Sites of Metastasis and Survival in Metastatic Renal Cell Carcinoma: Results From the Korean Renal Cancer Study Group Database

Abstract

Background: In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC.

Methods: This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed.

Results: A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1-6). The median age at the initiation of systemic therapy was 60 years (IQR, 29-88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months).

Conclusion: In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs.

Keywords: Carcinoma, Renal Cell; Molecular Targeted Therapy; Neoplasm Metastasis; Prognosis; Survival.

Fig. 1. Distribution of renal cell carcinoma metastases by location. (A) Whole cohort (multiple metastases included). (B) Single-organ metastasis in the absence of any other disease sites.

Fig. 2. OS for patients with mRCC. (A) OS according to the IMDC risk groups. (B) OS according to the number of metastatic organs. (C) OS according to histological subtypes.

OS = overall survival, mRCC = metastatic renal cell carcinoma, IMDC = International Metastatic Renal Cell Carcinoma Database Consortium, RMST = restricted mean survival time, CI = confidence interval, RCC = renal cell carcinoma.

Fig. 3. CSS based on the site of metastatic involvement in metastatic renal cell carcinoma. Survival time is presented in ascending order of median survival. Patients with multiple sites of metastatic involvement were included in the analyses of all groups according to their metastases. CSS was calculated from the time of diagnosis of metastatic disease to death from cancer or censored at the time of the last follow-up. The adjusted HR was reported by comparing involved with non-involved sites of metastasis, adjusted by International Metastatic Renal Cell Carcinoma Database Consortium risk groups and the number of metastatic organs. An adjusted HR > 1 indicates worse CSS.

CSS = cancer-specific survival, HR = hazard ratio, RMST = restricted mean survival time, CI = confidence interval.

Fig. 4. Survival for single-organ metastasis in the absence of any other sites of disease. (A) Cancer-specific survival. (B) Progression-free survival of first-line targeted therapy.

RMST = restricted mean survival time, CI = confidence interval, mRCC = metastatic renal cell carcinoma.