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Advances in Renal Cell Carcinoma

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

Deadline for manuscript submissions: closed (31 March 2026) | Viewed by 9565

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Special Issue Editors

Prof. Dr. Philipp Ivanyi

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Guest Editor

Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover, Germany
Interests: real world analysis; urogenital cancers; sarcoma; head and neck cancers; renal cell carcinoma

Dr. Hendrik Eggers

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Guest Editor

Department of Hematology and Oncology, Städtisches Klinikum Braunschweig, Celler Street 38, 308114 Braunschweig, Germany
Interests: lung cancer; renal cell carcinoma; real world analysis; risk factors

Special Issue Information

Dear Colleagues,

Medical treatment of renal cell carcinoma has experienced groundbreaking improvements over the last few decades. Evolving from an unselected immunotherapy with interferons and a type of treatment that only benefits very few patients, a broad range of highly effective therapies are available nowadays, including targeted therapies and immunotherapy. Treatment for this malignancy has demonstrated unparallel improvements in survival for patients who are deemed to be incurable. With the advances in medical treatment, an improved understanding of the diverse biological causes of the diseases and the multimodal care of RCC patients with individualized local and medical treatment sequencings represent the future scientific challenges.

Following these dramatic changes, there is still an urgent need to understand the advantages and characteristics of our current treatment strategies in different settings and populations. Therefore, this Special Issue will highlight all aspects of state-of-the-art therapy, including but not limited to special patient populations, prognostic or predictive markers and real-world application experiences.

We welcome all studies who share our fascination for this topic and help to understand how we can treat patients in the most effective manner possible.

Prof. Dr. Philipp Ivanyi
Dr. Hendrik Eggers
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-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

renal cell carcinoma
treatment
metastatic
prediction
medical treatment
immunotherapy
multimodal therapy
targeted therapy

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Published Papers (6 papers)

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Research

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15 pages, 1478 KB

Open AccessArticle

The Predictive Value of Computed Tomography and HA3D Nephrometry Scores for Complications After Partial Nephrectomy: A Prospective Pilot Study

by Agostino Fraia, Sara Riolo, Francesco Di Bello, Salvatore Papi, Ivan Di Giulio, Giovanni Costa, Roberto Knez, Tommaso Silvestri, Bernardino de Concilio, Massimiliano Creta, Nicola Longo, Guglielmo Zeccolini and Antonio Celia

Cancers 2026, 18(7), 1047; https://doi.org/10.3390/cancers18071047 - 24 Mar 2026

Viewed by 404

Abstract

Background/Objectives: Accurate preoperative assessment of renal tumor complexity is essential for surgical planning and for predicting perioperative outcomes after partial nephrectomy (PN). RENAL and PADUA nephrometry scores, traditionally derived from two-dimensional (2D) computed tomography (CT) imaging, are widely used to quantify renal tumor complexity and surgical risk. However, the introduction of hyperaccuracy three-dimensional (HA3D) models has enabled enhanced anatomical visualization, potentially improving the assessment of surgical difficulty and the prediction of postoperative complications. The aim of this study was to compare conventional CT-based RENAL and PADUA scores with HA3D-derived nephrometry scores in predicting perioperative complications in patients undergoing robot-assisted or laparoscopic PN. Methods: A total of 17 consecutive patients with intermediate- or high-complexity category renal tumors (RENAL ≥ 7) and moderate- or high-risk category tumors (PADUA ≥ 8) were prospectively enrolled. Preoperative demographic and clinical parameters, as well as intraoperative and postoperative data, were prospectively collected. Tumor characteristics were evaluated using both CT-based RENAL and PADUA scoring systems and HA3D nephrometry reconstruction. Associations between nephrometry scores and perioperative outcomes were assessed using Spearman’s correlation. Predictive performance for postoperative complications and early chronic kidney disease (CKD) was evaluated using receiver operating characteristic (ROC) analysis. Results: Overall, 41% and 35% of cases were downgraded according to three-dimensional (3D) RENAL and PADUA complexity–risk category assessment, respectively. Operative time demonstrated a moderate correlation with 3D RENAL (ρ = 0.57) and 3D PADUA (ρ = 0.49) scores. ROC curve analysis demonstrated numerical differences in area under the curve (AUC) values between 3D- and 2D-based nephrometry scores in predicting overall complications (RENAL: 0.61 vs. 0.54; PADUA: 0.69 vs. 0.46). 3D RENAL score demonstrated numerically higher AUC values for early postoperative CKD compared with 2D RENAL score (AUC: 0.72 vs. 0.67). Conclusions: HA3D-based nephrometry scores were associated with enhanced anatomical visualization, frequent downgrading of tumor complexity–risk categories, and numerical differences in predictive performance for postoperative complications and early renal functional decline compared with conventional CT-based scores. These findings suggest a potential role for HA3D modeling in preoperative planning for PN. However, given the limited sample size, these observations should be interpreted as exploratory and hypothesis-generating, and warrant validation in larger multicenter cohorts. Full article

