Original article
Effect of reclassification of the IMDC model in patients with metastatic renal cell carcinoma treated with targeted therapy in the first-line and second-line settings

https://doi.org/10.1016/j.urolonc.2016.02.023Get rights and content

Highlights

  • Reclassification of the IMDC model after targeted therapy may be prognostic in mRCC.

  • Up to 30% of cohorts are reclassified into different risks in the 1st-line setting.

  • Up to 20% of cohorts are reclassified into different risks in the 2nd-line setting.

  • Overall survivals are newly stratified by using the IMDC model reclassification.

Abstract

Purpose

To investigate the prognostic effect of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model reclassification after targeted therapy administration in metastatic renal cell carcinoma (mRCC).

Patients and method

A total of 245 mRCC patients treated with targeted therapy are included. The IMDC model reclassification is performed at 1 month after treatment induction of both first-line and second-line targeted therapy.

Results

Of the 245 patients, 74 (30.2%) are divided into different risk groups by the IMDC model reclassification after first-line targeted therapy, and patients newly classified with intermediate risk tend to have better overall survival than those remaining in the primary poor-risk group (P = 0.018). Of the 119 patients treated with subsequent second-line targeted therapy, 25 (21.0%) are divided into different risk groups by the IMDC model reclassification after second-line targeted therapy, and patients newly classified with poor risk tend to have increased all-cause mortality compared with those remaining in the primary intermediate-risk group (P = 0.007), whereas patients newly classified with intermediate risk tend to have better overall survival than those remaining in the primary poor-risk group (P = 0.034).

Conclusion

Approximately a quarter of the mRCC patients are classified into different risk groups of the IMDC model following targeted therapy administration in the first-line and second-line settings. There is a significant difference in overall survival of subgroups after the IMDC model reclassifications.

Introduction

Renal cell carcinoma (RCC) is the seventh most common cancer in males and the ninth most common cancer in females, accounting for 2% to 3% of all adult malignancies [1], [2]; up to 30% of patients with RCC experience systemic spread of the disease, called metastatic RCC (mRCC) [3]. Since 2006, the standard treatment of care in patients with mRCC consists of systemic therapy with targeted agents [1], [2], [4], [5], [6], [7], [8]. These novel agents mainly target 2 different pathways, namely the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways [4], [5], [6].

To predict outcomes, the “International Metastatic Renal Cell Carcinoma Database Consortium” (IMDC) model has been designed and validated [9], [10], [11]. The IMDC model proposed by Heng et al. includes 6 readily assessable factors: time from diagnosis to treatment, Karnofsky performance status, hemoglobin, neutrophil count, platelet count, and serum calcium concentration, and is used for pretreatment risk stratification. However, few studies have reported prognostic information after treatment in this era of targeted therapy [12], [13], [14], [15]. We here investigated whether the reclassification of the IMDC model after targeted therapy administration would provide prognostic information of patients with mRCC.

Section snippets

Methods

After institutional review board approval, a total of 7 Japanese institutions, Keio University Hospital, and 6 affiliated institutions, provided data on 311 consecutive patients with mRCC who received first-line targeted therapy, either anti–VEGF-targeted drugs or mTOR inhibitors. Among these patients, we included 245 patients with complete data for classification by the IMDC model before and after administration of first-line targeted therapy. For the IMDC model classification, patients were

Characteristics and outcomes in patients treated with first-line targeted therapy

Patient characteristics of 245 subjects are presented in Table 1. In total, 134 (54.7%), 50 (20.4%), 43 (17.6%), and 4 (1.6%) patients were treated with sunitinib, sorafenib, axitinib, and pazopanib, respectively, whereas 14 (5.7%) patients were treated with temsirolimus. A total of 75 (30.6%) patients underwent prior immunotherapy, and 181 (73.4%) patients underwent prior nephrectomy before initiation of first-line targeted therapy. The 1-year and 3-year overall survival rates of the entire

Discussion

In this decade, the treatment strategy of patients with mRCC has dramatically changed from the prior gold standard of immunotherapy to targeted therapy that focuses on the VEGF-associated molecules and mTOR-associated molecules [1], [2], [4], [5], [6], [17], [18], [19]. To predict outcomes, researchers have investigated possible indicators for survival [20], [21], [22], [23]; tumor size reduction and growth rate after targeted therapy were subsequently identified as possible factors [20], [21].

Conclusion

Approximately a quarter of the present patients were reclassified into the different IMDC risk groups at 1 month after targeted therapy administration in the first-line and second-line settings. Furthermore we found a significant difference in overall survival of subgroups after the IMDC model reclassification.

Disclosure

Dr. Mizuno reports receiving grants from The Japan Agency for Medical Research and Development (AMED), personal fees from Pfizer, and grants and personal fees from Novartis during the conduct of the study;

Dr. Mikami reports receiving grants from The Japan Agency for Medical Research and Development (AMED) during the conduct of the study.

Dr. Oya reports receiving grants from The Japan Agency for Medical Research and Development (AMED), grants and personal fees from Pfizer, grants and personal

Acknowledgments

The authors would like to thank every member of the Keio Collaboration Study of Renal Cell Carcinoma. The following institutions participated in this study: Keio University School of Medicine, Tokyo, Japan; Saitama Medical University International Medical Center, Hidaka, Saitama, Japan; National Defense Medical College, Tokorozawa, Saitama, Japan; Saiseikai Central Hospital, Tokyo, Japan; Saitama City Hospital, Saitama, Japan; National Hospital Organization Saitama Hospital, Wako, Saitama,

References (23)

Cited by (5)

  • Development of novel ACN (albumin, C-reactive protein and neutrophil-to-lymphocyte ratio) prognostication model for patients with metastatic renal cell carcinoma receiving first-line molecular-targeted therapy

    2021, Urologic Oncology: Seminars and Original Investigations
    Citation Excerpt :

    The high fraction of the intermediate risk group assessed by the 2 conventional models is consistent with previous studies and has been considered as their potential disadvantage [4,6–9]. In fact, considering the heterogeneity of the intermediate risk group classified by these 2 models, there have been several attempts to subdivide this group by introducing another index to enable a more precise prediction of the risk of mRCC patients [10,26]. Here, we would like to describe several limitations of this study.

  • Feasibility of the ACL (albumin, C-reactive protein and lactate dehydrogenase) model as a novel prognostic tool in patients with metastatic renal cell carcinoma previously receiving first-line targeted therapy

    2020, Urologic Oncology: Seminars and Original Investigations
    Citation Excerpt :

    This result is consistent with previous findings, and has been highlighted as a critical disadvantage of these 2 conventional models [4,6–9]. Based on the heterogeneity of intermediate risk patients, attempts have been made to improve the ability of the IMDC model to predict the outcomes of this group of patients by subdividing them into 2 groups according to the positive numbers of risk factors [23,24]. Several limitations of the present study need to be addressed.

  • Prognostic value of neutrophil-to-lymphocyte ratio in patients with metastatic renal cell carcinoma treated with first-line and subsequent second-line targeted therapy: A proposal of the modified-IMDC risk model

    2017, Urologic Oncology: Seminars and Original Investigations
    Citation Excerpt :

    In sequential treatments of this targeted therapy era, changes in biomarkers before and after treatment may become important when demonstrating a decision-making and counseling for patients. Our recent work examined the effect of the IMDC risk reclassification after targeted therapy administration [30], and we found that approximately a quarter of patients with mRCC were reclassified into a different risk group 1 month after targeted therapy administration in both first-line and second-line settings. In this report, some patients experienced a recovery from neutrophilia, and some were worse after treatment.

1

These authors jointly directed this work.

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