Moving the Needle in Undifferentiated Pleomorphic Sarcoma: Overview of Paradigm

In this episode of OncChats: Moving the Needle in Undifferentiated Pleomorphic Sarcoma, experts discuss the latest advancements in the multimodal treatment of undifferentiated pleomorphic sarcoma (UPS) of the extremities, including the role of immunotherapy, radiation, and surgery in improving patient outcomes.

Femino: Welcome to [a new series of] OncLive® OncChats, brought to you by the University of Southern California [USC] Sarcoma Program at the Keck School of Medicine and Norris Cancer Center. We’re thrilled to have you join us as we dive into the latest updates in the multispecialty treatment of undifferentiated pleomorphic sarcoma of the extremities.

In this [series], we’ll be exploring cutting-edge insights, innovative treatment strategies, and the collaborative approach that’s shaping the future of care for this complex and rare condition. Whether you’re a healthcare professional or simply interested in learning more, we hope you find this discussion informative and impactful.

My name is J. Dominic Femino, MD, and I will serve as your moderator today. I am an associate professor of clinical orthopedic surgery at the Keck School of Medicine of USC and the chief of the USC Musculoskeletal Oncology Center. Our expert panelists for today’s discussion are sarcoma specialists from medical oncology, radiation oncology, and orthopedic surgery—all of the USC Sarcoma Program. I will ask them to please introduce themselves.

Agulnik: Yes, thank you, and thanks for having me. I am a professor of clinical medicine in the Department of Medicine at Keck Medicine of USC, and I am a sarcoma specialist.

Zuckerman: I’m Dr Lee Zuckerman. I’m an associate professor of orthopedic surgery, specializing in orthopedic oncology with a focus on sarcoma with limb salvage.

Lim: Hi, nice to meet you. Thanks for having me. I’m an assistant professor of radiation oncology and a sarcoma specialist.

Femino: Thank you. I’d like to give you an overview of our topic today. Undifferentiated pleomorphic sarcoma, or UPS, is a type of high-grade malignant soft tissue tumor that’s characterized by significant cellular pleomorphism and the absence of a specific line of differentiation. Historically known as malignant fibrous histiocytoma, it is now classified as undifferentiated pleomorphic sarcoma. UPS typically presents as a rapidly growing mass, often located in the extremities or retroperitoneum. It is known for its aggressive behavior with a high propensity for local recurrence and distant metastases. The diagnosis of UPS is one of exclusion, made after ruling out other specific types of sarcomas through histologic assessment, immunohistochemistry, and molecular genetic studies.

Recently, immunotherapy, radiation therapy, and surgery are emerging as a growing and promising combination for the treatment of UPS of the extremities. Pembrolizumab [Keytruda], an anti–PD-1 immune checkpoint inhibitor, has shown efficacy in various malignancies, including soft tissue sarcomas. The Stand Up to Cancer Sarcoma Alliance for Research through Collaboration [SARC] 032 trial demonstrated that the addition of pembrolizumab to preoperative radiotherapy and surgery significantly improved disease-free survival in patients with stage III UPS of the extremities compared with radiation and surgery alone.

The multimodal approach addresses both local and systemic disease control, offering a comprehensive treatment strategy for stage III UPS of the extremities. The combination of pembrolizumab, radiotherapy, and surgery represents a significant advancement in the management of this aggressive sarcoma subtype.