The Association Between Small Primary Tumor Size and Prognosis in Metastatic Renal Cell Carcinoma: Insights from Two Independent Cohorts of Patients Who Underwent Cytoreductive Nephrectomy

Abstract

Background: One of the main challenges in the management of renal cell carcinoma (RCC) is risk-stratifying patients who present with metastatic disease. Tumor size is an important predictor of survival in the localized setting; however, this feature has not been explored fully in patients presenting with M1 RCC.Objective: To assess the impact of tumor size on survival in patients with metastatic RCC who underwent cytoreductive nephrectomy (CN).Design, setting, and participants: We queried the Memorial Sloan Kettering (MSK) nephrectomy database for patients who presented with M1 disease and underwent CN between 1989 and 2016 (n = 304). Primary tumor size was obtained from pathology reports. Data from the International Metastatic Database Consortium (IMDC) were used for validation purposes (n = 778).Outcome measurements and statistical analysis: Overall survival (OS) estimates were computed using the Kaplan-Meier method. Cox regressions were used to test the association between tumor size and OS in univariate and multivariable analyses. Tumors ≤4 cm were compared with larger masses. Secondary analyses were performed to assess the robustness of these findings. Results and limitations:Clear cell tumors ≤4 cm were significantly associated with improved OS in both the MSK (hazard ratio [HR]: 0.35, 0.17-0.72, p = 0.004) and IMDC (HR 0.54, 0.36-0.83, p = 0.004) cohorts. The association was observed even after adjusting for known prognostic factors (HR 0.40, 0.14-1.14, p = 0.09 and HR: 0.54, 0.33-0.90, p = 0.02 in the MSK and IMDC cohorts, respectively). Limitations of this study include the absence of patients who were considered poor surgical candidates as well as potential selection bias. Conclusions:The primary tumor size ≤4 cm was independently associated with improved OS in patients with metastatic clear cell RCC who underwent CN. Additionally, the association between primary size and survival was found to be nonlinear. These findings suggest that there is a group of small metastatic RCCs that can convey a better overall prognosis. The potential role of primary tumor size when risk stratifying patients with M1 RCC should be explored further to determine its utility during clinical decision making.

An evaluation of the role of tumor load in cytoreductive nephrectomy

“…The median volume of primary tumors (PV) was 225cm 3 , this was non-normally distributed, with a negative skew (p=0.007). The median total volume of disease (TV) was 236cm 3 , with patients' TV predominantly restricted to the primary tumor (Figure 1). Only three tumors had a volume of metastatic disease (MV) greater than PV, the median percentage of TV resected was 96.7%.…”

“…We have previously reported that primary tumor size is an independent predictor of survival following cytoreductive nephrectomy. 3 However, this finding did not consider that tumor volume can vary, even in tumors with identical maximum axial diameter, depending on the shape of disease. 4 Previous studies by Pierorazio et al and Barbastefano et al showed that the fraction of disease resected in a cytoreductive nephrectomy may be significant for survival outcomes, with improved outcomes when a minimum of 90-95% of all disease is debulked.…”

Management of Metastatic Nonclear Renal Cell Carcinoma: What Are the Options and Challenges?

“…Translational work suggests that some primary tumors may harbor progressive clones leading to rapid metastasis [13], but CARMENA did not support that CN was beneficial. In addition, due to the size of the tumor, ablation may be an alternative to a surgical approach that may include partial nephrectomy [14][15][16]. In summary, after establishing the diagnosis of the subtype reliably by an RMB, immediate systemic therapy should be preferred in analogy to first-level evidence for ccRCC.…”

Impact of Primary Tumor Size on Prognosis in Patients With Metastatic Renal Cell Carcinoma Receiving Cytoreductive Nephrectomy: A Population Study of a Chinese Center and the US SEER Database

“…Patients with a lower tumor burden may have a potential survival benefit by undergoing CN, which could be added to individual decision-making procedures. 9 …”

“…Recently, DiNatale et al reported that a primary tumor size ≤ 4 cm was independently associated with improved overall survival (OS) in patients with metastatic clear cell RCC who had undergone surgery earlier. 9 In the present study, we retrospectively examined the data of mRCC patients who had undergo CN retrieved from the database of a Chinese center and the Surveillance, Epidemiology, and End Results (SEER) program and aimed to determine how the size of the primary tumor affects the prognosis of mRCC patients.…”