Global variation in the long-term outcomes of ypT0 rectal cancers

Background: Colorectal cancer mortality presents world-wide variation. In rectal cancers presenting a complete/nearly-complete tumor response (ypT0/ypTis) following neoadjuvant treatment, the features correlated to nodal metastases and relapses still need to be defined. Methods: An international cohort study enrolling ypT0/ypTis rectal cancers surgically treated from 2012 to 2017 was conducted. A propensity matching was used to balance nodal-positive and nodal-negative patients and statistical analyses were performed to investigate survivals, using a bootstrap model for internal validation. The features correlated with nodal metastasis were studied. Countries with partici- pating centers were ranked using the World Bank (WBI), Human Development (HDI) and Global Gender Gap (GGG) indexes to compare survivals. Results: 680 ypT0/ypTis from 52 European, Australian, Indian and American Institutions were analyzed. Mean follow-up was of 30.4 months. 96.5% were treated with total mesorectal excision, 7.2% were nodal- positive and 8.8% relapsed. Distal cancers (HR 0.71 95%CI: 0.56-0.91) and nodal metastasis and nodal metastasis (HR 3.85 95%CI:1.12e13.19) correlated with worse DFS, whereas a younger age was of borderline significance (HR 0.95 95%CI:0.91e0.99). The bootstrap analysis validated the model on 5000 repetitions. A short-course radiotherapy (OR 0.18 95%CI:0.09e0.37) correlated with the occurrence of nodal metastasis. Those countries classified in the low/medium-WBI, medium-HDI and lower-GGG ranks documented worse DFS curves (respectively p < 0.0001, p < 0.0001 and p 0.0002). However, the clinical stages were similar and patients from medium-HDI countries received more adjuvant chemotherapy than the others (p < 0.0001). Conclusion: Sub-groups at risk for relapses and nodal metastasis were identified. A global variation exists also when benchmarking a rectal cancer complete regression.