Breaking New Ground in Cervical Metastatic Carcinoma of Unknown Primary: Neoadjuvant Immunochemotherapy's Pathologic...

Cervical metastatic carcinoma of unknown primary (CMCUP) poses significant therapeutic challenges because of its aggressive biology and the absence of standardized treatment protocols. While neoadjuvant immunochemotherapy (NICT) has demonstrated efficacy across various malignancies, its application in CMCUP remains poorly characterized.

This retrospective cohort study evaluated 98 consecutive patients with CMCUP treated at a tertiary cancer center between 2015 and 2024. Patients were stratified into NICT (n = 33) or traditional therapy (n = 65). Primary endpoints included pathologic complete response and objective response rate; secondary endpoints comprised major pathologic response (mPR), extranodal extension, surgical margin status, 3 year recurrence-free survival (RFS), overall survival (OS), and treatment-related adverse events.

The NICT cohort demonstrated favorable pathologic outcomes, with 45.5% achieving pathologic complete response and 69.7% attaining mPR. Radiologic assessment showed stable disease in 63.6% (objective response rate 36.4%), yet pathologic analysis revealed significant tumor regression in patients with mPR (11/23 with initial radiologic stable disease). NICT substantially reduced clinical extranodal extension (24.2% vs. 66.2%, p<0.001) and positive margin rates (9.1% vs. 27.7%, p = 0.03). Survival analysis favored NICT, with a 3 year RFS of 78.8% versus 49.2% (p = 0.011) and OS of 84.8% versus 61.5% (p<0.05). Multivariable analysis confirmed NICTs independent prognostic value for both RFS (hazard ratio 0.45; 95% confidence interval 0.24-0.87, p = 0.014) and OS (HR 0.55; 95% confidence interval 0.32-0.93,  p =  0.017). Treatment was well-tolerated, with grade 3/4 adverse events limited to vomiting, leukopenia, and pneumonia.

NICT induces significant pathologic regression and improves survival outcomes in CMCUP, demonstrating dual benefits of enhanced resectability and disease control. These results support prospective evaluation of NICT in this high-risk population.