Neil Mendhiratta, MD, MS, discusses the treatment landscape for patients with kidney cancer during Kidney Cancer Awareness Month.
Although patients with early-stage kidney cancer often experience a favorable prognosis, there are remaining unmet needs for patients with high-risk disease and those who are at an increased risk of disease recurrence, underscoring the need for further advances in the adjuvant space and effective biomarkers to better personalize therapy, according to Neil Mendhiratta, MD, MS.
“Kidney cancer is one of the most common urologic malignancies that we treat as urologists and as medical oncologists,” Mendhiratta said in an interview with OncLive®. “[Although] there’s excellent prognosis for [patients with] early-stage disease, there are still patients who require early intervention. It’s important to get the word out there about advances in treatment options and to [ensure] that patients follow up with their providers and understand those options so that they can benefit from early intervention in these situations.”
Mendhiratta is an assistant professor of urology at the GW School of Medicine & Health Sciences in Washington DC.
In honor of Kidney Cancer Awareness Month, which occurs annually in March, Mendhiratta joined us for an interview to discuss data updates in renal cell carcinoma (RCC), including those shared during the
Mendhiratta: As a urologic oncologist, I’m focused primarily on the localized space. Some of the recent trials that we’re paying attention to and are causing a shift in the paradigm of how we treat kidney cancer are those that focus on treatment in the adjuvant space. [Although] outcomes for [patients with] early-stage, localized disease with surgery are in general excellent, there are a number of patients who have either high-risk features or locally advanced disease who are at a high likelihood of recurrence. Therefore, understanding whether there are strategies that can help reduce that risk of recurrence can be beneficial.
[Data from the phase 3] KEYNOTE-564 trial [NCT03142334] showing that the addition of adjuvant pembrolizumab [Keytruda] can improve outcomes with respect to not just disease-free survival [DFS] but also overall survival [OS] certainly have been practice-changing for many providers.1 We saw recently at ASCO GU [with] the [phase 3] LITESPARK-022 trial [NCT05239728] that there’s a benefit with adding belzutifan [Welireg], which targets HIF-2α, to pembrolizumab, in terms of further reducing the risk of recurrence and prolonging DFS.2 We’ll [have to] wait to see whether that translates to an OS benefit, but many of us remain optimistic.
There’s [also] been a lot of work in terms of sequencing therapies in the advanced and metastatic spaces, including the addition of novel agents like belzutifan. Certainly, we’re all interested to see data from [the phase 3] LITESPARK-011 trial [NCT04586231] as well.
It’s not a one-size-fits-all [approach] in terms of treatments for patients with localized disease as well as [those with] advanced disease. Some of the ways where we are trying to individualize treatments strategies have to do with identifying patients who are at risk of developing more aggressive RCC vs those who may have more indolent disease. [One] risk factor [is] a family history that can indicate a hereditary syndrome. We know that recognition of those hereditary syndromes can make a difference in terms of outcomes for these patients.
[We also want to] make sure that we know whether these patients are at risk of [developing] aggressive tumors, such as those with HLRCC [hereditary leiomyomatosis and renal cell cancer] or SDH [succinate dehydrogenase] deficiencies. [This] can really make a difference in treating early-stage, localized disease. We’re still looking to identify good biomarkers for patients who are going to benefit from adjuvant treatments, certain IO [immuno-oncology] combinations, or IO/TKI [tyrosine kinase inhibitor] combinations. This remains one of the challenges in kidney cancer treatment, but certainly [it’s something] we’re looking forward to understanding better so we can more specifically tailor our treatment strategies to each patient.
[First], the treatment of [patients with] non–clear cell RCC, certainly in the advanced space, accounts for approximately 20% to 30% of RCC cases and unfortunately has been understudied in terms of treatment strategies for advanced disease. That remains a challenge for many patients and for the field. In the localized space, we struggle sometimes with overtreatment for low-risk and indolent tumors as well as benign entities.
Some of the ways that we’re going to help reduce that risk of over treatment will be with new diagnostic modalities, which will hopefully help us differentiate clear cell RCC from benign entities that can sometimes look similar in terms of radiographic appearance. Recent data [have also] shown us the utility of Tc-sestamibi SPECT/CT, which has excellent sensitivity and specificity for renal oncocytoma, so we can better identify patients who may not benefit from aggressive early interventions.
I’m excited to see a couple of things be developed in the future. One is biomarker development for identification of patients who benefit from certain treatment strategies, such as immunotherapies and targeted therapies. The other is better understanding the role of cytoreductive nephrectomy, which, as a urologic oncologist, is relevant to my practice. We’ve seen that there may not always be a benefit to upfront cytoreductive nephrectomy, but with the novel therapies that are now available, including IO therapies and TKI combination therapies, questions remain. We’re seeing that the paradigm has shifted from upfront cytoreductive nephrectomy to potentially delayed cytoreductive nephrectomy and [we need to know] whether that benefits patients.
One of the trials that’s exploring [this question] is the [phase 3] SWOG 1931/PROBE trial [NCT04510597], which is looking at delayed cytoreductive nephrectomy after 3 months of FDA-approved systemic therapy vs continued systemic therapy.3 That’s one that I’m keeping an eye on.
Certainly in the localized space, we’re seeing an increased incidence of small renal masses, but still overall excellent long-term outcomes for patients who are treated appropriately. We are seeing that active surveillance has become a viable strategy for many patients with small renal masses without significant reduction in cancer-specific survival or OS.
A major shift over the past decade or so has been the introduction of immunotherapy agents for advanced and metastatic disease, which really changed the outlook for [these] patients. Many patients [can] have long-term, durable responses, which was rarely seen before. The outlook is very promising, and we are still determining the best sequencing of therapies for these patients.
