Introduction
Soft tissue sarcomas (STSs) are rare malignant tumours that represent approximately 1% of all adult malignancies [
1]. Approximately 15–20% of all STS arise in the retroperitoneum, with a 5-year overall survival (OS) rate in the range of 39–70% [
2,
3]. Retroperitoneal sarcomas (RPSs) often progress asymptomatically and are thus only detected incidentally when the substantially enlarged tumour compresses the surrounding organs [
4]. Patients presenting with back pain or abdominal distention already have a large tumour with close proximity to critical structures, such as major vessels. With respect to the treatment of RPS, the use of adjuvant radiotherapy and chemotherapy varies widely among institutions because of the lack of evidence supporting their benefit [
5]. Thus, surgical resection remains the cornerstone of therapy and the only potentially curative therapy for patients with RPS [
5].
Guidelines on the surgical management of RPS are still lacking and remain controversial, owing to its low incidence [
6]. For example, the criteria for unresectability remains undefined, and the indication and eligibility for surgical resection vary by medical centre. Patients with residual macroscopic disease are often referred to specialised centres because the appropriateness of en-bloc resection for organs adherent to the tumour needs to be determined intraoperatively. The trans-Atlantic RPS working group recently updated the consensus on management of primary RPS in adults [
7]. The update established criteria for technical non-resectability as involvement of the superior mesenteric artery, aorta, coeliac trunk, and/or portal vein; bone involvement; growth into the spinal canal; invasive extension of retrohepatic inferior vena cava leiomyosarcoma into the right atrium; and infiltration of multiple major organs and/or major vessels [
7]. However, vascular reconstructions, which enable radical resection of RPSs in patients with advanced disease, have been successfully performed in many studies [
8,
9]. The inferior vena cava (IVC) and iliac veins (IVs) were the most common vessels involved in RPS resection [
9]. Aggressive resection with involved major blood vessels such as the IVC and IVs may improve R0 resection rates; however, the benefit of converting R1 to R0 resections is unclear, and vascular resection might be associated with an increased risk of postoperative complications [
10]. Therefore, to determine the relative benefit and disadvantages of an aggressive surgical approach with vascular resection in patients with RPS, we conducted a systematic review to assess the safety and long-term survival results of vascular resection. We also conducted a meta-analysis to compare the clinical outcomes between vascular resection and tumour resection alone in patients with RPS.
Discussion
In this study, an aggressive surgical approach with vascular resection achieved acceptable rates of postoperative morbidity and mortality. The results of the meta-analysis demonstrated that the rates of postoperative morbidity and mortality were not significantly different between the extended resection group and tumour resection alone group. In addition, vascular resection achieved similar local recurrence or OS. For this systematic review and meta-analysis, we obtained all evidence so far published on the safety and long-term outcomes of vascular resection in RPS. To our best knowledge, our study is the first meta-analysis to comprehensively assess this issue.
Involvement of major vessels can be an indirect sign of the aggressiveness of RPSs [
38], for which a multidisciplinary collaboration, including vascular surgeons, should be established [
10,
34]. The decision for vascular reconstruction should be based on comprehensive evaluation of distant metastasis, tumour grade, organs involved, and the general condition of the patient. Furthermore, the feasibility and efficacy of vascular resection for RPS are yet to be determined. A single centre cohort study and a retrospective review of patients with intra-abdominal and RPSs showed that oncovascular surgery enables the radical resection required for good local control of RPSs and is associated with an acceptable level of complications peri-operatively and during follow-up [
34]. The review of literature identified 37 articles with 110 patients, however, most of which were case reports. Besides, they did not perform a meta-analysis on the safety and long-term outcomes of vascular resection in RPS.
In this study, the results of included studies showed that most of the patients received total gross excision (R0/R1). We divided the studies into primary iliocaval leiomyosarcoma group and RPSs with vascular resection group. Postoperative early mortality rates were 0–20% and 0–8% in primary iliocaval leiomyosarcoma group and RPSs with vascular resection group, respectively. Major complication rates were 6–54% and 7%-54% in primary iliocaval leiomyosarcoma group and RPSs receiving vascular resection group, respectively. The 5-year OS rates were 33–78% and 50–69% in the primary iliocaval leiomyosarcoma group and RPSs with vascular resection group. The overall early postoperative mortality rate, major complication rate, and 5-year OS rate were similar between the primary iliocaval leiomyosarcoma group and RPSs with vascular resection group. The short-term and long-term outcomes were equivalent with the patients received extended resection including adjacent organs observed in some previous studies [
39‐
41]. Thus, resection and reconstruction of the major vessels for en-bloc resection of RPS can be performed feasibly and safely.
