UPS, called malignant fibrous histiocytoma (MFH) previously, which was recognized as the most common STS in adults, accounting for 50% of diagnoses. However, the pathological diagnosis of UPS shown no evidence of true histiocytic differentiation, meaning it encompasses the morphologic manifestations of a variety of poorly differentiated tumors rather than being a single entity.[14] So the diagnosis and treatment of UPS are still highly challenging because of the confused pathological classification. MRI is commonly used as a non-invasive effective diagnostic tool for STS. Characteristics of UPS in the MRI are mostly presented as the irregular, lobular, or oval-shaped tumors with a large scale, sometimes necrosis and liquefaction can be found in the center of mass.
R1/R2 resection margins identified as predictors of poor outcomes. Herein, the R0 resection margin was an only independent favorable prognostic factor that was correlated with LRFS, DMFS, and OS. The resection margin was found to be the prognostic factor that was effectively correlated with the duration of survival. Peiper et al.[12] proposed that positive microscopic margins were correlated with an elevated local recurrence rate (RR = 4.8, P-value < 0.01). Özkurt et al.[23] studied 14 cases of confirmed bone UPS and it was found that the 5-year survival rate of patients with wide resection and border resection were 81.9% and 33.3% (P-value < 0.05), which reveals that surgical excision with wide margins and adjuvant chemotherapy provided adequate control of the disease and longer survival. Just like some article says that surgery striving for negative margins, with radiotherapy, is the treatment of choice.[10, 14, 22]
With respect to tumor size, winchester et al.[24] evaluated the prognostic factors of 319 UPS patients and revealed that tumor size (greater than 5 cm) and deep subcutaneous fat infiltration were significant factors that affect the local recurrence rate. In the existing study, compared with those with tumor sizes ≤ 5cm and > 5cm, the 5-year LR, DM and OS rates decreased by 11.3%, 18.4% and 16.7%, respectively. (Table 2) The extensive analysis of the data of more cases may contribute to better resolve the underlined problem.
The metastasis predominantly occurs in the lungs[10, 25] relative to regional lymph nodes[26]. Winchester et al.[13] suggested that the main factors that affect the distant metastasis of UPS were the tumor site, tumor size larger than 2cm, invasion beyond subcutaneous fat, and lymphovascular invasion. In the existing study, cox multivariate survival analysis found that > 60 years were at a higher risk of metastasis than the younger patients, and the chances of metastasis were lower in the R0 resection margin, as presented in Table 3. Furthermore, in multivariate analysis, the tumor site was an independent predictor correlated with DMFS, as depicted in Fig. 3F. Our findings of increased metastatic disease for the UPS in trunk is likely due to trunk tumors being more possibility and visible to hematogenous metastasis in the early stages of disease.
In the analysis of OS, the Cox multivariate survival analysis revealed that tumor site (P = 0.026), tumor size (P = 0.048), AJCC stage (P = 0.048), and resection quality (P = 0.001) were independent factors that affect postsurgical survival in UPS patients (all P-value < 0.05), as represented in Table 4. According to our cohort, for the patients having tumors of the trunk, the tumor size ≥ 5 cm and R1/R2, a more significant and effective approach should be adopted. Winchester et al.[24] found that age, immunosuppression, tumor size larger than 2 cm, and lymphovascular invasion were independent risk factors affecting overall prognosis. Simultaneously, the existing study revealed that patients with severe subcutaneous fatty infiltration of tumors had a bad prognosis rate. In the AJCC staging system, tumor size and tumor depth were significantly associated with the prognosis.
In the AJCC staging guidelines, tumor size is an important criteria for the judgment of soft tissue staging. Univariate analysis revealed that the size of the tumor was not considerably associated with LRFS and DMFS, but was closely associated with OS (P = 0.012), as shown in Fig. 2K. In multivariate analysis, tumor size (≥ 5cm) was not an independent prognostic factor affecting LRFS, DMFS, and OS (all P > 0.05). Furthermore, in 2009, Lehnhardt et al.[16] also shown that tumor size ≥ 5 cm was considerably associated with the OS, which was in line with Chen and Al-Agha[25, 27]. Peiper et al.[12] found that tumor size (RR = 6.0, P༜0.01) was a significant factor that affects the DFS of UPS patients. Larger tumors suggest a higher ability to divide and proliferate, a wider range of invasion, a higher degree of malignancy, and more complicated surgical methods, so the first visit to the professional sarcoma center is critical.
In the existing study, Univariate K-M analysis revealed that the local recurrence at diagnosis was a significant factor that affects the local recurrence rate, distant metastasis rate, and OS rate (P-value < 0.05). But in multivariate analysis, the presentation of tumor was not an independent prognostic factor affecting local recurrence rate, distant metastasis rate, and OS rate, with P values of 0.076, 0.091, and 0.162, respectively. Lehnhardt et al.[16] shown that a considerable variation was found between the group presenting with primary tumors (5-year survival: 84%, P-value < 0.05) and recurrent tumors (5-year survival: 62%, P-value < 0.05), which is correlated with our existing research work. The prognosis for patients with UPS of the extremities depends predominantly on adequate wide resection of the primary tumor, which is same to the idea that complete surgical resection was the most important UPS treatment strategy for UPS[17]. In short, the local recurrence at diagnosis and then R0 resection in the first therapy may play a crucial role in patient prognosis.
The value of adjuvant radiotherapy and chemotherapy in the diagnosis and treatment of soft tissue sarcoma has been mixed. Radiotherapy is mostly considered to be an effective mean to control local tumor recurrence, but in this study, it was not found that radiotherapy has any significance in the control of UPS. Trials from Gronchi suggested an overall survival benefit with five cycles of adjuvant full-dose epirubicin plus ifosfamide in localised high-risk soft-tissue sarcoma of the extremities or trunk wall[28, 29]. Adjuvant chemotherapy was associated with improved LRFS only in patients >/= 30 years[30]. Pazopanib and immune checkpoint inhibitors are a new attempt in UPS treatment[31–33]. Undifferentiated pleomorphic sarcoma is an immunologically active subtype of soft tissue sarcoma, which is particularly amenable to immune checkpoint inhibitors[33]. Immunohistochemical biomarkers significantly contribute to predicting the rate of recurrence, metastasis, and OS rate. A significant predictive index for evaluating the effect of VEGFR receptor inhibitors in the treatment of advanced soft tissue sarcoma, TP53 plays a significant role in the diagnosis and treatment of UPS[34].
As a retrospective study, although this study has given us a crucial hint, there are some shortcomings in the existing study. Firstly, the statistics on chemotherapy and radiotherapy are not sufficient due to the low incidence rate of the underlined disease, limited samples, and a large time span and the significant evaluation of the adjuvant therapy is also very difficult. Nevertheless, the accumulation and analysis of more comprehensive medical data for UPS can objectively reflect the characteristics and outcome of the disease that needs to be improved.