Top Clinical Trials at ESTRO 2025: Organ Preservation and Quality of life after Total Neoadjuvant Therapy for LA Rectal Cancer

Fresh from the stage at ESTRO 2025 – Gani Cihan presented the the impact of Total Neoadjuvant Therapy (TNT) for rectal cancer. TNT has been a promising approach in enhancing pathological complete response (pCR) and improving disease-free survival in rectal cancer patients. However, despite its potential, data on long-term organ preservation, quality of life, and functional outcomes have remained limited. This study, conducted across four major centers in Germany, aimed to address these gaps and provide further insights into the efficacy of TNT in rectal cancer management.

Study Design and Methods

This multi-center phase II trial focused on patients with cT1/2N1-2 or cT3N0/N1-2 rectal cancer located within 12 cm of the anal verge. Participants underwent chemoradiotherapy (CRT) with 50.4 Gy and concomitant fluorouracil and oxaliplatin, followed by three cycles of FOLFOX chemotherapy, as per the CAO/ARO/AIO-12 trial. Patients achieving a clinical complete response (cCR) were then assigned to a “watch & wait” (W&W) approach instead of undergoing immediate surgery.

The primary endpoint was the rate of clinical complete response (cCR), while secondary endpoints included long-term oncological outcomes, toxicity, and quality of life metrics. These were assessed using the Low Anterior Resection Syndrome (LARS) score, Wexner score for fecal incontinence, and late toxicity as per CTC-AEv5.0.

Results

Patient Outcomes

• Out of 91 patients receiving TNT, 34 patients (37%) achieved a clinical complete response (cCR).
• Two additional patients had local excision of residual findings and achieved pathological complete response (pCR), leading to 36 patients (40%) assigned to organ preservation.
• Three-year TME-free survival rate was 21% (95% CI, 14-32%).

Functional Outcomes

LARS Scores

• At 18 months: TME-free patients had a mean LARS score of 17 vs 28 in those who had immediate TME (p=0.02).
• At 36 months: TME-free patients had a mean LARS score of 11 vs 26 in those who had immediate TME (p<0.01).

Wexner Scores for Fecal Incontinence

• At 6 months: TME-free patients had a mean score of 3.1 vs 7.5 in those who had immediate TME (p=0.003).
• At 12 months: TME-free patients had a mean score of 3.2 vs 7.8 in those who had immediate TME (p=0.003).

Late Toxicity

• 25% of patients with immediate TME experienced Grade 3/4 toxicity (13 out of 53 patients).
• Only 5% of patients with sustained cCR experienced Grade 3/4 toxicity (1 out of 20 patients).

Key Takeaways

The data presented at ESTRO 2025 underscores the potential of TNT with CRT and FOLFOX as a viable alternative to traditional surgical approaches for rectal cancer, offering the promise of organ preservation without compromising long-term outcomes. While more work is needed to refine the treatment and response criteria, these results offer hope for patients who seek effective treatment with reduced risk of debilitating long-term side effects.

With continued advancements in imaging and personalized medicine, the future of TNT in rectal cancer looks promising, offering not only improved survival rates but also enhanced quality of life for patients.

About ESTRO 2025

ESTRO 2025 brings together around 7,000 participants from over 80 countries, showcasing the latest research in clinical radiation oncology, radiobiology, medical physics, technology, and brachytherapy. Leading doctors and scientists from around the world present groundbreaking findings, in line with the conference theme: “Transformative innovation through collaboration”. ESTRO 2025 is the annual congress of the European Society for Radiotherapy and Oncology (ESTRO), an organisation dedicated to advancing cancer treatment through radiotherapy and multimodal approaches. ESTRO promotes education, science, and research and advocates for universal access to radiotherapy. With nearly 10,000 members worldwide, it supports radiation oncology professionals and the broader oncology community in their daily practice.

Read ESTRO 2025 Updates on OncoDaily.