Locoregional Treatment in Patients With Metastatic Cervical Cancer: Benefit of Dose Escalation Strategies

Purpose: The objective of this work was to examine the benefit of an intensive locoregional treatment including an image guided adaptive brachytherapy (IGABT) among patients with cervical cancer and extrapelvic extension. Methods and Materials: Medical records of consecutive patients with a metastatic cervical cancer and receiving external beam radiation therapy and IGABT boost in Gustave Roussy Institute as part of their first line of treatment were examined. Depending on tumor sites, patients received pelvic ± para-aortic external beam radiation therapy. For those with visceral or supradiaphragmatic lymph node metastases, chemoradiation was delivered after usually 3 cycles of chemotherapy. All patients received a brachytherapy boost, guided by magnetic resonance imaging and aimed at increasing the dose to the high-risk clinical target volume (CTV_HR). Local control (LC), patient overall survival (OS), progression-free survival, and radiation therapy–related side effects were examined, and prognostic factors were searched. Results: One hundred sixty-four patients were included; 76.2% had para-aortic lymph node extension without distant metastasis (N2) and 23.8% had distant metastatic sites (M1). There was not a statistically significant difference in survival between both groups. With a median follow-up of 36 months, OS, progression-free survival, and LC at 3 years were 55.5% (95% CI, 48%-64%), 40.6% (95% CI, 38%-54%), and 90% (95% CI, 85%-96%), respectively. In multivariate analysis, a D90CTV_HR dose ≥80 Gy was significant for better OS (hazard ratio, 0.96; 95% CI, 0.94-0.98; P <.001). Most toxicities were mild to moderate, with 2% grade 3 late urinary toxicity, 7% late grade 2 vaginal sequelae, and 1 grade 3 proctitis. During follow-up, rectovaginal fistula occurred in 2 patients without local relapse. Conclusions: IGABT permits dose escalation and high LC rates for patients with cervical cancer and extrapelvic extension. Dose/effect relationships for survival were shown. Because of high frequency of distant events, systemic intensification should be tested more specifically among these patients.