Session Item

Intensified neoadjuvant treatment improves disease-free survival in patients with locally advanced rectal cancer, but recurrence or distant metastases still occur in one of four patients. We analysed the probability of treatment failure after curative treatment and the overall survival after treatment failure within three clinical phase II/III trials.

Data from 1935 patients from the CAO/ARO/AIO-94, CAO/ARO/AIO-04, and CAO/ARO/AIO-12 trial were pooled. Occurrence of R2 resection, local recurrence or metachronous distant metastases were defined as treatment failure event. The log-rank test was used to calculate the difference in overall survival after treatment failure. The percentage of treatment failure according to ypTNM classification or trial was calculated by dividing the number of DFS events and the number of patients at risk within the specific period. The t-Test was used to calculate the difference between time to treatment failure and clinical trial, respectively ypTNM classification and Pearson correlation was used to estimate correlation between overall survival and disease-free survival.

498 of 1935 patients endured a treatment failure. Median time to treatment failure was significantly longer in the CAO/ARO/AIO-94 trial (18months) compared to the CAO/ARO/AIO-94 (14 months) and the CAO/ARO/AIO-12 trial (14.5 months, P<0.001). Pearson’s correlation coefficient between OS and DFS changed from 0.92 [CAO/ARO/AIO-94], 0.80 [CAO/ARO/AIO-04] to 0.74 [CAO/ARO/AIO-12] but remained highly significant. Overall survival after treatment failure significantly improved over the last three decades. 3-years survival was 32.0% in the CAO/ARO/AIO-94, 42.8% in the CAO/ARO/AIO-04 and 74.3% in the CAO/ARO/AIO-12 trial (P<0.001) (1year: 66%, 79%, 90%). Probability of treatment failure decreases with time but 9.5% of all treatment failures in the CAO/ARO/AIO-94 occurred after 60 months. Distant metastases account for the highest proportion of treatment failure while proportion of local recurrence slightly increase after 48 months. Post-surgical ypTNM classification did not only correlated with risk of treatment failure (0 to 12 months period: ypT0: 1.1%; ypT+:8.0% and ypN+:19.8%) but treatment failure in patients with pCR occurred significantly later (26 months) than in patients with postsurgical positive node status (12 months, P<0.035).

The improved overall survival after treatment failure in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy should encourage us to perform structured follow-up and motivate patients to participate. The longer time to treatment failure in patients with pathologic complete remission should be considered in follow-up concepts in the context of organ preservation. Further clinical trials to analyse different treatment options for patients with metachronous metastases or local recurrence are needed to optimize treatment both in terms of survival but also in terms of maintaining quality of life.