Pathological complete response following systemic therapy with carboplatin–paclitaxel plus pembrolizumab for initially unresectable mismatch repair-deficient advanced endometrial cancer: two case reports

• Two advanced dMMR endometrial cancers achieved pathological complete response after TC plus pembrolizumab. • Profound regression enabled avoidance of bowel resection in a case with suspected sigmoid colon invasion. • Radiographic CR rates in KEYNOTE-868 support deep responses with first-line chemo-immunotherapy in dMMR disease. • These cases motivate prospective evaluation of cCR-guided, surgery-sparing strategies with close surveillance. Mismatch repair-deficient (dMMR) endometrial cancer is highly sensitive to immune checkpoint inhibition. Although pembrolizumab combined with carboplatin and paclitaxel is now a first-line standard treatment for advanced or recurrent dMMR endometrial cancer, there is limited evidence regarding the effectiveness of this treatment for initially unresectable cancer. We report two patients with advanced dMMR endometrial cancer who achieved a pathological complete response (pCR) after initial systemic carboplatin–paclitaxel plus pembrolizumab therapy. Case 1 was a 77-year-old woman diagnosed with FIGO 2008 stage IIIB (cT3bN0M0) grade 3 endometrioid carcinoma who had suspected sigmoid colon and ureter involvement and poorly controlled diabetes mellitus. Primary surgery with complete resection was considered unfeasible because of the anticipated surgical invasiveness and high risk of postoperative complications; therefore, the initial treatment was systemic therapy with carboplatin–paclitaxel plus pembrolizumab. Marked radiologic regression was achieved, bowel resection was avoided at surgery, and a pCR was confirmed. Case 2 was a 60-year-old woman with FIGO 2008 stage IVB (cT1bN2M1) grade 1 endometrioid carcinoma with suspected metastases in the pelvic, para -aortic, and left supraclavicular lymph nodes. After six cycles of systemic carboplatin–paclitaxel plus pembrolizumab therapy, cytoreductive surgery showed no residual viable carcinoma, confirming a pCR. These cases demonstrate that chemo-immunotherapy can induce a pCR in advanced dMMR endometrial cancer and may deepen the treatment response. Initial carboplatin–paclitaxel plus pembrolizumab therapy may enable less invasive surgery. These findings support the investigation of surgery-sparing approaches for dMMR endometrial cancer.