(P 224) THE ROLE OF NEOADJUVANT CHEMOTHERAPY IN RETROPERITONEAL SARCOMA. A CASE-MATCHED ANALYSIS.

Objective: Retroperitoneal sarcomas (RPS) are rare tumors with variability of clinical and prognostic presentation. Nowadays, extended surgery remains the mainstay of RPS treatment. Despite improvement in surgical outcomes, neoadjuvant strategies are needed in order to decrease the risk of local recurrence (LR), and the risk of distant metastases (DM). In particular, high-grade dedifferentiated liposarcoma (DDLPS) and leiomyosarcoma (LMS), which have a prevalent risk of DM, would benefit from a neoadjuvant therapy. The STRASS study does not support the use of neoadjuvant radiotherapy (NRT) for LMS and high-grade DDLPS. The impact of neoadjuvant chemotherapy (NCT) on oncological prognosis in patients with RPS remains to be clarified. A new randomized study (STRASS 2) is focusing the role of NCT on high-grade LMS and DDLPS. The aim of this study was to analyze the characteristics and the oncological outcomes of patients with RPS treated with NCT compared with patients treated with upfront surgery, performing a case-matched analysis to reduce the selection bias.Methods: We retrospectively reviewed all consecutive patients who underwent surgery for RPS at our center between January 1998 and December 2019. Inclusion criteria were: diagnosis of LMS or DDLPS, tumor grade 2-3. Exclusion criteria were: neoadjuvant radiotherapy, progression disease after NCT, R2 resection. A 1:1 match was performed between patients with RPS treated with NCT and patients treated with upfront surgery. The selected patients were matched according to histopathological subtype (LMS, DDLPS), presentation of tumor (primary, recurrence), and tumor size. The primary endpoint were overall survival (OS), local recurrence-free survival (LRFS), and distant metastases-free survival (DMFS).Results: A total 196 patients with a histopathological diagnosis of LMS or DDLPS were selected. By using the inclusion and exclusion selection criteria, we found 28 patients who underwent NCT for RPS, which were case matched with 28 patients treated with upfront surgery. Median age in the matched series (N=56) was 59.5 years (IQR 50-68). Thirty-two patients (57.1%) had a RP LMS, and 24 patients (42.9%) had a RP DDLPS We found 44 patients with RPS (26 right RPS, and 17 left RPS), and 13 patients (23.2%) had pelvic sarcoma. Twenty-eight patients (50.0%) presented with primary RPS, and 28 patients (50.0%) presented with recurrent RPS. The median follow-up was 32.4 months (range 2-243).Overall, 31 patients (55.4%) died; 14 (/28, 50.0%) and 17 (/28, 60.7%) in the NCT and upfront surgery group, respectively. The OS rate at 1-,3-, and 5-years was 77.8%, 54.2%, 46.5%, and 100%, 69.8%, 51.8% in patients treated with NCT or not, respectively. Overall, 21 patients (37.5%) had LR, and 22 patients (39.3%) had DM. In the NCT group, 8 (/28, 28.6%) and 12 (/28, 42.9%) had LR and DM, respectively. In the upfront surgery group, 13 (/28, 46.4%), and 10 patients (/28, 35.7%) had LR and DM, respectively. The LRFS rate at 1-,3-, and 5-years was 80.8%, 69.6%, 69.6% and 89.1%, 56.7%, 46.4% in patients underwent NCT or not, respectively. The DMFS rate at 1-,3-, and 5-years was 67.4%, 39.0%, 39.0% and 89.3%, 76.5%, 55.7% in patients underwent NCT or not, respectively. Figures 1-3 show the Kaplan-Meier curves of the matched series. There was no significant difference neither in terms of OS (p=0.228) or in terms of LRFS (p=0.719) between patients treated with NCT an patients treated with upfront surgery. However, patient who underwent upfront surgery had significantly better DMFS compared to NCT group (p=0.02).Conclusion: Two homogeneous groups of patients with retroperitoneal high-grade LMS or DDLPS treated with NCT were accurately case matched with patients treated with upfront surgery, showing similar oncological outcomes in terms of OS and LRFS. However, the upfront group showed a better DMFS compared with NCT group. Our analysis showed that additional evaluations of differences in tumor features are necessary to better characterize the oncological prognosis. There are concerns that NCT in RPS resectable at diagnosis could delay surgical treatment with only minimal benefit. However, the potential of NCT to treat micrometastases is of particular importance in LMS and high grade DDLPS. To date, the role of NCT in RPS remains uncertain, and therefore data from STRASS 2 are awaited to better understand differentiation between patients who respond to NCT from others. These future results will select subgroup of patient who will truly benefit from NCT.