Presentation Authors: Andrew Silagy*, Renzo DiNatale, Roy Mano, Julian Marcon, Kyle Blum, New York City, NY, Eduard Reznik, New York, NY, Jonathan Coleman, Paul Russo, Ari Hakimi, New York City, NY
Introduction: Developing metastatic renal cell carcinoma (mRCC) is an insidious, iterative process, diagnosable only after metastatic burden is sufficiently large to be detected by contemporary imaging techniques. A recent publication demonstrated unique evolutionary pathways to metastases. We aimed to investigate whether mutations correlated with the metastatic sites at the time of cytoreductive nephrectomy.
Methods: After obtaining IRB approval, we queried our prospectively maintained database identifying 514 patients who underwent a nephrectomy, with clear cell histology and mRCC prior to surgery or within 90 days post-operatively.All patients with MSK-IMPACT genetic sequencing were further evaluated. Baseline clinicopathological characteristics, 22 unique metastatic sites and survival outcomes were recorded. Sites were subsequently grouped into thoracic, nodal, bone, abdominal and other. We used Chi-squared and multivariate analyses to test whether mutations were associated with metastatic locations and if this affected patient outcomes.
Results: Our cohort included 110 patients; 77% male with a median survivor follow up of 34 months (IQR: 22 - 46). The median number of metastatic sites per patient was 2 (IQR: 1-2). Clinicopathological characteristics, disease sites and mutational events are illustrated in Figure 1. Patients with oligometastatic disease (â‰¤2 metastatic organs) compared with disseminated disease trended towards improved overall survival (HR 0.61 (CI: 0.33 - 1.12) p= 0.1). TP53 was significantly associated with disseminated disease (71% vs 20%; p=0.008).
Conclusions: This study characterized the distribution of mRCC relative to a targeted panel of mutations, demonstrating that TP53 was significantly associated with disseminated metastases. Patients with oligometastatic disease had longer survival after cytoreductive nephrectomy. Investigation is being undertaken into the mutational clonality and whether mutations can improve nomograms for cytoreductive nephrectomy.
Source of Funding: This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748