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Prognostic POLE proofreading may reduce overtreatment of endometrial cancer
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POLE proofreading mutations may be independently prognostic for endometrial cancer and could help reduce overtreatment, according to data from a European study.
Endometrial cancer is the most common gynecological malignancy in the world, and its incidence is on the rise due to increased obesity and aging in the general population, according to the study background.
Most cases (80%) are detected at an early stage because it tends to be a symptomatic disease.
Women with grade 3 cancers or even further advanced disease are more frequently being treated with adjuvant chemotherapy.
Risk stratification is based on clinical factors such as age, as well as pathologic factors of the tumor.
Despite refinement in the use of postoperative treatment in endometrial cancer during the past 2 decades, both overuse and underuse of adjuvant therapy remain problematic.
Some patients with stage I endometrial cancer with risk factors need to receive vaginal brachytherapy to prevent one recurrence. Meanwhile, 8% to 10% of patients develop distant metastases that could have been prevented with adjuvant chemotherapy.
Ian P.M. Tomlinson, MD, PhD, of the molecular and population genetics laboratory at Wellcome Trust Centre for Human Genetics at the University of Oxford in the United Kingdom, and colleagues looked at whether presence of POLE proofreading mutations — which occur in approximately 7% of all endometrial cancers — may help predict prognosis.
They performed targeted POLE sequencing in endometrial cancers from the PORTEC-1 and -2 trials, which included 788 participants. Those results were combined with those of an additional 628 participants from three additional series.
Researchers performed meta-analysis to generate hazard ratios for RFS and cancer-specific survival of POLE-mutant endometrial cancers.
POLE mutations were detected in 6.1% of participants from PORTEC-1 and -2, and they were associated with a high tumor grade (P<.001). Women with POLE-mutant endometrial cancers had lower rates of recurrence (6.2% vs. 14.1%) and endometrial cancer-related death (2.3% vs. 9.7%) than women who did not have POLE mutations.
Differences in RFS (multivariable-adjusted HR=0.43; 95% CI, 0.13-1.37) and cancer-specific survival (HR=0.19; 95% CI, 0.03-1.44) were not significant in the total PORTEC cohort.
Researchers identified 109 participants with grade 3 tumors. Of those patients, 0 of 15 with POLE-mutant endometrial cancers recurred compared with 29 of 94 (30.9%) with POLE wild-type cancers (multivariable-adjusted HR for RFS=0.11; 95% CI, 0.001-0.84).
In the additional series,’ researchers reported no endometrial cancer-related events in any of the 33 POLE-mutant cancers. Researchers calculated a multivariable-adjusted, pooled HR of 0.33 for RFS (95% CI, 0.12-0.91) and 0.26 for cancer-specific survival (95% CI, 0.06-1.08).
“POLE proofreading mutations predict favorable endometrial prognosis, independently of other clinicopathological variables, with the greatest effect seen in high-grade tumors,” Tomlinson and colleagues wrote. “This novel biomarker may help to reduce overtreatment in endometrial cancer.”
Disclosure: The researchers report no relevant financial disclosures.
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