Our data support the hypothesis that resection of major vessels should not be considered a contraindication to surgery in RPSs because the short-term and long-term clinical outcomes were similar between vascular resection group and tumour resection alone group. These results might be explained by the following reasons. Criteria mentioned in the included studies for vascular resection were encasement, involvement or vascular occlusion. Although the histological subtype, FNCLCC grade, tumour status were similar between vascular resection group and tumour resection alone group in propensity-matched analyses, status of involvement of major vessels were different between the two groups, which can be regarded as a more aggressive behavior [
38]. Of note, resection of major vessels might improve surgical resection margins as compared with partial excision or no surgery. Our previous studies have indicated that surgical resection margins are correlated with long-term survival, and OS was higher in R0 resection than in R1 resection and in R1 resection than in R2 resection [
42]. Thus, adjacent major vessels with evidence of direct invasion should be resected to avoid R2 resection.
With respect to the techniques for major vascular resection and reconstruction for RPS excision, different surgical strategies are needed for intraoperative situations. The most common major vessel involved in RPS is the IVC [
43]. The methods of reconstruction of the IVC include blood vessel transplantation, repair, and ligation. Retroperitoneal tumours involving the IVC are usually divided into three segments: the infrarenal segment, the suprarenal infrahepatic segment, and the retrohepatic segment. Based on the results of included studies in this systematic review, most of the postoperative early mortality occurred in the patients with retroperitoneal tumours involving the retrohepatic segment of IVC. The main causes of death were hepatic failure and pulmonary embolism [
17,
19,
20]. Primary sarcomas originating from the aorta are rare. Most of the arterial reconstructions in RPS patients were caused by secondary involvement, or encasement of the aorta wall or iliac arteries [
43]. In cases of arterial resection, primary anastomosis is rarely feasible due to the length of the resection. Arterial reconstructions are usually performed using artificial vascular graft in an anatomic position. To improve the short-term results of surgical treatment, for RPSs with abundant blood supply from preoperative imaging examinations, especially those fed from the lumbar artery, middle sacral artery or internal iliac artery, tumour supply vessel embolisation was introduced in clinical practice. Studies have shown that early transarterial embolisation of the tumour supply vessels could significantly reduce intraoperative blood loss, operation time, and postoperative complication rate [
44].
Major vessel injuries during oncological surgery can lead to serious bleeding, requiring massive transfusion [
45]. To ensure the successful surgical resection of the advanced tumours, a multidisciplinary team, including vascular surgeons, is an essential component of the preoperative planning and co-operation with the postoperative management [
46]. Locally advanced tumours involving adjacent major vessels require cooperation of the oncovascular surgeon as a multidisciplinary team member. Oncovascular surgery can be defined as cancer resection with concurrent ligation, or reconstruction of a major vascular structure [
47]. Studies have continually supported the feasibility of surgical intervention with durable oncologic outcomes in various tumour pathologies with major vascular involvement, including pancreatic cancer, renal cell carcinoma, and cholangiocarcinoma [
48]. Patients with RPS invading or intimately surrounding major vessels at the time of diagnosis have traditionally been regarded as a limitation for complete surgical resection and might result in an increased surgical morbidity. Advancements in vascular surgery techniques have resulted in the possibility of radical treatment being offered to RPS patients with major vessel involved which previously could not be operated on [
34].
The strengths of our review include its comprehensive search and methodological robustness. We searched all available literature to exclude studies with overlapping cohorts and analysed large-scale studies. However, the present study also had some limitations. First, this review is based on non-confirmatory studies and secondary outcomes, and the histological subtype, FNCLCC grade, tumour status, and adjuvant therapy varied among the studies. Relevant data of some characteristics were lacking, possibly introducing bias. Second, there were an insufficient number of studies and patients included for meta-analysis, and subsequent subgroup analysis. Thus, the recommendations for these comparisons have a relatively weak power. A long-term prospective study in these areas is warranted. Finally, all trials included in the meta-analysis used an open-label design, which might introduce bias. However, assessment of the methodological quality of the included studies indicated that most studies had a low or medium risk of bias.
In conclusion, en-bloc resection with involved major vessels enables radical resection required for good local control of retroperitoneal sarcomas. Aggressive resection with involved major vessels can be performed safely with an acceptable level of complications and equivalent DFS and OS to that without vascular involvement. In patients with RPS, major blood vessels invasion would no longer be considered as technical non-resectability.
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