How do I score the risk of a patient with metastatic clear cell renal carcinoma and multiple metastases?

Risk Scoring for Metastatic Clear Cell Renal Carcinoma

For a patient with metastatic clear cell renal carcinoma and multiple metastases, use the International Metastatic RCC Database Consortium (IMDC) risk scoring system, which is the gold standard for risk stratification in metastatic disease. 1, 2

IMDC Risk Scoring System

The IMDC system uses six adverse prognostic factors to stratify patients 1, 2:

1. Karnofsky performance status <80% 1, 2
2. Hemoglobin below the lower limit of normal 1, 2
3. Time from diagnosis to treatment <1 year 1, 2
4. Corrected calcium above the upper limit of normal 1, 2
5. Platelets greater than the upper limit of normal 1, 2
6. Neutrophils greater than the upper limit of normal 1, 2

Risk Category Classification

Count the number of adverse factors present and classify the patient as follows 1, 3:

• Favorable risk (0 factors): Median overall survival not reached, 75% 2-year survival 3
• Intermediate risk (1-2 factors): 27 months median overall survival, 53% 2-year survival 3
• Poor risk (3-6 factors): 8.8 months median overall survival, 7% 2-year survival 3

Clinical Application

The IMDC system is applicable across all lines of therapy and in non-clear cell histology, making it versatile for ongoing treatment decisions 1, 2. This model has demonstrated superior predictive value compared to the older Memorial Sloan Kettering Cancer Center (MSKCC) system in the era of targeted therapies 1.

Important Clinical Considerations

For patients with multiple metastases specifically, note that the number and sites of metastatic disease carry prognostic significance beyond the standard IMDC criteria 4, 5. Patients with two or more metastatic organs have significantly worse outcomes (HR 3.77) compared to those with single-organ involvement 5.

Within the intermediate-risk group (which comprises approximately 50% of metastatic patients), additional refinement may be warranted 6, 5:

• Elevated platelet count identifies a subgroup with particularly poor outcomes (18 months median OS versus 29 months for normal platelets) 6
• C-reactive protein ≥1 mg/dL (HR 2.89) and neutrophil-to-lymphocyte ratio ≥3 (HR 2.57) further stratify intermediate-risk patients 5

Critical Pitfall to Avoid

Do not rely solely on radiographic findings to establish metastatic disease without tissue confirmation when feasible 1, 2. Tissue analysis comparing cells from metastatic sites to the primary tumor, with PAX8 and CAIX expression, sets the standard for diagnosing metastatic disease 1, 2. However, radiographic diagnosis is acceptable when previous renal carcinoma has been established or when metastatic tissue is not easily accessible 2.