Neoadjuvant Chemoradiotherapy in the Downstaging of Locally Advanced Rectal Cancer and its Impact on Progression–Free Survival

Summary Introduction The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (NACRT) followed by radical surgery, which allows to reduce local recurrence, downsize the tumor and facilitate its R0 resection. Aim of the study The aim of this study was to evaluate the downstaging of LARC after NACRT and to assess the impact of downstaging on progression–free survival (PFS). Materials and methods 65 patients diagnosed with LARC from 2012 to 2018, who received NACRT with subsequent radical surgery were identified in the Pauls Stradins Clinical University Hospital in Riga and included in this retrospective study. Average follow–up period was 31 months. Data were analysed with SPSS Statistics 22.0, Wilcoxon signed–rank test and Kaplan–Meier survival analysis were performed. Results Overall, 66.7% (n=40) of patients experienced a downstaging in response to NACRT, of which 37.5% (n=24, p=0.004) had a downstaging of T and 63.3% (n=38, p=0.0001) of N. 12–month PFS was 87.8%, 24–month PFS – 66.1% and 3–year PFS – 62.7%, median PFS (mPFS) was not met. 3–year PFS of those patients treated with intravenous 5FU/LV boluses was significantly higher (76.5%) than those who received oral tegafur (45.6%, mPFS 32 months), p=0.038. 3–year PFS of patients with downstaged T was 85.9%, compared to 52.1% without it; mPFS not met, p=0.04. Similarly, 3–year PFS of patients with downstaged N was 71.5%, compared to 43.3% without it (mPFS 24 months), p=0.112. Lymphatic and vascular invasion were associated with significantly lower PFS compared to the patients with absent lymphatic and vascular invasion (p=0.0001 and p=0.014, respectively), while perineural invasion did not show any impact on PFS. Age at diagnosis, tumor location, type of surgery and adjuvant chemotherapy did not have a significant impact on PFS. Conclusions Results confirm the efficacy of NACRT in LARC in the downstaging of T and N. Downstaging of LARC, intravenous chemotherapy and absence of lymphovascular invasion are associated with significantly increased PFS.