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.

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 (

 <.001 for the overall comparison), as was the rate of metastatic disease (

 = .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. 

. September 14, 2016. doi: 10.1056/NEJMoa1606220.

“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%&mdash;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.”

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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 trial each therapy was associated with a low prostate-specific mortality rate of about 1%.

Similar Survival Rates Reported Across Treatment Options for Localized Prostate Cancer

“We found that there were really no quality-of-life differences between these 2 groups of men, which was a nice surprise,” said lead author Jennifer Cullen, PhD, MPH, director of the CPDR Epidemiological Research Program. “We were concerned that those who had cancer would have worse mental health, because of a confirmed cancer diagnosis.”

The findings suggest that AS “is a reasonable option in low-risk patients in terms of promoting and maintaining a high level of quality of life relative to those patients without cancer,” Cullen said.

Data for the years 2007-2014 were evaluated. Of the 1204 subjects who met study eligibility requirements, 420 (35%) had a negative prostate needle biopsy (noncancer group) and 787 (65%) had a positive prostate needle biopsy for cancer. Of the men with a positive finding, 411 (52%) were diagnosed with low-risk prostate cancer, 89 of whom were placed on AS.

Cullen and researchers used 2 questionnaires with established validity and reliability—EPIC, a prostate cancer specific instrument, and SF-36, a general health assessment test to determine health-related quality-of-life (HRQoL) measures. Findings were assessed at biopsy (baseline) and annually for up to 3 years. The researchers said they undertook the study because it is poorly understood how HRQoL of men who select AS compares with the HRQoL of men at similar risk, but without prostate cancer.

“In our study, we focused on 2 patient subsets—one group that was biopsied was found to not have cancer. The other group had cancer but was at such low risk that it was a comfortable option for the physician to advise the patient that he was eligible for active surveillance,” said Cullen, a research assistant professor in the department of surgery at the Uniformed Services University of the Health Sciences.

EPIC measures 4 paired subscales evaluating urinary, sexual, bowel, and hormonal function and bother. SF-36 measures 8 subscales that can be combined into a physical component summary and mental component summary scores. Both tests offer subscale scores that range from 0 to 100, with higher scores indicating better HRQoL. HRQoL surveys were administered before or after biopsy (baseline), and at 3, 6, 12, 18, 24, 30, and 36 months after a positive biopsy or 12, 24, and 36 months after a negative biopsy. The researchers reported that only baseline surveys and those from 12, 24, and 36-month points were included in the analysis.

The researchers found that the only time HRQoL trends differed were for urinary function and mental health subscales, with the group undergoing AS reporting additional decreases of approximately 2 points per year. Cullen and colleagues attributed this finding as a regression to the mean, particularly with regard to urinary functions, which was higher in the AS group at baseline. They reported that the changes did not result in statistically significant or clinically meaningful differences in adjusted mean scores of these subscales at 3 years.

The decision for a patient to choose active surveillance is a complex one, said Cullen. “There are a number of factors that go into the decision. It could be that the physician strongly recommends it, the patient may have a preference to avoid surgery or radiation therapy, or the patient’s spouse might recommend against surgery or radiation therapy.” She noted that surgery and radiation can result in sexual, urinary, and bowel dysfunction, “so there are serious consequences in pursuing aggressive treatment. A man in his 50s or 60s may want to delay treatment because of those adverse events that affect these core functions,” she said.

The interplay between patient and physician is important and she pointed out that “all of the patients who participated were seen in a multidisciplinary clinic where they have a chance to meet with a radiation oncologist, surgical oncologist, and even a nurse educator.” All the health team members had a chance to meet and all treatment options were on the table, she said.

This setting could have biased the results, she cautioned, because the general population does not always have the same level of access to healthcare facilities and consistency in follow-up care, as in the military population who participated in the study. In addition, armed forces personnel tend to be “very loyal to this health system, so we don’t see the high rates of attrition that might occur outside of this military cohort.”

“We know overwhelmingly that most men with a prostate-cancer diagnosis are going to have a positive outcome. I’m confident in saying that their quality of life remains high during the 3-year period after diagnosis,” she said. “But because this is 1 study that examined 1 military cohort, more studies should be undertaken to repeat the analysis,” Cullen concluded.

Pham KN, Cullen J, Hurwitz LM, et al. Prospective quality of life in men choosing active surveillance compared to those biopsied but not diagnosis with prostate cancer. 

. 2016;196(2):392-8. doi: 10.1016/j.juro.2016.02.2972.

Men with positive needle biopsy for prostate cancer who underwent active surveillance (AS) exhibited no difference in quality-of-life compared with men who had a negative prostate needle biopsy, according to an analysis of data from the US Department of Defense Center for Prostate Disease Research (CPDR) Multicenter National Database.

Men with positive needle biopsy for prostate cancer who underwent active surveillance exhibited no difference in quality-of-life compared with men who had a negative prostate needle biopsy.

October 2016 | Oncology Live Urologists in Cancer Care®

Similar Survival Rates Reported Across Treatment Options for Localized Prostate Cancer

QOL in Men Undergoing Monitoring for Prostate Cancer Similar to Men With No Disease