Background: Enhanced recovery after surgery (ERAS) protocols are known to reduce postoperative complications and improve short-term outcomes by minimizing the surgical stress response (SSR). Retrospective reviews of large cohorts suggest that they may also have an impact on long-term oncological outcomes. In 2016, Mari et al published a randomized trial on ERAS protocol and the impact on the SSR; they found that IL-6 was less expressed in patients who undergo laparoscopic colorectal surgery within an ERAS protocol compared with controls. The aim of the present study is to report the long-term oncological outcomes of patients enrolled 5 years after the conclusion of the study. Methods: Patients enrolled had received the indication for major colorectal surgery, aged between 18 and 80 years, with American Society of Anesthesiologists (ASA) grades I to III, autonomous for mobilization and walking, eligible for laparoscopic technique. In total, 140 patients were enrolled and randomized into 2 groups of 70 patients each. Among these patients, 52 in the ERAS group (EG) and 53 in the Standard group (SG) had colorectal cancer. For them, a 5-year oncological follow-up according to the NCCN16 guidelines was planned. IL-6, C-reactive protein, prolactine, white blood cell count, albumin, and prealbumin were compared between oncological patients in the EG and in the SG. Results: EG showed lower IL-6 on postoperative day 1 (21.2±9.1 vs. 40.3 ±11.3; P<0.05) and on day 5 (14.9±6.2 vs. 38.7±8.9; P<0.05), lower C-reactive protein on day 1 (48.3±15.7 vs. 89.4±20.3; P<0.05) and on day 5 (38.3±11.4 vs. 74.3±19.7; P<0.05), and lower pre-albumine on day 5 (18.9±7.2 vs. 12.3±6.9; P<0.05) compared with SG. Median oncological follow-up was 57 months [46.5 to 60]. There was no statistically significant difference in overall survival (log rank=0.195) and disease-free survival (Log rank=0.089) between groups. Cancer-specific survival was significantly better (log rank=0.038) in the EG compared with patients in the SG. Conclusions: ERAS protocol applied to colorectal laparoscopic surgery for cancer is able to minimize the SSR. As a possible result, cancer-specific survival seems to be improved in patients within enhanced protocols. However, even though there may be an association between an excess of SSR and worse oncological outcomes, the favorable effect of ERAS protocols toward better overall and disease-free survival is yet to be demonstrated.

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