What is the role of radiation therapy in the treatment of rectal cancer?

Role of Radiation Therapy in the Treatment of Rectal Cancer

Preoperative radiotherapy is the standard of care for locally advanced rectal cancer, as it reduces local recurrence rates and has less toxicity than postoperative radiotherapy. 1

Risk-Stratified Approach to Radiation Therapy

Early-Stage Rectal Cancer

• For very early tumors (T1 sm1, malignant polyps), local procedures such as transanal endoscopic microsurgery (TEM) may be appropriate without radiation 1
• For early favorable cases (cT1-2, some early cT3, N0) above the levators, surgery alone using total mesorectal excision (TME) technique is appropriate 1

Intermediate-Risk Rectal Cancer

• For most cT3 tumors without threatened circumferential resection margin (CRM) and some cT4 tumors (e.g., vaginal or peritoneal involvement only), preoperative radiotherapy followed by TME is recommended 1
• Short-course radiotherapy (25 Gy in 5 fractions over 1 week) followed by immediate surgery (<10 days) is a convenient and low-toxicity option 1
• Alternative approach is long-course chemoradiotherapy (46-50.4 Gy in 1.8-2 Gy fractions) with concurrent 5-FU-based therapy 1

Locally Advanced Rectal Cancer

• For most advanced cases (cT3 with positive CRM, cT4 with invasion of organs not readily resectable), preoperative chemoradiotherapy with 50.4 Gy in 1.8 Gy fractions with concurrent 5-FU-based therapy is recommended 1
• Surgery should follow 6-8 weeks after completion of chemoradiotherapy 1
• For elderly patients (≥80-85 years) or those unfit for chemoradiotherapy, short-course radiotherapy (5×5 Gy) with delayed surgery (6-8 weeks) is an option 1

Recent Advances in Radiation Therapy for Rectal Cancer

Total Neoadjuvant Therapy (TNT)

• TNT, which includes neoadjuvant chemotherapy and either short-course radiation or long-course chemoradiotherapy, has emerged as an important treatment approach 1
• In the context of TNT, chemotherapy delivered after radiation is preferred based on the OPRA phase II randomized trial, which showed higher rates of TME-free survival at 3 years 1
• TNT with triplet chemotherapy before chemoradiotherapy may be considered for patients at greater risk of distant metastases 1

Radiation Therapy Approaches

• Long-course chemoradiotherapy is preferred over short-course radiotherapy based on the RAPIDO trial showing lower rates of locoregional failure (6% vs 10%) 1
• Short-course radiotherapy remains a viable option, particularly in settings where initiation of radiation therapy may be slower 1

Nonoperative Management (NOM)

• NOM may be discussed as an alternative to TME for patients who have a clinical complete response following neoadjuvant therapy 1, 2
• For patients with rectal cancer for whom TME would result in permanent colostomy or inadequate bowel continence, NOM is strongly recommended as appropriate 2
• Restaging with tumor response assessment approximately 8-12 weeks after completion of radiation/chemoradiation is necessary for NOM 2

Technical Aspects of Radiation Therapy

• Treatment volumes should include the rectum and mesorectal, presacral, internal iliac, and obturator nodes 3
• External iliac nodes should be included for tumors invading anterior organs/structures 3
• Inguinal and external iliac nodes should be included for tumors involving the anal canal 3
• Modern radiation techniques (3D conformal planning) should be used to reduce toxicity 1

Common Pitfalls and Caveats

• Preoperative treatment is preferred over postoperative treatment due to decreased toxicity and improved efficacy 1
• Postoperative chemoradiotherapy should only be considered if preoperative radiotherapy was not given and there are high-risk features (positive circumferential margins, perforation in tumor area) 1
• Quality assurance in TME surgery is crucial for optimal outcomes, as poor surgical technique can negate the benefits of radiation therapy 1
• For very low rectal tumors, even without signs of extramural growth (cT2), preoperative radiotherapy may be indicated due to the small distance to the mesorectal fascia 1
• Combinations of 5-FU with other cytostatics (oxaliplatin, irinotecan) or targeted biological drugs have shown higher pathologic complete response rates but also increased toxicity 1

Future Directions

• Personalized approaches based on tumor characteristics and response to treatment are being developed 4, 2
• Organ preservation strategies with selective use of radiation and chemotherapy are gaining importance 4, 2
• Advanced radiation techniques aim to increase efficacy while decreasing toxicity to allow for more aggressive chemotherapeutic combinations 5, 4