Impact of PD1 blockade added to neoadjuvant chemoradiotherapy on rectal cancer surgery: post-hoc analysis of the randomized POLARSTAR trial

Abstract Background The addition of PD1 blockade to neoadjuvant chemoradiotherapy (CRT) has been shown to significantly increase pCR rates in locally advanced rectal cancer (LARC). Yet, its impact on total mesorectal excision (TME) remains unknown. Methods A post-hoc analysis of the randomized POLARSTAR trial, which enrolled patients with LARC at eight major colorectal cancer centres in Beijing to compare neoadjuvant CRT plus PD1 blockade with CRT alone, was undertaken. Patients received one of three combinations of neoadjuvant treatments before TME surgery: CRT plus concurrent PD1 blockade (concurrent group), CRT plus sequential PD1 blockade (sequential group), and CRT alone (control group). Several parameters related to TME surgery were studied. Results For the concurrent group, the sequential group, and the control group, 52, 46, and 45 patients respectively were included in this analysis. The proportion of patients undergoing sphincter-saving plus one-stage anastomosis surgery was 92% (48 of 52), 96% (44 of 46), and 87% (39 of 45) respectively. The proportion of patients without a stoma was 21% (11 of 52), 17% (8 of 46), and 11% (5 of 45) respectively. The grade 3/4 surgical complication rate was 4% (2 of 52), 7% (3 of 46), and 4% (2 of 45) respectively. Significant differences were observed between the sequential group and the control group with respect to the proportion of patients with TRG0 (37% versus 18% respectively; P = 0.040), ypT0/is ypN0 (39% versus 20% respectively; P = 0.046), and a low neoadjuvant rectal (NAR) score (54% versus 31% respectively; P = 0.025). Conclusions Neoadjuvant CRT plus PD1 blockade enhances pathological tumour regression and is beneficial to the successful implementation of TME in patients with LARC. Validations with larger sample sizes are warranted.