What are the benefits of proton therapy in neoadjuvant treatment of T2N2 (Tumor size 2, Node involvement 2) rectal cancer?

Benefits of Proton Therapy in Neoadjuvant Treatment of T2N2 Rectal Cancer

Proton beam therapy offers no clear benefit over conventional radiotherapy in the neoadjuvant treatment of T2N2 rectal cancer, as there is no demonstrated advantage in disease control or prevention of late toxicity compared to intensity-modulated radiation therapy (IMRT). 1

Dosimetric Advantages of Proton Therapy

• Proton beam therapy demonstrates significantly less irradiation of organs at risk (OAR) compared to conventional photon-based radiotherapy in rectal cancer treatment 2
• Studies show significantly reduced radiation exposure to the small bowel with proton therapy compared to both three-dimensional conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) 2
• Similar dosimetric benefits are observed for bladder and pelvic bone marrow, potentially reducing treatment-related toxicity 2

Clinical Outcomes and Evidence Limitations

• Despite dosimetric advantages, there is no clear clinical benefit of proton therapy over existing IMRT photon therapy in terms of disease control outcomes 1
• The NCCN panel, echoing ASTRO's position, states that proton therapy is an option for cancer treatment but has not demonstrated superior outcomes over IMRT 1
• The costs associated with proton beam facility construction and treatment delivery are significantly higher than conventional radiotherapy 1
• Quality-of-life data from proton therapy shows concerning rates of incontinence, bowel dysfunction, and impotence, with only 28% of men maintaining normal erectile function after therapy 1

Current Standard Neoadjuvant Approaches for T2N2 Rectal Cancer

• Total neoadjuvant therapy (TNT) is currently the preferred approach for locally advanced rectal cancer, including T2N2 disease 1, 3
• Standard neoadjuvant options include:
  • Long-course chemoradiotherapy (50.4 Gy with concurrent 5-FU-based chemotherapy) 1
  • Short-course radiotherapy (25 Gy in 5 fractions) followed by chemotherapy 1
  • Neoadjuvant chemotherapy alone (FOLFOX) with selective use of chemoradiotherapy based on response 1

Considerations for T2N2 Rectal Cancer Treatment

• The PROSPECT trial demonstrated that selective omission of chemoradiotherapy following favorable response to neoadjuvant chemotherapy may be considered for selected patients 1
• After a median follow-up of 58 months, disease-free survival was similar between FOLFOX alone and chemoradiotherapy groups (HR, 0.92; 95% CI, 0.74–1.14) 1
• Patient-reported outcomes showed worse short-term adverse effects with FOLFOX but better long-term outcomes regarding fatigue, neuropathy, and sexual function compared to chemoradiotherapy 1

Radiation Technique Selection

• Three-dimensional precision radiotherapy techniques such as 3D-CRT or VMAT/IMRT are standard approaches for rectal cancer 1
• The radiation field should include the tumor with a safety margin of 2-5 cm, presacral lymph nodes, internal iliac lymph nodes, and obturator lymph nodes 1
• Standard pelvic dose is 45.0-50.4 Gy over 25-28 fractions, with a single fraction dose of 1.8-2.0 Gy 1

Conclusion for Clinical Practice

• While proton therapy shows promising dosimetric advantages in sparing organs at risk, there is insufficient evidence to recommend it over standard IMRT for T2N2 rectal cancer 1, 2
• Head-to-head clinical trials are needed to determine the definitive role of proton beam therapy in rectal cancer treatment 1
• For now, conventional approaches with IMRT or 3D-CRT remain the standard radiation modalities for neoadjuvant treatment of T2N2 rectal cancer 1