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Advanced RCC Care
My Thoughts on the Care of Advanced Renal Cell Carcinoma Today

Released: May 30, 2023

Mary Weinstein Dunn
Mary Weinstein Dunn, MSN
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Key Takeaways
  • Immune checkpoint inhibitors and vascular endothelial growth factor receptor tyrosine kinase inhibitors are the upfront treatment of choice for most patients with advanced or metastatic renal cell carcinoma.
  • A wealth of treatment options allow for extensive consideration of individualized patient and disease factors as part of sequencing strategy, including treatment history, strength of evidence, adverse event profile, and patient comorbidities, preference, and financial concerns.
  • Effective adverse event management is an essential component of treatment sequencing that relies on proactive patient education and open channels of communication between all members of the care team.

Renal cell carcinoma (RCC) is one of the most common cancers affecting adults in the United States, with roughly 82,000 new diagnoses and almost 15,000 deaths predicted in 2023. For nonmetastatic or localized RCC, surgical resection remains the mainstay treatment, with additional adjuvant therapy for select patients. The KEYNOTE-564 trial recently demonstrated disease-free and overall survival benefits of adjuvant treatment with pembrolizumab in patients with clear-cell histology, pT3 or higher disease, and M1 with no evidence of disease within 1 year of resection, so we recommend discussing this option with patients meeting those characteristics. Shared decision-making in this scenario should include the high risk of disease recurrence along with the patient’s complete health status and any practical barriers to continued systemic therapy.

First-line Therapy for mRCC
Treatment strategies for metastatic RCC (mRCC) are guided by risk stratification encompassing a patient’s performance status, time from diagnosis, and laboratory values (hemoglobin, calcium, platelets, and neutrophils). Patients with favorable risk typically receive frontline treatment with a combination of immune checkpoint inhibitor (ICI) and vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI), but VEGFR TKI monotherapy or surveillance may also be considered. Patients with intermediate or poor risk may be treated with an ICI and VEGFR TKI combination or with dual ICI therapy. Patient preferences and individual disease characteristics are always additional contributing factors in treatment selection. Of interest, the CARMENA study has shown no additional survival benefit of nephrectomy prior to systemic therapy for patients with mRCC and intermediate or poor risk, suggesting that debulking surgery may be optional based on individual patient factors such as degree of extrarenal disease and symptomatology.

Treatment Sequencing After Disease Progression
The number of treatment options now available for mRCC is both a blessing and a curse when it comes to sequencing strategies after disease progression. In addition to the ICI and VEGFR TKI classes already mentioned, mTOR inhibitors and novel targeted agents may also be considered for second line and later treatment. Clinical trials are also always a valuable option. A wealth of clinical trial data exists to evaluate the efficacy of targeted therapy in mRCC, but individual factors such as the patient’s response to first-line treatment, the provider’s familiarity with a particular agent, and financial or access concerns also come into play.

Optimizing Treatment Tolerability
Managing the tolerability of each treatment is vital to allow patients to experience maximal benefit throughout sequencing. Because combination therapies are so frequently used in mRCC, attention must be given to overlapping toxicity profiles and the usual timing of those toxicities. For example, hepatitis can be caused by both ICIs and TKIs with similar time to onset, so determining the likely etiology and best treatment modification can be tricky. Of note, residual toxicities associated with first-line treatment may still be present or may be at risk for recurrence as a patient reaches subsequent lines of therapy. Taking a detailed social history at the outset can help determine which potential toxicity profiles would be most acceptable for a patient. Upfront patient education is key to managing expectations, establishing monitoring and communication patterns, and reacting quickly so AEs can be managed early when they are less severe. Often, a team of specialists work together both proactively in treatment selection and reactively to manage AEs as they arise, particularly for patients with comorbid conditions.

Your Thoughts?
What are your biggest challenges in the treatment of patients with advanced RCC? Please post a comment in the box below to start the discussion.

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