medwireNews: The 15-year data from the ProtecT trial show low rates of prostate cancer-specific mortality among men with prostate-specific antigen (PSA)-detected, localized disease regardless of whether they received active monitoring, prostatectomy, or radiotherapy.
“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,” note the researchers in The New England Journal of Medicine.
“However, these reductions did not translate into differences in mortality at 15 years, a finding that emphasizes the long natural history of this disease,” they add.
The author of a linked editorial – Oliver Sartor, from Tulane Medical School in New Orleans, Louisiana, USA – points out that “the management of localized prostate cancer has undergone a wholesale change since 1999 when the ProtecT trial was started.”
He continues: “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.”
In the UK-based trial, 1643 men diagnosed with localized prostate cancer after undergoing a PSA test were randomly assigned to receive active monitoring, prostatectomy, or radiotherapy. Applying contemporary risk stratification tools to the baseline data revealed that 20.5–26.4% of men had intermediate-risk disease, while 2.5–9.6% had high-risk disease.
After a median follow-up of 15 years, data were available for 1610 (98%) participants and showed that a comparable proportion of patients in each treatment group had died of prostate cancer, at 3.1%, 2.2%, and 2.9% in the active monitoring, prostatectomy, and radiotherapy groups, respectively.
The findings were similar for death from any cause – a total of 21.7% of participants died during the follow-up period, “with a similar distribution across the three groups,” report Freddie Hamdy (University of Oxford, UK) and co-investigators.
Metastatic disease occurred in a greater proportion of men who received active monitoring than those who underwent prostatectomy or radiotherapy, at 9.4% versus 4.7% and 5.0%, respectively. Patients in the active monitoring arm were also more likely to begin long-term androgen deprivation therapy, at rates of 12.7% versus7.2% and 7.7%, respectively, and reach the composite endpoint of clinical progression, at 25.9% versus 10.5% and 11.0%.
A prespecified analysis by age indicated that the risk for prostate cancer-specific mortality was lower with active monitoring than either of the radical options among participants younger than 65 years of age, whereas the converse was true for those aged 65 years or older.
“This finding could reflect potential benefits of prompt radical treatment among older men but should be interpreted cautiously and warrants further exploration,” write Hamdy et al.At the end of the 15-year period, 333 patients (61.1%) in the active monitoring group had received radical treatment, “an absolute increase of 6.3 percentage points from the 291 men (54.8%) who had received radical treatment at 10 years,” note the researchers.
They add that 24.4% of men in the group were alive and had not received either radical treatment or androgen deprivation therapy at this timepoint.
In light of the current findings, the study authors conclude that “[m]en 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.”
But they add: “Longer-term follow-up to 20 years and beyond will be crucial to continue to evaluate possible differential effects of various treatments.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group
N Engl J Med 2023; doi:10.1056/NEJMoa2214122
N Engl J Med 2023; doi:10.1056/NEJMe2300807