As reported in the Journal of Clinical Oncology by Kerkmeijer et al, the Dutch/Belgian phase III FLAME trial has shown that the addition of a focal boost to the intraprostatic lesion in patients receiving external-beam radiotherapy (EBRT) improved biochemical disease–free survival—without worsening late toxicity—in patients with localized prostate cancer.
Study Details
In the single-blind trial, 571 patients with intermediate- and high-risk localized prostate cancer from four sites in the Netherlands and Belgium were randomly assigned between November 2009 and February 2015 to receive the addition of a focal boost to EBRT (n = 284) or standard EBRT (n = 287). All patients received 77 Gy (in 2.2 Gy fractions) to the entire prostate, with the focal boost group receiving an additional simultaneous integrated boost up to 95 Gy (up to 2.7 Gy fractions) to the intraprostatic lesion; organ-at-risk constraints were prioritized over the focal boost dose. The primary endpoint was 5-year biochemical disease–free survival.
Biochemical Disease–Free Survival
Median follow-up was 72 months. Biochemical disease–free survival at 5 years was 92% in the focal boost group vs 85% in the control group (difference = 7%, 95% confidence interval [CI] = 4.2%–9.8%). Kaplan-Meier analysis showed a significant benefit of focal boost through 7 years of follow-up (P < .001). On multivariate analysis, the hazard ratio was 0.45 (95% CI = 0.28–0.71, P < .001).
In unadjusted analysis, no differences between groups were observed for distant metastasis–free survival (P = .26), prostate cancer–specific survival (P = .49), or overall survival (P = .50). On multivariate analysis, hazard ratios were 0.48 (P < .001) for disease-free survival, 0.72 (P = .22) for distant metastasis–free survival, 0.69 (P = .45) for prostate cancer–specific survival, and 1.26 (P = .27) for overall survival.
Toxicity
For the focal boost vs control groups, the cumulative incidence of late grade ≥ 2 and grade ≥ 3 genitourinary toxicity was 27.8% vs 23.0% (P = .19) and 5.6% vs 3.5% (P = .22). The cumulative incidence of late grade ≥ 2 and grade ≥ 3 gastrointestinal toxicity was 12.7% vs 12.2% (P =.86) and 1.4% vs 1.4% (P = .99).
Quality-of-life assessment with the EORTC QLQ-Prostate Cancer module (scores 1–100) for up to 5 years showed that urinary quality of life declined from baseline at 1 month after treatment and improved within 1 year in both groups; bowel quality of life declined by < 5 points from baseline in both groups and remained at similar levels thereafter; and sexual quality of life among patients not receiving hormonal therapy never declined by > 5 points from baseline in either group. No statistically significant differences in any domain were observed between groups.
The investigators concluded, “The addition of a focal boost to the intraprostatic lesion improved biochemical disease–free survival for patients with localized intermediate- and high-risk prostate cancer without impacting toxicity and quality of life. The Focal Lesion Ablative Microboost in Prostate Cancer [FLAME] study shows that a high focal boost strategy to improve tumor control while respecting organ-at-risk dose constraints is effective and safe.”
Uulke A. van der Heide, PhD, of The Netherlands Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Dutch Cancer Society. For full disclosures of the study authors, visit ascopubs.org.
