At a median of 10 years, prostate cancer–specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring.— Freddie C. Hamdy, FRCS, FMedSci, and colleagues
Tweet this quote
In the UK ProtecT trial reported in The New England Journal of Medicine, Freddie C. Hamdy, FRCS, FMedSci, of the University of Oxford, and colleagues found no significant differences in prostate cancer–specific or overall mortality among men with clinically localized prostate cancer detected by prostate-specific antigen (PSA) testing who underwent active monitoring, surgery, or radiotherapy.1 Metastases and disease progression were more common with active monitoring. Median follow-up in the study was 10 years.
Study Details
In the study, 1,643 men aged 50 to 69 years (median, 62 years) were randomized between 1999 and 2009 to receive active monitoring (n = 545), surgery (n = 553), or radiotherapy (n = 545). Long-term androgen-deprivation therapy was offered when indicated and/or if PSA levels reached ≥ 20 ng/mL. The primary outcome measure was prostate cancer mortality at a median of 10 years of follow-up.
Assigned treatment was received within 9 months of randomization by 88% of the monitoring group, 71% of the surgery group, and 74% of the radiotherapy group. By the end of follow-up, more than 85% of the surgery and radiotherapy groups had received radical treatment. Radical treatment was received by 54.8% of the active monitoring group. In those patients in the active monitoring group who received radical treatment, 49% underwent surgery, 33% received per-protocol radiotherapy, 9% received nonprotocol radiotherapy, 8% received brachytherapy, and 1% received high-intensity focused ultrasound therapy.
Outcomes After Monitoring, Surgery, or Radiation for Prostate Cancer
- No differences in prostate cancer–specific or overall mortality were observed with active monitoring compared with surgery or radiotherapy among men with localized prostate cancer detected by PSA testing.
- Metastases and disease progression were more common in the active monitoring group.
- Patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups.
Survival
During the median 10-year follow-up, prostate cancer–specific deaths (n = 17) occurred in 8 patients in the monitoring group (1.5 deaths per 1,000 person-years), 5 in the surgery group (0.9/1,000 person-years), and 4 in the radiotherapy group (0.7/1,000 person-years; P = .48 for overall comparison). Prostate cancer–specific survival was ≥ 98.8% in all groups. Hazard ratios (HRs) were 0.51 (95% confidence interval [CI] = 0.15–1.69) for radiotherapy vs monitoring, 0.80 (95% CI = 0.22–2.99) for radiotherapy vs surgery, and 0.63 (95% CI = 0.21–1.93) for surgery vs monitoring. All-cause death rates/1,000 person-years were 10.9 with active monitoring, 10.1 with surgery, and 10.3 with radiotherapy (P = .87 for overall comparison).
Metastases and Disease Progression
Metastases were more common in the active monitoring group (33 patients, 6.3/1,000 person-years) vs the surgery group (13 patients, 2.4/1,000 person-years) and the radiotherapy group (16 patients, 3.0/1,000 person-years; P = .004 for overall comparison). Disease progression was more common in the monitoring group (112 patients, 22.9/1,000 person-years) vs the surgery group (46 patients, 8.9/1,000 person-years) and the radiotherapy group (46 patients, 9.0/1,000 person-years; P < .001 for overall comparison).
It was estimated that 27 men would need to be treated with prostatectomy vs active monitoring to avoid 1 case of metastatic disease, 33 would need to be treated with radiotherapy vs active monitoring to avoid 1 case of metastatic disease, and 9 would need to be treated with either prostatectomy or radiotherapy vs monitoring to avoid 1 case of clinical disease progression.
The investigators concluded: “At a median of 10 years, prostate cancer–specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring.”
Patient-Reported Outcomes
In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups.— Jenny L. Donovan, PhD, FMedSci, and colleagues
Tweet this quote
As reported by Jenny L. Donovan, PhD, FMedSci, of the University of Bristol, and colleagues in a companion article in The New England Journal of Medicine,2 patient-reported outcomes in urinary, bowel, and sexual function and associated effects on quality of life, as well as in anxiety, depression, and general health-related quality of life, were assessed before diagnosis, at 6 and 12 months, and then annually for up to 6 years. Cancer-related quality of life was assessed at 5 years.
Their results included these findings:
- Prostatectomy was associated with the worst effect on sexual function and urinary continence; despite evidence of some recovery over time, these outcomes remained worse vs radiotherapy and monitoring over 6 years.
- A negative effect of radiotherapy on sexual function reached a peak at 6 months, and then it recovered somewhat and stabilized. Radiotherapy had no marked effect on urinary continence. Urinary voiding and nocturia problems were worst in the radiotherapy group at 6 months but were similar to those in the other groups after 12 months.
- Sexual and urinary function declined gradually in the active monitoring group.
- Bowel function was worst with radiotherapy at 6 months; it then recovered somewhat except for a persistent increased frequency of bloody stools. Bowel function was generally unchanged in the prostatectomy and monitoring groups.
- Effects on quality of life of reported urinary, sexual, and bowel function reflected the reported changes in function.
- No significant differences among groups were observed for anxiety, depression, general health–related quality of life, or cancer-related quality of life.
The investigators concluded: “In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups.”
Dr. Hamdy; Dr. Donovan; J.A. Lane, PhD, of the University of Bristol; and David E. Neal, FRCS, FMedSci, of the University of Oxford, contributed equally to the two articles in The New England Journal of Medicine. ■
Disclosure: The study was funded by the UK National Institute for Health Research. For full disclosures of the study authors, visit www.nejm.org.
References
