Comparison of two validated nomograms in patients with localized soft tissue sarcoma of the extremities and trunk wall
Tadashi Iwai1,2
, Kiyohito Takamatsu1, Sho Dohzono1, Hidetomi Terai2
Keywords: Nomograms; prognosis; localized soft tissue sarcoma (localized STS); chemotherapy
Submitted Sep 17, 2025. Accepted for publication Nov 12, 2025. Published online Dec 22, 2025.
doi: 10.21037/cco-25-115
Soft tissue sarcomas (STSs) are rare non-epithelial neoplasms originating in connective tissues. The development of evidence-based diagnostic and prognostic guidelines is complicated by limited data, given their rarity and heterogeneity (1). According to the World Health Organization classification, STSs comprise approximately 80 distinct histological subtypes, each with unique morphological, histological, immunohistochemical, and molecular characteristics. These tumors often display variable age distributions, tumor locations, and biological features (2). Patients with STS are at an elevated risk for distant metastases (DM) and mortality, particularly in the presence of large tumor size, deep location, or high histological grade (3). DM occur in 20–50% of patients with STS, leading to poor prognoses (4). Several different types of nomograms have been created to predict the survival of patients with STSs (5-7).
The Memorial Sloan Kettering Cancer Center (MSKCC) nomogram was created using historical United States cohort data, focusing on extremity STS (8). The PERSARC and Sarculator nomograms were developed from multicenter cohorts of European and Canadian patients (9,10). These nomograms can accurately predict local recurrence, overall survival (OS), and DM in patients with STSs of the extremities (11). The Sarculator and PERSARC nomograms represent the most commonly used tools for clinical decision-making regarding STSs. The variables included in Sarculator are age, tumor size, Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) grade, and histological type, whereas PERSARC uses age, sex, tumor size, histological type, tumor depth, and FNCLCC grade (only 2 and 3). In some randomized controlled trials, high-grade and deeply-seated tumors of >5 cm were defined as high-risk (12-14). The predicted 5-year OS for patients classified as high-risk under the Sarculator and PERSARC nomograms are ≤60% and ≤66%, respectively. However, few studies have compared these two nomograms directly. Therefore, this study aimed to evaluate these two risk-predicting models in a population-based cohort of patients with localized STSs of the extremities and trunk wall and to make a comparison with the risk classifications they returned (15). Authors also compared the two models with other risk classification systems commonly used to select patients for perioperative chemotherapy (15).
Adult patients (aged ≥18 years) who had been treated for primary STS of the extremities or trunk at Oslo University Hospital (from 1998 to 2017) were retrospectively extracted from a prospectively maintained institutional database (15). Data from each patient (n=664) were inserted into both the PERSARC and Sarculator predictive models (15). The patients were also classified into varying high-risk classifications according to the following alternative criteria: (I) deeply located tumors of ≥5 cm in size and FNCLCC grades of 3; (II) deeply located tumors of ≥5 cm in size and FNCLCC grades 2–3; (III) American Joint Committee on Cancer stage III tumors; and (IV) the standard used in the Scandinavian Sarcoma Group (SSG) study (15). In the phase II trials performed by the SSG, high-risk patients were selected based on tumor sizes of ≥8.0 cm with vascular infiltration, necrosis, and invasive growth patterns (16,17). The correlations between the 5-year OS or 5-year probabilities of DM predicted by the PERSARC and Sarculator models were calculated using Pearson’s correlation coefficient (r). Several separate Cox regression models were built, each including two binary variables: one defining the risk group (low vs. high), in accordance with each of the several classification criteria, and another indicating whether perioperative chemotherapy was administered. The interaction between the two binary variables was also included, to estimate the effect of perioperative chemotherapy within the high-risk group defined by each classification system.
Overall, 569 patients with FNCLCC grade 2 or 3 tumors had their 5-year predicted survival estimated using PERSARC and Sarculator, for which the comparison is shown in Table 1. The results of the analysis demonstrated a strong correlation (Pearson’s correlation coefficient, 0.84–0.91) between the risk classifications generated using the PERSARC and Sarculator models for the predicted 5-year OS and DM. Furthermore, patients classified as high-risk by only one of the models (58 patients: 32 PERSARC and 26 Sarculator, respectively) had similar outcomes to those who were classified as high-risk by both the models. Previous studies have shown an association between perioperative chemotherapy and improved outcomes in patients classified as high-risk by either model (18-21). Author’s findings are consistent with these results, as administration of chemotherapy was related to improved OS and disease-free survival in patients classified as high-risk by either model. Notably, the combined high-risk group showed a particularly favorable response to perioperative chemotherapy.
