Synchronous vs metachronous metastatic disease: Impact of time to metastasis on outcome in metastatic renal cell carcinoma patients treated with targeted therapy

Abstract

Background: Patients (pts) with metastatic renal cell carcinoma (mRCC) may present with primary metastases (synchronous disease) or develop metastases during follow-up (metachronous disease). The impact of timing of metastatic disease outbreak on outcomes from targeted therapy (TKI) is unclear. Method(s): We used the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to assess overall survival (OS) and time to treatment failure (TTF) on first line TKI, and performed Cox regression analyses comparing synchronous (metastases 3-12 mo, >1-2 yrs, >2-7 yrs, and>7yrs). Result(s): In 7386 pts with mRCC treated with first line TKI, 3906 pts (53%) had synchronous and 3480 pts (47%) had metachronous metastases. Synchronous vs metachronous disease by intervals >3-12 mo, >1-2 yrs,>2-7 yrs,>7yrs correlated with lower age at TKI initiation (mean 61 yrs vs 61, 62, 63, 66 yrs, respectively, p<0.0001), higher rate of non-clear cell histology (14% vs 12%, 10%, 10%, 7%, respectively, p<0.0001), and higher rate of IMDC risk features (mean 2.3 vs 1.6, 0.9, 0.9, 0.8, p<0.0001). Compared with synchronous disease, the longer time to metastases was significantly associated with improved OS and TTF from TKI therapy initiation in multivariable Cox regression, adjusted for nephrectomy status, histology (cc vs ncc), IMDC risk factors (Hgb, Corrected calcium, Neutrophil, platelets, Karnofsky performance status), number of metastasis (1 vs>1), age at TKI initiation and year of TKI initiation (2003-2007, 2008-2012, 2013-2016). Conclusion(s): Timing of metastases post initial RCC diagnosis impacts outcome with targeted therapy inmRCC. Thismay need to be taken into consideration in clinical trial designs.