NACRE: A randomized study comparing short course radiotherapy with radiochemotherapy for locally advanced rectal cancers in the elderly—Preliminary results.

Abstract

4 Background: Neoadjuvant therapy followed by total mesorectal surgery is the standard of care for locally advanced rectal carcinoma (RC). In the elderly, often underrepresented in clinical trials, but who represent a very large number of patients, therapeutic proposals are not based on high levels of evidence. The NACRE study investigated the role of short course radiotherapy with delayed surgery in this population. Methods: The PRODIGE 42-GERICO 12 NACRE is a multicenter randomized clinical trial aimed at comparing Arm A preop radiochemotherapy (RCT) (50 Gy, 2Gy/fraction [fr]; 25 fr + capecitabine) and delayed surgery and Arm B short course radiotherapy (25 gy, 5Gy/fr, 5fr) and delayed surgery. Eligible patients (pts) had cT3 or cT4 (or cT2 of the very low rectum), M0 rectal adenocarcinomas <12 cm from the anal verge, age ≥75years, and WHO PS ≤2. Randomization was stratified by center, T (T2/T3-T4) stage and Age (≤80 or >80 years). Two primary end-points will be analyzed according to the hierarchical sequential procedure: firstly R0 resection rate (non-inferiority test with a 8% non-inferiority margin), secondly preservation of autonomy using IADL score (superiority test with 15% absolute difference margin); secondary end-point will be survival and toxicity. We present here the results for R0 resection, survival and toxicities. Results: 29 sites randomized 101 patients from 01/2016 to 08/2019, 59 were males (58.4%), median age was 80 years (range 75-91). Pts characteristics were well balanced. 14% of pts in arm A did not receive all of the planned neoadjuvant treatment compared to 0% in arm B. The R0 resection rate in arm B (86.0% [IC95% 73-94%]) was not-inferior to the R0 resection rate in arm A (89.8% [ic95% 77-97%]), p=0.04 (non inferiority test). With a median follow-up of 15.8 months (CI95%: 14.8-26.0), the 6 months death rate was 10.0% (CI95%: 3.0-22.0) in arm A and 3.92% (CI95%: 0 -13.0) in arm B. There is a significant difference in overall survival between the two arm in favor of arm B (p=0.04, LogRank test), and there is a trend in favor of arm B for specific survival (p=0.06 LogRank test). Disease free survival is not statistically different (p=0.9). 13 serious adverse events were observed in arm A during preoperative phase, 7 in arm B, 16 and 10 respectively during the post-operative phase. Conclusions: These preliminary results show that short course radiotherapy with delayed surgery is associated with better compliance than radiochemotherapy in elderly patients and could give an advantage in overall survival. This regimen may be preferred in elderly patients. Clinical trial information: NCT02551237.