Table 1
| Results of this research | PERSARC | Sarculator |
|---|---|---|
| Median 5-year predicted OS | ||
| Total | 72.5% | 77.5% |
| High-risk group | 50.5% | 58.9% |
| Low-risk group | 82.4% | 84.7% |
| The number of patients | ||
| High-risk | 221 | 215 |
| Low-risk | 348 | 354 |
OS, overall survival.
Previous studies that evaluated the PERSARC and Sarculator models are presented in Table 2 (9-11,18-34). Unlike the data available for PERSARC, studies evaluating the Sarculator model encompass a broader range of STS locations, including the extremities, trunk, and retroperitoneum. To our knowledge, there have been no previously published studies directly comparing these two validated nomograms in patients with STS of the extremities and trunk; however, some oncologists have discussed differences between Sarculator and MSKCC prognostic nomograms (31,33).
Table 2
| Authors of the research publication about PERSARC and Sarculator | Year | Participants | Tumor location | Validation | Features | Reference |
|---|---|---|---|---|---|---|
| Van Praag et al. | 2017 | Aged >18 years patients high-grade (FNCLCC grade III only), primary STS | Extremities | External | First paper about PERSARC | (9) |
| Non-recurrent and non-metastatic | ||||||
| Treated with curative intent | ||||||
| Rueten-Budde et al. | 2018 | Aged >18 years patients high-grade, primary STS | Extremities | Internal | Time-varying effect of risk factors | (22) |
| Those without a treatment plan and treated with curative intent | ||||||
| Smolle et al. | 2019 | Aged >18 years patients high-grade, primary STS | Extremities | External | Flexible parametric competing risk regression models (FPCRRMs) | (23) |
| Non-recurrent and non-metastatic | ||||||
| Treated with curative intent | ||||||
| Acem et al. | 2020 | Aged >18 years patients high-grade, primary STS | Extremities | External | Age-related differences (18–39 vs. 40–69 vs. 70+ years) | (24) |
| Non-recurrent and non-metastatic | ||||||
| Treated with curative intent | ||||||
| Rueten-Budde et al. | 2021 | Aged >18 years patients high-grade, primary STS | Extremities | External | Time-varying effect of risk factors | (25) |
| Those without a treatment plan and treated with curative intent | ||||||
| Hagenmaier et al. | 2021 | Aged >18 years patients high-grade (FNCLCC grade III only), primary STS | Extremities | External | Individualized treatment decision making | (26) |
| Non-recurrent and non-metastatic | ||||||
| Treated with curative intent | ||||||
| Acem et al. | 2022 | Aged >18 years patients high-grade, primary STS | Extremities | External | The effect of perioperative chemotherapy | (18) |
| Non-recurrent and non-metastatic | ||||||
| Treated with curative intent | ||||||
| Kruiswijk et al. | 2023 | Aged >18 years patients high-grade, primary STS | Extremities | External | VALUE-PERSARC to reduce decisional conflict | (27) |
| Those without a treatment plan and treated with curative intent | ||||||
| Kruiswijk et al. | 2024 | Aged >18 years patients high-grade, primary STS | Extremities | External | VALUE-PERSARC to support treatment decisions | (28) |
| Those without a treatment plan and treated with curative intent | ||||||
| Callegaro et al. | 2016 | Aged >18 years patients primary STS | Extremities | External | First paper about Sarculator | (10) |
| Non-recurrent and non-metastatic | ||||||
| Operated with curative intent | ||||||
| Pasquali et al. | 2018 | Aged >18 years patients high-grade, primary STS | Extremity and trunk | External | High-risk soft tissue sarcomas treated with perioperative chemotherapy | (19) |
| Non-recurrent and non-metastatic | ||||||
| Treated with curative intent | ||||||
| Pasquali et al. | 2019 | Aged >18 years patients primary STS | Extremity and trunk | External | The impact of chemotherapy | (20) |
| Non-recurrent and non-metastatic | ||||||
| Operated with curative intent | ||||||
| Wong et al. | 2020 | Aged >18 years patients primary retroperitoneal sarcoma | Retroperitoneum | External | Retroperitoneal sarcoma. Difference between Sarculator and MSKCC prognostic nomograms. Asian patients | (29) |
| Non-recurrent and non-metastatic | ||||||
| Operated with curative intent | ||||||
| Lim et al. | 2021 | Aged >18 years patients | Retroperitoneum | External | Locally recurrent retroperitoneal sarcoma | (30) |
