Towards a 'Lyon molecular signature' to individualize the treatment of rectal cancer. Prognostic analysis of a prospective cohort of 94 rectal cancers T1-2-3 Nx MO to be the basis of a molecular signature

Purpose. - In 1998 a translational research was initiated in Lyon aiming at identifying a prognostic 'bio-molecular signature' in rectal cancer. This paper presents the clinical outcome of the patients included in this study. Patients and methods. - A total of 94 patients were included between 1998 and 2001. A staging with recto-scopy and biopsies was performed before treatment. In case of surgery, the operative specimen was analysed to evaluate the pathological response. There were two types of treatment: neoadjuvant radiotherapy (with or without concurrent chemotherapy) followed by surgery (76 cases) and radiotherapy alone with 'contactherapy' often associated with external beam radiotherapy (18 patients). Results. - The patients had a mean age of 63 years. Stage was T1: 4, T2: 24, T3: 65 and T4: 1. The overall survival of the 94 patients was 62% at 8 years with a rate of distant metastases of 29%. Rate of local recurrence at 8 years was 6% in the neoadjuvant group and 16% in the radiotherapy group with an overall 8 years survival in both groups respectively: 64% and 53%. There was a trend towards more metastases in cT3, tumour diameter above 4 cm, circumferential extension. There was a significant increase in the risk of metastases for ypT3, ypN1-2 and Dworak score 1-2-3. In multivariate analysis ypT3 was significantly associated with a high rate of metastases (55%; P = 0.0003). Conclusion. - The rate of distant metastases is a major prognostic factor. These clinical results will serve as the base line to identify a 'bio-molecular signature' which could complement the TN(M) classification. (authors)