What is the ideal radiotherapy dose to treat prostate cancer? A meta-analysis of biologically equivalent dose escalation.

Abstract

To determine if increasing the biologically equivalent dose (BED) via various radiation fractionation regimens is correlated with clinical outcomes or toxicities for prostate cancer. We performed a meta-analysis that included 12,756 prostate cancer patients from 55 studies published from 2003 to 2013 who were treated with non-dose-escalated conventionally fractionated external beam radiation therapy (non-DE-CFRT), DE-CFRT, hypofractionated RT, and high dose rate brachytherapy (HDR-BT; either mono or boost) with ⩾5-year actuarial follow-up. BEDs were calculated based on the following formula: (nd[1+d/(α/β)]), where n is the number of fractions, and d is dose per fraction; assuming an α/β of 1.5 for prostate cancer and 3.0 for late toxicities. Mixed effects meta-regression models were used to estimate weighted linear relationships between BED and the observed percentages of patients experiencing late toxicities or 5-year freedom from biochemical failure (FFBF). Increases in 10 Gy increments in BED (at α/β of 1.5) from 140 to 200 Gy were associated with 5-unit improvements in percent FFBF. Dose escalation of BED above 200 Gy was not correlated with FFBF. Increasing BED (at α/β of 3.0) from 98 to 133 Gy was associated with increased gastrointestinal toxicity. Dose escalation above 133 Gy was not correlated with toxicity. An increase in the BED to 200 Gy (at α/β of 1.5) was associated with increased disease control. Doses above 200 Gy did not result in additional clinical benefit.