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Research Article: Watch-and-wait after immunotherapy-containing neoadjuvant treatment in pMMR/MSS locally advanced rectal cancer: a multicenter real-world study

Date Published: 2026-08-10

Abstract:
Watch-and-wait (W&W) is an organ-preserving option for rectal cancer patients who achieve clinical complete response (cCR), but post-cCR outcomes after immunotherapy-containing neoadjuvant treatment in proficient mismatch repair (pMMR)/microsatellite stable (MSS) locally advanced rectal cancer (LARC) remain unclear. We evaluated post-cCR oncological and organ-preservation outcomes in this selected population. This multicenter retrospective cohort study included patients with pMMR/MSS LARC who achieved cCR after immunotherapy-containing neoadjuvant treatment at three medical centers and subsequently underwent W&W. Eligible patients had at least 12 months of post-cCR follow-up. Disease progression, survival, and organ-preservation outcomes were evaluated, and survival was estimated using the Kaplan–Meier method. Twenty-five patients were included, with a median post-cCR follow-up of 26 months (range, 14–40 months). Three patients (12.0%) developed disease progression, including two with local regrowth and one with lung metastasis. Both local regrowths were treated with R0 salvage surgery. The estimated 2-year disease-free survival was 87.4% (95% CI, 65.7%–95.8%). Twenty-three patients (92.0%) avoided radical surgery, and 22 patients (88.0%) maintained disease-free organ preservation. This multicenter study provides preliminary real-world evidence on W&W after cCR in highly selected patients with pMMR/MSS LARC treated with immunotherapy-containing neoadjuvant regimens, but larger prospective comparative studies with longer follow-up are required before its feasibility and oncological safety can be established.

Introduction:
Watch-and-wait (W&W) is an organ-preserving option for rectal cancer patients who achieve clinical complete response (cCR), but post-cCR outcomes after immunotherapy-containing neoadjuvant treatment in proficient mismatch repair (pMMR)/microsatellite stable (MSS) locally advanced rectal cancer (LARC) remain unclear. We evaluated post-cCR oncological and organ-preservation outcomes in this selected population.

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