Para-Aortic Lymph Node Failure After Definitive Chemoradiation for Locally Advanced Cervical Cancer

Purpose: The role for prophylactic extended field para-aortic radiation therapy (EFRT) in patients with locally advanced cervical cancer (LACC) undergoing definitive chemoradiation with brachytherapy (CRT-B) is not well established. As a result, practice patterns for prophylactic EFRT vary. Our primary aim was to determine pretreatment risk factors for para-aortic lymph node (PALN) failure after definitive pelvic radiation only. Our secondary aim was to compare clinical outcomes for patients who underwent pelvic radiation only versus prophylactic EFRT at our institution.

Methodology: We performed a multicenter single institution retrospective review of all patients with FIGO stage IB2-IVB LACC who underwent definitive CRT-B from 2013 to 2022 with at least 3 months follow up. Descriptive statistics were performed on clinical and treatment characteristics. For patients treated with pelvic radiation alone, univariate analysis was performed to assess factors associated with PALN failure. Kaplan Meier method was used to compare progression free survival (PFS) for patients treated with pelvic radiation alone versus prophylactic EFRT. Statistical analysis was performed in SAS.

Results: 150 patients met the inclusion criteria and were included in this analysis. Forty-five percent (n=67) had FIGO IB2-II disease and 55% (n=83) had FIGO III-IV disease. Most common external beam radiotherapy (EBRT) doses were 45-50.4 Gray (Gy) in 1.8 Gy per fraction (97%) and median HDR dose was 28 Gy in 4 fractions. 126 patients (84%) received pelvic radiation only and 24 (16%) received EFRT either prophylactically (n=8) or due to positive para-aortic nodes at presentation (n=16). Most patients were treated with intensity-modulated radiation therapy (IMRT) (n=134, 89%) and received concurrent chemotherapy (n=144, 96%). Median follow up was 28.5 months (IQ range: 11.3-38.3). After pelvic radiation only, 9.5% (n=12) of patients experienced PALN failure; 67% (8/12) had positive pelvic nodes (N+) and the highest level of nodal involvement was common iliac in only one patient. Parametrial extension was present in 58% (7/12) of patients with PALN failure, and 67% (8/12) had disease abutting or invading the bladder. On univariate analysis, only overall treatment time (OTT) was significantly associated with PALN failure; OTT was 67 days in patients with PALN failure versus 55 days in those without (p=0.01). Two-year PFS among patients treated with pelvic radiation alone versus prophylactic EFRT was 64.5% versus 58.3%, respectively (p=0.61). Among the 8 patients who underwent prophylactic EFRT there were no PALN failures and no reported acute grade 3 or higher GI toxicities. There was 1 late adverse event of grade 4 rectal proctitis.

Conclusions: The incidence of PALN failure after definitive pelvic radiation for LACC is 9.5%. Reducing OTT may decrease the risk of PALN failure. Patients with positive pelvic nodes, parametrial extension, and Stage IVA disease may also benefit from prophylactic EFRT, especially given that EFRT appears to be well tolerated.

References: