For prostate cancers detected by screening, cancer-specific mortality was low at 15-year follow-up regardless of whether patients underwent active monitoring, prostatectomy, or radiotherapy, results from the phase III randomized ProtecT study showed.

Among over 1,600 men from the U.K. with prostate cancers detected by a prostate-specific antigen (PSA) test, death from their malignancy occurred in 45 patients, including 17 in the group randomized to active monitoring, 12 in the prostatectomy group, and 16 in the radiotherapy group (P=0.53 for the overall comparison), reported Freddie C. Hamdy, MD, of the University of Oxford in England, and colleagues.

Death from any cause occurred in 21.7% of the men in the study, with similar numbers between the groups, they noted in the New England Journal of Medicine.

"Our findings provide evidence that greater awareness of the limitations of current risk-stratification methods and treatment recommendations in guidelines is needed," Hamdy and team wrote. "Men with newly diagnosed, localized prostate cancer and their clinicians can take the time to carefully consider the trade-offs between harms and benefits of treatments when making management decisions."

The authors also reported that metastases developed in 51 men in the active-monitoring group, 26 in the prostatectomy group, and 27 in the radiotherapy group, while long-term androgen deprivation therapy was initiated in 69, 40, and 42 men, respectively.

Clinical progression occurred in 141 men in the active-monitoring group, 58 in the prostatectomy group, and 60 in the radiotherapy group.

By the end of follow-up, 133 men in the active-monitoring group were alive without receiving radical treatment or starting androgen deprivation therapy.

Hamdy and team said that while radical treatments such as prostatectomy or radiotherapy reduce the incidence of metastasis, local progression, and long-term use of androgen deprivation therapy compared with active monitoring, "these reductions did not translate into differences in mortality at 15 years, a finding that emphasizes the long natural history of this disease."

"Thus, our findings indicate that depending on the extent of side effects associated with early radical treatments, more aggressive therapy can result in more harm than good," they wrote. "Clinicians may avoid overtreatment by ensuring that men with newly diagnosed, localized prostate cancer consider critical trade-offs between short-term and long-term effects of treatments on urinary, bowel, and sexual function, as well as the risks of progression."

In an editorial accompanying the study, Oliver Sartor, MD, of Tulane University School of Medicine in New Orleans, noted that despite the "laudatory nature" of the trial, the results raise certain issues.

For example, he said that the vast majority of patients had low or favorable intermediate risk "and would today be considered appropriate candidates for active surveillance."

"The patients who were at unfavorable intermediate risk or high risk represent an underpowered subgroup," he added. "Conclusions regarding underpowered subgroups are not appropriate on the basis of the ProtecT data, especially when numerous excellent guidelines are available to guide appropriate decision making."

Furthermore, Sartor observed that the kind of active monitoring used in this study would not be used today, and that the increased rate of metastasis seen in the active-monitoring group would likely decline with current active surveillance protocols.

"Taken together, the management of localized prostate cancer has undergone a wholesale change since 1999 when the ProtecT trial was started," Sartor wrote. "Even so, the results of this trial provide valuable data to inform decision making in the large group of men with low- or intermediate-risk prostate cancer."

For this study, 1,643 men ages 50 to 69 were enrolled to evaluate the effectiveness of treatments, with 545 randomly assigned to receive active monitoring, 553 to undergo prostatectomy, and 545 to undergo radiotherapy

Median age at diagnosis was 62 years, and median PSA level was 4.6 ng/mL. More than a third had intermediate- or high-risk disease at diagnosis.

Follow-up data at 15 years were available for 1,610 (98%) men in the study.

Among the 318 patients for whom data on the cause of death were available, 31.8% were from cardiovascular or respiratory diseases and 51.6% were from other cancers.