Journal of Clinical Oncology

Focal Boost to the Intraprostatic Tumor in External Beam Radiotherapy for Patients With Localized Prostate Cancer: 10-Year Outcomes of the FLAME Trial

K Karolína Menne Guricová (Floris J. Pos, MD, PhD, and Karolína Menne Guricová, MSc, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands; Jochem R.N. van der Voort van der Zyp, MD, PhD, Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; Robert J. Smeenk, MD, PhD, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands; Uulke A. van der Heide, PhD, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands;Karin Haustermans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium, Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; and Cédric Draulans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium) C Cédric Draulans (Floris J. Pos, MD, PhD, and Karolína Menne Guricová, MSc, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands; Jochem R.N. van der Voort van der Zyp, MD, PhD, Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; Robert J. Smeenk, MD, PhD, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands; Uulke A. van der Heide, PhD, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands;Karin Haustermans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium, Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; and Cédric Draulans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium) F Floris J. Pos (Floris J. Pos, MD, PhD, and Karolína Menne Guricová, MSc, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands; Jochem R.N. van der Voort van der Zyp, MD, PhD, Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; Robert J. Smeenk, MD, PhD, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands; Uulke A. van der Heide, PhD, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands;Karin Haustermans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium, Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; and Cédric Draulans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium) L Linda G.W. Kerkmeijer (Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands) E Evelyn M. Monninkhof (Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands) R Robert J. Smeenk (Floris J. Pos, MD, PhD, and Karolína Menne Guricová, MSc, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands; Jochem R.N. van der Voort van der Zyp, MD, PhD, Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; Robert J. Smeenk, MD, PhD, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands; Uulke A. van der Heide, PhD, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands;Karin Haustermans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium, Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; and Cédric Draulans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium) M Martina Kunze-Busch (Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands) H Hans C.J. de Boer (Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands) J Jochem R.N. van der Voort van der Zyp (Floris J. Pos, MD, PhD, and Karolína Menne Guricová, MSc, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands; Jochem R.N. van der Voort van der Zyp, MD, PhD, Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; Robert J. Smeenk, MD, PhD, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands; Uulke A. van der Heide, PhD, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands;Karin Haustermans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium, Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; and Cédric Draulans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium) K Karin Haustermans U Uulke A. van der Heide (Floris J. Pos, MD, PhD, and Karolína Menne Guricová, MSc, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands; Jochem R.N. van der Voort van der Zyp, MD, PhD, Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; Robert J. Smeenk, MD, PhD, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands; Uulke A. van der Heide, PhD, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands;Karin Haustermans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium, Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; and Cédric Draulans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium)

Abstract

The FLAME trial hypothesized that focal boosting of intraprostatic tumor lesion(s) in addition to standard external beam radiotherapy (EBRT) improves biochemical disease-free survival (bDFS). In this multicenter randomized phase III trial, patients with intermediate- and high-risk prostate cancer (PCa) were assigned to the standard (EBRT of 77 Gy in 35 fractions to the whole prostate gland) or focal boost arm (standard EBRT with a focal boost of up to 95 Gy to magnetic resonance imaging–visible lesion(s)). Initial 5-year results showed a significant improvement in the focal boost arm for bDFS without additional toxicity. Here, we report bDFS, disease-free survival (DFS), local DFS, regional lymph node DFS, distant metastasis-free survival (DMFS), and overall survival (OS) after a 10-year follow-up. Dose-response curves were created using the dose heterogeneity in the study arm. Between 2009 and 2015, 571 patients were randomly assigned. The 10-year bDFS was 71% in the standard arm versus 86% in the focal boost arm. A significant improvement was also observed for other end points, except DMFS and OS. However, the dose-response curve suggests an association between dose and distant metastatic failure. The 10-year results demonstrated the sustained benefit of focal boosting on bDFS. By preventing biochemical failure, men are spared the potential burden of PCa recurrence.

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Article Details

Volume / Issue Vol. 43, Issue 28
Published October 01, 2025
Pages 3065-3069
ISSN 0732-183X
Publisher Lippincott Williams & Wilkins

Journal Info

Journal of Clinical Oncology

Lippincott Williams & Wilkins
ISSN: 0732-183X Health Sciences

Authors (11)

K

Karolína Menne Guricová

Floris J. Pos, MD, PhD, and Karolína Menne Guricová, MSc, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands; Jochem R.N. van der Voort van der Zyp, MD, PhD, Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; Robert J. Smeenk, MD, PhD, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands; Uulke A. van der Heide, PhD, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands;Karin Haustermans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium, Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; and Cédric Draulans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium

C

Cédric Draulans

Floris J. Pos, MD, PhD, and Karolína Menne Guricová, MSc, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands; Jochem R.N. van der Voort van der Zyp, MD, PhD, Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; Robert J. Smeenk, MD, PhD, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands; Uulke A. van der Heide, PhD, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands;Karin Haustermans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium, Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; and Cédric Draulans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium

F

Floris J. Pos

Floris J. Pos, MD, PhD, and Karolína Menne Guricová, MSc, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands; Jochem R.N. van der Voort van der Zyp, MD, PhD, Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; Robert J. Smeenk, MD, PhD, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands; Uulke A. van der Heide, PhD, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands;Karin Haustermans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium, Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; and Cédric Draulans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium

L

Linda G.W. Kerkmeijer

Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands

E

Evelyn M. Monninkhof

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

R

Robert J. Smeenk

Floris J. Pos, MD, PhD, and Karolína Menne Guricová, MSc, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands; Jochem R.N. van der Voort van der Zyp, MD, PhD, Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; Robert J. Smeenk, MD, PhD, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands; Uulke A. van der Heide, PhD, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands;Karin Haustermans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium, Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; and Cédric Draulans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium

M

Martina Kunze-Busch

Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands

H

Hans C.J. de Boer

Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands

J

Jochem R.N. van der Voort van der Zyp

Floris J. Pos, MD, PhD, and Karolína Menne Guricová, MSc, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands; Jochem R.N. van der Voort van der Zyp, MD, PhD, Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; Robert J. Smeenk, MD, PhD, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands; Uulke A. van der Heide, PhD, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands;Karin Haustermans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium, Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; and Cédric Draulans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium

K

Karin Haustermans

U

Uulke A. van der Heide

Floris J. Pos, MD, PhD, and Karolína Menne Guricová, MSc, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands; Jochem R.N. van der Voort van der Zyp, MD, PhD, Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands; Robert J. Smeenk, MD, PhD, Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands; Uulke A. van der Heide, PhD, Department of Radiation Oncology, Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands;Karin Haustermans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium, Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium; and Cédric Draulans, MD, PhD, Department of Oncology, KU Leuven, Leuven, Belgium

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