Neoadjuvant anti-PD-1 monotherapy followed by watch-and-wait strategy in dMMR/MSI-H colorectal cancer: a multicenter real-world study.

OBJECTIVE

This study aimed to assess the long-term results of the watch-and-wait (W&W) strategy in patients with clinical stage II/III mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) colorectal cancer (CRC) who received neoadjuvant anti-PD-1 monotherapy.

METHODS

This retrospective study enrolled stage II/III dMMR/MSI-H CRC patients from four Chinese tertiary hospitals between August 1, 2020 and February 28, 2025. All participants received neoadjuvant anti-PD-1 monotherapy followed by W&W approach. post hoc, endoscopic complete response (eCR) was defined as no suspicious mucosal lesion on white-light or chromoendoscopy (flat scar or normal mucosa allowed) and negative targeted biopsies from the primary tumor site. The primary outcomes were disease-free survival (DFS) and overall survival (OS). The study is registered in the Chinese Clinical Trial Registry (www.chictr.org.cn ChiCTR2500100474).

RESULTS

A total of 49 patients managed with W&W strategy were enrolled, and all met the post hoc eCR criteria. Radiological evaluation showed clinical complete response in 21 patients (44%), partial response in 17 (35%) and stable disease in 10 (21%). One patient lacked evaluable imaging. Median neoadjuvant treatment duration was 6 months (IQR 4-8), with a median of 12 treatment cycles (IQR 8-16). Treatment-related adverse events were grade 1-2 in 14 patients (29%); no grade 3-4 events occurred. At a median follow-up of 35 months (range 9-60), no local regrowth, distant metastasis, or death was recorded. The estimated 3-year DFS and OS are both 100%.

CONCLUSION

In this cohort, patients with dMMR/MSI-H CRC who met eCR after neoadjuvant anti-PD-1 monotherapy had excellent long-term outcomes when managed with W&W strategy. These findings support the potential utility of endoscopic assessment for selecting candidates for organ preservation, but prospective validation of standardized criteria is warranted.