Molecular profiling reduces need for radiotherapy in endometrial cancer

Molecular profiling reduces need for radiotherapy in endometrial cancer | Image Credit: © Chutima - © Chutima - stock.adobe.com.

Radiation may be reduced through molecular profiling in women with endometrial cancer, according to a recent study published in Radiotherapy and Oncology.¹

Addressing overtreatment in high-intermediate risk patients

While adjuvant radiotherapy is often used to reduce the odds of recurrence in women receiving treatment for high-intermediate risk endometrial cancer, the amount of treatment necessary often differs between patients. This may cause some patients to receive more treatment than necessary, leading to increased adverse events with no additional benefits.¹

"By using molecular profiling, we can tailor treatment to each patient’s individual risk," said Anne Sophie VM van den Heerik, MD, lead trial investigator from The Leiden University Medical Centre.¹

PORTEC-4a trial provides strong evidence

The randomized PORTEC-4a trial provided the strongest evidence indicating efficacy from molecular profiling toward safely reducing exposure to radiotherapy among women receiving treatment for early-stage endometrial cancer. Additionally, this method identified patients requiring more intensive treatment.¹

Presenters of the study at the 2025 Annual Congress of the European Society for Radiotherapy and Oncology noted the need to refine treatment strategies, as endometrial cancer is the most common gynecological cancer in high-developed countries. Additionally, incidence is increasing worldwide.¹

Key findings presented include increased precision, reduced overtreatment, and improved outcomes for patients with increased recurrence risk when using molecular profiling. This also highlights improved outcomes in patients who are often undertreated when only given vaginal brachytherapy.¹

Defining risk factors

There were 592 women with high-intermediate risk endometrial cancer from 8 European countries included in the final analysis. These patients were aged at least 18 years and received their diagnosis following total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy.²

International Federation of Gynecology and Obstetrics stage 1A and grade 3 invasion was reported as a high-intermediate risk factor of endometrial cancer. Other risk factors included stage 1B grade 1 or 2 or lymph-vascular space invasion in patients aged at least 60 years, stage 1B grade 3, and stage 2 microscopic or grade 1 invasion.²

Individualized treatment reduces radiotherapy

Patients were randomized 2:1 to receive either molecular risk-profile-based treatment or standard care. Vaginal recurrence was reported as the primary outcome of the analysis, with secondary outcomes including recurrence-free and overall survival, pelvic and distant recurrence, 5-year vaginal control, adverse events, and health care costs.²

With risk categories identified through molecular profiling, participants were able to receive individualized treatment.¹ This included 46% of participants being able to safely avoid radiotherapy.

Pelvic radiotherapy was provided as a substitute to vaginal brachytherapy in patients with an unfavorable molecular profile. Following treatment, these patients had improved locoregional control. Additionally, their recurrence rate was 8.4%, vs 30.5% among patients undergoing standard treatment without molecular profiling.¹

A step toward personalized care

These results indicated safety from molecular profiling toward sparing approximately half of the patients from radiotherapy, keeping survival rates high. The data also highlighted the benefits of a more intensive radiation approach to reduce the risk in patients with an unfavorable molecular profile.¹

"This approach allows us to safely reduce radiotherapy for many women while ensuring that those who need it receive the most effective therapy,” said van den Heerik. “It’s a major step towards more personalized and less invasive cancer treatment."¹

References

1. Phase III trial shows molecular profiling can safely reduce radiation for women with endometrial cancer and optimise treatment for patients at a higher risk patients. European Society for Raiotherapy and Oncology. May 4, 2025. Accessed June 23, 2025. https://www.eurekalert.org/news-releases/1081953.
2. van den Heerik ASVM, Horeweg N, Nout RA, et al. PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer. Int J Gynecol Cancer. 2020;30(12):2002-2007. doi: 10.1136/ijgc-2020-001929