Late onset of bone metastases as a prognostic parameter in metastatic renal cell cancer (mRCC): A single-center experience in 82 mRCC patients treated with sunitinib.

Abstract

523 Background: Bone metastasis (BM) is considered a negative prognostic marker in metastatic renal cell carcinoma (mRCC). Here, we address the impact of BM onset on overall survival (OS) in mRCC patients during targeted therapy. Methods: Patients with BM who received sunitinib (SU) as 1st targeted treatment at our center between May 2005 and December 2012 were included in this retrospective analyzes. Treatment was performed according to local standard and patients were followed for survival. Spine surgery, fracture or irradiation were considered skeletal related events (SRE). Results: Out of 128 mRCC patients with BM, 82 patients had SU as 1st line targeted agent. 57 (69.5%) patients suffered from BM at initial diagnosis of mRCC (=synchronous BM [sBM]), while 25 (30.5%) patients developed BM during treatment course (=metachronous BM [mBM]). Baseline characteristics showed different histological gradings for sBM compared to mBM patients (p=0.029) and higher frequency of ≥3 metastatic organ sites prior to SU for sBM patients (sBM: n=40 [70.2%] vs. mBM: n=10 [40%], p=0.016). In Kaplan-Meier analysis, sBM patients showed a reduced mean OS from SU start (sBM 23.5 [95%CI:18.6-28.3] vs. mBM 41.3 [95%CI:31.7-50.9] month, p=0.001), whereas PFS during SU treatment was similar (sBM: 8.1 [95%CI:3.9-12.3] vs. mBM: 8.7 [95CI:2.7-14.8] months, p=0.93). Bisphosphonate treatment and SRE revealed no differences between subgroups (p=0.62), while spinal compression occurred in 6 patients with sBM, but none with mBM (p=0.153). 2nd-line targeted agents were less frequently administered in sBM patients (sBM n=17 vs. mBM: n=10). Multivariate Cox-regression confirmed MSKCC score (OR: 2.6 [95%CI:0.99-7.28], p=0.052), liver metastases (OR: 2.66 [95%CI:1.28-5.51], p=0.009], and sBM [OR: 2.45 [95%CI:1.19-5.08], p=0.016) as independent prognostic parameters for reduced OS after SU start. Conclusions: In our cohort, OS in patients with sBM was significantly reduced compared to mBM patients, despite similar PFS with SU and SRE rate. Despite the lower incidence of subsequent therapies in sBM, a more aggressive biology is likely to be the cause of these findings.