Endoscopic and imaging outcomes of PD-1 therapy in localised dMMR colorectal cancer

Background Neoadjuvant immune checkpoint blockade (IO) is emerging as a therapeutic option for patients with deficient mismatch repair (dMMR) colorectal cancer (CRC) given high pathologic response rates. The aim of the study was to characterize imaging and endoscopic response to IO. Methods A retrospective analysis of patients with localized dMMR CRC that received at least one cycle of neoadjuvant anti-PD-1 therapy was conducted. Endoscopy, imaging, and pathologic outcomes were reviewed to determine response to treatment according to standardized criteria. Results 38 patients had received neoadjuvant anti-PD-1 for the treatment of localized or locally advanced CRC (median 8 cycles). Among evaluable cases (n=31 for endoscopy and n=34 for imaging), the best endoscopic response was complete response (CR) in 45% of cases and best radiographic response was CR in 23% of cases. Imaging CR rate after ≤ 4 cycles of IO (n=1) was 6% compared to 44% after > 4 IO cycles (n=7). Among 28 patients with imaging and endoscopy available, a discrepancy in best response was noted in 15 (54%) cases. At a median follow-up of 28.2 months from IO start, 18 patients underwent surgical resection of which 11 (61%) had pathologic CR (pCR). 72% and 42% of patients had non-CR on imaging and endoscopy respectively despite pCR or no evidence of progression ≥6 months after completion of IO among non-operatively managed patients. Conclusions Discrepancy between imaging and endoscopy are prevalent, and that irregularities identified on these modalities can be identified despite pathologic remission. Improved clinical response criteria are warranted.