Preoperative (preop) radiotherapy (RT) +/- 5FU/folinic acid (FA) in T3-4 rectal cancers: results of the FFCD 9203 randomized trial.
Reviewer: Christopher Dolinsky, MD
University of Pennsylvania School of Medicine
Last Modified: May 16, 2005
Presenter: J.P. Gerard
Presenter's Affiliation: Center Antoine Lacassagne, Nice, France
Type of Session: Scientific
- Multiple studies have demonstrated the safety and efficacy of preoperative radiation therapy for the treatment of advanced rectal cancer.
- Data in patients given preoperative radiation therapy alone show unacceptably high rates of local failure (25-45%).
- Many studies have demonstrated improved outcomes with concurrent chemotherapy and radiation therapy in the preoperative setting
- In properly selected groups of patients, a combination of chemotherapy and radiation therapy (CRT) before surgical resection is considered the standard of care.
- This study was designed in 1992, before there was a large body of data supporting the use of CRT preoperatively.
Materials and Methods
- A multi-institutional phase III prospective study randomized 762 patients with T3 or T4 rectal cancers to either preoperative radiation therapy or preoperative radiation therapy with 5-fluorouracil.
- Radiation was the same in both arms and was given in 25 fractions to 45Gy in 5 weeks.
- 5-fluorouracil was given as a 350 mg/m2 IV bolus with 20mg/m2 of folinic acid for 5 days during weeks 1 and 5 of radiation.
- Patients were eligible if a digital rectal examination could be performed, they had T3 or T4 tumors, were younger than 80 and had ECOG performance status 0 or 1.
- Overall survival was the primary endpoint.
- Pathologic complete response, disease free survival, local control and toxicities were secondary endpoints.
- Surgery was performed at 3-10 weeks post treatment, and total mesorectal excision was suggested but not required.
- Following surgery, all patients were scheduled to receive 4 more cycles of chemotherapy.
- Median follow-up is 69 months.
- Groups were well balanced among a variety of demographic and disease factors including: gender, age, T stage, N stage and distance from the anal verge.
- The CRT arm had improved 5 year local failure rates compared to the radiation alone arm (8% vs 16.5%).
- Five year disease free survival and overall survival rates were not significantly different between the arms (DFS: CRT 56% vs RT 59%, OS: CRT 66% vs. RT 67%)
- Pathologic complete response rates were significantly higher in the CRT arm compared to the radiation alone arm (12% vs. 3.7%).
- There was no difference in rate of negative margins or rate of sphincter sparing operation performed between the two arms.
- When examining various subgroups, the addition of chemotherapy always remained significantly related to improved local control.
- CRT was significantly related to increased grade 3 or 4 toxicity compared to radiation alone (14.6% vs. 2.7%).
- For T3/T4 rectal cancers treated preoperatively, CRT produces increased toxicity compared to radiation alone.
- CRT increases the rate of disease sterilization as measured by pathologic complete response rate.
- CRT increases the likelihood of local control compared to radiation alone.
- There is not an improvement in either overall survival, disease free survival, or sphincter preservation seen with CRT compared to radiation alone.