other life-threatening conditions.”
Commenting on the ProtecT results, Anthony D’Amico (Brigham and Women’s Hospital and Dana–Farber Cancer Institute, Boston, Massachusetts, USA) suggests: “[I]f a man wishes to avoid metastatic prostate cancer and the side effects of its treatment, monitoring should be considered only if he has life-shortening coexisting disease such that his life expectancy is less than the 10-year median follow-up of the current study.”
Moreover, in light of the comparable disease-specific mortality for the radical-treatment groups, he believes that “men with low-risk or intermediate-risk prostate cancer should feel free to select a treatment approach using the data on health-related quality of life and without fear of possibly selecting a less effective cancer therapy.”
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