Session Item

Downstaging in locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiation (nCRT) treatment is defined as a decrease in pathological vs preoperative T-category, N-category, or disease stage.

Several studies have shown that downstaging is a potential early predictor of nCRT efficacy. The proper definition of downstaging and its impact on survival outcomes remain to be defined.

The aim of this analysis is to evaluate the impact of downstaging on survival outcomes in a pooled dataset of several randomized trials of neoadjuvant radiotherapy in LARC. 

Pooled and treatment subgroup analysis were performed on 8 large international rectal cancer trials: Accord 12/0405, EORTC 22921, FFCD 9203, CAO/ARO/AIO-94, CAO-ARO-AIO-04, INTERACT, I-CNR-RT, and TROG 01.04.

All selected patients were older than 18 years, had undergone nCRT with or without adjuvant chemotherapy (CT) followed by surgery, and with information on at least one among T-, N-, or stage downstaging. Metastatic patients or those who underwent conservative surgery, such as minimally invasive transanal excision (TAMIS) or transanal endoscopic microsurgery (TEM), were excluded from the analysis. Overall survival at 5 years (5yOS), distant metastasis free survival at 2 years (2yDMFS) and disease free survival at 2 years (2yDFS) rates were calculated using Kaplan Meier analysis.

Patients were defined as downstaged when the difference of clinical and pathological stages (respectively on T value, N value and the TNM stage) was greater than or equal to 1.

Kaplan Meier curve, Logrank test and univariate logistic regression were used for data analysis. A p-value less than 0.01 was considered as a statistical significant value.

Overall, 4167 of 9564 LARC patients satisfied the inclusion criteria of this pooled dataset and were analyzed in this study. Patient characteristics are shown in Table 1.

Out of all patients, the 5yOS was 78% (95% CI: 76.80 - 79.70), the 2yDMFS was 81.1% (95% CI: 79.80 - 82.30) and the 2yDFS was 80.8% (95% CI: 79.60 - 82.10). Kaplan Meier analysis using Logrank test demonstrated that OS, DMFS and DFS are significantly higher in T-, N-, or stage- downstaged patients (p<0.01).

According to the univariate logistic regression analysis, 5yOS, 2yDMFS and 2y DFS were statistically significantly associated (p<0.01) with the downstaging of LARC patients assessed by T-status, N-status and disease stage. 

Downstaging is a very challenging variable for the assessment of the outcomes in LARC. According to the findings obtained in the pooled analysis presented in the current study, downstaging was favorably associated with all survival and disease control outcomes. On the basis of the studies described in the literature, a more focused analysis of this endpoint may lead to the identification of different disease subgroups. These subgroups may benefit from different types and intensifications of treatment in the perspective of personalized medicine.