No Overall Survival Advantage for Escalated-Dose vs Control-Dose Conformal Radiotherapy for Prostate Cancer at 10 Years
As reported in The Lancet Oncology by Dearnaley et al, the 10-year follow-up of the phase III open-label MRC RT01 trial showed continued benefit of escalated-dose vs control-dose conformal radiotherapy in biochemical progression-free survival in patients with prostate cancer but no overall survival advantage.
Study Details
In this international trial, 843 men with histologically confirmed T1b to T3a, N0, M0 prostate cancer with prostate specific antigen (PSA) < 50 ng/mL were randomly assigned to receive escalated-dose conformal radiotherapy (74 Gy/37 fractions; n = 422) or control-dose conformal radiotherapy (64 Gy/32 fractions, the standard dose at the time the trial began; n = 421) between January 1998 and December 2001. All patients received neoadjuvant androgen deprivation therapy for 3 to 6 months before the start of conformal radiotherapy and through the end of conformal radiotherapy. The coprimary outcome measures were biochemical progression-free survival and overall survival.
Preliminary findings reported after 5 years of follow-up showed that the escalated-dose group had improved biochemical progression-free survival but was associated with increased risk of acute and late toxicities.
No Overall Survival Benefit
After median follow-up of 10.0 years, 10-year overall survival was 71% in the escalated-dose group and 71% in the control-dose group (hazard ratio [HR] = 0.99, P = .96). Ten-year biochemical progression free survival was 55% vs 43% (HR = 0.69, P = .0003). In analysis by stratification factors, hazard ratios for overall survival were 0.96 (95% confidence interval [CI] = 0.54–1.70) among patients at low risk of seminal vesical involvement and 1.01 (95% CI = 0.76–1.34) among those with intermediate risk; hazard ratios for biochemical progression-free survival were 0.80 (95% CI = 0.54–1.18) and 0.66 (95% CI = 0.52–0.83), respectively.
By National Comprehensive Cancer Network risk groups of low, intermediate, and high, hazard ratios for overall survival were 0.77 (95% CI = 0.32–1.87), 1.13 (95% CI = 0.73–1.74), and 0.95 (95% CI = 0.68–1.34) and hazard ratios for biochemical progression-free survival were 0.61 (95% CI = 0.46–0.79), 0.84 (95% CI = 0.59–1.19), and 0.61 (95% CI = 0.34–1.09). There were no significant differences in risk of prostate cancer death (HR = 1.06, P = .79) or non–prostate cancer death (HR = 0.96, P = .78).
The escalated-dose group had reduced risk of initiation of androgen deprivation therapy (HR = 0.76, P = .04) and improved progression-free survival (HR = 0.76, P = .03). There were no differences between groups in risk of metastasis (HR = 0.94, P = .76) or metastasis-free survival (HR = 0.94, P = .72).
The investigators concluded, “At a median follow-up of 10 years, escalated-dose conformal radiotherapy with neoadjuvant androgen deprivation therapy showed an advantage in biochemical progression-free survival, but this advantage did not translate into an improvement in overall survival. These efficacy data for escalated-dose treatment must be weighed against the increase in acute and late toxicities associated with the escalated dose and emphasise the importance of use of appropriate modern radiotherapy methods to reduce side-effects.”
Matthew R. Sydes, MSc, of Medical Research Council Clinical Trials Unit at University College London, is the corresponding author for The Lancet Oncology article.
The study was funded by the UK Medical Research Council. Dr. Sydes, Mahesh K. B. Parmar, DPhil, Gordana Jovic, PhD, and Claire Murphy, BSc, are employees of the UK Medical Research Council.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
