Long-term results of the Dutch randomized prostate cancer trial: impact of dose-escalation on local, biochemical, clinical failure, and survival

Abstract

Purpose: Nowadays, advanced irradiation techniques make it possible to escalate safely the dose in prostate cancer. We studied the effect of a higher dose on tumor control in a randomized trial with a median follow-up of 110 months.

Patients and methods: Patients with T1b-T4N0 prostate cancer (n=664) were randomized between 78 Gy and 68 Gy. Primary endpoint was biochemical and/or clinical failure (BCF) according to the American Society for Therapeutic Radiology and Oncology (ASTRO) guidelines (3 consecutive rises), and to Phoenix (nadir plus 2 μg/L). Secondary endpoints were clinical failure (CF), local failure (LF), prostate cancer death (PCD), and overall survival (OS). Explorative subgroup analyses were performed.

Results: BCF rate (HR=0.8; 20% less events) and LF rate (HR=0.5; 50% less events) were significantly lower in the 78 Gy arm (p<0.05). CF, PCD and OS were similar in both arms. A significant heterogeneity of treatment effect was found for PSA cutoffs between 7 and 10 μg/L.

Conclusion: We observed significantly less BCF and LF in the high-dose arm. This suggests improvement of the therapeutic ratio. However, we observed similar rates of CF and PCD at the current update. More follow-up is needed to investigate which patients benefit in terms of prolonged OS.

Trial registration: ClinicalTrials.gov NCT00692107.

Keywords: Clinical trial; Dose-escalation; Prostate cancer.