Adjuvant CCRT in Resected Rectal Adenocarcinoma
For patients with resected rectal adenocarcinoma who did not receive preoperative therapy, postoperative chemoradiotherapy should be administered using 5-FU/leucovorin or capecitabine concurrently with pelvic radiation (45-50.4 Gy), followed by adjuvant chemotherapy for a total perioperative treatment duration not exceeding 6 months. 1, 2
When Postoperative CCRT is Indicated
Postoperative CCRT should be selectively used in patients with unexpected adverse histopathological features after primary surgery if preoperative radiotherapy was not given. 1 These high-risk features include:
- Positive circumferential resection margin (CRM+) 1
- Perforation in the tumor area 1
- Incomplete mesorectal resection 1
- Extranodal deposits or nodal deposits with extracapsular spread close to the mesorectal fascia 1
- Stage III disease (T3N1 or higher) 1
Preferred Treatment Sequence
The standard sequence is: 5-FU/leucovorin × 1 cycle → concurrent CCRT → 5-FU/leucovorin × 2 cycles. 1 An alternative sequence is: 5-FU/leucovorin × 2 cycles → concurrent CCRT → 5-FU/leucovorin × 2 cycles. 1
Concurrent Chemoradiotherapy Regimens
During radiation therapy, use one of the following concurrent chemotherapy regimens:
- Continuous infusion 5-FU 225 mg/m² over 24 hours, 7 days/week during radiation (preferred) 1
- 5-FU 400 mg/m² IV bolus + leucovorin 20 mg/m² IV bolus for 4 days during weeks 1 and 5 of radiation 1
- Capecitabine 825 mg/m² twice daily, 5-7 days/week during radiation (Category 2B alternative) 1
Radiation should be delivered at 45-50.4 Gy to the pelvis with a 2-cm margin around the tumor bed. 1, 3
Adjuvant Chemotherapy After CCRT
Following completion of CCRT, administer adjuvant chemotherapy using:
- 5-FU 500 mg/m² IV bolus + leucovorin 500 mg/m² IV over 2 hours, once weekly for 6 weeks × 2 cycles (each cycle = 6 weeks on, 2 weeks off) 1
- Alternative: 5-FU 380 mg/m²/day days 1-5 + leucovorin 20 mg/m² days 1-5 every 28 days × 2 cycles 1
- Capecitabine 1250 mg/m² twice daily days 1-14 every 3 weeks (Category 2B) 1
FOLFOX (oxaliplatin + 5-FU/leucovorin) is listed as Category 2B for postoperative adjuvant therapy, but evidence supporting oxaliplatin in the purely adjuvant setting (without neoadjuvant oxaliplatin) is limited. 1, 4
Critical Timing Considerations
Adjuvant treatment must start as early as possible, no later than 8 weeks after surgery, and preferably the delay should not exceed 12 weeks even with postoperative complications. 2 Each 4-week delay results in a 14% decrease in overall survival. 5
The total duration of perioperative therapy (CCRT + adjuvant chemotherapy) should not exceed 6 months. 2
Important Caveats
Upper rectal cancers (>12 cm from the anal verge) above the peritoneal reflection do not benefit from preoperative or postoperative CCRT and should be treated as colon cancer with surgery followed by adjuvant chemotherapy alone. 1
For patients who received preoperative chemoradiotherapy, postoperative adjuvant chemotherapy alone (without additional radiation) is recommended, not postoperative CCRT. 5, 2 The evidence for adjuvant chemotherapy after neoadjuvant CRT is weaker than in colon cancer and probably limited to disease-free survival rather than overall survival. 2
Continuous infusion 5-FU or oral capecitabine during CRT are recommended rather than bolus 5-FU due to superior efficacy. 1
Monitoring During Treatment
Monitor for Grade 3-4 toxicities including diarrhea, leukopenia, and perianal skin reactions. 3, 6 Dose modifications should follow standard protocols, with treatment delays until neutrophils ≥1.5 × 10⁹/L and platelets ≥75 × 10⁹/L for Grade 3-4 myelosuppression. 7
For patients with severe renal impairment (creatinine clearance <30 mL/min), reduce oxaliplatin dose to 65 mg/m² if using FOLFOX. 7