Overall survival of patients with localized soft tissue sarcoma treated with or without adjuvant chemotherapy (DEEPSARC): a real world nationwide retrospective cohort study in France.

Abstract

Whether adjuvant chemotherapy (AC) improves overall survival (OS) after complete resection in localized soft tissue sarcoma (STS) remains unproven and optional in guidelines. We measured OS in patients with operated non-metastatic STS treated with or without AC in the nationwide exhaustive NETSARC+ registry. The DEEPSARC project linked the NETSARC+ registry and the French nationwide health data system (SNDS) into a retrospective cohort. Adults with non-metastatic, undergoing primary surgical resection between 2012 and 2017 were included, excluding those with incomplete linkage data or prior neoadjuvant chemotherapy. We analysed the entire series of 8331 patients with successful linkage and a complete-case subset of 4296 patients. Survival with or without AC were compared using crude and multivariate Cox proportional hazards regression models, including adjustment for confounders and inverse probability of treatment weighting (IPTW). Sensitivity analyses and subgroups analysis in high-risk patients were performed. In the complete-case series, the commonest histotypes were liposarcoma (30%), undifferentiated pleomorphic sarcoma (23%) and leiomyosarcoma (17%). Overall, 389 (9.1%) patients received AC and, compared with those not receiving AC, had fewer comorbidities and presented more high-risk tumour features. With 5.8 years median follow-up, 5-yr OS was 61% (95%CI: 60-63) in the entire series, and 64% (95%CI: 63-66) in the complete-case analysis. 5-yr OS was inferior in patients receiving AC, both in the entire series (50% [47%-54%] vs. 63% [61%-64%]) and in the complete-case analysis (53% [48-59%] vs. 65% [64-67%]). After adjustment (HR = 1.46 [1.12-1.93]) or IPTW (HR = 1.56 [1.17-2.08]), AC remained associated with inferior OS. Findings were consistent across sensitivity and subgroup analyses. In this real-world nationwide study, AC was not associated with superior OS, but rather with an inferior OS in patients operated of a localized STS and did not compensate for the adverse prognostic profile of treated patients. Future research should therefore focus on identifying predictive biomarkers in order to better identify patients who are likely to derive real benefit from systemic treatment. This work was supported by the Health Data Hub; the Institut National Du Cancer and the French Ministry of Health (Direction Générale de l'Offre de Soins, DGOS) for the NETSARC, RRePS and RESOS networks; the INTERSARC+ program; the Agence Nationale de la Recherche; the LYriCAN+ program; the Ligue Nationale contre le Cancer; the Ligue contre le Cancer (Comité de l'Ain); the Fondation ARC; and the European Reference Network for Rare Adult Solid Cancers.