Incomplete Cancer Surgery Correlates With Loss of Immune Surveillance and Hyper-Progression of Disease.

Abstract

Background: Surgery is potentially curative for solid cancers; however, in cases of incomplete surgery, the impact of surgery on immune surveillance in the residual tumor microenvironment is not known. We sought to understand how surgery impacts immune populations in a residual tumor and correlates with overall survival in patients with primary pleomorphic liposarcoma.

Methods: This retrospective cohort study was conducted by searching the UCLA Sarcoma Program database for all patients with a histologic diagnosis of primary pleomorphic liposarcoma from 1995 to 2015. Patient follow-up was carried out through 2021. Patients were stratified by completeness of initial surgery: microscopically complete (R0), microscopically incomplete (R1), and grossly incomplete (R2). Six out of seven patients with an initial R2 resection underwent short-interval re-resection to negative margins within 120 days (R2-to-R0). We used immunofluorescence microscopy to characterize changes in immune populations of the tumor microenvironment.

Results: On multivariate analysis of this 32-patient cohort, age, tumor size, and R2-to-R0 resection were significantly associated with mortality. The hazard ratio for mortality after R2-to-R0 resection was 109 (p value < 0.01). The median overall survival for patients with R2-to-R0 resection was 2.0 years compared to 8.5 years for an upfront R0 resection (p value < 0.001). Immunofluorescence on four pairs of initial and re-resected tumors revealed a postoperative accumulation of suppressive myeloid and T regulatory immune populations in the residual microenvironment.

Discussion: We found that an initial incomplete surgery correlated with the accumulation of suppressive immune populations in the residual tumor microenvironment and mortality-a phenomenon we call hyper-progression of disease. Our findings have implications for therapeutically targeting immunosuppressive populations in the perioperative period to improve patient survival.