What are the NCCN (National Comprehensive Cancer Network) guidelines for managing renal cell carcinoma?

NCCN Guidelines for Renal Cell Carcinoma Management

The NCCN Guidelines for Kidney Cancer provide comprehensive multidisciplinary recommendations for managing clear cell and non-clear cell renal carcinoma, with treatment approaches based on disease stage, risk stratification, and histology. 1

Overview and Epidemiology

• Renal cell carcinoma (RCC) comprises approximately 3.8% of all new cancers, with an estimated 76,080 Americans diagnosed with kidney and renal pelvis cancers in 2021 1
• The median age at diagnosis is 64 years, with approximately 85% of kidney tumors being RCC 1
• Clear cell histology (ccRCC) accounts for approximately 70% of RCC cases, with less common types including papillary, chromophobe, translocation, and collecting duct tumors 1
• Established risk factors include smoking, obesity, and hypertension, with several hereditary types also existing (most commonly von Hippel-Lindau disease) 1
• RCC primarily metastasizes to the lung, bone, liver, lymph nodes, adrenal gland, and brain 1

Prognostic Models for Metastatic Disease

• The NCCN Guidelines incorporate two major prognostic models for risk stratification in metastatic RCC 1:

1. MSKCC (Memorial Sloan Kettering Cancer Center) Criteria:

   • Five prognostic factors: interval from diagnosis to treatment <1 year, Karnofsky performance status <80%, elevated LDH, elevated serum calcium, and low hemoglobin 1
   • Patients are classified as low risk (0 factors), intermediate risk (1-2 factors), or poor risk (≥3 factors) 1

2. IMDC (International Metastatic RCC Database Consortium) Model:

   • Six clinical parameters to stratify patients into favorable, intermediate, and poor prognosis groups 1
   • Includes four of the five MSKCC factors plus additional prognostic indicators 1

Treatment Recommendations

First-Line Therapy for Advanced/Metastatic Clear Cell RCC

• The NCCN Guidelines have recently shifted risk categorization, now separating "favorable risk" from combined "intermediate/poor risk" categories for treatment recommendations 2

• For favorable risk patients:

  • Preferred regimens include VEGF-targeted therapies such as pazopanib and sunitinib (both category 1) 1
  • Clinical trials are always considered appropriate options 1

• For intermediate/poor risk patients:

  • Immunotherapy combinations (CPI+CPI) or immunotherapy plus TKI combinations (CPI+TKI) are now standard first-line treatment 3
  • Treatment selection should be individualized based on tumor extent, treatment urgency, comorbidities, and patient preferences 3

Subsequent Therapy

• Selection of second-line therapy is based on individual criteria, with limited data available for optimal sequencing after progression on first-line therapy 3
• Pazopanib has shown efficacy as subsequent therapy for patients with clear cell carcinoma after first-line treatment with another tyrosine kinase inhibitor 1

Follow-Up Recommendations

• The NCCN Guidelines include specific recommendations for follow-up of patients with RCC after primary treatment 1
• Follow-up protocols are tailored based on risk of recurrence, with more intensive surveillance for higher-risk disease 1

Special Considerations

• The 5-year survival rate for localized RCC has improved to 92.6% (during 2007-2013), while advanced disease survival remains much lower at 11.7% 1
• The most important prognostic determinants include tumor stage, grade, local extent, presence of nodal metastases, and evidence of metastatic disease at presentation 1
• NCCN strongly encourages participation in clinical trials for all eligible patients 1
• The most recent NCCN Guidelines (Version 2.2024) continue to evolve with new systemic therapy options for advanced RCC based on emerging clinical data 4

Common Pitfalls and Caveats

• Treatment decisions should be made as part of a "shared decision" process with patients, considering individual factors beyond just risk stratification 3
• The NCCN Guidelines are intended to assist with clinical decision-making but cannot incorporate all possible clinical variations and are not meant to replace clinical judgment 1
• Unusual patient scenarios (presenting in <5% of patients) are not specifically addressed in the guidelines 1
• Ongoing clinical studies are evaluating therapy optimization, including triple combinations (CPI+CPI+TKI) and treatments for non-clear cell histological subtypes 3