Impact of Prostate Gland Size ≥60 cc on Physician and Patient-Reported Toxicity after High Dose Rate Prostate Brachytherapy

Abstract

Prostate volume of ≥60 cubic centimeters (cc) has been a relative contraindication to treatment with interstitial prostate brachytherapy (BT), with some studies showing associations between large prostate size and increased acute toxicity. These studies primarily used low dose rate BT. Few studies have explored toxicity in men with large glands undergoing high dose rate (HDR) BT. We compared the acute patient and physician reported toxicity between men undergoing HDR BT with gland size <60 cc and those with gland size ≥60 cc. We performed a retrospective cohort study of men undergoing prostate HDR BT as part of a prospectively maintained database. The 13.5 Gy x 2 was used for monotherapy and 13.5-15 Gy x 1 for boost to supplement EBRT. Gland size was determined using pre-treatment MRI or TRUS. The International Prostate Symptom Score (IPSS) and Expanded Prostate Cancer Index Composite Short Form (EPIC-26) were used to assess urinary, bowel, and sexual function at baseline and in follow-up. The Common Terminology Criteria for Adverse Events (CTCAE) v4.0 criteria were used to assess genitourinary (GU) and gastrointestinal (GI) toxicity. Baseline demographic and clinical characteristic data were compared between men with gland size <60 cc and those with gland size ≥60 cc using Fisher’s exact and non-parametric Wilcoxon Rank Sum tests. Patient-reported toxicities were compared using Generalized estimating equations (GEE) with an independent weight matrix to account for the correlation between multiple observations. Physician reported toxicities were assessed using a generalized linear mixed effects model. One hundred nineteen men were included in this analysis. Median follow-up was 7.6 months. Median prostate size was 36 cc (range: 13.9-91.9 cc). Thirteen men (10.9%) had a gland size ≥60 cc. There were no differences in baseline urinary medication use, baseline IPSS, or baseline EPIC-26 domain scores between the two groups. There were no differences in mean IPSS over time between the two groups (p=0.9). Men with gland size ≥60 cc had a greater decline in the EPIC-26 urinary incontinence domain score at 1 month (p<0.01) that met criteria for minimal clinically important difference (MCID), but no difference at 3 or 6 months. Men with gland size ≥60 cc had higher urinary irritative/obstructive domain scores at 3 months (p=0.03) that met criteria for MCID, but no difference at 1 or 6 months. There was no difference between groups in bowel or sexual domains. There was a trend towards higher acute urinary retention (AUR) in the ≥ 60 cc group (p=0.06). There was no difference in grade ≥2 GU toxicity and grade ≥2 GI toxicity. Men with prostate gland size of ≥60 cc have no difference in acute physician-reported toxicity, but a trend towards worse AUR and worse urinary incontinence at one month, yet better urinary irritative/obstructive scores at 3 months. Further investigation is needed to limit the impact of therapy on urinary function in men with gland size ≥60 cc.