Resection of retroperitoneal DDLPS with adequate margins is often challenging because of its anatomical characteristics and the presence of important surrounding organs, which result in frequent recurrence. It is crucial that both the tumor and any potentially infiltrated adjacent structures are removed en bloc in a single session [13,14,15]. Bonvalot et al. reported that patients diagnosed with retroperitoneal sarcoma who underwent surgery between 2000 and 2009 over a nine-year period had a high long-term survival rate and a low rate of local recurrence [16]. In particular, favorable outcomes were observed for small or low-grade tumors.

The findings of the present study suggest that a third surgery significantly increases OS and PFS in patients with non-aggressive (SUVmax values: < 4) DDLPS. Patients who undergo complete (macroscopic) or compartmental resection (R0 or R1) of the primary tumor exhibit an improved prognosis, with a 5-year OS rate of 54–70%; however, local recurrence is observed in 41–50% of these cases within 5 years of surgery [17, 18]. The prognosis of patients with retroperitoneal sarcoma with SUVmax values of ≥ 4 was poorer than that of the patients with SUVmax values of < 4. A comparison of the 84 patients who underwent FDG-PET and were evaluated using SUVmax values revealed that the prognosis was significantly favorable in the low-malignancy group (Supplemental Fig. 1). This finding is supported by the fact that recurrence occurred within two years in most patients (92%) who experienced a second recurrence. Wakamatsu et al. examined the characteristics of low and high SUVmax groups in DDLPS [8]. In the low SUVmax group, the majority of tumors were classified as FNCLCC grade II, whereas 45.5% (15 of 33) of tumors in the high SUVmax group were classified as FNCLCC grade III. Because tumor grade is a significant prognostic factor, they hypothesized that the shorter prognosis observed in patients with a high SUVmax could be attributed to the higher incidence of grade III tumors. However, the prognosis of patients with a high SUVmax and grade II tumors is poorer than that of patients with a low SUVmax and grade II tumors. These findings suggest that SUVmax has potential clinical utility in refining the prognostic assessment of patients with DDLPS, particularly those with grade II tumors.

Local recurrence remains common even after optimal resection of retroperitoneal liposarcomas, and is the most frequent cause of death. Adjuvant radiation therapy (RT) and chemotherapy may be valuable treatment options for improving local control, particularly in patients with margins of involvement or high-grade tumors. The EORTC Surgery With or Without Radiotherapy for Retroperitoneal Sarcoma (STRASS) trial evaluated the role of preoperative radiotherapy in the treatment of retroperitoneal sarcomas, including DDLPS [19]. In total, 266 patients with retroperitoneal sarcoma, including those with dedifferentiated liposarcoma, were enrolled. These patients were randomized into two groups: one receiving preoperative radiotherapy followed by surgery and the other undergoing surgery alone. The results of the STRASS trial indicated that neoadjuvant radiotherapy did not significantly improve local control or overall survival in patients compared with surgery alone. Specifically, the benefits of radiotherapy appear to be limited for dedifferentiated liposarcomas. However, the trial findings suggested that individual patient and tumor characteristics might influence the effectiveness of radiotherapy, highlighting the need for personalized treatment approaches. In addition, several small trials have shown marked variations in the RT dose, fractionation, concurrent use of chemotherapy, delivery method (external beam or brachytherapy), timing (preoperative, intraoperative, or postoperative), and energy carriers (photons, electrons, protons, or carbon ions) [14].

Chemotherapeutic drugs, such as anthracyclines (doxorubicin) and the alkylating agent ifosfamide, have been used in many cases. Eribulin, trabectedin, and pazopanib were established as effective second- or third-line options for treating resistant disease [20,21,22]. Several reports have suggested an efficacy rate of 10–20% [23,24,25,26]. The STRASS-2 trial is an ongoing Phase III clinical study aimed at determining whether preoperative (neoadjuvant) chemotherapy can improve outcomes in patients with high-risk retroperitoneal sarcoma, specifically focusing on subtypes such as DDLPS and leiomyosarcoma [27]. The trial is being conducted in multiple countries, including Europe, the USA, Canada, Japan, and Australia, with a target enrollment of 200 patients. The goal of this study was to assess whether adding chemotherapy before surgery enhances disease-free survival compared to surgery alone. Recently, clinical trials on MDM2 inhibitors have indicated that they may be effective treatment option [28]. Evaluation of the effects of RT and chemotherapy in 50 patients with second recurrence revealed no significant differences. However, performing RT and chemotherapy in addition to surgery tended to improve the prognosis, indicating that it may aid in decision-making based on the situation.

The rate of major postoperative complications in major series was 15–20% [29, 30]. Among 1007 patients with primary retroperitoneal sarcoma, a serious postoperative complication (Clavien-Dindo ≥ 3) was observed in 16.4% of patients, 10.5% required reoperation, and 1.8% died within 30 d of surgery in a previous study [29]. In the present study, the rate of Grade II complications increased with each additional surgery; however, no Grade III or higher complications were observed. It can be inferred that the favorable outcomes were likely attributable to meticulous postoperative systemic management and effective coordination with physicians and nurses from other departments. Intravenous patient-controlled analgesia or hydration therapy during fasting has been used to manage postoperative pain in almost all patients. Factors contributing to the increase in Grade II complications include securing central venous access and blood transfusions.

The present study had some limitations that should be acknowledged. First, because it was conducted at a single institution, the generalizability of the findings may be limited. Differences in patient demographics, treatment protocols, and diagnostic practices at other centers may affect the applicability of our results to a broader population. Second, being a retrospective study, it is inherently subject to selection and information biases. Data collection relied on existing medical records, which may not have captured all relevant variables or may have included inaccuracies. Third, potential confounding variables such as variations in treatment adherence, patient comorbidities, and other external factors were not accounted for in the analysis. These factors could influence the study outcomes and introduce additional sources of bias.