Neoadjuvant Systemic Therapy Induces Fair Response Rate for High-Risk Retroperitoneal Sarcoma

Responses to neoadjuvant systemic therapy in patients with high-risk retroperitoneal sarcoma (RPS) led to clinical benefit in roughly three-quarters of patients and varied according to disease histology and the number of treatment cycles, according to a retrospective study whose results were published in Cancer.

These data suggest that disease progression on neoadjuvant therapy could potentially be used to predict patient survival post-surgery, while subtype-specific regimens still need further validation in this area.

“In this series of patients with RPS treated with neoadjuvant systemic therapy over a 10-year time span, partial responses were possible in almost a quarter of the cases, whereas most tumors demonstrated stable disease,” wrote the investigators who were led by William W. Tseng, MD. “Disease progression on systemic therapy was clearly associated with worse outcomes. The current analysis provides data to begin defining the role of neoadjuvant systemic therapy in RPS and help to optimize the design of an upcoming prospective trial.”

According to the RECIST 1.1 criteria, none of the patients analyzed (n = 158) demonstrated a complete response, but 37 patients (23%) experienced a partial response (PR), 88 (56%) had stable disease (SD), and 33 (21%) demonstrated progressive disease (PD). Regardless of the analyzed tumor response, all patients underwent complete resection.

Of the patients who demonstrated progressive disease before surgery, their overall survival was significantly worse than other patients (P = .005). In regard to clinical outcomes, more positive outcomes were seen with specific regimens intended to treat grade 3 dedifferentiated liposarcoma and leiomyosarcoma.

“Our findings show that neoadjuvant systemic therapy can result in a radiographic tumor response in almost a quarter of patients with RPS,” the investigators wrote. “The majority of patients (79%), in fact, can experience a clinical benefit (PR + SD) with this approach. Therefore, our results suggest that in clinical practice, neoadjuvant systemic therapy may be helpful in the management of RPS.”

Overall, patients with a median of 3 cycles of neoadjuvant therapy (interquartile range, 2-4 cycles) administered for high-risk RPS were analyzed. While the regimens were mostly anthracycline based, the investigators emphasized that there was significant heterogeneity in chosen therapy.

Eligible patients were treated for high-risk RPS at 13 different referral centers between 2008 and 2018. The investigators compared overall survival and “cumulative incidences of local recurrence and distant metastasis” with the goal of determining predictors of radiologic tumor responses and to assess clinical outcomes.

The investigators recognized the retrospective design and “relatively low numbers of events, particularly for histologic subtype analyses,” as limiting factors of the data. Moreover, they explained that bias was present because there were a limited number of referral centers who treated the targeted cohort.

“In daily practice, the decision making to initiate and continue with neoadjuvant systemic therapy should be multidisciplinary with continual input from the surgical oncologist to assess for the risk of unresectability with PD,” wrote the researchers.

Reference:

Tseng WW, Barretta F, Conti L, et al. Defining the role of neoadjuvant systemic therapy in high-risk retroperitoneal sarcoma: a multi-institutional study from the transatlantic Australasian retroperitoneal sarcoma working group. Cancer. Published November 18, 2020. doi: 10.1002/cncr.33323.