Locally Recurrent Soft Tissue Sarcoma Growth Rate Predicts Survival

Patients who underwent resection of locally recurrent extremity or truncal soft tissue sarcoma (STS) and were younger or had a high local recurrence (LR) growth rate had a higher incidence of disease-specific death (DSD), according to a recent study published in JAMA Network Open.¹

Surgical resection is the standard course of treatment for adults with localized STS. Almost 20% of patients with the disease experience LR by 10 years after surgery, even with preoperative radiation.^1,2 LR rates have remained relatively stable, between 6% and 10%, at experienced high-volume centers, and recurrence brings significant management challenges. As such, researchers aimed to obtain more granular prognostic information to efficaciously guide treatment decisions in the locally recurrent setting.

The study included patients 16 years and older who underwent curative-intent R0 resection or R1 resection of a localized STS in the US between July 1, 1982, and December 31, 2021. There were 3211 patients with a median age of 55 years; of them, 46% were female. Furthermore, 253 patients experienced LR without prior or synchronous recurrence and underwent LR resection. Of the 253 patients included in the LR cohort, the median age was 64 years, and of them, 45% were female. The median follow-up for all 3211 patients was 6.1 years from the time of primary resection.

In the LR cohort, 60 patients had low-grade primary tumors, and of them, 12 had high-grade recurrences. The high-grade recurrences included extraskeletal chondrosarcomas, fibrosarcoma, leiomyosarcoma, myxoid or round cell liposarcoma, and myxofibrosarcoma. Additionally, 45 of the remaining patients with low-grade primary tumors had low-grade recurrences, and the other 3 had unknown recurrence grades.

Six of 193 with high-grade primary tumors had low-grade recurrences; these consisted of extraskeletal chondrosarcoma and myxofibrosarcoma. Of the remaining 187 patients, 183 had high-grade recurrences and 4 had an unknown recurrence grade.

After the median follow-up of 5.3 years for patients who underwent LR resection, 83 died of disease. The factors associated with a higher incidence of DSD included age at the time of LR resection (HR, 0.99; 95% CI, 0.97-1.00; P = .02), grade of LR (HR, 2.51; 95% CI, 1.29-4.88; P = .007), R1 and R2 LR resection margins vs R0 LR resection margins (HR, 1.91; 95% CI, 1.24-2.96; P = .003), LR size (HR, 1.06; 95% CI, 1.04-1.09; P < .001), disease-free interval (HR, 0.98; 95% CI, 0.97-0.99; P = .004), multifocal LR (HR, 2.40; 95% CI, 1.47-3.91; P < .001), and average LR growth rate (HR, 1.14; 95% CI, 1.09-1.19; P < .001).

Patients with LR growth rates less than or equal to 0.68 cm/mo and who had low-grade recurrences had lower rates of DSD compared with other patients. A second incidence of LR was associated with R0 vs R1 margin status, but the LR growth rate itself was not. Overall, patients with rapid LR growth rates, which were higher than 0.68 cm/mo, were at significant risk of DSD; these patients were also more likely to have aggressive tumors.

This study was limited as it was a retrospective single-institution study and is thus subject to selection bias. Additionally, because the data used date back to 1982, some histological examination findings have been reclassified.

“Average LR growth rate along with LR histological grade can be used as a tool to select patients with LR who would potentially benefit from systemic therapy in addition to surgical treatment of their LR,” the study authors concluded. “In particular, high-grade recurrences with average growth rates higher than 0.68 cm/mo should be considered for systemic therapy before further procedures.”

References

1. Li GZ, Seier K, Qin L, et al. Growth rate and outcomes in locally recurrent extremity and truncal soft tissue sarcoma. JAMA Netw Open. 2024;7(9):e2431530. doi:10.1001/jamanetworkopen.2024.31530

2. Nikitas J, Kendal JK, Savjani RR, et al. Five-day preoperative radiation therapy for patients with high-risk soft tissue sarcoma: a nonrandomized clinical trial. JAMA Netw Open. 2025;8(12):e2550195. doi:10.1001/jamanetworkopen.2025.50195