Priming the tumor microenvironment with pembrolizumab and radiotherapy for durable cures in high-risk localized undifferentiated pleomorphic sarcoma and pleomorphic/dedifferentiated liposarcoma.

SU2C-SARC032 establishes addition of perioperative pembrolizumab as a new treatment option for high-risk localized extremity soft tissue sarcoma (STS). For patients with stage III undifferentiated pleomorphic sarcoma or dedifferentiated/pleomorphic liposarcoma, addition of neoadjuvant and adjuvant pembrolizumab to preoperative radiation therapy (RT) and surgery improved 2-year disease-free survival by 15% compared with RT and surgery alone. This commentary highlights key insights from the trial: (1) the cooperative activity between pembrolizumab and RT, (2) the need for biomarker-driven patient selection, and (3) the potential for circulating tumor DNA to guide adjuvant treatment decisions. Recognizing the heterogeneity of STS, we emphasize the importance of future trials incorporating comprehensive correlative analyses to identify predictors of response and to optimize treatment strategies. Furthermore, we highlight the need for equitable access to advanced diagnostics and personalized treatment approaches so that the benefits of SU2C-SARC032 can be realized for patients with STS throughout the world.