Primary tumor response to targeted agents in patients with metastatic renal cell carcinoma

Abstract

Background: The recent development of multiple targeted agents for metastatic renal cell carcinoma (mRCC) has changed the treatment paradigm; hence the benefit and optimal timing of cytoreductive nephrectomy is being reevaluated.

Objective: To determine primary tumor response to treatment with targeted agents in patients with mRCC.

Design, setting, and participants: We reviewed the clinical and radiographic data of all mRCC patients seen at our institution between November 2004 and December 2009 without prior systemic treatment who received targeted therapy with their primary tumor in situ.

Measurements: Two independent reviewers measured the diameter of primary and metastatic tumors at baseline and subsequent scans, using Response Evaluation Criteria Solid Tumors (RECIST) v.1.1 to assess disease response.

Results and limitations: We identified 168 consecutive patients with a median 15 mo of follow-up and a median maximum tumor diameter of 9.6 cm. Median maximum primary tumor response was -7.1% (interquartile range: -14.0 to -0.1). A total of 61 patients had multiple studies available for evaluation. In 43 patients with <10% decrease in primary tumor within in the first 60 d, median maximum response was -7.2% at 154 d versus -24.5% maximum response at 174.5 d for 18 patients with ≥10% decrease in primary tumor during the initial 60 d.

Conclusions: Decrease in primary tumor diameter >30% while on targeted therapy for mRCC is rare, with most patients demonstrating minimal or no decrease in primary tumor diameter. Early response predicts a better overall primary tumor response.

Fig. 1

Waterfall plot showing primary tumor maximum overall response to treatment with targeted agents. Bold lines indicate partial response and progressive disease, as defined by Response Evaluation Criteria Solid Tumors.

Fig. 2

Primary tumor responding to therapy with sunitinib. Before therapy (left), the large primary tumor and lymphadenopathy would make cytoreductive nephrectomy difficult and possibly dangerous. After therapy (right), the response in the primary tumor and lymph nodes enabled this patient to undergo laparoscopic nephrectomy.

Fig. 3

Primary tumor response to a targeted agent according to the amount of response. Most patients show minimal response or tumor stability during treatment.

Fig. 4

Box plot demonstrating variable primary tumor response to different targeted agents. The shaded box represents the 25th and 75th percentiles, with the ends of lines demonstrating two standard deviations and outliers shown as dots for each type of therapy.