Relative risk of cancer-related death differed according to age of diagnosis.
Men with prostate-specific antigen (PSA)-detected and clinically localized prostate cancer have survival benefits regardless of treatment option, according to the results of a 15-year follow-up to the UK’s 1999 Prostate Testing for Cancer and Treatment (ProtecT) trial published in the New England Journal of Medicine (NEJM). However, the study authors noted that radical treatments such as prostatectomy or radiotherapy did not improve survival outcomes.
“New systemic therapies for progressive disease have become increasingly available, and it is likely that these treatments contributed to lengthening survival in the men with metastases in our trial,” wrote study authors in the NEJM article.
The ProtecT trial evaluated the efficacy of conventional treatment for clinically localized prostate cancer detected with PSA testing. They randomized more than 1600 men to receive active monitoring, prostatectomy, or radiotherapy.
Since this study, and since the updated recommendations of the US Preventative Services Task Force, US prostate cancer-related mortality is unchanged. Investigators conducted a 15-year follow-up of ProtecT trial to better understand why.
The follow-up analyzed the efficacy of each of these conventional therapies using risk-stratification analysis. Patients were stratified by subgroup, including age (younger vs. older than age 65 years), Gleason grade group, tumor type, PSA level, cancer stage, and risk-stratification score.
At baseline, 76% of participants had stage 1 lower-risk disease, according to the commonly used Gleason score. According to other risk-stratification tools, 24.1% of men had intermediate disease and 9.6% had high-risk disease. The primary outcome was death from prostate cancer, and secondary outcomes were death from any cause, metastases, disease progression, and initiation of long-term androgen-deprivation therapy.
The results showed that 97% of patients survived after 15 years, regardless of treatment type. While radiotherapy was more favorable early on, active monitoring was more favorable later. The study authors noted that this suggests neither has a superior outcome on mortality.
Additionally, the study authors explained that age at diagnosis affected risk of cancer-related death. Among those aged younger than 65 years at diagnosis, active monitoring or prostatectomy were associated with reduced risk of death compared to radiotherapy. Those aged 65 years and older benefited more from prostatectomy or radiotherapy.
In addition, early and radical treatment was shown to reduce risk of disease progression compared to active monitoring, but had a larger host of adverse events. However, aggressive treatment did not reduce risk of mortality, so the study authors suggested avoiding this form of overtreatment for prostate cancer.
Among patients who died during the study, 31.8% died from a cardiovascular or respiratory disease and 51.6% died from another type of cancer. Of the patients who had diagnosed metastases, risk of death was lower with active monitoring.
The study authors noted that the study included limitations. Primarily, investigators did not use contemporary multiparametric MRI or position-emission tomography with prostate-specific membrane antigen, nor did they include image-targeted biopsies.
“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 [disease] management decisions,” study authors wrote in the article.
Hamdy F, Donovan J, Lane J, et al. Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med. 2023. doi:10.1056/NEJMoa2214122