Preoperative concurrent chemoradiotherapy (CT-RT) improves local control in T3-4 rectal cancers. Results of the FFCD 9203 randomized trial

Reviewer: James M. Metz, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2005

Presenter: J Gerard
Presenter's Affiliation: Centre Antoine Lacassagne, Nice, France
Type of Session: Scientific

Background

There has been a dramatic shift over the past few years to using preoperative radiation therapy for rectal cancer as opposed to using it in the postoperative setting. Some of the initial studies that showed a benefit to this shift used radiation therapy alone. This study compares the use of radiation therapy in the preoperative setting to the addition of 5FU to the same schedule.

Materials and Methods

Patients < 75 years old with T3-T4 rectal cancer that was palpable on digital rectal exam were eligible
Randomized to Radiation alone (RT) of 45 Gy in 25 fractions over 5 weeks vs CT-RT which included the same radiation plus bolus 5FU and Folinic Acid (FA)
Surgery was performed after 3-10 weeks.
All patients were scheduled to receive adjuvant 5FU-FA for 4 cycles postoperatively.
Patient characteristics were well balanced between the randomized treatment arms

Results

Pathologic complete response rate was 3.7% (RT) vs. 11.7% (CT-RT)
5 year Local failure rate was 16% (RT) vs. 8% (CT-RT)
There was no difference in DFS or OS between the groups
There was no difference in the sphincter saving surgery rate
Grade 3-4 toxiticy was 2.7%(RT) vs. 14.6% (CT-RT)
An analysis of different years based on the type of surgical excision that was available during accrual was performed - standard resection (1993-1998) vs. Total Mesorectal Excision (1999-2003). Local recurrence was 18% vs 11% (93-98) and 14% vs. 5% (99-03) both in favor of the CT-RT

Author's Conclusions

Combined CT-RT improves local control, sterilization of the surgical specimen with mild acute toxicity
CT-RT does not improve survival or improve sphincter preservation

Clinical/Scientific Implications

This study adds to the growing body of literature supporting the use of preoperative radiation therapy for locally advanced rectal cancer. The addition of chemotherapy clearly improves local control which adds to the historical data supporting 5FU being used with radiation. This study uses rather antiquated chemotherapy with 5FU given as a bolus infusion. Most centers have moved to using 5FU as a continuous infusion or orally to better complement the daily radiation therapy. This study did not improve the sphincter preservation rate, which is different from the results of the German Rectal Study. However, the tumors in this study were lower and more likely to be involving the sphincter, which may explain this result. Further studies, adding newer agents to preoperative radiation therapy are warranted. Ongoing studies include the addition of oxaliplatin, erbitux, and bevacizumab to this regimen.