Fifteen-year outcomes after monitoring, surgery, or radiotherapy for prostate cancer
In a widely publicized study in the lay media from the United Kingdom in which 15-year outcomes were reported in patients
with screening- detected prostate cancer who were randomly assigned to receive (1) active monitoring with PSA measurements (not true active surveillance with regular surveillance biopsies and MRI scans), (2) external beam radiotherapy, or (3) radical prostatectomy, the authors reported that the prostate cancer deaths occurred in 3% of all treatment groups and that there was no difference in all-cause mortality. The authors misleadingly (in Dr. Catalona’s opinion) concluded that patients need not rush to treatment because the outcomes were the same with or without treatment.
However, a major issue with this study is that the results were presented in terms of the initial treatment to which the patients were assigned at the time they enrolled in the study, not the actual treatment they received after randomization. This is important because 30% assigned to active monitoring converted to treatment at 3 years, 55% at 10 years, and 65% at 15 years for a total conversion rate to treatment of 61%. Moreover, some who did receive treatments only received such treatments up to 10 years after diagnosis. Another limitation of this study is that the median follow-up was 15 years, but some were followed for only 12 years. In patients with early prostate cancer, many cancer deaths occur after 15 years (see article on “More of the prostate cancer deaths occurred in men initially diagnosed with Gleason ≤6 than in those diagnosed with Gleason ≥7” in this issue of QUEST). Although there was no significant difference in deaths attributed to prostate cancer, significantly twice as many patients in the active monitoring group had clinical progression of their cancer, and more than twice as many developed metastases. Also, in contrast to the findings of most studies in the medical literature, they found that the usual risk stratification parameters (e.g., the diagnostic tumor stage, grade, PSA, or risk group) was not associated with patient outcomes. In listing the limitations of their study, the authors cautioned that longer- term follow-up will be crucial.
NEJM; 2023: DOI 10.1056/NEJMoa2214122