Surgery Often Sufficient for Pediatric Soft Tissue Sarcomas, New Research Suggests
A new study indicates that surgical removal is generally enough to treat low-risk non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) in children, and that high-risk patients with completely removed tumors may not always require additional radiation therapy.
A comprehensive report, published in Pediatric Blood & Cancer on November 11, 2025, analyzed data from two large clinical trials to refine risk assessment and treatment strategies for these rare childhood cancers. Researchers found that, for many young patients, a less aggressive approach can be highly effective.
Understanding Non-Rhabdomyosarcoma Soft Tissue Sarcoma
NRSTS encompasses a diverse group of cancers affecting the body’s soft tissues – muscles, fat, blood vessels, nerves, and other connective tissues. The current standard of care, according to the study, centers around surgical resection. “Primary tumor resection with wide margins is the mainstay of NRSTS treatment, and is safe without further adjuvant treatment for low-risk disease,” stated a senior researcher involved in the study.
However, the role of additional treatments like chemotherapy and radiation remains a complex question, particularly for patients with more advanced disease. In cases where tumors cannot be fully removed surgically, neoadjuvant radiotherapy and/or chemotherapy can be employed to shrink the tumor and potentially enable subsequent resection, though the chances of a complete cure remain lower.
The CWS-96 and CWS-2002P Trials: A Deep Dive
The new findings are based on data from the CWS-96 and CWS-2002P trials, both designed to minimize the use of chemotherapy and radiotherapy through a risk-based treatment approach. A total of 1,249 patients with localized NRSTS were enrolled across the two trials – 483 in CWS-96 and 445 in CWS-2002P.
Patients were categorized based on risk factors. The CWS-96 trial utilized the Intergroup Rhabdomyosarcoma Study (IRS) group, histology, and grade for risk stratification. The CWS-2002P trial incorporated IRS group, lymph node status, tumor histology, and tumor size.
Treatment protocols varied based on risk level. Low-risk patients in both trials underwent surgical resection alone. Standard-risk patients received hyperfractionated accelerated radiotherapy (HART) at a dose of 44.8 Gy. High-risk patients in CWS-96 received six cycles of chemotherapy (vincristine, actinomycin-D, ifosfamide, and adriamycin – VAIA), while those in CWS-2002P received an intensified adriamycin regimen (VAIA-III, with 320 mg/m2 adriamycin) alongside delayed resection and/or radiotherapy. Some patients in CWS-2002P also received maintenance treatment with cyclophosphamide and vinblastine.
Improved Survival in CWS-2002P, But Anthracycline Dose Doesn’t Appear Key
Overall, patients in the CWS-2002P trial demonstrated a superior 5-year overall survival (OS) rate of 81% compared to 73% in the CWS-96 trial (P = 0.024). Researchers attribute this improvement, in part, to the inclusion of a greater proportion of entities like fibromyxoid sarcoma, which tend to have a lower potential for metastasis. Improvements in surgical techniques, imaging, and surveillance over time also likely contributed to the better outcomes.
Interestingly, the study found that the higher dose of anthracycline used in the CWS-2002P trial did not translate into improved survival rates.
Surgery Alone Highly Effective for Low-Risk Patients
The data strongly supports surgical resection as a sufficient treatment for low-risk NRSTS. Across both trials, low-risk patients who underwent surgery alone achieved a 5-year event-free survival (EFS) rate of 82% and an overall survival rate of 93%. This reinforces the idea that more aggressive treatments can often be avoided in these cases.
Unanswered Questions Remain Regarding Standard-Risk Disease
While radiotherapy was recommended for standard-risk patients in the CWS-2002P trial, clinicians frequently combined radiotherapy with chemotherapy, mirroring the approach used in the CWS-96 trial. As a result, researchers noted that it’s difficult to draw definitive conclusions about the optimal treatment strategy for this patient group.
Implications for Future Treatment Strategies
The study’s authors emphasize the importance of entity-specific clinical trial data for high-risk patients. When clinical trials are unavailable, they suggest a regimen of ifosfamide and doxorubicin, with a preference for reduced anthracycline doses in postoperative chemotherapy cycles, while omitting vincristine and actinomycin-D.
Furthermore, the finding that high-risk patients who undergo complete surgical resection (R0 resection) have a comparable prognosis to those who receive radiation after incomplete resection warrants further investigation. This suggests that achieving complete surgical removal may be a critical factor in improving outcomes, even in high-risk cases. .
References:
Heinz AT, Schönstein A, Koscielniak E, et al. Children and Adolescents With Localised Non-Rhabdomyosarcoma Soft Tissue Sarcoma: Results of the CWS-96 and CWS-2002P Prospective Trials With Reclassification of the Trial Data Incorporating the Recent Soft Tissue Sarcoma Registry. Pediatr Blood Cancer. Published online November 11, 2025. doi:10.1002/pbc.32159
Sparber-Sauer M, Ferrari A, Kosztyla D, et al. Long-term results from the multicentric European randomized phase 3 trial CWS/RMS-96 for localized high-risk soft tissue sarcoma in children, adolescents, and young adults. Pediatr Blood Cancer. 2022;69(9):e29691. doi:10.1002/pbc.29691
Koscielniak E, Blank B, Vokuhl C, et al. Long-term clinical outcome and prognostic factors of children and adolescents with localized rhabdomyosarcoma treated on the CWS-2002P protocol. Cancers (Basel). 2022;14(4):899. doi:10.3390/cancers14040899
