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

Abstract

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, 3e214). As compared to favorable-IR, the unfavorable-IR group was associated with significantly higher rates of biochemical failure (HR, 2.87; 95% CI, 2.00e4.10; p ! 0.001) and distant metastasis (HR, 3.14; 95% CI, 1.78e5.50, p ! 0.001). For favorable-IR vs. unfavorable-IR groups, 5-year estimates of biochemical failure were 4.3% (95% CI, 2.6e6.1%) vs. 17.0% (95% CI, 13.6e20.5%; p ! 0.001), and for distant metastasis were 1.6% (95% CI, 0.5e2.6%) vs. 5.4% (95% CI, 3.3e7.4%; p ! 0.001), respectively. Patients with one unfavorable-intermediate risk factor (unfavorable-IRF; HR, 2.27; 95% CI, 1.54e3.36; p ! 0.001) and 2e3 unfavorable-IRFs (HR, 4.42; 95% CI, 2.89e6.76; p ! 0.001) had higher biochemical failure rates; similar findings were observed for distant metastasis (1 unfavorable-IRF: HR, 2.46; 95% CI, 1.34e4.53, p 5 0.004; 2e3 unfavorable-IRFs: HR, 4.76; 95% CI, 2.49e9.10, 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.

Clinical significance of unfavorable findings in intermediate‐risk prostate cancer patients for predicting treatment outcomes after contemporary, dose‐escalated multimodal radiotherapy

“…Several reports have validated IR‐based subclassification of patients treated via LDR‐BT 4,5 . Berlin et al 4 were the first to evaluate this subclassification, but their LDR‐BT cohort only included 258 patients.…”

“…Berlin et al 4 were the first to evaluate this subclassification, but their LDR‐BT cohort only included 258 patients. Tom et al 5 subsequently validated the prognostic utility of the 2019 NCCN favorable versus unfavorable IR prostate cancer subgroups in 1510 patients treated via LDR‐BT monotherapy. The follow‐up interval was short.…”

“…However, because the definition was established by reference to patients treated via EBRT, the applicability of this definition to patients treated via contemporary (much higher‐dose) irradiation awaits validation. Several reports have evaluated the subclassification using patients treated via LDR‐BT 4,5 . However, it is difficult to draw a definitive conclusion because of the small case numbers and short follow‐up periods.…”

Eligibility criteria according to EAU/ESTRO/SIOG guidelines for exclusive iodine-125 brachytherapy for intermediate-risk prostate adenocarcinoma patients: impact on relapse-free survival

“…Seventeen studies reported series of exclusive brachytherapy, including IR patients but mixed with low- [19][20][21][22][23] and high-risk (HR) patients [24][25][26][27][28][29][30][31][32][33][34][35], with a variable rate of patients receiving ADT up to 58.2% [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] (Table 5).…”

“…Up till now, no study has explored the prognostic role of PBC percentage, specifically among IR patients treated with BT alone. The validation of prognostic utility of the sub-classification of IR patients between FIR and UIR suggests a potential impact of PBC < 50% [17,24]. In Frank et al study, patients with GS 7, PSA < 10 ng/ml, and PBC ≤ 35% were eligible to BT alone [18].…”