[Prognostic factors and survival analysis in rectal cancer patients with poor response to neoadjuvant therapy]

Objective: To compare the impact of different treatment strategies on the survival outcomes in rectal cancer patients with poor response to neoadjuvant therapy, and to explore the survival-related influencing factors. Methods: A retrospective cohort study was conducted. Between January 2018 and November 2022, the clinical, pathological, and follow-up data of 106 rectal cancer patients who received neoadjuvant therapy and were evaluated as grade 4 or 5 based on the Magnetic Resonance Tumor Regression Grade (mrTRG) from the rectal cancer database at Peking Union Medical College Hospital were retrospectively collected. Based on the post-neoadjuvant therapy assessment, patients were classified into three groups: the chemotherapy-radiotherapy group (23 patients), the consolidation therapy group (18 patients), and the standard treatment group (65 patients). General condition, pathological findings, selection of neoadjuvant therapy, comorbidities, as well as 3-year expected DMFS and OS were observed in the three groups. Results: All 106 patients were followed up, with a median follow-up time of 28 (21, 38) months. The overall 3-year DMFS rate was 60%, and the 3-year OS rate was 74%. The 3-year DMFS in the standard treatment and consolidation therapy groups were 74% and 72%, respectively; the 3-year OS were 84%, 81%, respectively. The Log-rank test showed that there was no significant difference in the 3-year expected DMFS and OS between the standard treatment group and the consolidation therapy group (both P>0.05), but both groups had better survival outcomes than the chemotherapy-radiotherapy group (10% and 39%, respectively; all P<0.001). Multivariate Cox regression analysis indicated that the chemotherapy-radiotherapy only regimen was an independent risk factor for DMFS (HR=12.425, 95% CI: 4.436-34.594, P<0.001), and the independent risk factors for OS were chemotherapy-radiotherapy only regimen (HR=8.991, 95%CI:2.220-36.403, P=0.002) and age≥65 years (HR=3.495, 95%CI: 1.017-12.009, P=0.047). Stratified analysis showed that chemotherapy-radiotherapy only regimen was the independent risk factors for DMFS and OS in patients with extramural vascular invasion (EMVI) positive (n=66) and mesorectal fascial invasion (MRF) positive (n=56) (all P<0.05). Whether consolidation therapy was added to the standard neoadjuvant treatment regimen was not an independent factor affecting 3-year expected DMFS or OS in rectal cancer patients with poor response to neoadjuvant therapy. Further comparisons between the standard neoadjuvant treatment and consolidation therapy groups showed no statistically significant differences in spincter-preservation rate or postoperative complication rates (both P>0.05). However, the consolidation therapy group had a longer interval between the end of radiotherapy and surgery [80.1 (50.8, 109.4) days vs. 61.8 (48.8, 74.8) days, P<0.001], and a higher incidence of chemotherapy-related adverse effects ([10/18] vs. 26.2% [17/65], P=0.018). Conclusion: In rectal cancer patients with poor response to neoadjuvant therapy and clear adverse prognostic features before surgery (locally advanced stage, MRF positive or EMVI positive), the addition of short- or long-course chemotherapy-based systemic therapy does not provide short- or long-term survival benefits. Moreover, an extended chemotherapy duration increases the incidence of chemotherapy-related adverse effects.