Survival and clinical prognostic factors in metastatic non‐clear cell renal cell carcinoma treated with targeted therapy: A multi‐institutional, retrospective study using the Korean metastatic renal cell carcinoma registry

Abstract

Objectives The optimal treatment strategy for metastatic non‐clear cell renal cell carcinoma (mNCCRCC) is still elusive and mainly extrapolated from evidence available for metastatic clear cell renal cell carcinoma. The aim of the study was therefore to investigate the survival outcomes and prognostic factors affecting survival in patients with mNCCRCC treated with targeted therapy. Materials and methods We analyzed a total of 156 patients (8.1%) with mNCCRCC among the total cohort of 1922 patients in the Korean metastatic RCC registry. We used Kaplan‐Meier curve analysis to calculate the survival estimates for first‐line progression‐free survival (PFS), total PFS, and cancer‐specific survival (CSS). We also used the log‐rank test to compare the different groups and multivariate Cox‐proportional hazard regression analyses to evaluate the prognostic factors for survival. Results The mNCCRCC group had significantly inferior survival outcomes in terms of first‐line PFS, total PFS, and CSS (all P < 0.05). We found survival benefits in patients treated with first‐line vascular endothelial growth factor‐tyrosine kinase inhibitors (VEGF‐TKIs, first‐line PFS, and total PFS, all P < 0.05), cytoreductive nephrectomy (CSS, P < 0.0001), metastasectomy (CSS, P = 0.0017), and patients with metachronous metastasis (first‐line PFS, total PFS, and CSS, all P < 0.05). Liver metastasis was the only significant prognostic factor for both first‐line PFS and CSS (all P < 0.05). Conclusions In the current targeted therapy era, survival of mNCCRCC is still inferior in comparison with that of mCCRCC patients. We found survival benefits in patients treated with first‐line VEGF‐TKIs/CN/metastasectomy, and metachronous metastasis patients.

A Retrospective, Multicenter, Long-Term Follow-Up Analysis of the Prognostic Characteristics of Recurring Non-Metastatic Renal Cell Carcinoma After Partial or Radical Nephrectomy

“…Data of the 4,246 enrolled patients with RCC were obtained from two multicenter RCC databases—the nmRCC ( 8 ) and mRCC ( 9 ) databases—that were obtained from the Multicenter Korean National Kidney Cancer (MKNKC) database. A total of 464 (10.9%) patients with RCC were selected for this study.…”

“…This retrospective study was approved by the institutional review board of the National Cancer Center (approval number: NCC 2018-0045 and B1202/145-102), which waived the requirement for informed consent due to the retrospective nature of this study (8)(9)(10). All study procedures were performed in accordance with the tenets of the ethical guidelines and regulations of the Ethical Principles for Medical Research Involving Human Subjects of the World Medical Association Declaration of Helsinki.…”

“…The parameters analyzed in this study were baseline anthropometric characteristics, including age, sex, and underlying diseases; preoperative baseline laboratory findings, including serum albumin, hemoglobin, and creatinine; intraoperative nephrectomy information; pathology results, including pTNM stage, histology, Fuhrman nuclear grade, sarcomatoid differentiation, lymphovascular invasion, necrosis, and capsule invasion; and survival outcomes, including all-cause and cancer-specific deaths. The surgical procedures of partial and radical nephrectomies were documented in a previous study (8)(9)(10); however, no specific standardized protocol was followed for surgical procedures during the collection of data for the RCC database. For the initial postoperative imaging follow-up, imaging intervals, that is, either 1-or 3-month intervals, were not standardized and were based on the preference of the urologist for the postoperative surveillance protocol established at the time.…”

Role of metastasectomy in the management of renal cell carcinoma

“…In 2020, Dragomir et al conducted a 1:4 PSM analysis of 229 MTX patients and found that the median OS was significantly different compared to the matched group (81 months (interquartile range [IQR] 58 -Not reached (NR)) vs. 61 months (IQR 26 -NR; p = 0.0001), respectively (21). Similarly, MTX was also associated with improved cancer-specific mortality (CSM) and PFS (24,28,32,38,41,42). A large study by Wu et al in 2020 utilizing data from 2,911 mRCC patients found that MTX was significantly associated with decreased CSM (3-year cumulative incidence 52.6 vs. 59.2%, Hazard Ratio (HR) 0.875, 95% Confidence Interval (CI) 0.773-0.991; p = 0.015) (24).…”

Cabozantinib in advanced non-clear-cell renal cell carcinoma: is it the way clearer now?

“…In addition, a recent retrospective study, although involving only Asian patients (16), confirmed that the survival outcomes for the metastatic non clear cell RCC cohort were significantly inferior to the outcomes for the metastatic clear cell RCC cohort regarding to first-line PFS, total PFS, and cancer specific survival (CSS), except for the chromophobe and Xp 11.2 translocation groups that showed better survival outcomes compared to clear cell RCC. Contrariwise, first line PFS, total PFS and CSS for the other histologies evaluated in this study (like the collecting duct, papillary, and unclassified groups) were meaningfully poorer compared to those of the group clear cell RCC.…”