What is the recommended short‑course pre‑operative radiotherapy regimen (dose, fractionation, technique, and timing of surgery) for resectable locally advanced rectal cancer?

Short-Course Radiotherapy Protocol for Rectal Cancer

For resectable locally advanced rectal cancer, deliver 25 Gy in 5 fractions of 5 Gy each over 5 consecutive days, followed by total mesorectal excision (TME) surgery within 10 days of the first radiation fraction. 1, 2

Dose and Fractionation Specifications

• Total dose: 25 Gy delivered as 5 Gy per fraction over 5 consecutive days 1, 2
• Treatment schedule: One fraction daily for 5 consecutive days (Monday through Friday) 2
• No concurrent chemotherapy is required with standard short-course radiotherapy 1

Target Volume and Technique

• Target volume includes: 2
  • Primary tumor or tumor bed with 2-5 cm margin
  • Presacral lymph nodes
  • Internal iliac lymph nodes
  • Obturator lymph nodes
• Modern radiation techniques (IMRT, VMAT, or helical tomotherapy) should be used to optimize dose distribution 2

Timing of Surgery

Two distinct surgical timing options exist, each with specific indications:

Immediate Surgery Approach (Standard)

• Perform TME surgery within 10 days (ideally 3-5 days) after the first radiation fraction 1, 2
• This approach prioritizes convenience and rapid treatment completion 2
• Provides excellent local control with minimal toxicity 1, 3

Delayed Surgery Approach (Selective)

• Delay surgery for 6-8 weeks after completing radiotherapy 2, 4
• Specific indication: Elderly patients (≥80-85 years) or medically unfit patients who cannot tolerate chemoradiotherapy 1, 2
• This approach allows tumor downstaging similar to long-course chemoradiotherapy 2

Patient Selection Criteria

Short-course radiotherapy is appropriate for:

• Intermediate-risk tumors: Most cT3 tumors without threatened mesorectal fascia (MRI-defined CRM-negative) 1, 2
• Selected cT4a tumors: Those with vaginal or peritoneal involvement only 1, 2
• Node-positive disease (N+) in the intermediate-risk category 1, 2
• Very low cT2 tumors where distance to mesorectal fascia is small 1, 2
• Patients requiring rapid treatment completion 2

Do NOT use short-course radiotherapy for:

• Most locally advanced/non-resectable cases: cT3 with threatened/involved mesorectal fascia (CRM+), cT4 with organ involvement requiring en-bloc resection 1, 2, 5
• Patients requiring maximal tumor downstaging for sphincter preservation 2, 6
• Very early tumors (cT1-2, N0) that can be treated with surgery alone 2, 5

Critical Surgical Considerations

• TME technique is mandatory following any radiotherapy approach 1, 2, 5
• Achieve at least 5 cm distal margin on unfixed specimen 1
• Avoid damaging the mesorectal fascia during dissection, as this significantly impacts local recurrence rates 1
• For low-lying tumors requiring abdominoperineal excision, modify technique to avoid cone-shaped resection that increases risk of positive circumferential resection margin 1

Important Caveats and Pitfalls

Recent evidence reveals a critical concern: The NCCN now includes a specific caution that preoperative short-course radiotherapy may be associated with higher risk of local recurrence compared to long-course chemoradiotherapy (10% vs 6% 5-year locoregional failure rate) 4. Short-course radiotherapy should be avoided when optimal local control is the absolute priority. 4

Higher local recurrence rates occur specifically with:

• Lower third rectal tumors when combined with sphincter-saving surgery (11% vs 0% with long-course) 6
• This finding emphasizes the importance of patient selection based on tumor location 6

Accurate preoperative staging is essential:

• Use high-quality rectal MRI to assess mesorectal fascia involvement, extramural vascular invasion, and distance to circumferential resection margin 2, 5, 4
• Endorectal ultrasound is an alternative for T-staging 5, 6
• Incorrect staging leads to inappropriate treatment selection 5

Preoperative treatment is always superior to postoperative treatment due to better efficacy and reduced toxicity 1, 5

Alternative: Long-Course Chemoradiotherapy

When short-course radiotherapy is inappropriate, use 45-50.4 Gy in 1.8-2 Gy fractions with concurrent 5-FU-based chemotherapy, followed by surgery 6-8 weeks later 1, 5, 4. This approach provides superior tumor downstaging and better local control in high-risk patients 4, 7.