Session Item

Phase 2 and phase 3 studies use different primary endpoints in rectal cancer. This large variability results in inconsistency and difficulty in data interpretation.  The choice of the right endpoint to correlate with the outcome is still challenging, since it is still unclear what mechanisms impact on some long-term outcomes, such as survival. Considering tumor heterogeneity, validation of these aspects seems necessary in order to tailor cancer treatments. The objective of this study is to validate through a pooled analysis from international randomized trials in rectal cancer the early and intermediate endpoints as surrogate measures of overall survival (OS) in oncology trials.

Pooled and treatment subgroup analysis were performed on 11 large international rectal cancer trials: Accord 12/0405, Dutch trial, EORTC 22921, FFCD 9203, CAO/ARO/AIO-94, CAO-ARO-AIO-04, CHRONICLE, INTERACT, I-CNR-RT, Polish II and TROG 01.04.

All the selected patients were > 18 years old and received short course (SC-RT) or long-course RT (LG-RT)  with or without concomitant and/or adjuvant chemotherapy (CT) followed by surgery.  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.

Several variables (both "early", such as clinical staging, tumor location, surgical interval≥ 12 weeks, the downstaging of TNM, of the tumor and of the lymphnodes, neoadjuvant rectal (NAR) score, surgical procedure and "intermediate", such as local recurrence and distant metastases) were correlated with the 5- years OS. Pearson’s Chi-squared test was used for data analysis. A p-value less than 0.01 was considered as a statistical significant value.

A total of 5473 patients out of 9564 met the inclusion criteria and were subsequently analyzed. Patient characteristics are described in Table 1. All patients completed the RT course, of whom 988 (18%) underwent SC-RT and 4485 (82%) underwent LC-RT. For the entire sample, 2-year disease-free survival (DFS) was 80% (79-82%), 3-year DFS was 77% (75-78%), and 5-year overall survival (OS) was 75% (74% to 77%)

Results regarding early and intermediate endpoints on 5-years OS, with their respective statistical significance, are described in Table 2.

This pooled analysis of  5473 rectal cancer patients highlights and supports that early and intermediate endpoints could be considered surrogates of  overall survival. This suggests that future clinical trials on rectal cancer could be designed using these early and intermediate endpoints as primary or secondary outcomes.