TY - JOUR
T1 - Patterns of Failure Following External Beam Radiotherapy With or Without an Additional Focal Boost in the Randomized Controlled FLAME Trial for Localized Prostate Cancer
AU - Groen, Veerle H.
AU - Haustermans, Karin
AU - Pos, Floris J.
AU - Draulans, Cédric
AU - Isebaert, Sofie
AU - Monninkhof, Evelyn M.
AU - Smeenk, Robert J.
AU - Kunze-Busch, Martina
AU - de Boer, Johannes C.J.
AU - van der Voort van Zijp, Jochem
AU - Kerkmeijer, Linda G.W.
AU - van der Heide, Uulke A.
N1 - Funding Information:
Funding/Support and role of the sponsor: This study was supported by the Dutch Cancer Society (grant no. KWF 10088). The sponsor played no direct role in the study.
Publisher Copyright:
© 2021 European Association of Urology
Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PY - 2022/9
Y1 - 2022/9
N2 - Background: 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. Objective: To analyze the effect of a focal boost to intraprostatic lesions on local failure–free survival (LFS) and regional + distant metastasis–free survival (rdMFS). Design, setting, and participants: Patients with intermediate- or high-risk localized prostate cancer were included in FLAME, a phase 3, multicenter, randomized controlled trial. Intervention: 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. Outcome measurements and statistical analysis: 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. Results and limitations: 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. Conclusions: 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. Patient summary: 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.
AB - Background: 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. Objective: To analyze the effect of a focal boost to intraprostatic lesions on local failure–free survival (LFS) and regional + distant metastasis–free survival (rdMFS). Design, setting, and participants: Patients with intermediate- or high-risk localized prostate cancer were included in FLAME, a phase 3, multicenter, randomized controlled trial. Intervention: 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. Outcome measurements and statistical analysis: 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. Results and limitations: 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. Conclusions: 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. Patient summary: 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.
KW - Dose-response analysis
KW - External beam radiotherapy
KW - Focal boosting
KW - Patterns of failure analysis
KW - Prostate cancer
KW - Radiotherapy Dosage
KW - Disease-Free Survival
KW - Humans
KW - Brachytherapy/methods
KW - Proportional Hazards Models
KW - Prostatic Neoplasms/pathology
KW - Male
UR - http://www.scopus.com/inward/record.url?scp=85121687078&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2021.12.012
DO - 10.1016/j.eururo.2021.12.012
M3 - Article
C2 - 34953603
AN - SCOPUS:85121687078
SN - 0302-2838
VL - 82
SP - 252
EP - 257
JO - European Urology
JF - European Urology
IS - 3
ER -