(P 107) DOES THE USE OF ADJUVANT CHEMOTHERAPY IN LOCALIZED, RESECTABLE SOFT TISSUE SARCOMA LEAD TO BETTER SURVIVAL OUTCOMES? - A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Objective: The use of chemotherapy for localized, resectable soft tissue sarcoma (STS) remains controversial and treatment protocols vary widely across institutions. As a result, several randomized controlled trials (RCT) comparing the outcomes of patients treated with local therapy alone with those treated with local therapy and doxorubicin-based chemotherapy have been conducted. Importantly, two large meta-analyses of RCT covering the periods 1973-1990 and 1990-2007 were published. In the last two decades, results have been published from several additional RCT investigating the role of chemotherapy in the treatment of localized STS. Notably, the landmark study by Woll et al., a multicenter RCT on adjuvant doxorubicin and ifosfamide for localized STS, was missed by previous meta-analyses. The objective of this study was to reassess the impact of chemotherapy on local, distant, and overall recurrence as well as overall survival in patients with localized, resectable STS.

Methods: A literature review through PubMed and Embase databases was conducted to identify RCT published from inception to November 30th, 2023. Our inclusion criteria were the following: (1) RCT with adult patients diagnosed with localized, resectable STS, who were randomized to a treatment arm (local therapy AND adjuvant chemotherapy) or control arm (local therapy alone), and (2) report any of the four outcomes of interest: overall survival, local recurrence, distant recurrence, and overall recurrence. Studies were excluded if they included pediatric patients, patients with bone sarcomas, and/or patients with advanced, unresectable, or metastatic disease. The odds ratio (OR) of included studies were evaluated with a fixed-effects model (weighted with inverse variance). Absolute risk reduction (ARR) and number needed to treat (NNT) were also reported.

Results: A total of 22 RCT (2647 patients) were included. Adjuvant chemotherapy improved overall survival (OR =0.79, 95% CI, 0.67-0.93) and reduced local recurrence (OR=0.73, 95% CI, 0.58-0.92), distant recurrence (OR=0.72, 95% CI, 0.61-0.86) and overall recurrence (OR=0.70, 95% CI, 0.59-0.82). For overall survival, treatment with any form of chemotherapy had an ARR of 5% (95% CI, 2-9%; p=0.005) with a NNT to improve overall survival of 20. The ARR with treatment of any form of chemotherapy on local, distant, and overall recurrence was 3% (95% CI, 0.4-6%, p=0.03), 8% (95% CI, 4-12%; p< 0.001), and 9% (95% CI, 5-13%; p< 0.001), respectively. NNT to reduce local, distant, and overall recurrence was 33, 13, and 11, respectively. Doxorubicin-based chemotherapy alone did not increase overall survival or decrease local recurrence but was found to decrease distant and overall recurrence. Doxorubicin-ifosfamide chemotherapy was not found to decrease distant recurrence but did increase overall survival and decrease local and overall recurrence.

Conclusion: Overall, our study showed that adjuvant chemotherapy improved overall survival as well as reduced local, distant, and overall recurrence of disease. Although, by virtue of STS being more than a single disease process, but rather a heterogeneous collection of distinct subtypes, it is challenging to make over-generalizations about the benefits of a single type of treatment. Our study reflects the potential positive role of adjuvant chemotherapy, which has increasingly become more focused on histology-based therapy. Moreover, the risks of treating patients diagnosed with localized, resectable STS with adjuvant chemotherapy should be weighed against the benefits on a case-by-case basis due to the heterogeneity of histologic disease and presentation.