Image-guided adaptive brachytherapy for advanced cervical cancer spreading to the bladder and/or rectum: Clinical outcome and prognostic factors

Introduction: Refinements of brachytherapy techniques have led to better local control of locally advanced cervical cancer (LACC), especially with the development of image-guided adaptive brachytherapy (IGABT). Data on the efficacy of brachytherapy in cervical cancer spreading to adjacent organs are scarce. We report the experience of our institution in the treatment of these advanced tumors with IGABT. Materials and methods: Medical records of patients treated for a LACC spreading to the bladder and/or rectum between 2006 and 2020 at Gustave Roussy Institute were analyzed. Dosimetric parameters were collected and converted into 2 Gy per fraction equivalent doses, including the minimal dose received by 90% of the high-risk target volume (D₉₀ CTV_HR) and intermediate-risk target volume (D₉₀ CTV_IR), as well as the dose received by the most exposed 2 cm³ of the organs at risk. A Cox regression model was used to study the potential associations between clinical and dosimetric factors with survival endpoints and fistula formation. Results and statistical analysis: A total of 81 patients were identified. All patients received pelvic+/− para-aortic radiotherapy, 45 Gy in 25 fractions +/− boost to gross lymph nodes. Concomitant platinum-based chemotherapy was administered in 93.8% of cases. The median D₉₀ CTV_HR dose was 75.5 Gy_EQD2 (SD: 10.39 Gy_EQD2) and median CTV_HR volume was 47.6 cm³ (SD: 27.9 cm³). Median bladder and rectal D2_cm3 dose were 75.04 Gy_EQD2 (SD: 8.72 Gy_EQD2) and 64.07 Gy_EQD2 (SD: 6.68 Gy_EQD2). After a median follow-up of 27.62 ± 25.10 months, recurrence was found in 34/81 patients (42%). Metastatic failure was the most common pattern of relapse (n = 25). Use of a combined interstitial/intracavitary technique and D₉₀ CTV_HR ≥ 75.1 Gy_EQD2 were prognostic factors for OS in univariate analysis (HR = 0.24, 95%IC: 0.057–1, p = 0.023; HR = 0.2, 95%IC: 0.059–0.68, p = 0.0025, respectively). In multivariate analysis, a D₉₀ CTV_HR ≥ 75.1 Gy_EQD2 was significant for OS (HR = 0.23; 95%IC: 0.07, 0.78, p = 0.018). The occurrence of vesicovaginal fistula (VVF) was the most frequent pattern of local recurrence (HR = 4.6, 95%CI: 1.5–14, p = 0.01). Conclusion: Advances in brachytherapy modalities improved local control and survival while reducing toxicities. Enhancing local control through dose escalation and combined intracavitary/interstitial brachytherapy techniques is a major factor in patients cure probability, together with systemic intensification to better control distant events.