125I Interstitial brachytherapy with or without androgen deprivation therapy among unfavorable-intermediate and high-risk prostate cancer.

PURPOSE/OBJECTIVE(S): To determine if patients with unfavorable intermediate-risk (UIR), high-risk (HR), or very high-risk (VHR) prostate cancer (PCa) treated with 125I interstitial brachytherapy benefit from androgen deprivation therapy (ADT). MATERIALS/METHODS: We reviewed our institutional database of patients with UIR, HR, or VHR PCa, per 2018 NCCN risk classification, treated with definitive 125I interstitial brachytherapy with or without ADT from 1998-2017. Outcomes including biochemical failure (bF), distant metastases (DM), and overall survival (OS) were analyzed with the Kaplan-Meier method and Cox proportional hazards regression. PCa-specific mortality (PCSM) was analyzed with Fine-Gray competing-risk regression. RESULTS: Of 1033 patients, 262 (25%) received ADT and 771 (75%) did not. Median ADT duration was 6 months. By risk group, 764 (74%) patients were UIR, 219 (21%) HR, and 50 (5%) VHR. ADT was more frequently given to HR (50%) and VHR (56%) patients compared to UIR (16%; p<0.001), to older patients (p<0.001), corresponding with increasing PSA (p<0.001) and Grade Group (p<0.001). Median follow-up was 4.9 years (0.3-17.6 years). On multivariable analysis accounting for risk group, age, and year of treatment, ADT was not associated with bF, DM, PCSM, or OS (p≥0.05 each). CONCLUSION: Among patients with UIR, HR, and VHR PCa, the addition of ADT to 125I interstitial brachytherapy was not associated with improved outcomes, and no subgroup demonstrated benefit. Our findings do not support the use of ADT in combination with 125I interstitial brachytherapy. Prospective studies are required to elucidate the role of ADT for patients with UIR, HR, and VHR PCa treated with prostate brachytherapy.

Validation of the NCCN prostate cancer favorable- and unfavorable-intermediate risk groups among men treated with I-125 low dose rate brachytherapy monotherapy.

PURPOSE: To validate the 2019 NCCN subgroups of favorable- and unfavorable-intermediate risk (IR) prostate cancer among patients treated with brachytherapy, who are underrepresented in the studies used to develop the 2019 NCCN classification. METHODS: We included all 2,705 men treated with I-125 LDR brachytherapy monotherapy at a single institution, and who could be classified into the 2019 NCCN risk groups. Biochemical failure and distant metastasis rates were calculated using cumulative incidence analysis. RESULTS: Of 1,510 IR patients, 756 (50%) were favorable-IR, and 754 (50%) were unfavorable-IR. Median follow up was 48 months (range, 3-214). As compared to favorable-IR, the unfavorable-IR group was associated with significantly higher rates of biochemical failure (HR, 2.87; 95% CI, 2.00-4.10; p < 0.001) and distant metastasis (HR, 3.14; 95% CI, 1.78-5.50, p < 0.001). For favorable-IR vs. unfavorable-IR groups, 5-year estimates of biochemical failure were 4.3% (95% CI, 2.6-6.1%) vs. 17.0% (95% CI, 13.6-20.5%; p < 0.001), and for distant metastasis were 1.6% (95% CI, 0.5-2.6%) vs. 5.4% (95% CI, 3.3-7.4%; p < 0.001), respectively. Patients with one unfavorable-intermediate risk factor (unfavorable-IRF; HR, 2.27; 95% CI, 1.54-3.36; p < 0.001) and 2-3 unfavorable-IRFs (HR, 4.42; 95% CI, 2.89-6.76; p < 0.001) had higher biochemical failure rates; similar findings were observed for distant metastasis (1 unfavorable-IRF: HR, 2.46; 95% CI, 1.34-4.53, p = 0.004; 2-3 unfavorable-IRFs: HR, 4.76; 95% CI, 2.49-9.10, p < 0.001). CONCLUSIONS: These findings validate the prognostic utility of the 2019 NCCN favorable-IR and unfavorable-IR prostate cancer subgroups among men treated with brachytherapy. Androgen deprivation was not beneficial in any subgroup. Alternative treatment intensification strategies for unfavorable-IR patients are warranted.