Radiation Dose to the Intraprostatic Urethra Correlates Strongly With Urinary Toxicity Following Prostate SBRT: A Combined Analysis of 23 Prospective Clinical Trials

Abstract

Clinical trials of prostate SBRT have utilized a wide range of allowed doses to the intraprostatic urethra but the relationship between urethral dose and urinary toxicity has not been thoroughly evaluated. We aimed to characterize urinary toxicity outcomes according to urethral dose administered during prostate SBRT.We searched MEDLINE (PubMed) for published prospective studies of prostate SBRT through August 2020 that documented a maximum urethral dose metric (MUDM). Reported acute and late urinary toxicity rates were collected. Weighted correlation and weighted linear regression models were used to assess the associations between urinary toxicity rates and MUDM.Twenty-three unique studies (n = 2232 patients) met the inclusion criteria and included a wide range of MUDMs (EQD2 69 Gy to 141.75 Gy, a/b = 3). Median follow up ranged from 3-67 months (median 32 months). MUDM was strongly associated with urinary toxicity and was more closely associated with toxicity than prescription dose, including acute G2+ (r = 0.51, P = 0.02), late G2+ (r = 0.9, P < 0.0001) and late G3+ toxicity (r = 0.7, P = 0.003). Weighted linear regression accounting for age, prostate size and baseline urinary function confirmed association between urinary outcomes and MUDM. The weighted correlation model predicted late grade 2+ urinary toxicity rates of 2.5%, 5%, 10% and 15% corresponding to MUDMs of 34.2 Gy, 37.7 Gy, 43.9 Gy and 49.4 Gy, respectively, for 5 fraction regimens. Within the studied dose range, each increase of 1 Gy to the MUDM corresponded to a 0.8% and 0.9% increase in acute G2+ and late G2+ toxicity, respectively.Radiation dose to the urethra correlates closely with urinary toxicity in prostate cancer patients treated with SBRT. Attention should be paid to urethral dose when delivering prostate SBRT to high doses and approaches for urethral dose reduction warrant further investigation. These techniques may be facilitated by online adaptive planning with daily urethral delineation.