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Advances in the Treatment of Kidney and Upper Urinary Tract Cancers

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 19319

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Dr. Łukasz Zapała

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Clinic of General, Oncological and Functional Urology, Medical University of Warsaw, Warsaw, Poland
Interests: non-muscle invasive bladder cancer
Special Issues, Collections and Topics in MDPI journals

Dr. Pawel Rajwa

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Guest Editor

Department of Urology, Medical University of Silesia, Zabrze, Poland
Interests: prostate cancer; urology; active surveillance; radical prostatectomy; MRI

Special Issue Information

Dear Colleagues,

Kidney and Upper Tract Urinary Cancers (UTUC) are diseases of increasing population coverage, the treatment of which are undergoing a continuous process of evolution. A characteristic feature of the picture composing the results of renal cell cancer (RCC) treatment is the significant heterogeneity of patients (including different stages of local advancement, different locations of metastases). Importantly, it is estimated that up to 30% of newly diagnosed RCC cases are patients with disseminated disease at the time of diagnosis. Therefore, predicting the response to modern treatment remains the unmet need of modern urologic oncology. Recent advancements in systematic treatment, i.e., immunotherapy, shed additional light on adjuvant treatment to be implemented in new clinical scenarios, including localized disease.

This Special Issue aims to cover novel approaches in the renal and urothelial cancers. We opt for original papers and reviews relating to advances in the treatment of Kidney and Upper Tract Urinary Cancers.

Dr. Łukasz Zapała
Dr. Pawel Rajwa
Guest Editors

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Keywords

renal cancer
urothelial cancer
immunotherapy
systemic therapy

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Published Papers (12 papers)

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Editorial

Jump to: Research, Review

4 pages, 167 KiB

Open AccessEditorial

Advances in the Treatment of Kidney and Upper Urinary Tract Cancers

by Łukasz Zapała and Paweł Rajwa

Biomedicines 2024, 12(3), 536; https://doi.org/10.3390/biomedicines12030536 - 27 Feb 2024

Viewed by 1013

Abstract

Kidney and upper tract urinary cancers (UTUC) are diseases of increasing population coverage, the treatment of which is undergoing a continuous process of evolution [...] Full article

(This article belongs to the Special Issue Advances in the Treatment of Kidney and Upper Urinary Tract Cancers)

Research

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13 pages, 2527 KiB

Open AccessArticle

Adverse Events of Cabozantinib as a Potential Prognostic Factor in Metastatic Renal Cell Carcinoma Patients: Real-World Experience in a Single-Center Retrospective Study

by Piotr Domański, Mateusz Piętak, Barbara Kruczyk, Jadwiga Jarosińska, Anna Mydlak, Tomasz Demkow, Marta Darewicz, Bożena Sikora-Kupis, Paulina Dumnicka, Wojciech Kamzol and Jakub Kucharz

Biomedicines 2024, 12(2), 413; https://doi.org/10.3390/biomedicines12020413 - 9 Feb 2024

Viewed by 1689

Abstract

Cabozantinib, an oral inhibitor targeting MET, AXL, and VEGF receptors, has become a key component of a sequential treatment strategy for clear cell renal cell carcinoma (ccRCC). The purpose of this work is to show that effective management of adverse events (AEs) during cabozantinib treatment and achieving a balance between AEs and treatment efficacy is crucial to achieving therapeutic goals. In this retrospective study, involving seventy-one metastatic RCC (mRCC) patients receiving second or subsequent lines of cabozantinib at the Department of Genitourinary Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, we explored the impact of AEs on overall survival (OS) and progression-free survival (PFS). AEs were observed in 92% of patients. Hypothyroidism during treatment was significantly associated with prolonged OS and PFS (HR: 0.31; p < 0.001 and HR: 0.34; p < 0.001, respectively). The occurrence of hand–foot syndrome (HFS) was also linked to improved OS (HR: 0.46; p = 0.021). Patients experiencing multiple AEs demonstrated superior OS and PFS compared to those with one or no AEs (HR: 0.36; p < 0.001 and HR: 0.30; p < 0.001, respectively). Hypothyroidism and HFS serve as valuable predictive factors during cabozantinib treatment in ccRCC patients, indicating a more favorable prognosis. Full article

