Reductions in Prostatic and Urethral Doses Are Associated With Less Acute Morbidity in Patients Undergoing Pd-103 Brachytherapy: Substantiation of the Rationale for Focal Therapy

Abstract

Interest in prostate brachytherapy dose reduction or focal treatment exists due to expected reductions in treatment morbidity, but analyses in the modern era have not generally corroborated relationships between prostate or urethral dose and urinary toxicity. However, such analyses have been performed on cohorts receiving uniform prescribed doses. We analyzed patients treated to differing prescription doses to assess for effects of dose reduction on acute urinary morbidity, and to estimate the magnitude of such effects. An IRB-approved database was utilized. Patients treated with Pd-103 to either 125Gy or 90-100Gy were assessed using patient-reported International Prostate Symptom Score (IPSS) at 1-month post-implant, based on published evidence showing urinary morbidity after Pd-103 peaks at 1-month. Patients in 90-100Gy cohort received supplemental EBRT 45Gy after their 1-month assessment, thus toxicities were measured prior to any contribution from EBRT. Baseline patient characteristics were compared to verify subgroup homogeneity. Univariate and multivariate stepwise logistic regression analyses were performed to determine predictors of developing >10 point increase from baseline IPSS at 1 month. Post-implant catheterization rates were compared between groups. One hundred ninety-one patients and forty patients were treated with 125Gy vs 90-100Gy Pd-103, respectively. Treatment groups were similar with respect to pre-and post-implant prostate volumes, number of seeds used, and initial IPSS. Prostate and urethra doses were uniformly higher for the 125Gy group compared to the 90-100Gy group. Prescription dose, Initial IPSS, Prostate V150, V175 and V200Gy (absolute doses), Urethral V100Gy, D5, D10, D20, D30, and D50 (absolute doses) were all significantly associated with or trended toward significance vs IPSS >10 from baseline. The multivariate model demonstrated that Prescription dose, Initial IPSS, Urethral D30, and Prostate V150, V175 and V200Gy were independent predictors of developing >10 point increase from baseline IPSS scores at 1-month follow up. Patients in the 90-100 Gy cohort had median IPSS increase from baseline of 9.7 and 60% freedom from 10-point IPSS increase at 1-month, compared to 14.1 and 29% in the 125Gy cohort (P = 0.004 and <0.001, respectively). Post-implant catheterization occurred in 7.3% of the patients treated to 125Gy versus 0% in the 90-100Gy cohort. Reduced prescription dose, urethral doses and volumes of high dose regions to the prostate correlated with reduced acute urinary morbidity after Pd-103 brachytherapy. This study suggests that focal treatment approaches with modest dose reductions to subregions of the prostate may reduce acute morbidity and potentially expand the number of patients eligible for brachytherapy. Further investigation is warranted to confirm these effects and the feasibility of focal approaches from a cancer control perspective.