Two-years Postradiotherapy Biopsies: Lessons from MRC RT01 Trial

Abstract Background The importance of 2-yr postradiotherapy prostate biopsy status remains uncertain. Objective To assess the value of 2 year post treatment biopsies in a randomised trial of radiotherapy dose escalation. Design, setting, and participants Between 1998 and 2001, 843 men with localised prostate cancer were randomised to receive either control-64Gy or escalated-74Gy conformal radiotherapy (CFRT) in the MRC RT01 trial in combination with 3–6-mo neoadjuvant androgen deprivation therapy. Prostate biopsies were planned at 2 yr from start of CFRT in suitable men. Outcome measurements and statistical analysis Prostate biopsy results and prostate-specific antigen (PSA) levels performed at 2 yr post-CFRT were evaluated with long-term biochemical progression free survival (bPFS) and overall survival. Outcome measures were timed from the 2-yr biopsy using a landmark approach. Results and limitations A 2-yr biopsy was performed in 312/843 patients. One hundred and seventy-seven patients were included in the per-protocol group with median follow-up of 7.8 yr from biopsy. Median PSA at biopsy was 0.5ng/ml. Sixty-four bPFS events were reported: 46/145 (32%) in patients with negative, 6/18 (33%) suspicious, and 12/14 (86%) positive biopsies. A positive biopsy was prognostic of worse bPFS, going forward, compared with negative and suspicious biopsies, hazard ratio (HR)=4.81 (95% confidence interval [CI]: 2.50–9.26, p p =0.42). PSA values at 2 yr between 1.01ng/ml and 2.09ng/ml were also associated with subsequent PSA failures (HR=2.71, 95% CI: 1.98–3.71), bPFS events (HR=2.45, 95% CI: 1.81–3.32), and prostate cancer-specific survival (HR=2.87, 95% CI: 1.08–7.64) compared with PSA ≤1.0ng/ml. Conclusions Two-year postradiotherapy prostate biopsies have limited value in patients with PSA control but both positive biopsy and higher PSA status are strongly associated with future bPFS events. A policy of selected biopsy may provide an opportunity for early salvage interventions. Patient summary Routine 2-yr postradiotherapy biopsy is not recommended but can be considered in selected patients with unfavourable post-treatment prostate-specific antigen levels who are suitable for early salvage treatments.