(This article belongs to the Special Issue Advances in Renal Cell Carcinoma)

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13 pages, 1122 KB

Open AccessArticle

Perceptions and Expectations of Pharmacist Interventions in Adverse Event Management During Drug Therapy for Metastatic Renal Cell Carcinoma: A Cross-Sectional Survey in Japan

by Tetsuya Wako, Go Kimura, Yasuhisa Fujii, Takahiro Osawa, Yosuke Uchitomi, Kazunori Honda, Miki Kondo, Ariko Otani, Yoshihide Mitsuda and Nobuo Shinohara

Cancers 2025, 17(24), 3951; https://doi.org/10.3390/cancers17243951 - 11 Dec 2025

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Abstract

Background: We investigated the role of pharmacists in adverse event (AE) management during renal cell carcinoma (RCC) drug therapy by surveying patients, physicians, and pharmacists. We identified the types of AEs for which pharmacist involvement is beneficial and explored measures to promote pharmacist intervention. Methods: This was an ad hoc analysis of a questionnaire-based cross-sectional web survey conducted from May to June 2022 among patients undergoing RCC drug therapy, physicians prescribing RCC treatments, and pharmacists involved in oncology care in Japan. Results: A total of 83 patients with metastatic RCC, 165 physicians, and 218 pharmacists were included. Among patients, 28.9% reported experiencing AEs or symptoms requiring pharmacist intervention. Most physicians (78.2%) and pharmacists (96.3%) supported pharmacist involvement in AE management. Notably, 35.6% of patients who reported no AEs or symptoms requiring pharmacist intervention acknowledged difficulty in communicating AEs to their physicians. Regarding desired pharmacist interventions for AEs, patients prioritized rash/pruritus, fatigue, and diarrhea; physicians emphasized stomatitis and anorexia; pharmacists identified constipation, stomatitis, and diarrhea. The most common reason patients valued pharmacist involvement was the reassurance of support from multiple healthcare providers. Physicians and pharmacists valued pharmacists’ greater familiarity with AE management, particularly considering physicians’ limited time. Raising awareness among patients and healthcare professionals, patient requests, and improving institutional support were strategies to enhance pharmacist involvement. Over 86% of healthcare professionals considered pharmaceutical outpatient clinics necessary to strengthen interdisciplinary collaboration. Conclusions: This study highlights widespread support among patients, physicians, and pharmacists for pharmacist involvement in managing AEs during RCC drug therapy. Full article

(This article belongs to the Special Issue Advances in Renal Cell Carcinoma)

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14 pages, 3262 KB

Open AccessArticle

Functional and Oncologic Outcomes in Single-Kidney Patients Treated with Robot-Assisted Partial Nephrectomy for Renal Tumors: Results from a Prospectively Maintained Dataset of a Single Tertiary Referral Center

by Antonio Andrea Grosso, Luca Lambertini, Fabrizio Di Maida, Giulia Carli, Pedro Ramos, Alessandro Sandulli, Vincenzo Salamone, Francesca Conte, Filippo Lipparini, Elena Ciaralli, Daniele Paganelli, Sofia Giudici, Rino Oriti, Riccardo Fantechi, Matteo Salvi, Gianni Vittori, Maria Rosaria Raspollini, Gabriella Nesi, Andrea Minervini and Andrea Mari

Cancers 2025, 17(12), 1978; https://doi.org/10.3390/cancers17121978 - 13 Jun 2025

