A major international study, PORTEC-4a, provides evidence that molecular profiling may safely reduce the need for radiotherapy in some women with early-stage endometrial cancer while identifying those who would benefit from more intensive treatment. The results, presented at ESTRO 2025, may mark a significant step forward in personalized cancer treatment.
Endometrial cancer is the most common gynecological cancer, and its incidence is rising globally. The PORTEC trials have played a key role in refining treatment strategies, ensuring that radiotherapy is used effectively while minimizing side effects.
PORTEC-4a
The findings from PORTEC-4a highlighted that molecular profiling can help tailor radiotherapy decisions based on individual tumor characteristics. Use of molecular profiling reduced overtreatment; nearly one-half of patients in the trial safely avoided radiation without compromising cancer control. It also improved outcomes for patients at a higher risk of cancer recurrence. The study suggests that patients with unfavorable tumor profiles may benefit from a more intensive radiation approach.
Key Findings
The randomized PORTEC-4a trial enrolled 592 women across eight European countries with high-/intermediate-risk endometrial cancer. Molecular testing classified tumors into risk categories, allowing treatment to be adapted accordingly: 46% of patients in the molecular profiling arm safely avoided radiotherapy.
Patients with an unfavorable molecular profile received a more intensive radiation approach, pelvic radiotherapy instead of vaginal brachytherapy, and the results suggested better locoregional control, with a recurrence rate of 8.4% compared to 30.5% in those who received standard treatment without molecular profiling.
"By using molecular profiling, we can tailor treatment to each patient’s individual risk," said Anne Sophie V.M. van den Heerik, MD, Lead Investigator of the PORTEC-4a trial, from The Leiden University Medical Centre, The Netherlands.
"This approach allows us to safely reduce radiotherapy for many women while ensuring that those who need it receive the most effective therapy. It’s a major step towards more personalized and less invasive cancer treatment."
Precision Oncology
"The PORTEC-4a trial is a game-changer," said Professor Matthias Guckenberger, President of ESTRO, Chairman of the Department of Radiation Oncology and full Professor at the University Hospital Zürich and University of Zürich.
"This research proves that precision medicine is transforming cancer treatment. By identifying patients who have the largest benefit from radiotherapy, we can maximize its impact, improve quality of life for thousands of women worldwide, and maintain excellent cancer control."
This has sparked growing interest in tailoring treatment using molecular profiling, a method that examines the genetic and biological features of a tumor to guide clinical decisions. It helps identify which patients are most likely to benefit from radiotherapy, and which can safely avoid it.
These findings pave the way for a more personalized approach to treating endometrial cancer, ensuring that each patient receives the most effective and least invasive treatment based on their tumor biology and risk profile, according to the investigators.
Disclosure: For full disclosure of study authors, visit ESTRO.org.
