This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Primary Soft Tissue Sarcomas of the Extremities: A Nationwide Retrospective Cohort Study of Histology-Specific Outcomes and Prognostic Factors
by
, ,
Marko Novak
1,*, 
Andraž Perhavec
1,2,
Barbka Novak Supe
3,
Olga Blatnik
4,
Marija Skoblar Vidmar
2,5,
Mojca Unk
2,6,
Sonja Kramer
1,
Saša Marušič
7 and
Manuel Ramanović
5,* 1
Division of Surgical Oncology, Institute of Oncology Ljubljana, Zaloška cesta 2, SI-1000 Ljubljana, Slovenia
2
Faculty of Medicine, University of Ljubljana, Kongresni trg 12, SI-1000 Ljubljana, Slovenia
3
Division of Anesthesiology and Intensive Care, Institute of Oncology Ljubljana, Zaloška cesta 2, SI-1000 Ljubljana, Slovenia
4
Department of Pathology, Institute of Oncology Ljubljana, Zaloška cesta 2, SI-1000 Ljubljana, Slovenia
5
Department for Radiotherapy, Institute of Oncology Ljubljana, Zaloška cesta 2, SI-1000 Ljubljana, Slovenia
6
Division of Medical Oncology, Institute of Oncology Ljubljana, Zaloška cesta 2, SI-1000 Ljubljana, Slovenia
7
Department for Radiology, Institute of Oncology Ljubljana, Zaloška cesta 2, SI-1000 Ljubljana, Slovenia
*
Authors to whom correspondence should be addressed.
Cancers 2026, 18(15), 2515; https://doi.org/10.3390/cancers18152515
Submission received: 6 July 2026
/
Revised: 29 July 2026
/
Accepted: 4 August 2026
/
Published: 5 August 2026
(This article belongs to the Section Cancer Survivorship and Quality of Life)
Simple Summary
Extremity soft tissue sarcomas (ESTSs) are rare, biologically heterogeneous mesenchymal malignancies that are best managed in specialized sarcoma referral centers. This nationwide retrospective cohort study analyzed 315 adult patients with primary localized ESTS treated at the only sarcoma referral center in the Republic of Slovenia. Patients were stratified into a high-risk group (HRG) and a low-risk group (LRG) based on histological subtype and metastatic potential. In the HRG, the 5-year overall survival was 69.8%, and the 5-year distant metastasis-free survival was 66.8%. High-risk tumors showed good limb preservation and local control but substantial distant failure, with pronounced histology-specific patterns: rhabdomyosarcoma and undifferentiated pleomorphic sarcoma had the highest metastatic rates, whereas myxofibrosarcoma carried the greatest local recurrence risk. Preoperative radiotherapy showed a borderline association with higher wound morbidity, while a microscopically negative margin of at least 1 mm significantly lowered the risk of local recurrence. Low-risk tumors had excellent outcomes with surgery alone, supporting treatment and follow-up de-escalation in this subgroup.
Abstract
Background/Objectives: The aim of this study was to determine the oncologic outcomes for adult patients with primary extremity soft tissue sarcoma (ESTS) treated at the sarcoma referral center in the Republic of Slovenia. Methods: Patients from a prospectively maintained institutional database treated between January 2009 and December 2023 were retrospectively analyzed. The cohort was stratified into a high-risk group (HRG) and a low-risk group (LRG). Survival analyses focused on the HRG. Multivariable Cox models were constructed for local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS), and predictors of major wound complications were evaluated using multivariable logistic regression. Results: Among 315 included patients, 242 (76.8%) were in the HRG. In this group the median age was 61.5 years, 82.6% of tumors were in the lower extremity, and median tumor size was 9.0 cm. The most common histological subtype was undifferentiated pleomorphic sarcoma (28.5%). Clear margins were achieved in 86.8%, major postoperative complications occurred in 19.0%, and 60.7% of patients underwent radiotherapy. Local recurrence developed in 11.2%, regional recurrence in 5.0%, and distant metastasis in 32.6%. The corresponding 5-year overall survival, disease-specific survival, LRFS, and DMFS were 69.8%, 73.7%, 87.9%, and 66.8% in the HRG, respectively. In the LRG, only one local recurrence occurred and the 5-year LRFS was 100.0%. Preoperative radiotherapy showed a borderline association with major wound complications in the HRG (OR 2.70, 95% CI 1.00–7.28, p = 0.050). Tumor grade and size remained independent predictors of distant metastases, whereas margin status was not significantly associated with LRFS or DMFS. The primary amputation rate in the whole series was 2.9%. Conclusion: Treatment of primary ESTS patients in a specialized national referral cancer center achieved good overall survival (69.8%), a high limb-salvage rate (97.1%), and good local control, affirming that routine primary amputation is rarely needed. Outcomes in high-risk histologies remained driven mainly by distant metastases and showed clear histology-specific differences, whereas low-risk histologies had excellent outcomes with surgery alone. Preoperative radiotherapy was associated with a higher risk of major wound complications.
Keywords:
extremity; soft tissue sarcoma; histology; surgical margins; radiotherapy; survival; referral center
