Clinical-Kidney cancer
The association between facility case volume and overall survival in patients with metastatic renal cell carcinoma in the targeted therapy era

https://doi.org/10.1016/j.urolonc.2018.06.013Get rights and content

Highlights

  • We demonstrated a volume-outcome association in a metastatic disease cohort.

  • Patients with mRCC had improved survival if treated at high-volume facilities.

  • Ten percent reduced all-cause mortality was observed at top 5% facilities by volume.

  • The volume-outcome association exists in medical oncology-managed metastatic cancer.

Abstract

Background

Improved overall survival of cancer patients treated by high-volume providers has been reported in surgical oncology and radiation oncology literature. Whether this volume-outcome association exists in medical oncology-managed metastatic solid tumors is uncertain. This study aimed to investigate the effect of facility case volume (FCV) on overall survival in patients with metastatic renal cell carcinoma (mRCC) diagnosed in the targeted therapy era.

Materials and methods

Adult patients diagnosed with mRCC between 2006 and 2015 were identified in the National Cancer Database. The primary exposure was FCV, which was defined by mRCC case volume of each treating facility. The association between FCV and all-cause mortality in mRCC was investigated in multivariable Cox regression model and validated with inverse propensity-score weighting method. Logistic regression was used to identify independent predictors for treatment at high-volume facilities. Covariates adjusted for were sociodemographics, tumor characteristics and treatment modalities.

Results

There were 31,329 mRCC patients identified. The mean follow-up time was 14.3 months. When FCV was coded as a continuous variable, each increment of 10 mRCC cases/y was associated with reduced all-cause mortality after baseline covariates adjustment [adjusted hazard ratio: 0.93, 95% confidence interval: 0.90–0.96, P value:<0.0001]. In dichotomized models, improved all-cause mortality was observed at cutoffs of 85th (4.3 cases/y), 90th (5.4 cases/y) and 95th (7.4 cases/y) but not at 50th (2.2 cases/y) and 75th (3.4 cases/y) percentiles. For illustrative purpose, 95th percentile was chosen and inverse propensity-score weighting-adjusted Kaplan–Meier curve demonstrated improved overall survival for mRCC patients treated at high-volume facilities (adjusted hazard ratio: 0.90, 95% confidence interval: 0.88–0.94, P value <0.0001; the 1-, 2-, 3-year survival rates were 41%, 26%, and 19% vs. 36%, 22%, and 16% for patients treated at high and low-volume facilities, respectively). Patients without insurance or with Medicaid status, with shorter travel distance, living in nonmetropolitan area or in area with lower averaged education level were less likely to be treated at high-volume facilities.

Conclusions

Patients diagnosed with mRCC in the targeted therapy era have improved overall survival when treated at high mRCC-volume facilities, suggesting a volume-outcome association in medical oncology-managed metastatic solid tumors.

Introduction

Renal cell carcinoma (RCC) has an estimated 63,990 new cases and 14,400 deaths in 2017 [1]. While the RCC survival rate had been traditionally poor, the 5-year survival rate had increased from 57% in 1987 to 1989 to 74% in 2006 to 2012 [1]. This improvement is likely due to 2 main factors: first is the diffuse use of imaging studies which resulted in increased detection of early-stage disease [2], [3]; the other is the targeted therapy (TT) era for advanced RCC beginning at the end of 2005 with 7 antiangiogenic drugs and 2 mammalian target of rapamycin inhibitors approved from 2005 to 2016 by the Food and Drug Administration [4]. Prior to the approval of nivolumab in November 2015 as second-line therapy for metastatic renal cell carcinoma (mRCC), the fundamental treatment for mRCC was TT with or without cytoreductive nephrectomy (CN) [5]. With such advancement in mRCC treatment since the end of 2005, the expertise of the treating facilities to keep up with new knowledge is essential in order to achieve the best patient outcomes.

In surgical oncology [6], [7], [8], [9], [10], [11], [12], there has been well-established evidence that surgical expertise improves with higher hospital/surgeon volume, which is reflected in decreased postoperative mortality [6], [7], higher rate of achieving negative margins [8], [10], [13], a higher yield in lymph node dissection [8], [10], [11], [12], [13] and improved long term survival [6], [7], [8], [9], [10], [11], [12]. In radiation oncology [14], [15], [16], [17], [18], there is also emerging evidence demonstrating improved overall survival in patients treated at high-volume facilities. However, there are limited data whether this volume -outcome association exists in hematology-oncology managed cancers [19], [20], [21], [22] especially in advanced solid tumors. Thus, the association between facility case volume (FCV) and overall survival (OS) in mRCC patients in the targeted therapy era was investigated. It was hypothesized that mRCC patients treated at high mRCC case volume facilities may have improved overall survival.

Section snippets

2.1. Data source

The National Cancer Database (NCDB) Participant Use Data File, which is a joint quality improvement program of the American College of Surgeons Commission on Cancer (CoC) and the American Cancer Society, was the data source for the present analysis. NCDB prospectively collects patient and facility characteristics. It captures 70% of newly diagnosed cancer cases in the United States [23] and is the largest cancer registry in the world. This study was exempted from review by Institutional Review

3.1. Baseline characteristics

There were 31,329 patients diagnosed with mRCC in 2006 to 2015 (Table 1). The median age at diagnosis was 64 (interquartile range 56–74). 20,699 (66.1%) were male. Overall, 14,690 patients (46.9%) received TT, 8,398 (26.8%) patients received CN, 3,663 (11.7%) received metastasectomy and 8,402 (26.8%) had radiation in the first treatment course. There were 11,339 (36.2%) patients treated in academic facilities.

3.2. Association between facility case volume and mRCC overall survival

The mean follow-up time was 14.3 months (median: 6.4 months, 95% confidence interval

Discussion

The present analysis is the first to demonstrate a volume-outcome association in a pure metastatic disease cohort of solid tumor patients. Using the largest hospital-based cancer database in the United States, it was demonstrated that increased FCV of mRCC cases was associated with improved overall survival in mRCC patients. This improved outcome was illustrated in contemporary patients treated at the top 5% facilities by mRCC volume with a 10% risk reduction in all-cause mortality. The major

Conclusions

In conclusion, patients with mRCC had improved overall survival if treated at high mRCC-volume facilities. These results suggest that expertise of the treating medical oncologists is gained through accumulating experience in daily practice similar to improved outcomes observed in high-volume providers of surgical oncology [6], [7], [8], [9] and radiation oncology [14], [15], [16], [17], [18] and have implications for delivery of quality oncology care.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest disclosures

Yu-Wei Chen and Jennifer Beach: none. Moshe C. Ornstein consulted for Pfizer. Laura S. Wood consulted for Exelixis. Kimberly D Allman consulted for Exelixis. Allison Martin consulted for Pfizer. Timothy Gillgan consulted for WellPoint. Jorge A. Garcia consulted for Sanofi, Pfizer, Bayer HealthCare Pharmaceuticals, Eisai, Exelixis, Medivation, and Genentech/Roche. Brian I. Rini consulted for Pfizer, Merck, and Corvus Pharmaceuticals.

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