Prostate cancer-specific mortality was low and there was no significant difference among treatments when men were assigned to the options of active monitoring, radical prostatectomy, or external-beam radiotherapy, a study found.
The ProtecT trial was designed to evaluate the effectiveness of the 3 treatments in men with prostate-specific antigen (PSA)-detected, clinically localized disease. From 1999 to 2009, 1,643 men agreed to undergo randomization to active monitoring (545 men), surgery (553 men), or radiotherapy (545 men). The primary outcome of this study was prostate cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. A second study of the same cohort analyzed patient-reported outcomes for function and quality of life.
Overall, 17 prostate cancer-specific deaths occurred during the study: 8 in the active-monitoring group (1.5 deaths per 1,000 person-years; 95% CI, 0.7 to 3.0), 5 in the surgery group (0.9 per 1,000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1,000 person-years; 95% CI, 0.3 to 2.0). The difference among the 3 groups was not statistically significant (P=0.48 for the overall comparison). No significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the 3 groups).
More men in the active-monitoring group developed metastases (33 men; 6.3 events per 1,000 person-years [95% CI, 4.5 to 8.8]) than in the surgery group (13 men; 2.4 events per 1,000 person-years [95% CI, 1.4 to 4.2]) or the radiotherapy group (16 men; 3.0 per 1,000 person-years [95% CI, 1.9 to 4.9]) (P=0.004 for the overall comparison). The researchers noted higher rates of disease progression in the active-monitoring group (112 men; 22.9 events per 1,000 person-years [95% CI, 19.0 to 27.5]) than in the surgery group (46 men; 8.9 events per 1,000 person-years [95% CI, 6.7 to 11.9]) or the radiotherapy group (46 men; 9.0 events per 1,000 person-years [95% CI, 6.7 to 12.0]) (P<0.001 for the overall comparison).
The researchers estimated that 27 men would need to be treated with prostatectomy instead of active monitoring to avoid 1 patient having metastatic disease and that 33 men would need to be treated with radiotherapy instead of active monitoring to avoid 1 patient having metastatic disease. A total of 9 men would need to be treated with either prostatectomy or radiotherapy to avoid 1 patient having clinical progression, they concluded.
The study results indicate that death from prostate cancer in in men with PSA-detected clinically localized disease remained low at a median of 10 years of follow-up, approximately 1%, regardless of the treatment used. The researchers wrote that this rate was considerably lower than was anticipated. All-cause mortality was about 10%.
“Men with newly diagnosed, localized prostate cancer need to consider the critical trade-off between the short-term and long-term effects of radical treatments on urinary, bowel, and sexual function and the higher risks of disease progression with active monitoring, as well as the effects of each of these options on quality of life,” the authors wrote.
The second study of the same cohort analyzed patient-reported outcomes such as patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life.
Prostatectomy had the greatest negative effect on sexual function and urinary continence, the authors wrote. Although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. Also, the study found that the negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group.
Bowel function was worse in the radiotherapy group at 6 months than in the other groups. It then recovered somewhat, except for an increasing frequency of bloody stools. Bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life.
An accompanying editorial for both studies stated that active monitoring, as compared with treatment of early prostate cancer, leads to increased metastasis. Men who desire to avoid metastatic progression of prostate cancer and the side effects of treatment should consider monitoring only if they have life-shortening, coexisting disease with life expectancy less than 10 years.
“In addition, given no significant difference in death due to prostate cancer with surgery versus radiation and short-course androgen-deprivation therapy, 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,” the editorial stated. Both studies and the editorial were published online Sept. 14 by the New England Journal of Medicine.