BACKGROUND: Histopathologic assessment of tumor viability has emerged as a potential predictive factor of outcomes in various cancers. This study evaluates the prognostic significance of viability in high-grade soft tissue sarcoma while accounting for different adjuvant regimens and clinical variables. METHODS: A retrospective chart review was conducted on 147 patients surgically treated for high-grade soft tissue sarcoma between 2010 and 2021 at a single institution. Perioperative, clinical and surveillance data were collected. Tumor viability was determined through histopathologic analysis by a board-certified pathologist. RESULTS: No significant differences in clinical variables were observed between groups with ≤10 % and >
10 % tumor viability. Neoadjuvant treatments, tumor grade, size, and depth did not independently affect tumor viability. There was no statistically decreased risk of local recurrence in the group with ≤10 % viability compared to the group with >
10 % viability (HR = 1.19, 95 % CI [0.57,2.50]) (p = 0.64). Margin status was the only variable that significantly increases the risk of LR on multivariate analysis. CONCLUSION: This cohort suggests that neoadjuvant radiotherapy, chemotherapy, or their combination did not influence tumor viability predictably. Notably, tumors without neoadjuvant treatment exhibited a high rate of necrosis, potentially confounding the interpretation of treatment effect. Other factors such as tumor type may play a more significant role in the cause of tumor necrosis than originally thought. Pathologic tissue response continues to offer value for the management of STS, but these findings underscore the need for further investigation into tumor viability in soft tissue sarcoma, targeting specific treatments analyzed in large collaborative studies.