RPSs consist a heterogeneous group of malignant tumors with very low incidence; and very little is known about their biological behavior and no specific causative compounds have been identified . Macroscopically clear margin is one of the important prognostic factors in RPS’s patients . However, securing a clear margin is quite challenging due to the tumor location. Malinka et.al, macroscopically clear margin was reported in 84% (51, total 61) . The other study, Hogg et. al, it was notified in 88.9% (80, total 90) . Our finding that all patients had a macroscopically clear margin is thus superior to conventional studies.
RPS patients were used all treatment method currently available, including surgical approaches, chemotherapy or target therapy, and Radiotherapy (RT). RT were treatment options we used to deal with patients. RT is usually used to control local recurrence or improve the surgical margin; however, it does not impact on distant metastasis or overall survival (OS) . Haas et al. reported that preoperative RT was associated with better local control in unadjusted univariate analysis among their three cohorts, but not after accounting for imbalances in prognostic variables . According to Turner et al., however, compared with resection alone, additional neoadjuvant RT was associated with multivisceral resection (87.5% vs. 66.1%, p = 0.02) and negative margins (72.5% vs. 30.6%, p < 0.001) . Roeder at al. also reported that combination of neoadjuvant Intensity-Modulated RT, surgery and intraoperative RT is feasible with acceptable toxicity and yields good results in terms of local control and overall survival in patients with high-risk retroperitoneal sarcomas (Estimated 3- and 5-year local control rates of 72%, estimated 3- and 5-year overall survival rates of 74%) . This method showed superior effectiveness at achieving a surgical margin compared to neoadjuvant RT alone (R0 in 6 patients [22%] and R1 in 22 patients [74%]). The combination method showed a rate with a macroscopically clear margin like ours (100%), but including several side effects and limitations. First, the combination method had more reported postoperative side effects. Nine patients (30%) had more than grade 3 postoperative side effects, 4 patients (15%) needed reoperations, and 2 patients died during the prolonged postoperative period. These rates are higher than ours: e.g., 2 patients (20%) underwent reoperation and none died postoperatively. Another limitation of the combination method is that it should only be administered to inpatients in a hospital with appropriate facilities for intensity-modulated and intraoperative RT. Thus, toward gaining a clear margin, a multidisciplinary surgical approach is a good option for treating patients with RPS.
The efficacy of chemotherapy or immunotherapy for RPS is limited. The role of adjuvant/neo-adjuvant systemic therapy is not well defined due to the rarity of the disease and paucity of randomized controlled data. The role of palliative systemic therapy is better established, however mostly through extrapolation of data from results on sarcomas of other locations . Currently, anthracycline-based therapy remains standard first-line treatment . But it induces response in just 15–35% of patients, irrespective of the histological subtype . Thus, complete surgical resection is considered a RPS treatment milestone. Several agents have recently emerged as second-line treatment options, including gemcitabine/docetaxel, high-dose ifosfamide monotherapy, trabectedin, pazopanib, and eribulin. According to PALETTE study, pazopanib significantly increased progression-free survival compared with placebo in metastatic soft-tissue sarcoma, progressing despite previous standard chemotherapy . According to Dickson at. al, the selective CDK4 and CDK6 inhibitor palbociclib inhibits growth and induces senescence in liposarcoma cell lines and there was favor of progression free survival nevertheless, there was no significant difference in progression free survival between patients who had or had not received prior systemic therapy (P = .70) . Depending on histology type, there are several randomized controlled trial about neo-adjuvant or systemic chemotherapy. The EORTC-1809-STBSG– STRASS 2 study, intended to be an international randomized multicenter, open-label phase 3 trial, with stratification by specific tumor histology and including only high-grade dedifferentiated liposarcoma and LMS . The study aim is to evaluate whether neoadjuvant chemotherapy reduces the development of distant metastasis in these well-defined histologic entities . Thus, we’re waiting for this result to know the efficacy of neoadjuvant chemotherapy.
Without doubt, complete surgical resection and securing a clear surgical margin is the most effective therapeutic method. However, as described above, surgical treatment is challenging for most surgeons because of the RPS location. To overcome this obstacle, neoadjuvant and/or adjuvant therapy was developed and the Trans-Atlantic RPS Working Group was established in 2013. This group insisted on the importance of a presurgical imaging study and multidisciplinary discussion for patients with RPS. They also noted that complete resection should be accomplished despite large adjacent organ resection . Thus, an interdisciplinary collaboration among teams of surgeons, anesthesiologists, and nurses is necessary to achieve complete RPS resection.
Several side effects were noted following a multidisciplinary approach to RPS resection. Though there were no deaths among our sample, reoperation was needed in 2 patients. One patient underwent wound revision and local flap coverage for wound necrosis 17 days postoperative. The other patient’s complications were more severe (i.e., bowel perforation, wound necrosis), requiring exploratory laparotomy with ileostomy and wound debridement with flap coverage almost one month postoperatively. Compared to pelvic exenteration for recurrent or advanced cervical cancer, one of the challenging surgeries in gynecological cancer, our multidisciplinary two-step approach made higher wound complication than pelvic exenteration. (20% vs. 4.3%) . Long hospitalizations (range, 9–69 days) and large estimated blood loss volumes (range, 300–20000 mL) were also found, despite 60% of patients receiving preoperative arterial embolization. Patients in all 10 cases also required transfused packed red blood cells, fresh frozen plasma, and/or platelets. Despite these severe complications, the multidisciplinary approach achieved a clear margin rate of 100%. Thus, it is a superior method compared to the conventional single-incision approach. According to Bizzarri, N. et al, minimal invasive surgery could be applied challenging surgery keeping same survival outcomes compared to conventional surgery . This two-step approach also has chance to be changed minimal invasive surgery using robotic system or other advanced surgical method. That could be decreased complication rates in RPS patients applied two-step approach. Further, this complication rate is lower than that found in combination RT and surgery, which achieved a similar clear surgical margin rate. In addition, using pre-operative vascular assessment (Tinelli’s Score) could be new options to achieve surgical margin and reduce blood loss [20, 23]. We had been discussed several factors influenced surgical status before surgery, and we did arterial embolization if cancerous mass located or invaded in major vessel. But we didn’t use of this evaluation system at pre-operation. So, we checked up our data retrospectively by using Tinelli’s Score. Among 10 cases, 6 cases (60%) were included in Grade 1 or 2 and 2 cases were in grade 3. One case was each in grade 4 and 5 and major vessel allograft was done in case noted grade 5 vessel invasion. Among 4 cases at upper grade 3, arterial embolization was conducted in 3 cases. So, checking of invasion grade in vessel, doing arterial embolization before surgery, and co-operation with vascular surgical team could make not only achieve for complete resection of tumor but also reduce blood loss and surgical complications in next surgery. Finally, applying enhanced recovery after surgery (ERAS) or a modified ERAS method, may reduce both hospitalizations and postoperative complications.
These findings support the need for a multicenter or randomized control study to test the effectiveness of the multidisciplinary approach, despite the Trans-Atlantic RPS Working Group’s current guideline that the multidisciplinary approach is superior for complete tumor resection.