Margin Status Likely Not a Factor in STS Recurrence

Outcomes of local recurrence or distant recurrence of extremity soft tissue sarcoma (ESTS) failed to differ significantly between patients with a microscopically positive margin (R1) or a microscopically negative margin (R0) following primary limb-sparing surgery and postoperative radiotherapy, according to a new analysis published in Radiology Case Reports of patients treated with the methodologies between 2004 and 2014.¹

These results were seen after the investigators retrospectively examined the medical records of individuals with localized ESTS who had been followed for at least 5 years or until disease recurrence, whichever occurred first. Seventeen of the patients had undergone R0 resection (mean [SD] age, 49.2 [21.9] years; 41.2% female patients) and 35 had undergone R1 resection (mean age, 51.9 [17.3] year; 48.6% female patients); primary end points were local recurrence and distance recurrence. Diagnosis was identified with International Classification of Diseases, Ninth Revision and Tenth Revision, Clinical Modification codes.

“The standard treatment of primary localized ESTS includes limb-sparing surgical resection with negative margins alone or combined with perioperative radiotherapy and/or chemotherapy to prevent local recurrence with maintaining optimal function,” the study authors wrote. “The optimal resection margin to prevent local recurrence still remains controversial in clinical practice.”

Tumor size was larger than 5 cm in 90.4% of all patients, 91.4% of the patients who underwent R1 resection, and 88.2% who underwent R0 resection. The most common location was a lower extremity, at 86.5%, 945.3%, and 70.6%, respectively. According to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system, most patients overall (71.2%) had grade 2 or 3 disease compared with 68.5% of the R1 group who had grade 1 or 2 disease and 78.2% of the R0 group with grade 2 or 3.

In this analysis, FNCLCC grade was linked to a risk of local disease recurrence for grade 3 vs grade 1 disease | Image Credit: SeventyFour - stock.adobe.com

Local recurrence was seen in 19.2% of the total patient population and distant recurrence, in 40.4%. In the R1 cohort, these totals were 11.4% and 40%, and in the R0 cohort, 35.3% and 41.2%. Liposarcoma in 25% of all patients was the most common tumor histopathology, of which 2 cases were low-grade liposarcoma.

When univariate and multivariate survival analyses were carried out for associations between local recurrence and resection margin, FNCLCC grade was linked to risk of local recurrence for grade 3 vs grade 1 disease (HR, 10.95; 95% CI, 1.29-92.63; P = .028); however, there was not a significant difference between R1 and R0 (HR, 0.39; 95% CI, 0.11-1.40; P = .151).

The 2 analyses also were carried out for associations between distant recurrence and resection margin. Again there was a significant association between FNCLCC grade and recurrence of grade 3 vs grade 1 disease (HR; 9.48; 95% CI, 2.08-43.24; P = .004), but not a difference in risk for local recurrence between the R1 and R0 cohorts (HR, 1.07; 95% CI, 0.43-2.66; P = .882). However, having a tumor in a lower extremity vs an extremity (adjusted HR [aHR], 0.23; 95% CI, 0.07-0.70; P = .010) and FNCLCC grade 3 vs grade 1 (aHR, 12.53; 95% CI, 2.67-58.88; P = .001) had significant associations with distant recurrence.

The study authors note that their findings “challenge the traditional emphasis on R0 resection,” because between the 2 margins they evaluated, R0 and R1, neither had a significantly different risk for local or distant recurrence of localized ESTS. Also that these findings echo previous studies, which concluded that a negative margin was not an independent factor for survival.^2-5

Their recommendation for future progress in this space is for larger studies to explore outcomes among a greater diversity of sarcoma types and larger patient groups, “to better highlight the path forward and confirm the results in broader clinical contexts.”

References

1. Chen CC, Wu YY, Kao JT, Chang CH, Huang SC, Shih HN. Impact of resection margin on outcome in soft‑tissue sarcomas of the extremities treated with limb‑sparing surgery and postoperative radiotherapy. Radiol Case Rep. 2024 Apr 20;19(7):2756-2759. doi:10.1016/j.radcr.2024.03.054

2. Kim YB, Shin KH, Seong J, et al. Clinical significance of margin status in postoperative radio therapy for extremity and truncal soft-tissue sarcoma. Int J Radiat Oncol Biol Phys. 2008;70(1):139-144. doi:10.1016/j.ijrobp.2007.05.067

3. Harati K, Daigeler A, Lange K, et al. Somatic leiomyosarcoma of the soft tissues: a single-institutional analysis of factors predictive of survival in 164 patients. World J Surg. 2017;41(6):1534-1541. doi:10.1007/s00268-017-3899-5.

4. Harati K, Kirchhoff P, Behr B, et al. Soft tissue sarcomas of the distal lower extremities: a single-institutional analysis of the prognostic significance of surgical margins in 120 patients. Oncol Rep. 2016;36(2):863-70. doi:10.3892/or.2016.4862. Epub 2016 Jun 8.

5. Olson CR, Suarez-Kelly LP, Ethun CG, et al. Resection status does not impact recurrence in well-differentiated liposarcoma of the extremity. Am Surg. 2021;87(11):1752-1759. doi:10.1177/00031348211054536