The most locally advanced International Federation of Gynecology and Obstetrics (FIGO) stage of cervical cancer is IVA disease, which is strictly defined by biopsy-diagnosed involvement of the mucosa of the bladder and/or rectum and accounts for only 1–5% of all cervical cancers [1]. The American Society for Radiation Oncology recommends external beam radiotherapy (EBRT) with brachytherapy, and concomitant cisplatin-based chemotherapy for at least 5 cycles [2]. Nonetheless, patients with stage IVA disease generally have poor outcomes, with frequent local and distant recurrence, and reported 5-year overall survival (OS) range from 10% to 52% [4,6]. In addition, little is known about the long-term side effects of treatment [4].

In the modern era of cervical cancer treatment, positron emission tomography–computed tomography (PET-CT), intensity-modulated radiotherapy (IMRT) and magnetic resonance imaging (MRI)-guided adaptive brachytherapy have expanded treatment options for patients with stage IVA disease. In the recent EMBRACE-I study, a cohort of 34 patients with stage IVA disease who received EBRT and MRI-guided adaptive brachytherapy had a 5-year OS rate of 52% [5], much higher than historical numbers. These patients also had a 5-year local control rate of 91%, which was substantially higher than the 3-year local control rate of 57% previously reported for patients who received EBRT only [6]. Given their improved outcomes and longer survival, standardizing treatment approaches and providing survivorship support to patients with stage IVA cervical cancer requires describing and quantifying the long-term toxicity of their treatment and its impact on quality of life.

Due to the rarity of the disease, studies of patients with stage IVA cervical cancer are restricted by small sample sizes and short follow-up times, both of which prevent the investigation of long-term clinical outcomes [1,7]. Patients with stage IVA cervical cancer, who often have large-volume disease and require larger radiation fields, are at high risk for acute and late radiation-related gastrointestinal (GI) and genitourinary (GU) toxicity [8,9]. In addition, those with bladder involvement at diagnosis can develop vesicovaginal fistulae (VVF) [7]. Fistulae occur in up to 50% of patients in response to both treatment-mediated tumor regression or direct tissue toxicity and ischemia [10]. However, VVF are most often described in the acute setting [11].

Herein, we describe the treatment and long-term clinical outcomes, including survival, VVF incidence, and late radiation-related toxicity, of a large cohort of patients with stage IVA cervical cancer with bladder involvement. Our findings will guide treatment strategies, enhance survivorship support, help clinicians counsel, anticipate and manage patients' treatment-related toxicities.