Dr Bowman on Distinctions Between Disease Characteristics and Treatment Response in ccRCC vs Non-ccRCC

“Most [RCC cases are] what’s referred to as clear cell, which [comprises approximately] 70% to 80% of kidney cancer cases. Most of [the research] you’re going to read about or hear about is [conducted in] that clear cell subtype… Unfortunately,a lot of our therapies that we’ve used for…non–clear cell [RCC], are borrowed from clear cell, but [these patients do not] respond in the same way.”

I. Alex Bowman, MD, a medical oncologist at Banner Health, discussed the differences in disease presentation and treatment outcomes among patients with clear cell renal cell carcinoma (ccRCC) vs non-ccRCC.

RCC is broadly categorized into 2 major subtypes: ccRCC and non-ccRCC, Bowman began. ccRCC represents approximately 70% to 80% of RCC cases and has been the primary focus of therapeutic research and clinical trials due to its prevalence, he said. Consequently, most of the standard treatments and advancements in kidney cancer have been directed toward this subtype, he explained.

In contrast, non-ccRCC encompasses a heterogeneous group of less common RCC histologies. These include papillary RCC (one of the most prevalent among non–clear cell subtypes), chromophobe RCC, translocation-associated RCC, and rare forms, such as collecting duct carcinoma and medullary carcinoma, Bowman reported. There is also an “unclassified” category, which includes tumors that do not fit neatly into existing histologic classifications, he noted. These subtypes have distinct biological behaviors and may not respond well to therapies developed for ccRCC, according to Bowman.

Historically, treatment strategies for non-ccRCC have been extrapolated from prior data in ccRCC, despite the underlying differences in tumor biology between these subtypes, Bowman continued. The standard of care for RCC typically consists of TKIs, which are primarily anti-angiogenic agents, he stated. These oral therapies target VEGF pathways to inhibit angiogenesis, a hallmark of RCC due to its highly vascular nature, he added. The rationale for the use of TKIs in both RCC subtypes stems from the success observed with these agents in ccRCC, where tumor growth and survival are closely linked to blood vessel proliferation, he emphasized.

However, clinical outcomes with TKIs in non-ccRCC have been modest, Bowman said. Objective response rates with TKI monotherapy in this setting generally range from approximately 20% to 30%, underscoring their limited efficacy when applied to biologically distinct tumors, he reported. As such, ongoing efforts are focused on developing and validating therapies that are more specifically tailored to the non-ccRCC population, acknowledging the need for a more individualized approach based on histologic subtype and molecular profile, Bowman concluded.