| Locally recurrent retroperitoneal sarcoma | ||||||
| Squires et al. | 2021 | Aged >18 years patients primary retroperitoneal sarcoma | Retroperitoneum | External | Retroperitoneal sarcoma. Difference between Sarculator and MSKCC prognostic nomograms | (31) |
| Non-recurrent and non-metastatic | ||||||
| Operated with curative intent | ||||||
| Pasquali et al. | 2022 | Aged >18 years patients high-grade, primary STS | Extremity and trunk | External | Neoadjuvant chemotherapy in high-risk soft tissue sarcomas | (21) |
| Non-recurrent and non-metastatic | ||||||
| Treated with curative intent | ||||||
| Voss et al. | 2022 | Aged >18 years patients primary STS | Extremity and trunk | External | US patients | (32) |
| Non-recurrent and non-metastatic | ||||||
| Operated with curative intent | ||||||
| Squires et al. | 2022 | Aged >18 years patients primary STS | Extremities | External | Difference between Sarculator and MSKCC prognostic nomograms | (33) |
| Non-recurrent and non-metastatic | ||||||
| Operated with curative intent | ||||||
| Zhao et al. | 2024 | Aged >18 years patients primary retroperitoneal sarcoma | Retroperitoneum | External | China patients | (34) |
| Non-recurrent and non-metastatic | ||||||
| Operated with curative intent | ||||||
| Newman-Hung et al. | 2025 | Aged >19 years patients primary STS of upper extremity | Upper extremity | External | Upper extremity soft tissue sarcoma | (11) |
| Non-recurrent and non-metastatic | ||||||
| Operated with curative intent |
FNCLCC, Fédération Nationale des Centres de Lutte Contre Le Cancer; FPCRRM, flexible parametric competing risk regression model; MSKCC, Memorial Sloan Kettering Cancer Center; STS, soft tissue sarcoma; US, United States.
Acem et al. clarified PERSARC’s decision curve analysis in a multicenter cohort of patients with high-grade STSs of the extremities (24). Their analysis demonstrated that PERSARC has significant clinical utility in determining the indication for perioperative chemotherapy, particularly when oncologists consider treating patients with predicted 5-year mortality rates of 6–45% (35). Pasquali et al. reported that the Sarculator model may also be effective in guiding treatment for high-risk STS patients undergoing perioperative chemotherapy (19). Furthermore, their findings indicated that high-risk patients with STSs of the extremities or trunk experienced improved outcomes when treated with adjuvant chemotherapy (20). Accordingly, it may be necessary to verify the decision curve analyses of both PERSARC and Sarculator in order to facilitate future comparisons within the context of perioperative chemotherapy.
This study has some limitations that should be considered. First, some patients were excluded because of missing data regarding tumor size and malignancy grade. Additionally, information related to specific variables, such as the high-risk criteria outlined in the SSG study, was unavailable for some included patients. Second, although patient data were prospectively collected, the study design was retrospective. Finally, over the lengthy study period, diagnostic and treatment protocols may have evolved, potentially impacting results.
This study concludes that patients with localized STSs of the extremities or trunk who are classified as high-risk by either the PERSARC or Sarculator model (or both) can be reliably considered as being at high-risk overall. Treatment via chemotherapy was associated with better outcomes in the resultant combined high-risk group. Therefore, authors recommend that such patients should be considered for perioperative chemotherapy. However, further prospective multicenter studies will be needed to clarify this in the future.
Acknowledgments
We are grateful for the invaluable support and various discussions with other members of the Department of Orthopedic Surgery.
Footnote
Provenance and Peer Review: This article was commissioned by the editorial office, Chinese Clinical Oncology. The article has undergone external peer review.
Peer Review File: Available at https://cco.amegroups.com/article/view/10.21037/cco-25-115/prf
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cco.amegroups.com/article/view/10.21037/cco-25-115/coif). The authors have no conflicts of interest to declare.
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