(This article belongs to the Special Issue Advances in the Treatment of Kidney and Upper Urinary Tract Cancers)

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9 pages, 794 KiB

Open AccessArticle

Expression of Basal Compartment and Superficial Markers in Upper Tract Urothelial Carcinoma Associated with Balkan Endemic Nephropathy, a Worldwide Disease

by Ljubinka Jankovic Velickovic, Ana Ristic Petrovic, Zana Dolicanin, Slavica Stojnev, Filip Velickovic and Dragoslav Basic

Biomedicines 2024, 12(1), 95; https://doi.org/10.3390/biomedicines12010095 - 1 Jan 2024

Cited by 1 | Viewed by 1307

Abstract

The aim of this study was to determine the association of basal compartment and superficial markers, comprising CK5/6, CD44, CK20, and the pathological characteristics of upper tract urothelial carcinoma (UTUC) associated with Balkan endemic nephropathy (BEN). Comparing the expression of the investigated markers in 54 tumors from the BEN region and 73 control UTUC, no significant difference between them was detected. In regression analysis, CK20 expression was not determined with expression of CK5/6, CD44, and the phenotypic characteristics of BEN and control UTUC. Parameters with predictive influence on the expression of CD44 in BEN UTUC included growth pattern (p = 0.010), necrosis (p = 0.019); differentiation (p = 0.001), and lymphovascular invasion (p = 0.021) in control UTUC. Divergent squamous differentiation in BEN tumors (p = 0.026) and stage in control tumors (p = 0.049) had a predictive influence on the expression of CK5/6. This investigation detected a predictive influence of the phenotypic characteristics of UTUC on the expression of basal compartment and superficial markers, with a significant influence of necrosis in BEN tumors (p = 0.006) and differentiation in control UTUC (p = 0.036). Full article

(This article belongs to the Special Issue Advances in the Treatment of Kidney and Upper Urinary Tract Cancers)

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20 pages, 10144 KiB

Open AccessArticle

Basement Membrane-Associated lncRNA Risk Model Predicts Prognosis and Guides Clinical Treatment in Clear Cell Renal Cell Carcinoma

by Xinxin Li, Qihui Kuang, Min Peng, Kang Yang and Pengcheng Luo

Biomedicines 2023, 11(10), 2635; https://doi.org/10.3390/biomedicines11102635 - 26 Sep 2023

Cited by 3 | Viewed by 1334

Abstract

The basement membrane (BM) affects the invasion and growth of malignant tumors. The role and mechanism of BM-associated lncRNAs in clear cell renal cell carcinoma (ccRCC) are unknown. In this study, we identified biomarkers of ccRCC and developed a risk model to assess patient prognosis. We downloaded transcripts and clinical data from the Cancer Genome Atlas (TCGA). Differential analysis, co-expression analysis, Cox regression analysis, and lasso regression were used to identify BM-associated prognostic lncRNAs and create a risk prediction model. We evaluated and validated the accuracy of the model using multiple methods and constructed a nomogram to predict the prognosis of ccRCC. GO, KEGG, and immunity analyses were used to explore differences in biological function. We constructed a risk model containing six BM-associated lncRNAs (LINC02154, IGFL2-AS1, NFE4, AC112715.1, AC092535.5, and AC105105.3). The risk model has higher diagnostic efficiency compared to clinical characteristics and can be used to forecast patient prognoses. We used renal cancer cells and tissue microarrays to verify the expression of lncRNAs in the risk model. We found that knocking down LINC02154 and AC112715.1 could inhibit the invasion ability of renal cancer cells. The risk model based on BM-associated lncRNAs can well predict ccRCC and guide clinical treatment. Full article

