Radiation Therapy for Extremity Soft Tissue Sarcoma: In the Absence of a Clear Survival Benefit, Why Do We Give It?

Abstract

Due in large part to several sentinel contributions from the National Cancer Institute (NCI), the local management of extremity soft tissue sarcoma (ESTS) today typically results in excellent local control and very good limb function. In 1982, Rosenberg et al. showed equivalent 5-year survival rates for limb-sparing surgery (LSS) plus radiation therapy (RT) compared with amputation and an acceptable 15 % local recurrence (LR) rate for LSS plus RT. Following publication of this landmark trial, amputation rates appropriately plummeted. In 1998, Yang et al. reported results from a second NCI randomized trial that compared LSS plus RT with LSS alone and showed a clear significant local control benefit for RT for both highand low-grade ESTS. A randomized trial from Memorial Sloan-Kettering Cancer Center (MSKCC) in 1996 affirmed the local control advantage for RT (in the form of brachytherapy) in addition to LSS. Several nonrandomized series have reported LR rates\15 % for LSS alone without RT, but others have shown unacceptably high rates of LR with this approach. Given the conflicting results for surgery alone from nonrandomized reports, and the clear local control advantage with RT demonstrated by randomized trials, the standard of care for most high-grade ESTS is LSS plus RT. The main and undisputed benefit of adjuvant RT is improved local control, and local control rates for LSS plus RT are\15 % in modern series. However, the effect of RT on overall survival is ambiguous. The aforementioned randomized trials as well as the 20-year update of the NCI trial reported by Beane et al. that accompanies this editorial, fail to show a statistically significant difference in survival with the addition of RT. Since RT has its own treatment-related toxicities and is not associated with an improvement in overall survival, should we stop using RT in conjunction with LSS? The report by Beane et al. shows a trend toward higher 20-year survival rates for LSS plus RT compared with LSS alone (71 vs. 64 %, p = 0.22). As the authors point out, this study was only powered to detect a 21 % survival difference. On the other hand, a review of 6,960 patients with high-grade ESTS showed a statistically significant improved 3-year survival rate of 73 % for LSS plus RT compared with 63 % for LSS alone (p 0.001). It is quite possible that adjuvant RT for ESTS does in fact confer a statistically significant survival advantage, but due to small patient numbers in most series, such a benefit has not been reliably demonstrated. This was the case for breast cancer. Most individual trials failed to show a significant association between local control and survival. Nevertheless, patients with breast cancer were still treated with RT because of the local control advantage it conferred. Ultimately, a meta-analysis of 42,000 patients demonstrated a clear link between improved local control and superior survival. Another potential benefit of adjuvant RT relates to the consequences of a LR. The development of a LR necessitates further surgery or surgeries and possible RT, and it may result in greater long-term toxicity than if RT had been delivered after the first definitive resection. In addition, development of a LR can have a devastating psychological impact. On the other hand, delivery of adjuvant RT is associated with toxicities, the severity of which must be factored into Society of Surgical Oncology 2014