What is the role of short-course radiotherapy (5 fractions of 5 Gy each) in the treatment of rectal cancer?

Role of Short-Course Radiotherapy in Rectal Cancer

Short-course radiotherapy (25 Gy in 5 fractions of 5 Gy each) is a highly effective, convenient, and low-toxicity preoperative treatment option for locally advanced rectal cancer that reduces local recurrence rates and should be followed by surgery within 1 week for immediate surgery or delayed 6-8 weeks for tumor downstaging. 1

Primary Indications for Short-Course Radiotherapy

Short-course radiotherapy is specifically recommended for:

• Intermediate-risk rectal cancers: Most cT3 tumors without threatened mesorectal fascia (mrf-), some cT4a tumors (limited peritoneal involvement), N+ disease, and very low cT2 tumors where distance to mesorectal fascia is small 1

• Patients requiring rapid treatment: The 1-week treatment schedule followed by immediate surgery (<10 days from first fraction) offers convenience and efficiency compared to 5-6 weeks of long-course chemoradiotherapy 1

• Elderly or medically unfit patients: For those ≥80-85 years or patients who cannot tolerate concurrent chemoradiotherapy, 5×5 Gy with delayed surgery (8 weeks) is an appropriate alternative 1

• Chinese guidelines specify: T3 tumors staged by endorectal ultrasound or MRI without requirement for sphincter preservation may receive short-course radiotherapy followed by surgery within 1 week 1

Two Distinct Timing Strategies

Immediate Surgery Approach

• Surgery performed <10 days after completing radiotherapy 1
• Minimal tumor downstaging expected 2
• Primary goal is local control rather than tumor regression 1
• Safe with no increased postoperative complications 3, 4

Delayed Surgery Approach

• Surgery delayed 4-8 weeks (or longer) after radiotherapy completion 1, 2, 5
• Allows significant tumor downstaging and regression 2, 5
• Pathological complete response rates of 8-15% reported 2, 4
• Higher tumor regression grades achieved with intervals >8 weeks (54.3% TRG 1-2) 5
• Feasible alternative with low toxicity 2

Comparison with Long-Course Chemoradiotherapy

While both approaches are acceptable, key differences include:

• Short-course advantages: More convenient (1 week vs 5-6 weeks), simpler logistics, proven equivalent local control when followed by immediate surgery 1

• Long-course chemoradiotherapy: Delivers 45-50.4 Gy with concurrent 5-FU-based chemotherapy, preferred for most locally advanced/non-resectable cases (cT3 mrf+, cT4b) 1

• Recent evidence: The RAPIDO trial concept combines short-course radiotherapy with full-dose neoadjuvant chemotherapy (6 cycles capecitabine/oxaliplatin) before surgery, aiming to improve disease-free survival 6

• Emerging approach: The UNION trial demonstrated that sequential short-course radiotherapy, immunotherapy, and chemotherapy significantly improved pathological complete response rates in locally advanced rectal cancer 1

Safety Profile and Surgical Outcomes

Short-course radiotherapy does not increase postoperative complications:

• No increase in postoperative mortality 3, 4
• Similar rates of anastomotic leak (5% vs 6.6% without radiotherapy) 3, 4
• Equivalent rates of wound infection, hemorrhage, urinary complications, and ileus 3, 4
• Improves sphincter-preservation rates: 100% low anterior resection with TME in radiated patients vs 82% in non-radiated patients 4
• Severe radiation-induced toxicity occurs in only 5.4% of patients 2

Technical Specifications

When administering short-course radiotherapy:

• Dose: 25 Gy total, delivered as 5 Gy per fraction over 5 consecutive days 1
• Target volume: Include tumor/tumor bed with 2-5 cm margin, presacral lymph nodes, internal iliac lymph nodes, and obturator lymph nodes 1
• Technique: Use 3D-CRT, VMAT, or IMRT to minimize small bowel exposure 1
• Surgery timing: Either <10 days for immediate approach or 4-8 weeks for delayed approach 1, 2

Critical Decision Points

Do NOT use short-course radiotherapy for:

• Very early tumors (cT1-2 N0 with clear margins) that require surgery alone 1, 7
• Most locally advanced non-resectable cases (cT3 mrf+, cT4b) where long-course chemoradiotherapy with 50.4 Gy and concurrent 5-FU is preferred 1
• Patients requiring maximal tumor downstaging for organ preservation where long-course chemoradiotherapy may be superior 7

Common Pitfalls to Avoid

• Preoperative treatment is always preferred over postoperative treatment due to superior efficacy and reduced toxicity 1
• Do not delay surgery beyond 10 days if using the immediate surgery protocol, as this deviates from the evidence-based regimen 1
• Ensure proper patient selection using high-quality MRI staging to assess mesorectal fascia involvement and extramural vascular invasion 1, 7
• Total mesorectal excision (TME) surgery is mandatory following radiotherapy to achieve optimal local control 1