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Focal Boost to the Intraprostatic Tumor in External Beam Radiotherapy for Patients With Localized Prostate Cancer
abstract
This abstract is available on the publisher's site.
Access this abstract nowPURPOSE
This study investigates whether focal boosting of the macroscopic visible tumor with external beam radiotherapy increases biochemical disease-free survival (bDFS) in patients with localized prostate cancer.
PATIENTS AND METHODS
In the phase III, multicenter, randomized controlled Focal Lesion Ablative Microboost in Prostate Cancer trial, 571 patients with intermediate- and high-risk prostate cancer were enrolled between 2009 and 2015. Patients assigned to standard treatment received 77 Gy (fractions of 2.2 Gy) to the entire prostate. The focal boost arm received an additional simultaneous integrated focal boost up to 95 Gy (fractions up to 2.7 Gy) to the intraprostatic lesion visible on multiparametric magnetic resonance imaging. Organ at risk constraints were prioritized over the focal boost dose. The primary end point was 5-year bDFS. Secondary end points were disease-free survival (DFS), distant metastases-free survival, prostate cancer-specific survival, overall survival, toxicity, and health-related quality of life.
RESULTS
Median follow-up was 72 months. Biochemical DFS was significantly higher in the focal boost compared with the standard arm (hazard ratio 0.45, 95% CI, 0.28 to 0.71, P < .001). At 5-year follow-up bDFS was 92% and 85%, respectively. We did not observe differences in prostate cancer-specific survival (P = .49) and overall survival (P = .50). The cumulative incidence of late genitourinary and GI toxicity grade ≥ 2 was 23% and 12% in the standard arm versus 28% and 13% in the focal boost arm, respectively. Both for late toxicity as health-related quality of life, differences were small and not statistically significant.
CONCLUSION
The addition of a focal boost to the intraprostatic lesion improved bDFS for patients with localized intermediate- and high-risk prostate cancer without impacting toxicity and quality of life. The Focal Lesion Ablative Microboost in Prostate Cancer study shows that a high focal boost strategy to improve tumor control while respecting organ at risk dose constraints is effective and safe.
Additional Info
Disclosure statements are available on the authors' profiles:
Focal Boost to the Intraprostatic Tumor in External Beam Radiotherapy for Patients With Localized Prostate Cancer: Results From the FLAME Randomized Phase III Trial
J. Clin. Oncol 2021 Jan 20;[EPub Ahead of Print], LGW Kerkmeijer, VH Groen, FJ Pos, K Haustermans, EM Monninkhof, RJ Smeenk, M Kunze-Busch, JCJ de Boer, J van der Voort van Zijp, M van Vulpen, C Draulans, L van den Bergh, S Isebaert, UA van der HeideFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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Urology
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.