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TAMPA, Fla. -- Adjuvant chemoradiation (CRT) for locally advanced endometrial cancer did not improve overall survival (OS) versus chemotherapy alone, according to long-term follow-up from a randomized trial.

After a median follow-up of 112 months, CRT ended up on the wrong side of a hazard ratio of 1.05, albeit a value that lacked statistical significance. Subgroup analysis failed to identify any patient group that benefited from the addition of radiation. As , CRT also did not improve recurrence-free survival (RFS) versus chemotherapy.

CRT did reduce the incidence of locoregional recurrence, but distance recurrences were more common with CRT, reported Daniela Matei, MD, of Northwestern University in Chicago, during the Society of Gynecologic Oncology annual meeting.

"I think the study was a definitive study. That's why we did it," said Matei.

A molecular analysis is ongoing in an attempt to identify potential biomarkers of benefit.

"However, considering that there is no difference in the entire group, it is hard to imagine that we're going to find a subgroup that benefits, but that remains to be seen," she added.

During a discussion that followed the presentation, Paul DiSilvestro, MD, of Women and Infants Hospital and Brown University in Providence, Rhode Island, asked whether the results will change practice "any more than we've seen." Jokingly, he added, "Is this something that gives us the opportunity to create radiation oncology support groups? I know we need to let them down easy."

"For those people who are still skeptical of the role of chemotherapy alone in the treatment of patients with stage III endometrial cancer, and were eagerly awaiting overall survival data, I think this should put an end to the questions. This is the definitive study to address that question," said Matei.

The results bring to conclusion a trial that was almost two decades in the making. Matei noted that she was pregnant with her daughter when she proposed the NRG Oncology to the organizing committee. That same daughter was recently accepted into college.

The primary objective of the trial was to determine whether cisplatin-based CRT improved RFS versus carboplatin-paclitaxel chemotherapy in surgical stages III/IVa uterine cancer. Several previous studies had addressed the same or similar questions without arriving at a clear answer. Also, the prior studies did not involve consistent patient populations, and different chemotherapy and CRT regimens were used.

GOG-258 included an analysis of OS, so follow-up continued after the primary analysis showed no improvement in RFS with the addition of radiation. The study included 813 patients, 736 of whom were included in efficacy analyses. About 70-75% of patients in both treatment arms had stage IIIC1/IIIC2 disease.

The OS analysis showed no significant difference between the two treatment strategies. The 5% greater relative risk with CRT was associated with 95% confidence intervals that ranged between 0.82 and 1.34.

The subgroup analysis showed no consistent pattern of benefit, although results for the variables more often fell on the side favoring chemotherapy.

"Chemoradiotherapy did not improve overall survival compared to chemotherapy," Matei reiterated. "Chemoradiotherapy did not improve overall survival in any subgroup. As previously reported, chemoradiotherapy did not improve recurrence-free survival compared to chemotherapy, but it did reduce the incidence of local recurrence [vaginal, pelvic, and para-aortic]."

Chemotherapy only is not the only acceptable approach to locally advanced endometrial cancer, according to Akila Viswanathan, MD, MPH, of Johns Hopkins Medicine in Baltimore. In an earlier report from GOG-258, the higher rate of para-aortic and pelvic recurrences seen in the chemotherapy-alone arm led many U.S. centers to adopt "sandwich" radiation after 3 cycles of chemotherapy, outback radiation after 6 cycles of chemotherapy, or concurrent CRT. Some centers did adopt chemotherapy alone.

In contrast, the international PORTEC-3 study established concurrent CRT as the standard of care over radiation alone, particularly for stage III endometrial cancer patients, she added.

"In the current report, there was no difference in overall survival after 112 months median follow-up time," Viswanathan, an American Society for Radiation Oncology clinical expert, told MedPage Today via email. "As a negative trial, this report should not change management compared to the earlier report. The recurrence and toxicity rates were not updated in this report."

"Though one may wonder what if the standard-of-care arms were reversed, the trial was not statistically planned or powered to address this question. Immunotherapy trials in this population may provide important future directions and define the role of adjuvant radiation based on recurrence patterns," she said.

This story has been updated to include comments from Viswanathan.

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