Aug. 20, 2026
Referral to a sarcoma center is critical for the management of retroperitoneal sarcoma (RPS), a rare malignancy often presenting with an insidious course, large tumor burden and high risk of recurrence. Although its low incidence limits the evidence base, recent studies have informed how Mayo Clinic surgical oncologists approach RPS care, from diagnosis, and treatment sequencing to long-term surveillance.
Sanjay P. Bagaria, M.D. is a surgical oncologist and sarcoma specialist at Mayo Clinic in Jacksonville, Florida. His team performs 30 to 50 sarcoma operations annually, including both primary and recurrent resections.
"Local teams often try to manage retroperitoneal sarcoma on their own, but you have to be heavily resourced to do this operation," Dr. Bagaria says. "The best chance for a cure is the first operation. Once it comes back, it will continue to come back."
Establishing a retroperitoneal sarcoma diagnosis
Diagnosis relies on high-quality imaging and pathologic assessment after image-guided core needle biopsy. Imaging helps determine tumor extent, including involvement of nearby structures and organs, which informs treatment recommendations and surgical planning. Sarcoma-specialized pathologists at Mayo Clinic confirm diagnosis and subtype, typically receiving tissue samples upon patient referral.
Among more than 70 sarcoma subtypes, liposarcoma and leiomyosarcoma most commonly occur in the retroperitoneum. Histologic subtypes further predict tumor behavior, including recurrence risk and metastatic potential. Tumor grade also refines risk stratification, with high-grade sarcomas associated with increased metastatic risk and greater consideration of systemic therapy, while low-grade tumor management often focuses on local control.
"The best chance for a cure is the first operation. Once it comes back, it will continue to come back."
Regardless of sarcoma subtype, all patients undergo evaluation by surgical, radiation and medical oncologists at Mayo Clinic. This multidisciplinary approach informs treatment selection and sequencing, even if all modalities are not ultimately indicated.
Primary retroperitoneal sarcoma resection
Complete RPS resection, defined as removal of all gross disease (R0/R1), remains the frontline treatment. It offers the best chance for a cure in patients with nonmetastatic RPS deemed resectable on imaging.
Margin status, determined on final pathology, is an important prognostic factor. Positive margins are associated with a higher local recurrence risk and inform consideration of adjuvant therapies. Outcomes are most favorable after the initial resection, whereas recurrence is associated with a high likelihood of subsequent recurrence despite repeat surgery.
"Most patients do well after surgery, but you have to be careful about selecting the right candidate based on imaging and overall health," Dr. Bagaria says. "What organs do we need to remove? Can the patient tolerate this operation? Should we consider radiation before or take a more palliative approach?"
Achieving clear margins often requires the removal of 2 to 4 organs, leading to frequent collaboration across specialties at Mayo Clinic. Planning for intraoperative multidisciplinary involvement ensures the appropriate expertise is immediately available, rather than requiring emergent support. During leiomyosarcoma resections in particular, vascular surgeons play a key role in blood vessel reconstruction.
Many patients require nephrectomy for complete tumor resection, which has historically led to kidney function and dialysis concerns. However, a study in the Journal of Surgical Oncology found that, while associated with a decline in renal function, nephrectomy during RPS resection rarely results in dialysis. Similarly, findings published in the Annals of Surgical Oncology showed that distal pancreatectomy achieves high rates of complete resection without compromising survival, despite increased morbidity.
Evolving evidence in treatment sequencing for retroperitoneal sarcoma
Given the high risk of recurrence, treatment planning focuses on the role and sequencing of adjunctive therapies. Radiation and chemotherapy may reduce the need for repeat resection and help mitigate cumulative surgical morbidity. Emerging data suggest that select sarcoma subtypes may respond to immunotherapy, although studying novel approaches remains challenging in this extremely rare disease.
Neoadjuvant radiation for well-differentiated liposarcomas
Randomized data indicate that neoadjuvant radiation therapy may reduce recurrence risk in well-differentiated liposarcoma, the most common subtype of liposarcoma. Radiation aims to sterilize microscopic disease at the resection margins, which surgeons cannot reliably assess intraoperatively given the tumor's size and infiltrative nature.
Neoadjuvant chemotherapy for high-grade sarcomas
Mayo Clinic is participating in an international trial evaluating the role of neoadjuvant chemotherapy in high-grade liposarcoma and leiomyosarcoma. Given that proliferative tumors generally respond better to chemotherapy, upfront systemic therapy may reduce tumor burden and treat early metastatic disease, potentially improving resectability and systemic control.
Management of recurrent retroperitoneal sarcoma
Most recurrences happen within 2 to 5 years after primary resection. Research shows that histology, tumor size and grade, presence of multifocal disease and extent of primary resection all influence outcomes, with histology also dictating the location of disease recurrence.
Patients should undergo CT scans of the chest, abdomen and pelvis about every three months for two years, followed by every six months for an additional three years in the absence of recurrence. After these five years of close surveillance, Mayo Clinic oncologists recommend continued lifelong imaging with annual CT scans to facilitate early detection.
"It's really important for patients to have a plan afterward and be cognizant of the fact that imaging is critical," Dr. Bagaria says. "The hardest part about this disease is that patients don't feel it. Without imaging, we have no clue."
Role of radiation and systemic therapy in recurrent sarcomas
Oncologists use radiation and chemotherapy selectively in recurrent RPS. Radiation provides local control for retroperitoneal recurrence, while systemic therapy primarily treats metastatic disease, such as pulmonary metastases.
Advancing sarcoma research at Mayo Clinic
Mayo Clinic oncologists participate in the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), a global collaboration advancing research through a shared database and integrated basic and translational efforts. Current studies focus on tumor biology at recurrence, multivisceral resection outcomes and the incidence of benign retroperitoneal tumors.
Additional research at Mayo Clinic includes investigations of sarcoma molecular drivers and imaging strategies. The institution has also established a sarcoma biobank of tissue and blood samples from consented patients.
"We are now reaching an inflection point where the dataset is getting large enough to tackle big questions with it," Dr. Bagaria says.
For more information
Kim DB, et al. Effect of nephrectomy for retroperitoneal sarcoma on post-operative renal function. Journal of Surgical Oncology. 2017;117:425.
Bagaria SP, et al. Morbidity and outcomes after distal pancreatectomy for primary retroperitoneal sarcoma: An analysis by the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group. Annals of Surgical Oncology. 2021;28:6882.
Bagaria SP, et. al. Distal pancreatectomy for primary retroperitoneal sarcoma — Clinical implications and future directions. Annals of Surgical Oncology. 2021;11:6890.
Refer a patient to Mayo Clinic.