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CHICAGO -- Prophylactic extended-field irradiation (EFI) for locally advanced cervical cancer significantly improved overall survival (OS), disease-free survival (DFS), and extrapelvic disease control, a retrospective study from China showed.

Overall, the analysis showed no difference in 5-year outcomes as compared with standard pelvic irradiation. After adjustment for imbalances in baseline characteristics, a propensity-matched analysis showed double-digit improvements in 5-year OS, DFS, para-aortic lymph node (PALN) control, and extrapelvic disease control in cervical cancer patients with FIGO stage IIIC1 disease.

Additional propensity-matched analyses identified patients with and without high-risk characteristics who benefited from EFI, reported Weiping Wang, PhD, of Peking Union Medical College Hospital in Beijing, during the American Society for Radiation Oncology (ASTRO) meeting.

"The incidence of severe chronic toxicities was higher in the EFI group than in the pelvic radiotherapy group, although the difference was not significant," said Wang. "FIGO stage IIIC1 can be used as an inclusion criterion in clinical trials comparing pelvic radiotherapy to prophylactic EFI in patients with cervical cancer."

Importance of Primary Treatment

Recent studies to improve and optimize treatment of cervical cancer have often focused on integration of immunotherapy and other systemic therapies. Wang's study showed that "another way to escalate treatment for cervical cancer is to increase the volume that is irradiated," said ASTRO invited discussant Emma Fields, MD, of Virginia Commonwealth University in Richmond.

"We all see that the response to the primary treatment with chemoradiation is often the most important factor in long-term local control and overall survival. This may be worthwhile investigating in a larger trial," she added.

Standard treatment for locally advanced cervical cancer consists of concurrent chemoradiation with standard-field pelvic irradiation, said Wang. However, PET/CT imaging yields false-negative results for PALN in about a fourth of patients with pelvic lymph nodes. Previous studies have shown that a majority of patients with lymph node failure have PALN failure.

Prophylactic EFI does not have an established role in the treatment of cervical cancer, and indications remain unclear, Wang continued. Pelvic lymph node involvement at diagnosis is associated with PALN involvement and treatment failure after standard pelvic irradiation. The FIGO staging system defines IIIC1 disease as spread to pelvic lymph nodes, and Wang and colleagues used FIGO stage IIIC1 to identify patients who might benefit from prophylactic EFI.

Investigators reviewed records of patients treated for cervical cancer at Peking Union Medical College Hospital from 2011 to 2015 and identified patients who had FIGO stage IIIC1 disease at diagnosis. Treatment consisted of definitive radiotherapy or concurrent chemoradiation. Lymph node involvement was determined by CT or PET/CT.

Standard pelvic irradiation consisted of intensity-modulated radiation with a 50.4-Gy total dose in 28 fractions to the pelvis only or pelvis and PALN region. Patients also received intracavitary brachytherapy and first-line cisplatin-based chemotherapy.

Key Findings

Data analysis included 280 patients, 161 treated with standard pelvic irradiation and 119 with EFI. Patients treated with EFI had more advanced disease, including T3 disease, bilateral pelvic lymph node involvement, common iliac node involvement, and larger pelvic nodal metastases.

Median follow-up was 47.2 months. An unadjusted analysis showed no differences in 5-year OS rates between standard pelvic irradiation and EFI (72.9% vs 72.2%), 5-year DFS rates (64.4% vs 66.0%), 5-year PALN control rates (93.2% vs 97.3%), or 5-year extrapelvic disease control rates (72.7% vs 80.9%).

Propensity-score matching resulted in 71 pairs of patients with well-balanced baseline characteristics, said Wang. Reanalysis of the data after matching shifted the 5-year outcomes in favor of EFI:

• OS: 85.0% vs 61.9%, P=0.025
• DFS: 77.9% vs 53.0%, P=0.004
• PALN control: 98.4% vs 89.7%, P=0.053
• Extrapelvic control: 91.2% vs 64.5%, P=0.002

Prior studies suggested that patients with spread to common iliac nodes, three or more involved nodes, or T3 disease are more likely to benefit from prophylactic EFI, said Wang. On the basis of presence or absence of those characteristics, investigators reanalyzed the data.

Initially, they found no significant benefit of EFI for any of the outcomes in either the high-risk or low-risk group. Propensity matching for the high-risk group yielded 32 pairs of patients with similar characteristics. The matched analysis showed numerical improvement with EFI for OS (84.3% vs 65.1%, P=0.135) and PALN control (100% vs 91.8%, P=0.132) and significant improvement in DFS (84.4% vs 54.9%, P=0.018) and extrapelvic control (90.6% vs 63.5%, P=0.033).

Among 158 low-risk patients, an unadjusted analysis also showed no differences in any of the 5-year outcomes between patients treated with standard pelvic irradiation and EFI. Propensity matching produced 39 patient pairs with balanced baseline characteristics. Propensity-matched analysis showed that EFI significantly improved OS (91.1% vs 61.8%, P=0.028), DFS (80.3% vs 53.8%, P=0.017), PALN control (100% vs 88.4%, P=0.043), and extrapelvic control (97.4% vs 67.4%, P=0.004).

Overall, nine patients (3.2%) developed grade 3/4 chronic toxicities, 1.2% with standard pelvic irradiation and 5.9% with EFI (P=0.067). Gastrointestinal toxicity (3.4%) accounted for most of the grade 3/4 events in the EFI group.

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