PO65

Abstract

Purpose This retrospective study compares high dose rate brachytherapy (HDR BT) monotherapy against HDR BT and external beam radiation therapy (EBRT), with and without androgen deprivation therapy (ADT), to determine non-inferiority of HDR BT alone in the treatment of unfavorable intermediate risk (UIR) prostate cancer. Materials/Methods Data were obtained from two registries from 1991-present. 633 patients with UIR prostate cancer treated with HDR BT were included. Patients who received only HDR BT received 42-45Gy/6 fractions (fx) or 27 Gy/2 fx. For HDR BT+EBRT, the HDR dose was 20-24 Gy/2 fx, 24 Gy/4 fx, or 15 Gy/1 fx. EBRT patients received 45 Gy/25 fx to the prostate +/- pelvic nodal radiation. GU/GI toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Treatment group differences were assessed via two-sample T test or ANOVA, and associations between categorical variable and treatment group were assessed via chi-squared or Fisher's exact test. Time-to-event analyses were carried out to evaluate relationship between treatments and primary outcome variables. Five primary endpoints were used to assess freedom from biochemical recurrence (FFBC), freedom from distant metastasis (FFDM), freedom from local failure (FFLF), cancer specific survival (CSS), and overall survival (OS). Univariate analysis was conducted using the Kaplan-Meier method and log-rank test to the primary event. For multivariate analysis, Cox proportional hazard (Cox PH) regression and Fine & Gray competing risk regression were carried out to adjust for potential confounders. For toxicity analysis, the association between the incidence of post-treatment severe GU/GI toxicity reaction, denoted grade 3 or higher, and the treatment group was evaluated via chi-squared or Fisher's exact test. Results Statistical comparisons for HDR, HDR+EBRT-ADT, and HDR+EBRT+ADT are summarized in Table 1. From the Kaplan-Meier curves and log-rank tests, no differences between the three cohorts were identified in all five survival outcomes (FFBC, FFDM, FFLF, OS, CSS), with 5-year survival for HDR, HDR+EBRT-ADT, and HDR+EBRT+ADT FFBC 99%, 95%, and 94% respectively. Multivariate analysis with Cox PH regression showed no differences in FFBC, FFDM, OS, and CSS with addition of EBT alone, or addition of EBT with ADT. Fine and Gray competing regression showed no difference in outcome for HDR, HDR+EBRT-ADT, and HDR+EBRT+ADT with respect to FFBC, FFDM, and CSS. Performing the likelihood ratio test to both the Cox PH and Fine & Gray competing regression models resulted in no differences in all survival outcomes with stable fits between treatment and non-treatment groups. In comparing CTCAE toxicities between the HDR, HDR+EBRT-ADT, and HDR+EBRT+ADT cohorts, no statistically significant differences were identified in GI and GU toxicities when comparing post-treatment and baseline toxicities. No Grade 2 or 3 GI toxicities were identified in any of the groups, while 8% and 1% of HDR patients, 10% and 1% of HDR+EBRT-ADT patients, and 12% and 2% of HDR+EBRT+ADT patients experienced Grade 2 or 3 GU toxicities. The presence of grade 3 or higher GU toxicities between the three groups were not found to be significant (p=0.91). Conclusions The results of this study demonstrate the non-inferiority of HDR BT treatment alone for UIR prostate cancer when compared to HDR+EBRT +/- ADT. The omission of EBRT, with or without ADT, can theoretically minimize occurrence of associated toxicities, although the data in this study do not demonstrate statistically significant differences likely due to the overall low frequency of toxicities reported. Given patients’ often reluctance in undergoing multiple procedures, especially when faced with the side effect profile of ADT, these results illuminate a viable road for HDR BT monotherapy in effective and durable control of UIR disease. This retrospective study compares high dose rate brachytherapy (HDR BT) monotherapy against HDR BT and external beam radiation therapy (EBRT), with and without androgen deprivation therapy (ADT), to determine non-inferiority of HDR BT alone in the treatment of unfavorable intermediate risk (UIR) prostate cancer. Data were obtained from two registries from 1991-present. 633 patients with UIR prostate cancer treated with HDR BT were included. Patients who received only HDR BT received 42-45Gy/6 fractions (fx) or 27 Gy/2 fx. For HDR BT+EBRT, the HDR dose was 20-24 Gy/2 fx, 24 Gy/4 fx, or 15 Gy/1 fx. EBRT patients received 45 Gy/25 fx to the prostate +/- pelvic nodal radiation. GU/GI toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Treatment group differences were assessed via two-sample T test or ANOVA, and associations between categorical variable and treatment group were assessed via chi-squared or Fisher's exact test. Time-to-event analyses were carried out to evaluate relationship between treatments and primary outcome variables. Five primary endpoints were used to assess freedom from biochemical recurrence (FFBC), freedom from distant metastasis (FFDM), freedom from local failure (FFLF), cancer specific survival (CSS), and overall survival (OS). Univariate analysis was conducted using the Kaplan-Meier method and log-rank test to the primary event. For multivariate analysis, Cox proportional hazard (Cox PH) regression and Fine & Gray competing risk regression were carried out to adjust for potential confounders. For toxicity analysis, the association between the incidence of post-treatment severe GU/GI toxicity reaction, denoted grade 3 or higher, and the treatment group was evaluated via chi-squared or Fisher's exact test. Statistical comparisons for HDR, HDR+EBRT-ADT, and HDR+EBRT+ADT are summarized in Table 1. From the Kaplan-Meier curves and log-rank tests, no differences between the three cohorts were identified in all five survival outcomes (FFBC, FFDM, FFLF, OS, CSS), with 5-year survival for HDR, HDR+EBRT-ADT, and HDR+EBRT+ADT FFBC 99%, 95%, and 94% respectively. Multivariate analysis with Cox PH regression showed no differences in FFBC, FFDM, OS, and CSS with addition of EBT alone, or addition of EBT with ADT. Fine and Gray competing regression showed no difference in outcome for HDR, HDR+EBRT-ADT, and HDR+EBRT+ADT with respect to FFBC, FFDM, and CSS. Performing the likelihood ratio test to both the Cox PH and Fine & Gray competing regression models resulted in no differences in all survival outcomes with stable fits between treatment and non-treatment groups. In comparing CTCAE toxicities between the HDR, HDR+EBRT-ADT, and HDR+EBRT+ADT cohorts, no statistically significant differences were identified in GI and GU toxicities when comparing post-treatment and baseline toxicities. No Grade 2 or 3 GI toxicities were identified in any of the groups, while 8% and 1% of HDR patients, 10% and 1% of HDR+EBRT-ADT patients, and 12% and 2% of HDR+EBRT+ADT patients experienced Grade 2 or 3 GU toxicities. The presence of grade 3 or higher GU toxicities between the three groups were not found to be significant (p=0.91). The results of this study demonstrate the non-inferiority of HDR BT treatment alone for UIR prostate cancer when compared to HDR+EBRT +/- ADT. The omission of EBRT, with or without ADT, can theoretically minimize occurrence of associated toxicities, although the data in this study do not demonstrate statistically significant differences likely due to the overall low frequency of toxicities reported. Given patients’ often reluctance in undergoing multiple procedures, especially when faced with the side effect profile of ADT, these results illuminate a viable road for HDR BT monotherapy in effective and durable control of UIR disease.