Dr Croll on Understanding Tumor Response to Systemic Therapy in RCC

“A lot of the work that we’re doing at Fox Chase is looking at the pathologic assessment of these [tumor specimens] after [patients] come out of surgery. We look at the local environment [of the tumor] to see what that immunotherapy or systemic therapy has done at a tumor level.”

Benjamin Croll, MD, a urologic oncology fellow at Fox Chase Cancer Center, discussed future research directions regarding improving the understanding of patient response to systemic therapy in renal cell carcinoma (RCC).

A major unmet need in RCC is improving the ability to accurately assess how tumors respond to systemic therapy, particularly in the era of immunotherapy, Croll began. Traditional imaging techniques have proven to be unreliable in many cases, as radiographic changes do not always reflect the true biologic effects of treatment, he continued. Unlike certain malignancies in which tumor shrinkage on imaging closely correlates with therapeutic efficacy, responses to immunotherapy can be much more difficult to interpret in RCC, he noted.

One reason for this challenge is that immunotherapies often induce complex changes within the tumor microenvironment, Croll explained. Rather than causing an immediate reduction in tumor size, these treatments can lead to infiltration by immune cells and other treatment-related changes that occupy the same physical space as the original tumor, he continued. As a result, imaging studies may show little or no reduction in tumor volume, even when a meaningful antitumor response has occurred, he said. This phenomenon limits the ability of conventional radiographic assessments to accurately predict treatment benefit and complicates clinical decision-making, he said.

To address this issue, investigators at Fox Chase Cancer Center are focusing on a more detailed pathologic evaluation of tumors following surgical resection, Croll said. By examining tissue specimens after surgery, researchers can directly assess the effects of systemic therapy on the tumor and its surrounding microenvironment, he noted. This approach provides a more comprehensive understanding of how treatment has altered the composition of the tumor, including the presence of immune infiltrates and other markers of therapeutic response, he added.

The goal of this work is to better characterize the biologic changes induced by immunotherapy and to develop more accurate methods for evaluating treatment effectiveness, Croll said. Such insights could ultimately improve patient selection, guide therapeutic decision-making, and help identify biomarkers associated with favorable outcomes, he said. By moving beyond imaging alone and incorporating pathologic analyses, researchers hope to gain a clearer understanding of treatment response and further refine the use of systemic therapies in cancer care, he concluded.