(This article belongs to the Special Issue Advances in the Treatment of Kidney and Upper Urinary Tract Cancers)

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18 pages, 8221 KiB

Open AccessArticle

A Neurosurgical Perspective on Brain Metastases from Renal Cell Carcinoma: Multi-Institutional, Retrospective Analysis

by Liliana Eleonora Semenescu, Ligia Gabriela Tataranu, Anica Dricu, Gheorghe Vasile Ciubotaru, Mugurel Petrinel Radoi, Silvia Mara Baez Rodriguez and Amira Kamel

Biomedicines 2023, 11(9), 2485; https://doi.org/10.3390/biomedicines11092485 - 7 Sep 2023

Cited by 1 | Viewed by 1384

Abstract

Background: While acknowledging the generally poor prognostic features of brain metastases from renal cell carcinoma (BM RCC), it is important to be aware of the fact that neurosurgery still plays a vital role in managing this disease, even though we have entered an era of targeted therapies. Notwithstanding their initial high effectiveness, these agents often fail, as tumors develop resistance or relapse. Methods: The authors of this study aimed to evaluate patients presenting with BM RCC and their outcomes after being treated in the Neurosurgical Department of Clinical Emergency Hospital “Bagdasar-Arseni”, and the Neurosurgical Department of the National Institute of Neurology and Neurovascular Diseases, Bucharest, Romania. The study is based on a thorough appraisal of the patient’s demographic and clinicopathological data and is focused on the strategic role of neurosurgery in BM RCC. Results: A total of 24 patients were identified with BM RCC, of whom 91.6% had clear-cell RCC (ccRCC) and 37.5% had a prior nephrectomy. Only 29.1% of patients harbored extracranial metastases, while 83.3% had a single BM RCC. A total of 29.1% of patients were given systemic therapy. Neurosurgical resection of the BM was performed in 23 out of 24 patients. Survival rates were prolonged in patients who underwent nephrectomy, in patients who received systemic therapy, and in patients with a single BM RCC. Furthermore, higher levels of hemoglobin were associated in our study with a higher number of BMs. Conclusion: Neurosurgery is still a cornerstone in the treatment of symptomatic BM RCC. Among the numerous advantages of neurosurgical intervention, the most important is represented by the quick reversal of neurological manifestations, which in most cases can be life-saving. Full article

(This article belongs to the Special Issue Advances in the Treatment of Kidney and Upper Urinary Tract Cancers)

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12 pages, 2187 KiB

Open AccessArticle

Catfish Egg Lectin Enhances the Cytotoxicity of Sunitinib on Gb3-Expressing Renal Cancer Cells

by Jun Ito, Shigeki Sugawara, Takeo Tatsuta, Masahiro Hosono and Makoto Sato

Biomedicines 2023, 11(8), 2317; https://doi.org/10.3390/biomedicines11082317 - 21 Aug 2023

Cited by 2 | Viewed by 1124

Abstract

Metastatic renal cell carcinoma (RCC) is not sufficiently responsive to anticancer drugs, and thus, developing new drugs for advanced RCC remains vital. We previously reported that the treatment of globotriaosylceramide (Gb3)-expressing cells with catfish (Silurus asotus) egg lectin (SAL) increased the intracellular uptake of propidium iodide (PI) and sunitinib (SU). Herein, we investigated whether SAL pretreatment affects the intracellular uptake and cytotoxic effects of molecular-targeted drugs in RCC cells. We analyzed Gb3 expression in TOS1, TOS3, TOS3LN, and ACHN human RCC cells. Surface Gb3 expression was higher in TOS1 and TOS3 cells than in TOS3LN and ACHN cells. In the PI uptake assay, 41.5% of TOS1 cells and 21.1% of TOS3 cells treated with SAL were positive for PI. TOS1 cell viability decreased to 70% after treatment with 25 µM SU alone and to 48% after pretreatment with SAL (50 µg/mL). Time-series measurements of the intracellular fluorescence of SU revealed significantly enhanced SU uptake in SAL-treated TOS1 cells compared to control cells. SAL treatment did not increase PI uptake in normal renal cells. Our findings suggest that adequate cytotoxic activity may be achieved even when SU is administered at a sufficiently low dose not to cause side effects in combination with SAL. Full article

