Mortality risk in clinical T1a renal cell carcinoma (RCC) with synchronous metastasis (SM): A comparative analysis of National Cancer Database (NCDB).
Authors: Melis Gür, Luke Wang, Franklin Liu, Dhruv Puri, Margaret F. Meagher, Juan Javier-Desloges, James Murphy, Brent S Rose, Aditya Bagrodia, Ithaar Derweesh, Rana R. McKay
Journal: Journal of Clinical Oncology (2025)

513 Background: The incidence of RCC has been rising, largely due to increased incidental detection from widespread imaging. Although SM with a primary renal tumor measuring &lt;4 cm (cT1a) is uncommon, its presence may influence survival outcomes and utility of cytoreductive nephrectomy. We sought to examine trends, metastatic patterns, treatments and survival outcomes of cT1a RCC with SM. Methods: All cases of RCC (age ≥ 18 years), diagnosed between 2004-2019, were extracted from the NCDB. The Cochran-Armitage test was utilized for trend analyses. Multivariable analyses were conducted to compare variables associated with all-cause mortality across metastatic sites. Results: Overall, 263,911 patients with T1a RCC were included in the analysis. Of these, 114,661 patients (43.4%) had cT1a tumor stage and within this group, 2,275 (2.0%) presented with SM. From 2004-2019, the proportion of SM cT1a decreased from 3.39% to 2.08% (AAPC=-0.037%; Cochran-Armitage p=0.830). The median follow-up was 8.8 months. The most common site of metastasis was bone (59%), followed by lung (35%), liver (16%), and brain (12%). Among SM cT1a patients, 11% underwent radical nephrectomy, 4.7% partial nephrectomy, 15.4% metastasectomy, and 45.2% received systemic therapy. Variables associated with all-cause mortality demonstrated in the table. Conclusions: Uniquely, bone was the most common metastatic site in cT1a RCC with synchronous metastasis, contrasting with the typical lung predominance in larger tumors. Primary tumor resection and receipt of systemic therapy showed potential survival benefits in patients with isolated metastases, while metastasectomy improved survival in brain-only metastases but not in bone-, lung-, or liver-only metastases.These findings highlight the heterogeneous nature of tumor biology in small renal masses and underscore the importance of tailored, multimodal treatment strategies for effective management of cT1a RCC with SM. Multivariable Cox regression models demonstrating variables associated with all-cause mortality in cT1a RCC with SM to lung, bone, liver, and brain. SM to Lung SM to Bone SM to Liver SM to Brain Variables HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value Age 0.98 (0.96-1.01) 0.178 1.03 (1.02-1.04) &lt;0.001 1(0.97- 1.03) 0.989 0.99(0.96- 1.03) 0.748 Surgery of Primary Site Nephrectomy 0.08(0.01- 0.72) 0.047 0.35(0.14- 0.86) 0.056 0.22(0.06-0.78) 0.039 0.08(0.02- 0.41) 0.005 Partial Nephrectomy 0.02(0.00- 0.31) 0.013 0.23(0.09- 0.60) 0.011 0.13(0.01- 2.35) 0.165 0.1(0.01- 0.97) 0.047 Metastasectomy 0.91(0.50- 1.67) 0.759 0.81(0.59- 1.10) 0.169 3.14(0.90- 11.0) 0.074 0.26(0.10- 0.68) 0.006 Systemic Therapy 0.36(0.23-0.57) &lt;0.001 0.57(0.44- 0.74) &lt;0.001 0.41(0.20- 0.85) 0.033 0.22(0.10- 0.48) &lt;0.001 HR = hazard ratio, CI = confidence interval.