Five pivotal studies presented at ESTRO 2025 showcase how radiotherapy is reshaping the landscape for anal and rectal cancers. From reduced-dose treatments to cutting-edge combinations with immunotherapy and chemotherapy, these innovations offer safer, more effective, and organ-preserving alternatives to traditional surgery.
Shorter, Lower-Dose Radiotherapy for Early-Stage Anal Cancer
The ACT4 PLATO trial, led by Professor David Sebag-Montefiore, demonstrated that a reduced-dose, shorter-course highly focused radiotherapy technique—IMRT—offers excellent tumor control with fewer side effects for early-stage anal cancer. The randomized phase II trial, conducted across 28 UK sites, showed similar efficacy and late toxicity levels using a reduced-dose IMRT regimen over 4.5 weeks and standard-dose IMRT over 5.5 weeks.
“Our results support moving toward shorter, more personalized radiotherapy,” said Dr. Sebag-Montefiore. “This approach reduces the treatment burden for both patients and health-care systems.”
Radiotherapy Alone and Radiotherapy Combined with Chemotherapy for Rectal Cancer
The STAR-TREC study showed that organ-preserving strategies are feasible for patients treated with radiotherapy alone as well as for patients treated with radiotherapy and chemotherapy. Among 344 patients at 37 international sites, 80% of those treated with chemoradiotherapy and 61% of those treated with radiotherapy alone could be spared surgery at 1 year.
“Avoiding surgery helps preserve bowel function and quality of life,” said Professor Corrie Marijnen, MD, of the Netherlands Cancer Institute. “This study shows that radiotherapy-based strategies (whether alone with more intensive treatment course, or combined with chemotherapy) can be a viable alternative for many patients.”
Immunotherapy/Radiotherapy Combo Eliminates Cancer in Two-Thirds of Patients
PRIME-RT, a trial conducted across the United Kingdom, found that 67% of evaluable patients receiving a short course of radiotherapy—meaning only five outpatient sessions (no overnight stay)—combined with immunotherapy had a complete response.
“By combining immunotherapy with radiotherapy, we are seeing higher response rates than expected, especially with short-course radiotherapy," said Professor Campbell Roxburgh, from the University of Glasgow.
Combining Radiotherapy With Immunotherapy and Chemotherapy for Better Organ Preservation
Similarly, in the STELLAR II trial from China, immunotherapy added to short-course radiotherapy and chemotherapy increased complete disappearance of the tumor to 45.5%, compared to 25% with standard treatment.
“By combining immunotherapy with short-course radiotherapy and chemotherapy, we may be able to improve survival rates and, crucially, help more patients avoid invasive surgery and its long-term effects,” said Professor Jing Jin, from the National Cancer Centre, China.
Short-Course Radiotherapy with Chemotherapy Boosts Long-Term Survival
The phase III STELLAR trial tracked 591 patients in China with locally advanced rectal cancer over 5 years. It found that short-course radiotherapy followed by chemotherapy improved survival by 8.4% compared to standard long-course chemoradiotherapy—with no negative impact on anorectal function or quality of life.
"This could be a game-changer for patients, offering a faster, equally safe, and potentially more effective option," said Dr. Jing Jin from the National Cancer Centre, China.
A New Paradigm in Rectal Cancer Treatment
Together, these five studies demonstrate the transformative potential of radiotherapy as a curative and organ-preserving treatment. As new data emerge, personalized radiotherapy strategies are offering patients safer, effective alternatives to surgery.
With these findings set to influence global clinical guidelines, the future of rectal cancer treatment is moving decisively toward combined radiotherapy-driven, organ-preserving solutions.
Disclosure: For full disclosure of all study authors, visit ESTRO.org.
