Focal Boost to the Intraprostatic Tumor in External Beam Radiotherapy for Patients With Localized Prostate Cancer

Focal Lesion Ablative Microboost in Prostate Cancer (FLAME) is a randomized, multicenter, phase III trial (N = 571) conducted at several centers in the Netherlands and Belgium testing whether dose escalation to an magnetic resonance imaging (MRI)–defined intraprostatic lesion was superior to standard whole prostate–only dose-escalated external beam radiotherapy. The experimental approach, termed a focal microboost, delivered to up to 95 Gy over 35 fractions compared with a dose of 77 Gy over the same duration in the standard arm. The microboost dose was reduced, if needed, to meet bladder and rectal constraints specific to each center. In this study, 84% of patients had National Comprehensive Cancer Network high-risk disease, and 65% of patients received androgen deprivation with radiation therapy. The primary endpoint was 5-year biochemical disease–free survival. After a median follow-up of 72 months, the microboost arm met its primary endpoint (92% vs 85%, respectively; HR, 0.45; P < .001). Overall survival was similar between the arms. Importantly, there were no significant differences in late-grade 2+ or 3+ genitourinary or gastrointestinal toxicity. 

The FLAME trial is potentially practice-changing. Although it is well-established that biochemical-based endpoints are not surrogate endpoints for overall survival, improved tumor control is desirable in its own right when achieved without an increase in toxicity or cost. There will be required learning on the part of centers to adopt such an approach as the target delineation was based on T2-weighted, diffusion-weighted imaging and dynamic contrast-enhanced sequences, similar to those used for the PI-RADS guidelines. Moreover, safe delivery using appropriate image guidance, as was done with gold fiducial markers on the FLAME trial, will be paramount to translating these promising results into general practice. Time will tell how the FLAME results will impact the use of a brachytherapy boost and whether similar or better biochemical control outcomes can be achieved without added toxicity or patient inconvenience. As cross-trial comparisons have limitations, dedicated trials will be required to establish the benefits and harms of MRI-guided microboost versus whole-gland boost strategies using stereotactic- or brachytherapy-based approaches. In summary, the FLAME microboost approach is a promising strategy to increase biochemical control when treating localized prostate cancer with radiotherapy.