Risk Factors and Clinical Features of Fistula after Concurrent Chemoradiation and Brachytherapy for Locally Advanced Cervical Cancer.

PURPOSE/OBJECTIVE(S): The standard treatment for locally advanced cervical cancer (LACC) is concurrent chemoradiation and brachytherapy (CRT-B). Fistula formation is a serious complication of treatment; however, risk factors and clinical outcomes are not well described. We sought to identify the incidence, risk factors and prognosis of radiation-induced fistula in women who underwent CRT-B for LACC.

MATERIALS/METHODS: A single institution retrospective review of patients treated with CRT-B for LACC from July 2013 to August 2022 across 3 centers was performed. Inclusion criteria were Stage IB-IVB cervical cancer treated with definitive intent. Patients with upfront or adjuvant surgery were excluded. Cox-proportional hazards model was performed to assess factors associated with fistula. Local control and fistula-free survival were estimated using the Kaplan-Meyer method. Clinical significance was defined as p < 0.05.

RESULTS: A total of 105 patients met the inclusion criteria and were included in this analysis. Patients consisted of FIGO Stage I (n = 20, 19%), Stage II (n = 22, 21%), Stage III (n = 46, 43.8%) or Stage IV disease (n = 17, 16.2%). 12 (11.4%) patients developed fistula following CRT-B; 1/12 patients (8.3%) had fistula present at time of diagnosis. Median time to fistula development was 12 months. Fistula was characterized as vesicovaginal/urethrovaginal in 58.3% (n = 7) and rectovaginal/intestinovaginal in 83.3% (n = 10), including 8 patients (66.7%) who had more than one type of fistula. 4/12 (33.3%) of patients with fistula had concurrent local recurrence. Patients were treated with conservative management (41.7%), hyperbaric oxygen (16.7%) and/or surgery (83.3%). Complications included infection (50.0%), urinary/bowel diversion (83.3%), hospitalization (50.0%) and death (8.3%). Fistula was resolved in 7/12 patients (58.3%) at time of last follow up. Higher BMI (p = 0.04) and use of hybrid applicators (p = 0.02) were associated with decreased likelihood of fistula development. Disease extension into bladder was associated with increased likelihood of fistula development (p = 0.03). Compared to former and never smoking, current smoking was associated with a higher risk of developing fistula (p = 0.04, OR 4.42, CI:1.07-18.34). Compared to intracavitary and hybrid applicators, the use of a Syed applicator was associated with increased likelihood of fistula development (p = 0.02, OR 8.00, CI: 1.37-46.55). Two-year local control was 82.5% (CI: 64.5-91.9) for Stage I-II, 80.7% (CI: 62.8-90.6) for Stage III, and 62.2% (CI: 30.1-82.9) for Stage IV. Two-year fistula free survival was 89.9% (CI: 80.6 - 94.9).

CONCLUSION: Women who undergo definitive chemoradiation for treatment of LACC have a 11.4% risk of fistula formation overall. The risk is higher amongst patients with current smoking, disease extension into bladder and Syed applicators. Overall two-year local control was 78.7% and fistula free survival was 89.9%.