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Top Line: Does dose escalation with a simultaneous integrated boost (SIB) improve biochemical control for prostate cancer?

The Study: The challenge with radiation dose escalation to the whole prostate is that, at some point, increased toxicity outweighs small improvements in disease control. Another approach has been to target MRI-defined disease. But does such an approach actually improve disease outcomes? In the FLAME trial, men with high (cT3, GS > 7, or PSA > 20) and intermediate (cT2, GS 7, or PSA 10-20) risk prostate cancer (i.e., not exactly the NCCN criteria) were randomized to receive 77 Gy in 35 fractions with or without a SIB up to 95 Gy to intra-prostatic disease defined by multi-parametric MRI. One or more GTV’s could be contoured, but there was no additional margin for the boost volume. OAR constraints had to be met at the cost of under-covering the boost volume (see those constraints here). Roughly two-thirds of men received ADT with most (>90%) receiving adjuvant as opposed to neoadjuvant ADT. At 5 years, biochemical disease-free survival was significantly higher with SIB than without (92 vs 85%), which resulted in a 50% relative reduction in biochemical failure. Did that gain come at the cost of higher toxicity? Nope. Remembering that OAR constraints were higher priority than boost volume coverage, there was no difference in late grade 2+ GU and GI toxicity. Grade 3+ GU toxicity was ~5% and GI toxicity was < 2% in both arms. One grade 4 GU event occured in the SIB arm. There was no difference in distant metastasis-free or overall survival.

TBL: Dose escalation with a focal, MRI-based boost while respecting critical organ constraints appears to improve biochemical control without increasing toxicity for higher risk prostate cancer. | Kerkmeijer, J Clin Oncol 2021

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