Cited by 2 | Viewed by 1745

Abstract

Background: Renal tumors in solitary kidneys require treatments that optimize both oncological and functional outcomes. Robot-assisted partial nephrectomy (RAPN) offers a balance between these needs and reduced morbidity. This study investigates the oncologic and functional outcomes of RAPN in solitary-kidney patients. Methods: We analyzed data from 1852 patients with cT1-T4N0M0 renal cell carcinoma treated by RAPN from January 2018 to June 2022. The cohort included patients with solitary kidneys based on preoperative characteristics, tumor staging and perioperative outcomes using the Trifecta criteria. Results: Of the study participants, 39 had solitary kidneys. Fifteen patients (38.6%) had an ASA score > 2, indicating a higher preoperative risk. The median PADUA score was 7 (IQR 8–9). Moreover, 28 (71.8%) patients had a chronic kidney disease stage > 2. Trifecta success was achieved in 26 (66.6%) of the cases. During a median follow-up of 36 months, tumor recurrence was observed in 12 patients (30.7%), with local recurrences in 4 (10.2%) and systemic recurrences in 8 (20.5%). A higher ASA score and global ischemic clamping were independent predictors of renal function decline at the third postoperative day and Trifecta failure. Only a higher ASA score significantly predicted a significant long-term decline in renal function. Nucleolar grade at pathological stage was the only factor significantly associated with tumor recurrence. Conclusions: RAPN is as an effective treatment for renal tumors in solitary kidneys, balancing oncological control and renal function preservation. Global ischemia and patient physical status are the most important factors influencing outcomes and highlight the importance of patient selection and tailored surgical strategies. Full article

(This article belongs to the Special Issue Advances in Renal Cell Carcinoma)

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14 pages, 4024 KB

Open AccessArticle

Changes of Prostate-Specific Membrane Antigen-Radioligand Uptake on PET with Systemic Therapy in Patients with Metastatic Renal Cell Carcinoma

by Sophie Carina Kunte, Adrien Holzgreve, Marcus Unterrainer, Josef Zahner, Hans Peter Schmid, Magdalena Schöll, Iulia Blajan, Gabriel T. Sheikh, Dirk Mehrens, Jozefina Casuscelli, Alexander J. Tamalunas, Rudolf A. Werner, Christian G. Stief, Michael Staehler and Lena M. Unterrainer

Cancers 2025, 17(11), 1736; https://doi.org/10.3390/cancers17111736 - 22 May 2025

Cited by 2 | Viewed by 1900

Abstract

Background/Objectives: Early treatment assessment in metastatic renal cell carcinoma (mRCC) remains challenging due to the limited accuracy of current imaging methods. Given prostate-specific membrane antigen (PSMA) overexpression in mRCC, PSMA PET is a promising approach. Despite numerous studies on PSMA imaging in mRCC, data on PSMA uptake changes during systemic therapy are scarce. We analyzed PSMA uptake on PET after treatment initiation in mRCC patients. Methods: A retrospective single-center analysis of mRCC patients who underwent [¹⁸F]PSMA-1007 PET/CT before (PET₁) and at a mean of 9.5 weeks after (PET₂) starting systemic therapy was conducted. PSMA uptake in metastatic lesions was compared by region and RCC subtype. Uptake differences between PET₁ and PET₂ were analyzed using an unpaired t-test. Results: This study included 25 patients (mean age 65.2 ± 14.7 years; 20 male) with mRCC. A total of 113 (PET₁) and 48 (PET₂) metastases were assessed. Lymph node metastases showed stable PSMA uptake (median SUV_max) after treatment (7.8 vs. 7.7, p = 0.77), while uptake by bone (6.4 vs. 12.4, p = 0.03) and lung metastases (4.5 vs. 8.1, p = 0.004) increased significantly. SUV stability in lymph nodes was independent of RCC subtype (ccRCC: p = 0.48, pRCC: p > 0.99). Bone (6.6 vs. 15.9, p = 0.008) and lung metastases (4.8 vs. 8.1, p = 0.02) had higher PSMA uptake in ccRCC, unlike pRCC (bone: 6.2 vs. 6.0, p = 0.86). Conclusions: Alterations of PSMA-radioligand uptake are seen in bone and pulmonary metastases but not in lymph node metastases after initiation of systemic treatment in patients with mRCC. ccRCC has a higher PSMA uptake than other RCC subtypes. Full article

(This article belongs to the Special Issue Advances in Renal Cell Carcinoma)