(This article belongs to the Special Issue Advances in the Treatment of Kidney and Upper Urinary Tract Cancers)

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16 pages, 1163 KiB

Open AccessArticle

Evaluation of Parameters Affecting the Occurrence of Systemic Inflammatory Response Syndrome in Patients Operated on Due to Kidney Tumors

by Mateusz Marcinek, Michał Tkocz, Kamil Marczewski, Robert Partyka, Leszek Kukulski, Krystyna Młynarek-Śnieżek, Bogumiła Sędziak-Marcinek, Paweł Rajwa, Adam Berezowski and Danuta Kokocińska

Biomedicines 2023, 11(8), 2195; https://doi.org/10.3390/biomedicines11082195 - 4 Aug 2023

Cited by 2 | Viewed by 1087

Abstract

The application and prognostic nature of systemic inflammatory reaction syndrome (SIRS) is still being researched, as using SIRS parameters to predict patient status is cheap, efficient, fast, and easy. The study aimed to determine SIRS markers and postoperative complications occurrence in patients undergoing kidney tumor surgery, and to verify if SIRS occurrence depends on age, sex, BMI (body mass index), comorbidities, patients’ general condition before the surgery, type of surgery, intraoperative blood loss, or intraoperative ischemia time. Body temperature, heart rate, respiratory rate, and leukocyte count were measured in patients (n = 285) operated on due to a kidney tumor on the first (T0) and third (T3) postoperative day. Univariable and multivariable logistic regression were used to analyze the factors affecting postoperative SIRS and complications occurrence. T0: SIRS developed in patients with higher BMI, >2 ASA points, and more substantial intraoperative blood loss. T3: SIRS developed in obese or overweight patients, with >2 ASA points, significantly higher relative HR change, lower relative body temperature change, respiratory rate, and leukocyte count. BMI values, preoperative general health status, and the amount of intraoperative blood loss in patients undergoing surgery due to a kidney tumor can contribute to SIRS occurrence. Patient’s sex, age, tumor size, type of surgery, operated side, and time of intraoperative ischemia do not affect SIRS occurrence. Full article

(This article belongs to the Special Issue Advances in the Treatment of Kidney and Upper Urinary Tract Cancers)

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14 pages, 3282 KiB

Open AccessArticle

Role of Nivolumab in the Modulation of PD-1 and PD-L1 Expression in Papillary and Clear Cell Renal Carcinoma (RCC)

by Joanna Bialek, Stefan Yankulov, Felix Kawan, Paolo Fornara and Gerit Theil

Biomedicines 2022, 10(12), 3244; https://doi.org/10.3390/biomedicines10123244 - 13 Dec 2022

Cited by 2 | Viewed by 1929

Abstract

The expression and cellular mechanisms of programmed cell death-1 protein (PD-1) and its ligands (PD-L1 and PD-L2) in renal cancer cells are not well known. Here, we aimed to investigate the response of renal carcinoma subtypes to the immune checkpoint inhibitor nivolumab and its impact on related signaling pathways. All cell lines analyzed (clear cell (cc)RCC (Caki-1, RCC31) and papillary (p)RCC (ACHN, RCC30)) expressed PD-1 and both ccRCC cell lines, and RCC30 expressed PD-L1. Nivolumab treatment at increasing doses led to increased PD-1 levels in analyzed cells and resulted in aggressive behavior of pRCC but diminished this behavior in ccRCC. The analysis of PD-1/PD-L1-associated signaling pathways demonstrated increased AKT activity in Caki-1 and RCC30 cells but decreased activity in ACHN and RCC31 cells, while ribosomal protein S6 remained largely unchanged. Androgen receptors are related to RCC and were predominantly increased in RCC30 cells, which were the only cells that formed nivolumab-dependent spheroids. Finally, all cell lines exhibited a complex response to nivolumab treatment. Since the pRCC cells responded with increased tumorigenicity and PD-1/PD-L1 levels while ccRCC tumorigenicity was diminished, further studies are needed to improve nivolumab-based therapy for renal carcinoma subtypes, especially the identification of response-involved molecular pathways. Full article

