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Cancers
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Advances in Locally Advanced and Metastatic Kidney Cancer
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Advances in Locally Advanced and Metastatic Kidney Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Metastasis".

Deadline for manuscript submissions: closed (15 April 2025) | Viewed by 2010

Special Issue Editors

Dr. Nirmish Singla

E-Mail Website
Guest Editor
The Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Interests: urologic oncology; kidney cancer; translational research; testicular cancer; upper tract urothelial carcinoma
Dr. Yasser Ged

E-Mail Website
Guest Editor
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Interests: kidney cancer; translational research; biomarkers; clinical trials; immune-oncology; testicular cancer

Special Issue Information

Dear Colleagues,

Our biological understanding and clinical management of kidney cancer has evolved considerably in recent years. In particular, the advent of novel immune checkpoint inhibitors has led to unprecedented responses in metastatic disease, with improvements in survival outcomes for patients. This has paved the way for the emergence of rational, synergistic combinations of immunotherapies and targeted therapies.

Advanced renal cell carcinoma (RCC) exhibits a wide clinical spectrum, ranging from non-metastatic, high-risk or locally advanced tumors, to oligometastatic disease, to more widely disseminated metastatic involvement. In the locally advanced space, increasing interest has turned to administering systemic therapies in the perioperative (neoadjuvant or adjuvant) setting to help reduce recurrence. In the study of oligometastatic disease, new approaches to the locoregional management of metastatic sites, such as stereotactic radiation, have been employed to delay or obviate the need for systemic therapy while minimizing morbidity. In more widely disseminated diseases, novel therapeutic agents and rational combinations continue to emerge for both clear cell and non-clear cell RCC histologies. The role and timing for cytoreductive nephrectomy in metastatic disease continue to evolve, and the ideal setting remains unknown at present. Furthermore, diagnostic, prognostic, and predictive circulating biomarkers continue to remain an active area of research interest across the spectrum of RCC, while diagnostic imaging has also seen advances in both diagnosis and potential theranostic applications.

In this Special Issue, we are seeking high-quality, novel work highlighting advances in locally advanced and metastatic kidney cancer, pertaining to the themes delineated above. We look forward to receiving your contributions.

Dr. Nirmish Singla
Dr. Yasser Ged
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • kidney cancer
  • renal cell carcinoma
  • locally advanced
  • oligometastatic
  • metastatic
  • novel therapeutics
  • diagnostic imaging
  • biomarkers
  • multimodal treatment
  • cytoreductive nephrectomy

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Published Papers (2 papers)

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Research

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19 pages, 1575 KiB  
Article
Characteristics and Outcomes of T1a Renal Cell Carcinoma Presenting with Metastasis
by Luke Wang, Melis Guer, Dhruv Puri, Franklin Liu, Sohail Dhanji, Margaret F. Meagher, Aastha Shah, Saeed Ghassemzadeh, Juan Javier-DesLoges, James Brugarolas, Payal Kapur, Aditya Bagrodia, Brent Rose, James D. Murphy, Ithaar H. Derweesh and Rana R. McKay
Cancers 2025, 17(3), 364; https://doi.org/10.3390/cancers17030364 - 23 Jan 2025
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Abstract
Objectives: The incidence of renal cell carcinoma (RCC) has been rising, largely due to increased incidental detection from widespread imaging. Although synchronous distant metastasis (SM) with a primary renal tumor measuring <4 cm (cT1a) is uncommon, its presence may influence survival outcomes and [...] Read more.
Objectives: The incidence of renal cell carcinoma (RCC) has been rising, largely due to increased incidental detection from widespread imaging. Although synchronous distant metastasis (SM) with a primary renal tumor measuring <4 cm (cT1a) is uncommon, its presence may influence survival outcomes and the utility of cytoreductive nephrectomy. We sought to investigate clinical characteristics, metastatic patterns, treatments, and survival outcomes of patients with T1a RCC. Methods: All patients aged ≥18 years diagnosed with RCC between 2004 and 2019 were extracted from the National Cancer Database. The Cochran–Armitage test was used for trend analysis, while multivariable analyses were conducted to identify variables associated with SM and to assess the impact of cytoreductive surgery on mortality across isolated metastatic sites. Kaplan–Meier analysis was performed to compare survival outcomes. Results: A total of 263,911 individuals diagnosed with T1a RCC were analyzed in the study. Among them, 114,661 patients (43.4%) were classified as having cT1a tumor stage, and of these patients with cT1a RCC, 2275 (2.0%) exhibited SM. The proportion of SM cT1a was 3.39% in 2004 and 2.08% in 2019, with an Average Annual Percent Change (AAPC) of −0.037% (p = 0.830). The most common sites of metastasis were bone (59%), followed by lung (35%), liver (16%), and brain (12%). Resection of the primary tumor and receipt of systemic therapy were significantly associated with reduced mortality among all metastatic sites, especially in individuals with lung-only metastases (HR = 0.02, p = 0.013). Metastasectomy was associated with improved survival in patients with brain-only metastases (HR = 0.26, p = 0.006) but did not demonstrate the same benefit in patients with bone-, lung- or liver-only metastases. The worst 5-year OS rate was observed in cases with metastasis to multiple sites, whereas isolated metastases had similar survival rates (p < 0.0001). Our findings are limited by retrospective study design. Conclusions: This comprehensive analysis of T1a RCC patients reveals that while synchronous metastasis is relatively uncommon (2.0%), it presents significant clinical challenges, with bone as the most common metastatic site, contrasting with the typical lung predominance in larger tumors. Primary tumor resection showed survival benefit in patients with isolated metastases, especially for lung-only metastasis. These findings highlight the heterogeneous nature of tumor biology in small renal masses and underscore the importance of tailored, multimodal treatment strategies for the effective management of SM T1a RCC. Full article
(This article belongs to the Special Issue Advances in Locally Advanced and Metastatic Kidney Cancer)
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Review

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21 pages, 856 KiB  
Review
Systemic Treatment of Locally Advanced or Metastatic Non-Clear Cell Renal Cell Carcinoma
by Joseph Vento, Tian Zhang, Payal Kapur, Hans Hammers, James Brugarolas and Qian Qin
Cancers 2025, 17(9), 1527; https://doi.org/10.3390/cancers17091527 - 30 Apr 2025
Viewed by 140
Abstract
Non-clear cell renal cell carcinoma (nccRCC) represents a heterogenous group of malignancies with varying degrees of clinical aggressiveness and response to different systemic therapies. As the characterization of subtypes of nccRCC continues to evolve, it is important to understand the evidence around systemic [...] Read more.
Non-clear cell renal cell carcinoma (nccRCC) represents a heterogenous group of malignancies with varying degrees of clinical aggressiveness and response to different systemic therapies. As the characterization of subtypes of nccRCC continues to evolve, it is important to understand the evidence around systemic treatments used in advanced or metastatic stages of specific subtypes. Here, we review the literature on systemic therapies in nccRCC, with a focus on prospective trials that included patients with papillary renal cell carcinoma (RCC), chromophobe RCC, RCC not further classified/unclassified RCC, translocation RCC, collecting duct RCC, and renal medullary carcinoma. We also review emerging treatments for other molecularly defined subtypes of this disease. Full article
(This article belongs to the Special Issue Advances in Locally Advanced and Metastatic Kidney Cancer)
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