RLS refers to a malignant sarcoma of mesenchymal tissue that originates in the smooth muscle tissue of the retroperitoneum. It is frequently found in retroperitoneal blood vessels, spermatic cords, and remnant embryonic tissues. RLS is relatively rare, accounting for approximately 20% of retroperitoneal soft tissue sarcomas, second in frequency after liposarcoma1.22. Mankin et al. studied 1,256 patients with high-grade malignant soft tissue tumors from the FOXPRO database. They found that leiomyosarcoma accounted for less than 5% of cases but had the highest mortality rate (up to 50%)23. Meanwhile, these patients died an average of 3 years after diagnosis23. Clinical outcomes for patients with leiomyosarcoma continue to be disappointing, and survival prediction results and associated predictors based on small reporting samples have been inconsistent.23,24,25,26. Patients with RLS have a poor 5-year survival rate and a poor prognosis, mainly due to the specific anatomical location of the retroperitoneum. The retroperitoneal space extends from the diaphragm to the extraperitoneal space of the pelvis. Tumors tend to grow insidiously, with inconspicuous clinical manifestations, resulting in the rapid formation of giant tumors that are difficult to remove in their entirety and prone to recurrence and distant metastasis, making diagnosis and treatment difficult . Therefore, accurate prediction of the survival rate of patients with RLS is essential for effective clinical management and medical decision-making.
In practice, it is difficult to predict a patient’s OS using a single prognostic factor; however, a combination of several independent prognostic factors can improve prediction accuracy. Traditional staging systems, such as AJCC’s TNM staging, divide patients into four stages based on the all-or-nothing principle of variable classification. However, they are no longer the most efficient way to categorize RLS patients into different prognostic groups.27. A new predictive model is therefore needed. The nomogram, which uses a simple graphical representation to provide an individualized prediction of survival outcome, has become an essential part of modern medical decision-making.28.29. The nomogram incorporates several prognostic variables, including continuous variables, and describes factors and outcomes associated with more complex prognostic relationships30. Additionally, compared to the SEER stage, the nomogram has a more robust predictive ability. Previous research has used nomograms for retroperitoneal sarcoma and leiomyosarcoma in non-retroperitoneal parts to guide patient management1,12,31. Patients with RLS, on the other hand, do not have a nomogram to follow. The poor prognosis and uniqueness of disease localization in patients with RLS necessitate the creation of a nomogram to estimate their OS.
In this study, 305 RLS patients were recruited from the SEER database. A nomogram was developed to predict OS of RLS patients at 1, 3 and 5 years. The nomogram showed good discrimination in the training and validation sets, and the predicted survival rate aligned with the actual survival rate. The DCA analysis also revealed that the nomogram has great clinical utility as a practical predictive tool. Additionally, the developed risk stratification system complemented the nomogram, allowing researchers to identify RLS patients at high risk of mortality and provide early warning for better management. RLS is difficult to eradicate, so recurrence and distant metastases complicate diagnosis and treatment. Accordingly, accurate prediction of the survival rate of patients with RLS appears to be essential for effective clinical management and medical decision-making.
In univariate Cox regression analysis, surgery, AJCC T stage, radiation therapy, chemotherapy, tumor size, tumor stage, and tumor grade were related to the OS of patients with the RLS (p4. Recent surgical advances have increased the 5-year survival rate for retroperitoneal sarcoma from 47.0% in 1998-2005 to 58.4% in 2002-2012 and the 10-year survival rate from 27.0 to 45.3 %32.33. However, most RLS patients had giant tumors at diagnosis, associated with a poor prognosis. According to An et al.patients with retroperitoneal tumors less than 10 cm had a 5-year survival rate of 78%, while those with tumors greater than 10 cm had a 5-year survival rate of 38%34. In addition, tumors readily adhere to surrounding blood vessels and organs, making it difficult to separate them from adjacent tissues, and intra-abdominal or distant metastases may occur due to the complex structure of the retroperitoneal space. In particular, tumors adjacent to the inferior vena cava frequently result in tumors that cannot be resected at R0. Complete resection, namely R0 and R1 resection, is the currently accepted goal of surgical resection35. Although studies have not proven a difference in survival between R0 and R1 resection, R2 resection has a poor prognosis35. Additionally, systemic metastases are the most common cause of post-resection failure in RLS. However, the overall survival of patients with RLS with distant metastases is significantly longer than that of patients with other sarcomas. Consequently, surgery for distant metastases is always necessary to reduce complications and improve the quality of life of patients, especially for those with low- and mid-grade tumors.35.36. Patients with high-grade tumors with early intra-abdominal recurrence, more frequent systemic metastases, and aggressive biological features may not benefit from extensive surgery. They may require other adjuvants or systemic treatment strategies.
The role of adjuvant radiation therapy and chemotherapy in the treatment of RLS is still being studied, but its unified recommendation is still under debate. Compared to surgery alone, sponsors prefer adjuvant radiotherapy and chemotherapy to improve local symptom control37.38. At the same time, opponents dispute the benefits and claim that they did not increase the rate of OS but rather brought side effects13,39,40,41. There is currently no level 1 evidence to support adjuvant radiotherapy and chemotherapy for the treatment of primary RLS. Therefore, it is also difficult to extrapolate the absolute benefits of radiation therapy and chemotherapy from historical data, as various factors influence treatment outcomes. Appropriate patient selection for radiation therapy and perioperative chemotherapy is still the subject of research. In the meantime, multicenter randomized trials are urgently needed to determine the best clinical strategy to improve local control in patients with RLS. High-grade tumors are a risk factor for systemic metastases and poor prognosis in patients with RLS. According to Lewis et al.median OS for patients with high-grade retroperitoneal sarcomas was 33 months, while for patients with low-grade sarcoma was 149 months9. Our research results also revealed a better prognosis for patients with low-grade tumors than for those with high-grade tumors. In addition, patients with distant metastases have a lower survival rate than patients with local or regional metastases. This trend illustrates the importance of early diagnosis of patients with RLS.
Despite the excellent predictive performance of the nomogram and the risk stratification system, this study has unavoidable limitations. First, it is based on retrospective research data, which may have selection bias. Second, some information is missing from the SEER database, such as comorbidities, severity of other organ metastases, surgical margin status, vascular invasion, and postoperative treatment. Finally, there are no other independent large-scale datasets to verify the nomogram and increase its external applicability. Going forward, there will be a need to continuously enrich the information in the SEER database, increase external verification of larger sample datasets, and constantly modify and improve the predictive value of the nomogram template.