What is the role of short course radiotherapy (radiation therapy) in treating locally advanced rectal cancer?

Short-Course Radiotherapy in Locally Advanced Rectal Cancer

Short-course radiotherapy (25 Gy in 5 fractions) is an effective treatment option for locally advanced rectal cancer that reduces local recurrence rates, but in the modern era, it should be integrated into total neoadjuvant therapy (TNT) regimens rather than used as monotherapy, with long-course chemoradiotherapy generally preferred when TNT is planned. 1

Evidence-Based Role and Efficacy

Short-course RT (25 Gy over 5 days) has demonstrated clear benefits in locally advanced rectal cancer:

• Local control: Multiple European trials, including the Swedish Rectal Cancer Trial, showed significant reductions in local recurrence rates and improved survival compared to surgery alone 1
• Long-term survival benefit: The Dutch TME trial demonstrated that 10-year survival improved significantly in stage III disease with negative circumferential resection margins (50% vs 40%; P=0.032) 1
• Equivalence to long-course: Direct comparisons showed no differences in local recurrence or overall survival between short-course RT and long-course chemoradiotherapy in Polish and Australian/New Zealand trials 1

Critical Safety Considerations

Important caveat: Long-term follow-up revealed increased secondary malignancies (14% vs 9%) and non-rectal cancer deaths in the RT group, negating survival advantages in node-negative patients 1. This underscores the importance of risk-stratified patient selection.

Short-course RT does not increase postoperative complications when performed correctly, with similar rates of anastomotic leak, wound infection, and mortality compared to surgery alone 2.

Modern Integration into Treatment Paradigms

Total Neoadjuvant Therapy Context

The RAPIDO trial fundamentally changed practice: Short-course RT (5×5 Gy) followed by six cycles of CAPOX or nine cycles of FOLFOX4 before surgery reduced 3-year disease-related treatment failure (23.7% vs 30.4%; P=0.019) compared to standard long-course chemoradiotherapy 3. This demonstrates that short-course RT is highly effective when combined with systemic chemotherapy in a TNT approach.

Current guidelines reflect this evolution:

• When TNT is planned: Long-course chemoradiotherapy is preferred over short-course RT, though short-course RT remains a viable option depending on circumstances 1
• Chemotherapy timing: When using short-course RT in TNT, chemotherapy should be delivered after radiation (consolidation approach) 1

Specific Clinical Scenarios for Short-Course RT

Optimal candidates for short-course RT followed by immediate surgery (within 1 week):

• T3 tumors staged by endorectal ultrasound or MRI without requirement for sphincter preservation 1
• Intermediate-risk tumors (most cT3 without threatened circumferential margin, some cT4a, N+) where immediate surgery is planned 1
• Patients requiring convenient, low-toxicity treatment with 25 Gy over 1 week 1

Not appropriate for short-course RT monotherapy:

• Most locally advanced non-resectable cases (cT3 with positive circumferential margin, cT4 with organ involvement) require preoperative chemoradiotherapy (50.4 Gy with concurrent 5-FU) followed by surgery 6-8 weeks later 1
• Patients where tumor downstaging or pathologic complete response is desired should receive long-course chemoradiotherapy, which achieves 13-15% pathologic complete response rates 1, 4

Delayed Surgery Strategy

Emerging evidence supports delaying surgery after short-course RT:

• A 2014 systematic review showed that delaying surgery 5-13 weeks after short-course RT (versus 1-2 weeks) resulted in significantly higher pathologic complete response rates with acceptable postoperative complications 1
• However, one trial comparing short-course RT with long-course chemoradiotherapy, both with delayed surgery, showed better 3-year disease-free survival with long-course treatment (75% vs 59%; P=0.022) 1

Technical Specifications

When delivering short-course RT 1:

• Dose: 25 Gy in 5 fractions over 1 week
• Surgery timing: Within 1 week for immediate approach, or 5-13 weeks for delayed approach
• Radiation field: Include tumor with 2-5 cm margin, presacral lymph nodes, internal iliac lymph nodes, and obturator lymph nodes
• Technique: Use 3D-CRT, VMAT, or IMRT to minimize small bowel exposure
• Small bowel constraints: Limit dose to <50 Gy (V15 <120 mL, V45 <195 mL per QUANTEC) 1

Risk-Stratified Algorithm

For early favorable cases (cT1-2, early cT3a with clear circumferential margin, N0):

• Surgery alone with TME is appropriate; radiation not required 1, 5

For intermediate-risk cases (most cT3 without threatened margin, some cT4a, N+):

• Short-course RT (25 Gy/5 fractions) followed by immediate surgery is a reasonable option 1
• Alternatively, consider TNT with short-course RT followed by chemotherapy for high-risk features 1

For high-risk locally advanced cases:

• TNT is preferred, with long-course chemoradiotherapy (45-50.4 Gy with concurrent 5-FU) favored over short-course RT 1
• If short-course RT is used, must be followed by full systemic chemotherapy before surgery 3

Quality of Life and Functional Outcomes

Important consideration: Patients receiving long-course chemoradiotherapy experienced more serious adverse events during treatment (5.6% radiation dermatitis vs 0%), while short-course RT patients had higher rates of permanent stoma (38% vs 29.8%) 1. However, overall health-related quality of life was not significantly different between approaches 1.

The increased risk of bowel obstructions and gastrointestinal complications with short-course RT must be weighed against treatment convenience and lower acute toxicity 1.