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NATIONAL HARBOR, Md. -- Survival in advanced cervical cancer improved significantly when patients received pelvic radiation in addition to chemotherapy, according to a retrospective study reported here.

Median overall survival (OS) increased by 7 months, and progression-free survival doubled with the addition of whole-pelvic radiotherapy (WPR) to chemotherapy for patients with stage IVB cervical cancer. The patients received a variety of chemotherapy regimens, as opposed to a specific regimen.

The survival improvement occurred with no increase in treatment-related morbidity, as reported at the meeting.

"Survival is extremely poor in stage IVB cervical cancer, but these data indicate there may be utility for whole-pelvic radiation without increasing morbidity," said , of the University of Oklahoma Health Sciences Center in Oklahoma City.

"The retrospective nature of the study introduced potential bias, including selection bias," she added. "Complication severity is difficult to determine, and treatment regimens were not standardized. Next steps should include a prospective study to define the standard of care for stage IVB cervical cancer patients."

The study illustrated the continuing importance of clinical judgment in an era that encourages adherence to clinical guidelines, said invited discussant , of the University of Texas MD Anderson Cancer Center in Houston.

"The National Comprehensive Cancer Network guidelines are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment, based on the best literature presently available," said Jhingran. "By definition, guidelines cannot incorporate all possible clinical variations and are not intended to replace good clinical judgment or individualization of treatment."

With improved chemotherapy and other aspects of care, patients with advanced cervical cancer are living longer, but often accompanied by more symptoms, Jhingran continued. Noting that WPR did not increase morbidity or complications in the retrospective analysis by Perkins, she said symptom palliation that radiation therapy often provides could improve the quality of life for patients who are now living longer.

In the United States, stage IVB cervical cancer is uncommon, accounting for about 5% of the 13,000 annual case volume of cervical cancer. However, patients with stage IVB cervical cancer have a poor prognosis, associated with a 5-year survival of about 15%, said Perkins.

Systemic therapy remains the cornerstone of treatment for IVB cervical cancer, consisting of a platinum agent and a taxane, and more recently, with bevacizumab (Avastin) for some patients. Clinical trials evaluating treatment for cervical cancer tend to include patients with stage IVB disease along with those who have recurrent or persistent disease in the same protocol.

Over the past 20 years, phase III intergroup trials of chemotherapy for patients with IVB and recurrent cervical cancer led to improved PFS (4.6 to 8.2 months) and OS (8.3 to 17.0 months). Perkins said all of the trials evaluated combination chemotherapy, and radiotherapy was added as needed.

Practices regarding the use of WPR to treat stage IVB cervical cancer vary. Administration of whole-pelvic radiation prior to chemotherapy usually has a goal of symptom relief and prevention of local recurrences, which can pose unique symptom challenges.

"Whole-pelvic radiation in the treatment of stage IV cervical cancer is used in practice, but its efficacy is currently unknown," said Perkins.

In an effort to clarify the efficacy of WPR in stage IVB cervical cancer, investigators at four centers performed a multicenter retrospective review. Review of medical records identified 127 patients with stage IVB cervical cancer treated at the four centers from 2005 to 2015.

Patients who received no treatment or entered hospice care were excluded, leaving 96 patients for data analysis: 62 who received only chemotherapy and 34 who received chemotherapy and WPR. The groups did not differ significantly with respect to demographic or clinical characteristics, including disease location at diagnosis.

The patients received a variety of chemotherapy regimens, but similar variation existed in the WPR and chemotherapy-only groups. Patients treated with chemotherapy only were more likely to receive bevacizumab (26% versus 12%, P=0.01), which Perkins attributed to change in treatment approaches during the 10-year period of the study.

Patients treated with WPR had a median PFS of 10 months compared with 5 months for patients who received only systemic therapy (P=0.01). Median overall survival was 14.1 months with WPR and 6.9 months without, also a statistically significant difference (P<0.01).

The frequency of pelvic morbidity did not differ between treatment groups, including ureteral obstruction, vaginal or rectal bleeding, pelvic infection, pelvic pain, and fistula.

"These data indicate that there may be utility for whole-pelvic radiation without increasing morbidity," said Perkins.

She acknowledged that the lack of "purity" in the treatment groups, as patients received a variety of chemotherapy regimens. Additionally, use of palliative radiation therapy could have reflected a need for direct treatment, and the incorporation of bevacizumab into systemic treatment during the study period might have affected the results.

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