What are the differences between long course and short course regimes in concurrent chemoradiotherapy (CCRT) for rectal cancer?

Differences Between Long-Course and Short-Course Regimens in CCRT for Rectal Cancer

For patients with locally advanced rectal cancer, long-course chemoradiotherapy is preferred over short-course radiotherapy due to better local control rates, greater tumor downsizing and downstaging potential, and improved suitability for organ preservation strategies. 1

Treatment Regimens Comparison

Long-Course Chemoradiotherapy (LC-CRT)

• Radiation dose: 50-50.4 Gy delivered in 25-28 fractions over 5-5.5 weeks 1, 2
• Concurrent chemotherapy: Typically capecitabine 825 mg/m² twice daily during radiation 2
• Surgery timing: Delayed surgery 6-8 weeks after completion of radiotherapy 1
• Best suited for:
  • Patients with higher-risk features requiring tumor downsizing 1
  • Cases where sphincter preservation is challenging 1
  • Patients considering non-operative management (NOM) after complete clinical response 1

Short-Course Radiotherapy (SC-RT)

• Radiation dose: 25 Gy delivered in 5 fractions over 1 week 1, 2
• Chemotherapy options:
  • Traditional approach: No concurrent chemotherapy
  • Modern approach: May include concurrent XELOX (capecitabine 625 mg/m² twice daily + oxaliplatin 50 mg/m² on day 1) 2
• Surgery timing:
  • Traditional: Immediate surgery (1-2 weeks)
  • Modern approach: Delayed surgery (≥8 weeks) with interval chemotherapy 1, 2
• Best suited for:
  • Elderly patients (>80 years) 3
  • Patients unfit for prolonged chemoradiotherapy 1

Comparative Outcomes

Tumor Response

• Pathological complete response (pCR):
  • Long-course: 13.2-23.1% 2, 4
  • Short-course with delayed surgery: 21.1-32.3% 2, 4
  • Short-course with immediate surgery: Lower pCR rates 1

Local Control and Survival

• Local control:
  • Long-course CRT shows better local control (6% locoregional failure) compared to short-course RT (10% locoregional failure) at 5 years 1
  • No significant difference in overall survival between approaches 1, 3, 4

Toxicity and Complications

• Acute toxicity:
  • Long-course: Higher rates of radiation dermatitis (5.6% vs 0%) 1
  • Short-course: Similar rates of grade ≥3 treatment-related toxicities (24.2% vs 22.2%) when using modern approaches 2
• Late toxicity:
  • Short-course: Higher rates of severe late toxicity grade ≥3 (12% vs 3%) 3
• Postoperative complications: No significant differences between regimens 2, 3

Functional Outcomes

• Permanent stoma rates: Higher in short-course (38.0% vs 29.8%) 1
• Quality of life: No overall difference in health-related quality of life 1

Clinical Decision Algorithm

1. Assess patient risk factors:

   • Age (>80 years favors short-course) 3
   • Comorbidities (significant comorbidities favor short-course) 1
   • Tumor characteristics (cT4, MRF+ status favors long-course) 1

2. Consider treatment goals:

   • If organ preservation is a priority → Long-course CRT 1, 5
   • If sphincter preservation is challenging → Long-course CRT 1
   • If rapid completion of radiation is needed → Short-course RT 1

3. Evaluate institutional factors:

   • Availability of radiation therapy (if RT initiation is delayed, consider starting with chemotherapy) 1
   • Experience with non-operative management protocols 5

Important Caveats

• The 2024 ASCO guideline recommends long-course CRT over short-course RT based on the RAPIDO trial showing higher locoregional failure rates with short-course RT (10% vs 6%) 1
• Short-course RT with delayed surgery and interval chemotherapy has shown comparable pathological responses to long-course CRT in some studies 2, 4
• Multiple-agent concurrent chemotherapy during radiotherapy is associated with improved overall survival compared to single-agent regimens, but must be balanced against potential toxicity 6
• Long-term follow-up of short-course RT has shown increased secondary malignancies (14% vs 9%) compared to surgery alone 1
• For patients considering non-operative management after complete clinical response, long-course CRT is preferred 1, 5