(This article belongs to the Special Issue Advances in the Treatment of Kidney and Upper Urinary Tract Cancers)

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12 pages, 1249 KiB

Open AccessArticle

High Pretreatment Serum PD-L1 Levels Are Associated with Muscle Invasion and Shorter Survival in Upper Tract Urothelial Carcinoma

by Ádám Széles, Petra Terézia Kovács, Anita Csizmarik, Melinda Váradi, Péter Riesz, Tamás Fazekas, Szilárd Váncsa, Péter Hegyi, Csilla Oláh, Stephan Tschirdewahn, Christopher Darr, Ulrich Krafft, Viktor Grünwald, Boris Hadaschik, Orsolya Horváth, Péter Nyirády and Tibor Szarvas

Biomedicines 2022, 10(10), 2560; https://doi.org/10.3390/biomedicines10102560 - 13 Oct 2022

Cited by 3 | Viewed by 1760

Abstract

Programmed death ligand-1 (PD-L1) is an immune checkpoint molecule and a widely used therapeutic target in urothelial cancer. Its circulating, soluble levels (sPD-L1) were recently suggested to be associated with the presence and prognosis of various malignancies but have not yet been investigated in upper tract urothelial carcinoma (UTUC). In this study, we assessed sPD-L1 levels in 97 prospectively collected serum samples from 61 UTUC patients who underwent radical nephroureterectomy (RNU), chemotherapy (CTX), or immune checkpoint inhibitor (ICI) therapy. In addition to pretreatment samples, postoperative and on-treatment sPD-L1 levels were determined in some patients by using ELISA. In the RNU group, elevated preoperative sPD-L1 was associated with a higher tumor grade (p = 0.019), stage (p < 0.001) and the presence of metastasis (p = 0.002). High sPD-L1 levels were significantly associated with worse survival in both the RNU and CTX cohorts. sPD-L1 levels were significantly elevated in postoperative samples (p = 0.011), while they remained unchanged during CTX. Interestingly, ICI treatment caused a strong, 25-fold increase in sPD-L1 (p < 0.001). Our results suggest that elevated preoperative sPD-L1 level is a predictor of higher pathological tumor stage and worse survival in UTUC, which therefore may help to optimize therapeutic decision-making. The observed characteristic sPD-L1 flare during immune checkpoint inhibitor therapy may have clinical significance. Full article

(This article belongs to the Special Issue Advances in the Treatment of Kidney and Upper Urinary Tract Cancers)

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14 pages, 8195 KiB

Open AccessArticle

The Four-Feature Prognostic Models for Cancer-Specific and Overall Survival after Surgery for Localized Clear Cell Renal Cancer: Is There a Place for Inflammatory Markers?

by Łukasz Zapała, Aleksander Ślusarczyk, Rafał Wolański, Paweł Kurzyna, Karolina Garbas, Piotr Zapała and Piotr Radziszewski

Biomedicines 2022, 10(5), 1202; https://doi.org/10.3390/biomedicines10051202 - 23 May 2022

