Patterns of Failure Following External Beam Radiotherapy With or Without an Additional Focal Boost in the Randomized Controlled FLAME Trial for Localized Prostate Cancer

• Published in: European urology Vol. 82; no. 3; pp. 252 - 257
• Main Authors: Groen, Veerle H., Haustermans, Karin, Pos, Floris J., Draulans, Cédric, Isebaert, Sofie, Monninkhof, Evelyn M., Smeenk, Robert J., Kunze-Busch, Martina, de Boer, Johannes C.J., van der Voort van Zijp, Jochem, Kerkmeijer, Linda G.W., van der Heide, Uulke A.
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 01.09.2022
• Subjects: Dose-response analysis; External beam radiotherapy; Focal boosting; Patterns of failure analysis; Prostate cancer; Dose-response analysis; Patterns of failure analysis; External beam radiotherapy; Prostate cancer; Focal boosting
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2021.12.012

Focal boosting up to 95 Gy in the FLAME trial improved rates of local failure and of regional + distant metastatic failure (rdMF) for patients with localized, mainly high-risk prostate cancer. Dose-response analyses showed the beneficial effect of higher doses to the tumor on rdMF and local failure, even when the boost dose of 95 Gy cannot be achieved because of dose constraints for organs at risk. Focal dose escalation in external beam radiotherapy (EBRT) showed an increase in 5-yr biochemical disease-free survival in the Focal Lesion Ablative Microboost in Prostate Cancer (FLAME) trial. To analyze the effect of a focal boost to intraprostatic lesions on local failure–free survival (LFS) and regional + distant metastasis–free survival (rdMFS). Patients with intermediate- or high-risk localized prostate cancer were included in FLAME, a phase 3, multicenter, randomized controlled trial. Standard treatment of 77 Gy to the entire prostate in 35 fractions was compared to an additional boost to the macroscopic tumor of up to 95 Gy during EBRT. LFS and rdMFS, measured via any type of imaging, were compared between the treatment arms using Kaplan-Meier and Cox regression analyses. Dose-response curves were created for local failure (LF) and regional + distant metastatic failure (rdMF) using logistic regression. A total of 571 patients were included in the FLAME trial. Over median follow-up of 72 mo (interquartile range 58–86), focal boosting decreased LF (hazard ratio [HR] 0.33, 95% confidence interval [CI] 0.14–0.78) and rdMF (HR 0.58, 95% CI 0.35–0.93). Dose-response curves showed that a greater dose to the tumor resulted in lower LF and rdMF rates. A clear dose-response relation for LF and rdMF was observed, suggesting that adequate focal dose escalation to intraprostatic lesions prevents undertreatment of the primary tumor, resulting in an improvement rdMF. Radiotherapy is a treatment option for high-risk prostate cancer. The FLAME trial has shown that a high dose specifically targeted at the tumor within the prostate will result in better disease outcome, with less likelihood of regional and distant disease spread. The FLAME trial is registered on ClinicalTrials.gov as NCT01168479.