Treatment Selection in Favorable Risk and Progression Considerations

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Favorable-risk patients with clear cell renal cell carcinoma present unique treatment challenges requiring careful consideration of treatment timing and regimen selection. The panel discusses how recent CheckMate 214 long-term data showing survival curve crossover at 9 years has transformed favorable-risk treatment paradigms. Tykodi emphasizes reduced concern about risk categorization, focusing instead on disease burden and patient tolerance for specific regimens. The delayed benefit in favorable-risk patients initially showed an ipilimumab plus nivolumab disadvantage, but long-term follow-up demonstrates eventual superiority with the HR improving to 0.8.

Active surveillance remains viable for truly indolent favorable-risk disease, particularly when imaging demonstrates minimal progression over extended periods. Treatment initiation depends on growth rate, symptom development, and patient preference for active intervention. When treatment is indicated, regimen selection follows similar principles as intermediate-risk disease, though some practitioners consider IO-TKI combinations for their higher response rates and potential for cytoreductive surgery eligibility.

Pseudoprogression management requires clinical correlation with radiographic findings, as most progression represents true disease advancement rather than immune-related pseudoprogression. The experts generally allow one additional scan interval for low-volume, asymptomatic progression before changing therapy, particularly in favorable-risk patients where the consequences of delayed treatment switch are less severe. Clinical deterioration accompanying radiographic progression indicates a true progression requiring immediate treatment modification. The rarity of confirmed pseudoprogression in clinical practice makes conservative management appropriate only in carefully selected patients with minimal disease burden and stable clinical status.