Abstract / Summary
Background Pathological response (pR) has increasingly been used as a surrogate marker of neoadjuvant treatment efficacy in soft tissue sarcoma (STS), yet evidence linking it to improved survival remains inconsistent. This review evaluates the prognostic value of pR in neoadjuvant-treated STS. Methods A systematic literature review identified clinical trials, observational, and retrospective studies assessing survival outcomes associated with pR, defined by residual viable tumour cells (RVT), necrosis, or fibrosis/hyalinization, in STS treated with neoadjuvant chemotherapy, radiotherapy, or chemoradiotherapy. Results were reported narratively given substantial heterogeneity between studies. Results Twenty-seven studies comprising 3957 patients (median 112, range 50–496) were included. Twenty-five reported RVT, eight necrosis, and seven fibrosis/hyalinization. Considerable variability was observed in the prognostic value of pR across studies. Low RVT predicted improved survival in 36% (9/25), high necrosis predicted decreased survival in 75% (6/8), and fibrosis/hyalinization was inconsistent (43% favourable, 29% unfavourable). Cut-off values, histological parameters and definitions, and patient and treatment characteristics varied widely. Analyses were predominantly unadjusted for confounders, including tumour grade, histological subtype, and resection margin. Conclusions Current evidence is insufficient to support pR as a reliable prognostic predictor. The prognostic value of RVT, necrosis, and fibrosis/hyalinization varies substantially across studies, likely reflecting differences in histological subtype, tumour biology, treatment heterogeneity, and methodological inconsistencies in pR assessment. Standardisation of histological parameters assessed, their definitions, and pR categorisation criteria is required to determine the prognostic relevance of pR in STS. The proposed CHIRE framework provides a practical foundation for harmonising pR assessment and reporting in future STS studies.