A multimodal neoadjuvant strategy incorporating PDT, RFA, and ICIs results in a notable pathological response and preservation of the sphincter in microsatellite stable low rectal cancer: A highly distinctive case report and literature review

Microsatellite stable (MSS) rectal cancer generally shows limited response to immunotherapy because of its low tumor mutational burden and immunosuppressive tumor microenvironment. Meanwhile, locally advanced low rectal cancer presents a major clinical challenge, as radical surgery often compromises anal sphincter function and postoperative quality of life. Emerging evidence suggests that photodynamic therapy (PDT) and radiofrequency ablation (RFA) can induce immunogenic cell death, promoting the release of tumor-associated antigens and damage-associated molecular patterns, thereby enhancing antitumor immune responses. Here, we report a case of locally advanced MSS low rectal cancer treated with a multimodal neoadjuvant regimen integrating sequential PDT and RFA with systemic therapy including immune checkpoint inhibitors, chemotherapy, and targeted therapy. This strategy achieved a near-complete pathological response (Tumor Regression Grade 1) and enabled successful sphincter-preserving radical surgery despite the tumor being located <5 cm from the anal verge. The treatment was well tolerated, with no severe treatment-related adverse events observed. This case suggests that combining local tumor ablation with systemic immunomodulatory therapy may represent a promising strategy to enhance immunotherapy responsiveness and facilitate organ-preserving treatment in selected patients with MSS rectal cancer.