Clinical Pearls & Morning Reports
Published April 26, 2023
Hamdy et al. recently published findings for the ProtecT trial at a median follow-up of 15 years regarding the relative effectiveness of active monitoring, prostatectomy, and radiotherapy on prostate cancer–specific and all-cause mortality, metastases, disease progression, and the initiation of long-term androgen-deprivation therapy. Read the NEJM Original Article here.
Q: What is the ProtecT trial?
A: In the United Kingdom between 1999 and 2009, a total of 82,429 men between the ages of 50 and 69 years at nine centers were enrolled in the Prostate Testing for Cancer and Treatment (ProtecT) trial to evaluate the effectiveness of conventional treatments in clinically localized prostate cancer that was detected on prostate-specific antigen (PSA) testing.
Q: What were the baseline characteristics of the men enrolled in the ProtecT trial?
A: Localized prostate cancer was diagnosed in 2664 men who had a life expectancy of at least 10 years and who were eligible for treatment. Of these men, 1643 underwent randomization to receive active monitoring (545 men), prostatectomy (553 men), or radiotherapy (545 men). The median age at diagnosis was 62 years (range, 50 to 69), and the median PSA level was 4.6 ng per milliliter (range, 3.0 to 18.9). At the time of diagnosis, approximately 77% of the men were deemed to have low-risk disease.
A: After a median follow-up of 15 years, 45 patients (2.7%) had died of prostate cancer: 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiotherapy group. No significant difference in prostate cancer mortality was found among the trial groups (P = 0.53). Death from any cause occurred in 356 patients (21.7%), with a similar distribution across the three groups. Radical treatments (prostatectomy or radiotherapy) reduced the incidence of metastasis, local progression, and long-term androgen-deprivation therapy by half as compared with active monitoring. However, these reductions did not translate into differences in mortality at 15 years. By the end of follow-up, 133 men (24.4%) in the active-monitoring group were alive and had neither received radical treatment nor started androgen-deprivation therapy.
A: The authors found no evidence of differential treatment effects on prostate cancer mortality among subgroups that were defined according to tumor grade at diagnosis, aggregate or maximum tumor length, tumor stage, PSA level, or risk-stratification method. However, they found a suggestion of an age effect in which men who were at least 65 years of age at the time of diagnosis appeared to have benefited from early radical treatment, whereas those who were younger than 65 years of age benefited more from active monitoring or surgery than from radiotherapy. This finding could reflect potential benefits of prompt radical treatment among older men but should be interpreted cautiously and warrants further exploration.