Management of favorable-risk patients with metastatic renal cell carcinoma: when to start and when to stop targeted therapy.

Targeted therapy has changed the treatment of metastatic renal cell carcinoma (mRCC). However, it is unclear if patients need to start systemic therapy immediately or if treatment can be deferred. Identification of the appropriate time to discontinue therapy is also uncertain. We reviewed treatment guidelines and trials evaluating targeted agents for mRCC to assess the evidence regarding commencing and discontinuing therapy for mRCC. Guidelines recommend that patients with mRCC receive targeted agents; however, they do not address when therapy should start. Risk factors based on Memorial Sloan-Kettering Cancer Center (MSKCC) or Heng criteria can be used to stratify patients. MSKCC prognostic factors include Karnofsky performance status (< 80%), high lactate dehydrogenase levels, low hemoglobin levels, high serum calcium levels, and time from diagnosis to start of therapy < 1 year. In patients with poor and intermediate risk (≥ 3 and 1-2 factors, respectively) and/or with high tumor burden, targeted therapy should commence as soon as possible. In patients with MSKCC good-risk disease and few disease symptoms, active surveillance may be appropriate. Regular monitoring is required so that treatment can be initiated upon evidence of active disease. Second-line therapy is usually commenced after disease progression; however, because of the limitations of radiologic assessment of response to targeted therapies, other factors may need to be considered to guide decisions regarding stopping or switching therapy. These include scenarios such as a mixed response to therapy. For selected patients at favorable risk, active surveillance may be feasible; however, strict monitoring is required.