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11 pages, 1558 KB

Open AccessArticle

Endovascular Downstaging: A New Method for Managing Renal Cell Carcinoma Tumor Thrombus Invading the Inferior Vena Cava Above the Hepatic Veins (Level III) or into the Heart (Level IV)

by John A. Libertino, Malik Ahmed, Thomas Piemonte and Jason Gee

Cancers 2025, 17(2), 264; https://doi.org/10.3390/cancers17020264 - 15 Jan 2025

Cited by 2 | Viewed by 3391

Abstract

Background: Renal cell carcinoma tends to invade venous structures, frequently extending beyond the inferior vena cava and into the heart itself, such as into the right atrium or right ventricle. Resection of tumor burden, particularly tumor thrombus, often requires cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA), which is not feasible for all patients. Methods: Described in this study is a novel, minimally invasive endovascular approach involving endovascular thrombectomy as a viable approach in these select patients. Results: There were no surgical complications, shorter operating times, less blood loss and an average length of stay of 5.5 days in the four patients undergoing this procedure. Conclusions: We demonstrate that this technique can eliminate the need for cardiac bypass and deep hypothermic cardiac arrest and its associated risks, thereby making surgery safer and more accessible for patients with advanced kidney cancers with an inferior vena cava tumor thrombus. Furthermore, it allows for this life-saving surgery to be carried out in medical centers or hospitals where cardiac surgery is unavailable, or when cardiopulmonary bypass is medically contraindicated. Full article

(This article belongs to the Special Issue Advances in Renal Cell Carcinoma)

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Review

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25 pages, 654 KB

Open AccessReview

Refining Prognostic Stratification in Clear Cell Renal Cell Carcinoma: Genomic, Tissue-Based, Circulating Biomarkers and Integrated Models

by Mariana Bianca Chifu, Simona Eliza Giușcă, Andrei Daniel Timofte, Constantin Aleodor Costin, Andreea Rusu, Ana-Maria Ipatov and Irina Draga Căruntu

Cancers 2026, 18(9), 1371; https://doi.org/10.3390/cancers18091371 - 25 Apr 2026

Viewed by 649

Abstract

Clear cell renal cell carcinoma (ccRCC) is characterized by marked biological heterogeneity, which limits the prognostic accuracy of conventional clinicopathological models. Increasing attention has therefore focused on identification of biomarkers that can enhance risk stratification throughout all stages of the disease. Starting from the current state of the art, this narrative review summarizes and critically appraises the evidence published over the past decade regarding prognostic biomarkers in ccRCC. The analysis is structured into four overarching domains: (i) genomic biomarkers, covering somatic alterations and transcriptomic signatures; (ii) tissue-based biomarkers, including immunohistochemical surrogates and immune microenvironment features; (iii) circulating biomarkers, such as systemic inflammation parameters and indices; and (iv) integrated predictive models, represented by emerging multi-omic approaches. Going through the broad framework of potential prognostic biomarkers, emphasis is placed on their individual and integrative value in relation to classic clinical-pathological factors and survival parameters. At the tissue level, chromosome 3p-related alterations constitute a central molecular feature of ccRCC. Among these, BAP1 loss has emerged as one of the most consistently validated indicators of aggressive tumor behavior. Disruption of the SETD2/H3K36me3 axis and immune-related biomarkers, including PD-L1 expression, have demonstrated prognostic associations in selected settings, although with variable and context-dependent performance. In the circulating compartment, plasma KIM-1 has shown prognostic relevance following nephrectomy, while postoperative detection of circulating tumor DNA (ctDNA) may identify patients at increased risk of recurrence. However, limited analytical sensitivity and methodological heterogeneity currently restrict the broader clinical applicability of ctDNA-based strategies. Systemic inflammatory indices, such as the neutrophil-to-lymphocyte ratio, show reproducible associations with outcomes but largely reflect host inflammatory status rather than tumor-specific biology. However, no single biomarker currently supports routine prognostic implementation in ccRCC. Future progress will likely depend on integrative models combining genomic, tissue-based, immune, and circulating parameters with established clinical variables. Prospective validation and clear demonstration of incremental clinical utility will be essential before such strategies can meaningfully inform therapeutic decision-making. Full article

(This article belongs to the Special Issue Advances in Renal Cell Carcinoma)

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