Cited by 4 | Viewed by 2048

Abstract

We aimed at a determination of the relevance of comorbidities and selected inflammatory markers to the survival of patients with primary non-metastatic localized clear cell renal cancer (RCC). We retrospectively analyzed data from a single tertiary center on 294 patients who underwent a partial or radical nephrectomy in the years 2012–2018. The following parameters were incorporated in the risk score: tumor stage, grade, size, selected hematological markers (SIRI—systemic inflammatory response index; SII—systemic immune-inflammation index) and a comorbidities assessment tool (CCI—Charlson Comorbidity Index). For further analysis we compared our model with existing prognostic tools. In a multivariate analysis, tumor stage (p = 0.01), tumor grade (p = 0.03), tumor size (p = 0.006) and SII (p = 0.02) were significant predictors of CSS, while tumor grade (p = 0.02), CCI (p = 0.02), tumor size (p = 0.01) and SIRI (p = 0.03) were significant predictors of OS. We demonstrated that our model was characterized by higher accuracy in terms of OS prediction compared to the Leibovich and GRANT models and outperformed the GRANT model in terms of CSS prediction, while non-inferiority to the VENUSS model was revealed. Four different features were included in the predictive models for CSS (grade, size, stage and SII) and OS (grade, size, CCI and SIRI) and were characterized by adequate or even superior accuracy when compared with existing prognostic tools. Full article

(This article belongs to the Special Issue Advances in the Treatment of Kidney and Upper Urinary Tract Cancers)

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Review

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17 pages, 370 KiB

Open AccessReview

Prostate Cancer in Transplant Receivers—A Narrative Review on Oncological Outcomes

by Karolina Hanusz, Piotr Domański, Kacper Strojec, Piotr Zapała, Łukasz Zapała and Piotr Radziszewski

Biomedicines 2023, 11(11), 2941; https://doi.org/10.3390/biomedicines11112941 - 31 Oct 2023

Cited by 1 | Viewed by 1665

Abstract

Prostate cancer (PCa) is a low tumor mutational burden (TMB) cancer with a poor response to immunotherapy. Nonetheless, immunotherapy can be useful, especially in metastatic castration-resistant PCa (mCRPC). Increased cytotoxic T lymphocytes (CTLs) density is correlated with a shorter overall survival (OS), an early biochemical relapse, and a generally poor PCa prognosis. An increased number of CCR4+ regulatory T cells (CCR4 + Tregs) relates to a higher Gleason score or earlier progression. The same therapeutic options are available for renal transplant recipients (RTRs) as for the population, with a comparable functional and oncological outcome. Radical retropubic prostatectomy (RRP) is the most common method of radical treatment in RTRs. Brachytherapy and robot-assisted radical prostatectomy (RARP) seem to be promising therapies. Further studies are needed to assess the need for prostatectomy in low-risk patients before transplantation. The rate of adverse pathological features in RTRs does not seem to differ from those observed in the non-transplant population and the achieved cancer control seems comparable. The association between PCa and transplantation is not entirely clear. Some researchers indicate a possible association between a more frequent occurrence of PCa and a worse prognosis in advanced or metastatic PCa. However, others claim that the risk and survival prognosis is comparable to the non-transplant population. Full article

(This article belongs to the Special Issue Advances in the Treatment of Kidney and Upper Urinary Tract Cancers)

16 pages, 290 KiB

Open AccessReview

The Role of Focal Therapy and Active Surveillance for Small Renal Mass Therapy

by Milena Matuszczak, Adam Kiljańczyk and Maciej Salagierski

Biomedicines 2022, 10(10), 2583; https://doi.org/10.3390/biomedicines10102583 - 14 Oct 2022

Cited by 3 | Viewed by 1781

Abstract

Small and low-grade renal cell carcinomas have little potential for metastasis and disease-related mortality. As a consequence, the main problem remains the use of appropriately tailored treatment for each individual patient. Surgery still remains the gold standard, but many clinicians are questioning this approach and present the advantages of focal therapy. The choice of treatment regimen remains a matter of debate. This article summarizes the current treatment options in the management of small renal masses. Full article

(This article belongs to the Special Issue Advances in the Treatment of Kidney and Upper Urinary Tract Cancers)

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