Stratification of patients with locally advanced rectal cancer (LARC) treated with preoperative chemoradiation (ChR), according to Valentini's nomograms (VN) and the Neoadjuvant Rectal Score (NAR). External validation in a single Institution.

Background

Preoperative ChR is the standard of care for LARC. The estimation of risk of locoregional (LR) or systemic recurrence (SR) or death is mainly based upon pathological and clinical features. Valentini et al. (JCO 2011) developed 3 nomograms to predict the 5-year probability of locoregional or distant control as well as overall survival (OS) with patients from 5 European randomized clinical trials. The NAR (Curr Colorectal Cancer Rep 2015) was developed after VN for OS combining the three variables (cT, ypT and ypN) with the greatest weight in the model. Both VN and NAR had an external validation.

Methods

158 consecutive patients from a single academic institution were diagnosed of LARC between 1998 and 2011 and treated with ChR followed by total mesorectal excision. Most of them received adjuvant chemotherapy (ACh). The variables used in the nomograms were sex, age, clinical stage, tumor location, radiotherapy dose, chemotherapy, surgical procedure and ypTNM stage. According to the score obtained, patients were divided in 3 groups of low (L), intermediate (I) and high (H) risk. Kaplan-Meier curves, Log-rank test and Cox regression analysis were performed. C-index was determined to assess the discrimination of the test.

Results

Median follow up was 54 months. VN 5 year OS was 83%, 77% and 67% for L, I and H risk groups, respectively (p = 0,023) and the NAR Score 5 year OS was 84%, 71% and 59% for L, I and H risk (p = 0,004). The c-index was 0,64 and 0,63, respectively. When the score was analyzed as a continuous variable, all 3 nomograms and the NAR had a statistically significant association with 5 year LR (HR 1,12; 95%CI 1,02-1,23, p = 0,02), 5 year SR (HR 1,07; 95%CI 1,03-1,12, p = 0,001), 5 year OS in VN (HR 1,10; 95%CI 1,05-1,14, p 

Conclusions

Validation of VN and the NAR in our series confirm their value to predict outcomes combining different variables in a statistical model. These predictive scores may be of interest to stratify patients according to their individual estimates of risk when designing trials of ACh.

Clinical trial identification

Legal entity responsible for the study

Hospital Clínico Universitario de Valencia

Funding

Hospital Clínico Universitario de Valencia

Disclosure

A. Cervantes: Receipt of honoraria or consultation fees: Merck Serono, Roche, Amgen, Bayer, Lilly. Participation in a company sponsored speaker's bureau: Roche, Merck Serono. All other authors have declared no conflicts of interest.