Effects of Preoperative Radiotherapy in Rectal Adenocarcinoma
Preoperative radiotherapy for rectal adenocarcinoma reduces local recurrence rates, increases postoperative morbidity, and down-stages tumors in up to 50% of cases, while being more effective than postoperative radiation. 1
Benefits of Preoperative Radiotherapy
Local Recurrence Reduction
- Preoperative radiotherapy significantly reduces local recurrence rates compared to surgery alone 1
- Short-course radiotherapy (25 Gy, 5 Gy/fraction followed by immediate surgery) effectively reduces local recurrence 1
- Long-course chemoradiotherapy combined with chemotherapy has shown even lower local recurrence rates (5%) compared to long-course radiotherapy alone (15%) 2
Tumor Downstaging
- Preoperative long-course radiotherapy achieves tumor downstaging in 46% of cases when used alone 2
- When combined with chemotherapy (5-FU or capecitabine), downstaging rates increase to 61% 2
- Pathological complete remission (pCR) can be achieved in approximately 13% of cases with long-course radiotherapy combined with chemotherapy 2
Survival Benefits
- Preoperative radiotherapy can improve overall survival in patients who undergo curative surgery 3
- Statistically significant improvement in overall survival has been demonstrated in patients treated with long-course radiotherapy combined with chemotherapy versus long-course radiotherapy alone 2
- Favorable prognostic factors for survival include age <50 years and absence of lymph node metastasis 4
Disadvantages and Complications
Postoperative Morbidity
- Preoperative radiotherapy may increase postoperative morbidity, though this is not consistently observed across all studies 5
- Short-term preoperative radiotherapy has not shown significant increases in postoperative complications in some studies 5
- The rate of major anastomotic leaks is comparable between patients receiving preoperative radiotherapy and those undergoing surgery alone (5% vs 6.6%) 5
Timing Considerations
- Due to decreased toxicity, preoperative chemoradiotherapy is preferred over postoperative chemoradiotherapy 1
- Surgery should be performed 6-8 weeks after completion of chemoradiotherapy to allow for optimal tumor response 1
- For short-course radiotherapy, surgery is typically performed within 10 days from the first radiation fraction 1
Treatment Algorithms
Risk-Stratified Approach
- For early, favorable cases (cT1-2, some early cT3, N0), surgery alone using total mesorectal excision (TME) is appropriate 1, 6
- For intermediate cases (most cT3 without threatened mesorectal fascia, some cT4a, N+), preoperative radiotherapy followed by TME is recommended 1
- For locally advanced, non-resectable cases (cT3 with threatened mesorectal fascia, cT4 with organ involvement), preoperative chemoradiotherapy followed by surgery 6-8 weeks later is recommended 1
Radiotherapy Options
- Short-course radiotherapy: 25 Gy in 5 fractions over 1 week, followed by surgery within 10 days 1
- Long-course chemoradiotherapy: 45-50.4 Gy in 1.8-2 Gy fractions with concurrent 5-FU (bolus, continuous infusion, or oral) 1
- For elderly patients or those with severe comorbidities who cannot tolerate chemoradiotherapy, short-course radiotherapy with delayed surgery may be an option 1
Common Pitfalls and Caveats
- Preoperative staging must be accurate to select appropriate patients for preoperative treatment - endoscopic ultrasound or rectal MRI is recommended 1
- The quality of the mesorectal excision significantly impacts outcomes and should be evaluated by the surgeon and/or pathologist 1
- Combinations of 5-FU with other cytostatics or targeted biological drugs have shown higher pathologic complete response rates but also increased toxicity 1, 6
- Pathological parameters reflecting tumor response to chemoradiotherapy are important surrogate markers for long-term clinical outcomes 7
- Post-chemoradiotherapy downstaging from clinical Stage II-III to pathological Stage 0-I indicates a favorable prognosis 7