Tegafur/Uracil

Ultra-fast-track (UFT) enhanced recovery after surgery (ERAS)—defined by on-table extubation, minimally invasive surgical technique and de-escalated ICU care—represents an intensified ERAS approach. Female patients remain under-represented in cardiac surgery research and experience worse postoperative outcomes. Therefore, we investigated possible gender-mediated differences in the outcomes of our UFT-ERAS program.

A total of 800 consecutive patients underwent UFT-ERAS for minimally invasive valve and aortic surgery at our institution from 01/2021 to 09/2024. Patients were divided by gender, and a retrospective cohort analysis was performed. The primary outcome was UFT-ERAS achievement, defined by a 0-5 score of postoperative milestones (on-table extubation, postoperative intermediate care, early physiotherapy, transfer to the general ward ≤24 h and hospital discharge ≤7 days). Secondary end points were major adverse cardiovascular events (MACE), reoperation for bleeding, reintubation, ICU readmission, acute kidney injury, atrial fibrillation, delirium and transfusion.

Women were older and had higher baseline risk scores. Overall, ERAS adherence and major postoperative complications were comparable between the sexes. Only discharge ≤7 days was less frequent, and postoperative transfusion need more frequent in women. In multivariable ordinal logistic regression adjusting for STS-PROM, age, and procedure type, sex was not independently associated with ERAS achievement (OR 0.88, 95% CI, 0.66-1.18).

In this predominantly low-risk patient cohort within a UFT-ERAS pathway, sex was not independently associated with overall ERAS achievement. However, women more frequently required transfusion and were less likely to be discharged within 7 days.

Given the superior relapse-free survival (RFS) and different safety profiles of 1 year of adjuvant S-1 or uracil/tegafur (UFT) for stage II/III rectal cancer, the benefit-risk of these 2 regimens was formally assessed using the net treatment benefit (NTB).

Individual patient data from the Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC) 35-C1 trial were used. S-1 and UFT were compared regarding RFS, incidence of grade ≥3 symptoms, and incidence of grade ≥3 laboratory abnormalities reported as adverse events (AEs). Laboratory abnormalities and symptoms were analyzed as binary variables and as counts. Univariate and multivariate NTBs were computed for various ways of prioritizing the outcomes.

The univariate NTB for RFS was 9.2% (95% CI, 3.4%-15.2%, P = .005) in favor of S-1. The univariate NTB was not statistically significant for any symptom. For grade ≥3 laboratory AEs, only thrombocytopenia was statistically significant in favor of UFT (NTB = −0.8%; 95% CI, −1.6% to −0.02%; P = .044). In the multivariate analysis considering RFS as the outcome of first priority, the incidence of grade ≥3 symptoms as second, and the incidence of grade ≥3 laboratory abnormalities as third, the multivariate NTB was 8.8% (95% CI, 2.7%-14.9%, P = .014) in favor of S-1. In sensitivity analyses according to age group, the NTB was generally positive for patients <70 years but nonsignificant for those ≥70 years old.

The reanalysis of the JFMC 35-C1 trial suggests that S-1 has a superior benefit-risk to UFT when RFS is considered as the outcome of first priority, followed by the incidence of grade ≥3 symptoms and of grade ≥3 laboratory abnormalities.