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

<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)

<0.001

0.57(0.44- 0.74)

<0.001

0.41(0.20- 0.85)

0.033

0.22(0.10- 0.48)

<0.001

HR = hazard ratio, CI = confidence interval.