Treatment options for men with localized prostate cancer include active surveillance, radical prostatectomy, or external-beam radiotherapy, but in the Prostate Testing for Cancer and Treatment (ProtecT) trial each therapy was associated with a low prostate-specific mortality rate of about 1%. Further, surgery and radiotherapy reduced the risk of cancer progression over time compared with active monitoring, but caused more unpleasant side effects.
“What we have learned from this study is that prostate cancer detected by PSA blood test grows very slowly, and very few men die of it when followed up over a period of 10 years—around 1%—irrespective of the treatment assigned,” said lead author Freddie C. Hamdy, MBChB, Nuffield Department of Surgical Sciences, University of Oxford, in a statement. “This is considerably lower than anticipated when we started the study.”
Researchers from the University of Oxford and the University of Bristol in the United Kingdom reviewed the prostate-specific antigen (PSA) tests of 82,429 men between 1999 and 2009. Men who received a diagnosis of localized prostate cancer were then randomized to active surveillance (545 men), surgery (553), or radiotherapy (545). The median age of the men who participated was 62 years (range, 50-69), and the median PSA level was 4.6 ng/mm (range, 3.0-19.9).
Researchers reported 17 prostate-specific deaths overall, with 8 in the active-surveillance group (1.5 deaths per 1000 person-years; 95% CI, 0.7-3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4-2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3-2.0). However, no significant differences were seen among the 3 groups (P = .87). The secondary outcome was all-cause mortality, including metastases, clinical progression, primary treatment failure, and treatment complications.
“This is the first time radiotherapy, surgery, and active monitoring treatments for prostate cancer have been compared directly,” said co-investigator Jenny L. Donovan, PhD, University Hospitals Bristol NHS Foundation Trust, in a statement. “The results provide patients and clinicians with detailed information about the effects and impacts of each treatment so that they can make an informed decision about which treatment to have.”
According to the researchers, the majority of men (88%) who were randomly assigned to active surveillance accepted their assignment, but a quarter of them had received radical treatment within 3 years after their initial assignment and over half had received treatment by the time 10 years passed.
“This is a very important study and what was undertaken was a Herculean task,” said Scott Eggener, MD, associate professor of surgery, University of Chicago. “I have tremendous respect for the investigators and men who participated. This data will inform public health policy for literally millions of men. Basically, of all the men who were diagnosed with prostate cancer, over 60% of them put their fate in the decision of the flip of a three-sided coin,” said Eggener, who is co-director of the Prostate Cancer Program at the university.
Disease progression among men who underwent surgery or radiation therapy was less than half the rate among men assigned active monitoring (P
<.001 for the overall comparison), as was the rate of metastatic disease (P
= .004 for the overall comparison). The researchers report that these differences show the effectiveness of immediate radical therapy over active monitoring, but these are not significant, nor have the findings ruled out equivalence in disease-specific or all-cause mortality.
“The findings reported provide an initial insight into the data,” said Eggener. “What everyone wants to know is what happens in 15 or 20 years and will the trends that we’re seeing now become more pronounced.”
Eggener pointed out that the trial was launched in 1999. The procedures for active monitoring and radiotherapy treatments were different back then compared with current treatments today. “The investigators provided the best care they could at the time,” he said. “Even current active monitoring is much better than what was available back then.”
The findings could inform public health policy and guidelines, said Eggener, and could be interpreted in a number of different ways.
“For example, if you took the position of being against screening, you could make a blanket statement that based on the findings of virtually no difference between these 3 modalities over 10 years, screening for prostate cancer should not be undertaken,” he said. “The flip side is that prostate cancer is slow growing, and based on the findings, we see 50% fewer men with metastasis at 10 years. The suggestion is that this number should only improve with longer follow-up, which would support the use of screening and treatment.”
The researchers concluded that men with newly diagnosed, localized prostate cancer need to discuss the trade-offs associated with 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.
Hamdy FC, Donovan JL, Lane JA, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. September 14, 2016. doi: 10.1056/NEJMoa1606220.