Focal Boost to the Intraprostatic Tumor in External Beam Radiotherapy for Patients With Localized Prostate Cancer: 10-Year Outcomes of the FLAME Trial
Karolína Guricová, Cédric Draulans, Floris J. Pos, Linda G.W. Kerkmeijer, Evelyn M. Monninkhof, Robert Jan Smeenk, Martina Kunze-Busch, Hans C.J. de Boer, Jochem van der Voort van Zyp, Karin Haustermans, Uulke A. van der Heide
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.