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Women with high-risk early-stage endometrial cancer did not have better survival if they received chemotherapy or radiation therapy after surgery, according to a retrospective review.

Median overall survival (OS) was about a year longer with adjuvant chemotherapy (8.52 vs 7.48 years with surgery alone), but the difference did not reach statistical significance. Disease-specific survival (DSS) also did not improve with chemotherapy, but the risk of relapse did decrease. Adjuvant radiation therapy failed to improve OS, DSS, or relapse-free survival (RFS).

"Although there are confounders with a retrospective study, when it comes to patient selection, there was no associated benefits seen with overall survival or disease-specific survival, and this strengthens our observation that no true difference exists," said Rachelle Findley, MD, of the University of Calgary in Alberta, during the Society of Gynecologic Oncology virtual meeting. "When we look to the future, a large prospective study would be needed to confirm our results from our retrospective data."

Surgery remains the cornerstone of treatment for endometrial cancer, and potential survival benefits with adjuvant therapy for stage I disease remain unclear. In an effort to bring some clarity to the setting, investigators reviewed medical records for patients with endometrial cancer treated at eight Canadian centers during 2000 to 2010, with follow-up of 10 to 15 years. They focused on high-risk stage I endometrial cancer, defined as stage Ib grade 3 endometrioid disease or myoinvasive non-endometrioid cancer.

From a total of 2,327 cases of stage I endometrial cancer, investigators identified 414 patients with high-risk disease and 1,903 patients with low-risk disease. During follow-up, 123 deaths (29.7%) occurred in the high-risk group and 351 (18.4%) occurred in the low-risk group. Relapse rates were 18.4% (n=76) and 8.8% (n=167) in the high- and low-risk groups.

The patients with high-risk disease had an age range of 33 to 91 years. Stage Ia disease accounted for 70.3% of cases and Ib for 29.2% of cases. Non-endometrioid histology predominated, at 85.5% versus 14.5% for grade 3 endometrioid histology. The mortality rate was 15.7% among patients with grade 3 endometrioid histology and 14% for those with non-endometrioid disease.

About two-thirds of the patients underwent lymphadenectomy, primarily examination of pelvic lymph nodes. About a third of the patients had lymphovascular space invasion. A fourth of the patients received adjuvant chemotherapy, and 56% received radiotherapy, primarily vaginal brachytherapy (21.5%) or combined brachytherapy and external-beam radiotherapy (27.8%).

Comparison of OS for patients with and without adjuvant chemotherapy yielded a nonsignificant relative risk (RR) of 0.70 in favor of chemotherapy (95% CI 0.46-1.14). OS was virtually identical with four or fewer cycles of chemotherapy versus five or six. Analysis of DSS produced an RR of 1.06 (95% CI 0.61-1.85). RFS represented the only significant advantage for chemotherapy (median 8.52 vs 6.92 years; HR 0.61, 95% CI 0.39-0.95, P=0.03). RFS did not differ by number of chemotherapy cycles.

Analyses of adjuvant radiotherapy showed no significant impact on OS (RR 0.90, 95% CI 0.63-1.20), DSS (RR 1.11, 95% CI 0.68-1.82), or RFS (8.20 vs 6.65 years, RR 0.73, 95% CI 0.51-1.02).

The results should be considered within the context of a small sample size, as the high-risk group represented only 18% of all the patients with stage I endometrial cancer, said Don Dizon, MD, of Lifespan Cancer Institute and Brown University in Providence, Rhode Island. Follow-up was too brief for a meaningful analysis of DSS. The median had yet to be reached, probably reflecting the small sample size and low number of endometrial cancer deaths.

The RFS findings are important, Dizon continued, as chemotherapy significantly improved RFS, and radiation therapy resulted in a trend toward better RFS (RR 0.73, P=0.07).

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