Preoperative Chemo-radiotherapy (CT-RT) Improves Local Control in T3-T4 Rectal Cancers: Results of the FFCD 9203 Randomized Trial

Reviewer: Chika Madu, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 17, 2005

Presenter: P. Romestaing
Presenter's Affiliation: CHU Lyon Sud, Lyon, France
Type of Session: Plenary


Based on prior studies on the role of chemo-radiation in the management of patients with locally advanced rectal cancers (LARC), there has been a consistent increase in local control in favor of chemo-radiation. The goal of this study was to evaluate the benefit of concurrent chemo-radiation when given in the pre-operative setting.

Materials and Methods

  • 762 patients were accrued between 1993-2003 at 59 centers
  • All patients had rectal adenocarcinoma which was palpable on rectal examination
  • Other inclusion criteria were T3-4 lesions, no distant metastases, <75 years old
  • Patients were randomized to pre-operative radiation alone or pre-operative chemo-radiation
  • Radiotherapy was given in the form of external beam, 45Gy in 1.8Gy daily fractions
  • Chemotherapy was 5-FU (350mg/m2) and Leucovorin (FA) (20mg/m2) given on days 1-5 on weeks 1 and 5
  • Median time to surgery was 5.3 weeks (range 3-10 weeks) post neo-adjuvant treatment
  • All patients were to receive 4 cycles of 5-FU and FA adjuvantly
  • This study was designed to detect a 10% improvement (from 52%-62%) in 5-yr overall survival (OS) with pre-operative chemo-radiotherapy
  • Secondary end-points were pathologic complete response (pCR), local control, disease free survival (DFS), and rate of sphincter sparing


  • 733 of the 762 patients were eligible for evaluation. The rest were excluded due to age, distant metastasis, refusal of treatment
  • 89% of the patients had T3 lesions, while 11% had T4 lesions
  • Median follow up was 69 months
  • 96% of patients completed their radiation, 84% of those assigned to neo-adjuvant chemotherapy completed chemotherapy, 99% completed surgery in the radiation only arm, 97% in the CT-RT arm, and only 73% of patients in both arms completed adjuvant chemotherapy
  • There was no difference in 5 year OS between the 2 arms, 66.5% (RT only) vs. 67% (CT-RT)
  • There was no difference in DFS, or sphincter sparing surgery
  • There was a significant difference in rates of pCR in favor of CT-RT (11.7% vs 3.7%; p=<0.0001)
  • There was a significant difference in grade 3-4 toxicity (2.7% for RT alone, 14.6% for CT-RT; p=<0.0001)
  • Local failure rates for RT vs CT-RT was 16.5% vs. 8% (No p-value was given)

Author's Conclusions

  • Pre-operative CT-RT seems to increase the rate of moderate acute toxicity
  • CT-RT improves the rate of pCR and local control
  • There is no improvement in OS or sphincter preservation with CT-RT
  • Pre-operative concurrent CT-RT should be the standard for LARC

Clinical/Scientific Implications

This is a very important trial with regard to the management of LARC. Pre-clinical and clinical data have shown the importance of integrating chemotherapy into the treatment course for LARC. Radiotherapy has also shown an advantage with regard to local control. A combination of both modalities in the post-operative setting as shown by NSABP R01 clearly gives a benefit in local control. However, treatment toxicities have been found to be lower with pre-operative CT-RT vs. post-operative CT-RT. The standard now is to give pre-operative CT-RT when possible to patients with LARC. The German trial showed a benefit in local control and sphincter preservation, however, this trial fails to show a benefit in sphincter preservation, but continues to show improved local control rates. Of note is that the patients enrolled in this FFCD 9203 trial prior to 1999 did not all undergo a total mesorectal excision (TME) which is the recommended surgery. 301 patients were enrolled from 1999-2003 and all underwent TME. It is unclear whether this may have changed the findings in anyway. Future directions in this field then entail further investigations with targeted therapy and cytotoxic agents in order to improve OS in these patients with LARC.

From the National Cancer Institute