Adjuvant treatment of rectal cancer has been largely superseded by neo-adjuvant therapy (link to Rectal locally advanced fluorouracil (protracted infusion) chemoradiation protocol).
Evidence to support this protocol predates the widespread adoption of total mesorectal excision (TME), a surgical technique that has significantly reduced locoregional recurrence rates.
In 1985, the landmark GITSG-7175 trial established the rationale for post-operative radiotherapy for rectal cancer.r It randomised 227 patients to one of four arms (202 completed data collection) following complete surgical resection of Dukes stage B2 and C adenocarcinoma of the rectum:
- No adjuvant therapy (n=58)
- Radiotherapy (n=50)
- Chemotherapy (n=48)
- Radiotherapy and chemotherapy (n=46)
Median follow up was 6.5 years and 5 year disease free survival was 67% for the chemoradiotherapy arm vs 45% for surgery alone (p=0.0005). Overall survival was not significantly different between groups.
The Norwegian Adjuvant Rectal Cancer Project Group consolidated the results of GITSG-7175 by following 144 patients with Dukes B and C rectal cancer for a minimum of 4 years.r Participants randomised to surgery alone had significantly higher rates of local recurrence compared with surgery and postoperative chemoradiotherapy using bolus fluorouracil (30% vs 12%, p=0.01). The 5-year recurrence free survival was 46% for surgery alone compared with 64% for surgery and chemoradiotherapy (p=0.01). Overall survival rates at 5 years were 50% for surgery alone and 64% after adjuvant treatment (p=0.05).
Figure 1: Recurrence-free survival and overall survivalr
© BR J SURG 1997
Currently, completion TME is considered standard of care after transanal excision for high risk (poorly differentiated, margin positive or with lymphovascular space invasion) rectal cancer. Adjuvant chemoradiotherapy in these patients should only be considered for patients on a clinical trial, or in those who refuse or are unsuitable for completion TME. The TESAR trial is currently underway to investigate whether adjuvant radiotherapy following EMR is non-inferior to TME in adequately resected intermediate risk T1-2 rectal cancer.r
Timing of chemoradiotherapy
Variation exists in the sequence of adjuvant radiotherapy and chemotherapy for locally advanced rectal cancer. A study of 308 patients undergoing adjuvant rectal chemoradiotherapy found no difference in disease free survival at 10 years between patients who started radiation on day 1 of cycle 1 of chemotherapy compared with day 1 of cycle 3 of chemotherapy.r For patients undergoing abdominoperineal resection though, subgroup analysis showed a significant improvement in 10 year disease free survival for the early radiotherapy group (63% vs 40%, p=0.043).r