Date Published: April 23, 2019
Publisher: Public Library of Science
Author(s): Zhijian Zhao, Wenqi Wu, Xiaolu Duan, Guohua Zeng, Yongda Liu, Randall J. Kimple.
There has been significant uncertainty in the selection of candidates for cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC). This report investigates the influence of site-specific metastases (bone, brain, liver, and lung) on the survival benefit of CN.
Within the Surveillance, Epidemiology and End Results database (2010–2014), 1113 mRCC patients treated with CN (n = 618) or no surgery (NS, n = 495) met the selection criteria. 168 pairs of patients using propensity scores were matched to balance the selection bias of undergoing CN. Multivariable competing risks regression analysis was used to calculate cancer-specific mortality (CSM) and overall survival (OS). Cases were subdivided to investigate the advantages of each procedure.
Before or after matching, CN led to better OS and lower CSM in Kaplan-Meier analysis. In matched cohort, decreased CSM after CN compared to without CN were consistently found in most subgroups stratified by age, T stage, and patients with ≤2 site-specific metastases. However, patients with ≥ 3 site-specific metastases, or patients with ≥cT3 stage combined with ≥ 2 site-specific metastases were not benefit from the cytoreductive nephrectomy.
The potential benefit of CN disappeared in patients with ≥ 3 site-specific metastases, or patients with ≥cT3 combined with ≥ 2 site-specific metastases.
Metastatic renal cell carcinoma (RCC) accounts for one-third of the total RCC. Systemic treatments, including immunotherapy and targeted therapies, are commonly used for these patients. Cytoreductive nephrectomy (CN) is most often performed with the goal of achieving palliation from symptoms or reduction the primary gross tumor before or after systemic treatment as part of integrated management strategy. Some published data have reported the benefit of CN in immunotherapy era with improved overall survival (13.6 vs 7.8 mo) [3–5], as well as in the setting of patients with targeted therapy [6–9]. However, these studies also point toward the importance of selecting patients who should undergo CN, as there are certain subgroups of patients with mRCC who may not benefit from CN. Indeed, there has been significant uncertainty in the selection of candidates for CN, and the impact of CN on survival might be largely influenced by primary tumor and metastases characteristics. Currently CN is recommended in mRCC patients with a good performance status, large primary tumors and low metastatic volume, although recently the CARMENA trial showed that sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with mRCC who were classified as having intermediate-risk or poor-risk disease.
A total of 1113 eligible cases were identified: No surgery (NS) (n = 495), and CN (n = 618). A total of 702 patients (63.1%) died of mRCC and 54 patients (4.8%) died of other causes. Of these cancer-related deaths, 376 of 495 (76.9%) occurred in the NS group and 326 of 618 (52.7%) in the CN group. Patient characteristics are listed in Table 1. CN patients seem to be younger, less likely to have positive regional lymph node, and less sites metastases, but more likely to have higher T grade (each p<0.0001). Specially, in all patients 662 (59.5%) patients were diagnosed with lung metastases, 421 (37.8%) patients were diagnosed with bone metastases, 179 (16.1%) patients were diagnosed with liver metastases, and 122 (10.9%) patients were diagnosed with brain metastases. A total of 711 (63.9%) patients have a less than one specific metastases organ while 248 patients (22.2%) patients have two specific organ metastases and 79 (7.1%) have multiple organ metastases. After propensity-score matching, preoperative characteristics were well balanced (Table 1). Clear evidence of the benefit provided by CN in the metastatic renal carcinoma patients is lacking, but nonrandomized evidence suggests a possible survival advantage for this approach, which was reviewed in a meta-analysis. Indeed, strict criteria for selecting candidates originated from most studies, namely, which included only those patients with a good performance status or excluded patients with symptomatic or untreated brain metastases or those with exclusive bone metastases or multiple metastases at one single organ. These stringent inclusion and exclusion criteria mean that upcoming results from these trials will not provide data that are generalizable to real world practice. Several studies have focused on the survival outcomes in patients with metastases in the bone[9,19], liver, lung, and brain[21,22] and higher tumor grades , and found them as negative predictors of OS. However, no study paid attention to the important role of the number of metastatic sites on the prognosis of patients with mRCC. Source: http://doi.org/10.1371/journal.pone.0215861