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Cancers
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Advances in Locally Advanced and Metastatic Kidney Cancer (2nd Edition)
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Advances in Locally Advanced and Metastatic Kidney Cancer (2nd Edition)

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

Deadline for manuscript submissions: closed (30 April 2026) | Viewed by 2936

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
Special Issues, Collections and Topics in MDPI journals
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 Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the second edition of a previous issue on the topic of “Advances in Locally Advanced and Metastatic Kidney Cancer”.

Our biological understanding and clinical management of kidney cancer has advanced significantly in recent years. In particular, the introduction of novel immune checkpoint inhibitors has led to unprecedented responses in metastatic disease and improved patient survival. These developments have 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 setting, there is increasing interest in administering systemic therapies in the perioperative (neoadjuvant or adjuvant) setting to 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 disease, 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 optimal setting remains uncertain. Furthermore, diagnostic, prognostic, and predictive circulating biomarkers remain an active area of research interest across the spectrum of RCC, while advances in diagnostic imaging are contributing to both improved diagnosis and potential theranostic applications.

In this Special Issue, we are seeking high-quality, original work that highlights advances in locally advanced and metastatic kidney cancer, pertaining to the themes outlined 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 250 words) can be sent to the Editorial Office for assessment.

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-anonymized 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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Review

13 pages, 892 KB  
Review
VEGF-TKI Outcomes in Metastatic Renal Cell Carcinoma According to Prior Immune Checkpoint Inhibitor or VEGF-TKI: A Scoping Review and Exploratory Analysis
by Elizabeth Nally, Agne Jovaisaite, Sara Coca Membribes, Garima Priyadarshini, Catherine Graham, Alan MacDonald, Francesca Jackson-Spence, Bernadett Szabados and Thomas Powles
Cancers 2026, 18(5), 807; https://doi.org/10.3390/cancers18050807 - 2 Mar 2026
Viewed by 1313
Abstract
Background/Objectives: Most patients with metastatic renal cell carcinoma (mRCC) progress on first-line immune checkpoint inhibitor (ICI). Subsequent vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) is standard. Due to the rapid evolution in treatment landscape, data directly comparing outcomes of VEGF-TKI [...] Read more.
Background/Objectives: Most patients with metastatic renal cell carcinoma (mRCC) progress on first-line immune checkpoint inhibitor (ICI). Subsequent vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) is standard. Due to the rapid evolution in treatment landscape, data directly comparing outcomes of VEGF-TKI following ICI versus VEGF-TKI alone are limited. This scoping review aimed to explore whether VEGF-TKI following prior ICI is associated with improved outcome, potentially reflecting a treatment sequence effect. Methods: PubMed/MEDLINE and ClinicalTrials.gov were searched systematically to identify phase 2/3 prospective clinical trials that investigated VEGF-TKI in patients who had progressed after ≥1 therapy published from 2004. Included studies were summarised by prior therapy and reported outcomes. Data from subgroups/arms were extracted and weighted overall response rate (ORR), progression free survival (PFS) and overall survival (OS) calculated for patients pretreated with VEGF-TKI versus ICI. An exploratory, hypothesis generating analysis was performed comparing outcomes between patients who received prior VEGF-TKI only or ICI-based therapy. Results: In total, 17 clinical trials were included: 2538 patients had prior VEGF-TKI (15 subgroups/arms) and 724 prior ICI-based therapy (11 subgroups/arms). In prior VEGF-TKI, weighted mORR was 8% (IQR 6–16%) versus 28% (IQR 20–41%) post-ICI. Weighted mPFS was 3.9 m (IQR 3.6–5.4) with prior VEGF-TKI versus 8.3 m (IQR 7.4–10.3) in prior ICI group. Weighted mOS was 15.2 m (IQR 11.1–16.6) versus 22.1 m (IQR 10.9–22.1) with prior ICI. Conclusions: Improved outcomes in ICI pretreated population in this exploratory analysis suggests ongoing biological benefit of ICI therapy. As prospective 2L randomised studies are not feasible, we conclude that VEGF therapy in pretreated mRCC is at least as good, if not better, since the introduction of 1st line ICI. Full article
(This article belongs to the Special Issue Advances in Locally Advanced and Metastatic Kidney Cancer (2nd Edition))
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13 pages, 1682 KB  
Review
Perioperative Immune-Checkpoint Inhibition in Renal Cell Carcinoma: Lessons Learned and Future Directions
by Adam Adika and Matthew Zibelman
Cancers 2026, 18(3), 527; https://doi.org/10.3390/cancers18030527 - 6 Feb 2026
Cited by 2 | Viewed by 1154
Abstract
Background/Objectives: Localized renal cell carcinoma (RCC) unfortunately has a suboptimal rate of metastatic recurrence. Immune-checkpoint inhibition (ICI), commonly known as immunotherapy, is being increasingly utilized in the management of other localized cancers. The objective of this paper is to review the most [...] Read more.
Background/Objectives: Localized renal cell carcinoma (RCC) unfortunately has a suboptimal rate of metastatic recurrence. Immune-checkpoint inhibition (ICI), commonly known as immunotherapy, is being increasingly utilized in the management of other localized cancers. The objective of this paper is to review the most recent literature as it pertains to ICI in localized RCC, highlight major lessons learned across clinical trials, and then suggest new directions based on these lessons and on new technologies. Methods: English-language articles were identified in PubMed/Google Scholar/Scopus. Selection priority was placed on prospective clinical trials. Particular emphasis was placed on disease-free survival (DFS), overall survival (OS), and clinical trial design. Novel approaches to the diagnosis, risk stratification, and management of RCC were also queried. Results: The KEYNOTE-564 trial demonstrated DFS and OS benefits of adjuvant pembrolizumab in high-risk clear cell RCC. Although discordance exists with adjuvant ICI in the IMmotion-010 and CheckMate-914 trials, preliminary data from the RAMPART trial also reveal a DFS benefit for adjuvant durvalumab–tremelimumab. The PROSPER trial failed to show a benefit for perioperative nivolumab, but ongoing neoadjuvant/perioperative ICI trials show promise. Subtle differences in design exist across the mentioned trials and are arguably clinically significant. Several new diagnostic tools and technologies have been identified for use in RCC. Conclusions: By applying the lessons learned from the differences in clinal trial design, along with leveraging new diagnostic tools and technologies, there is great potential to more accurately stratify risk amongst patients with localized RCC and therefore better identify the patients who are most likely to benefit from perioperative ICI. Full article
(This article belongs to the Special Issue Advances in Locally Advanced and Metastatic Kidney Cancer (2nd Edition))
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