Renal Cancer Patients Research Articles

Perioperative and Oncological Outcomes of Percutaneous Radiofrequency Ablation versus Partial Nephrectomy for cT1a Renal Cancers: A Retrospective Study on Groups with Similar Clinical Characteristics.

Over the recent years, progress in imaging techniques has led to an increased detection of kidney tumours, including small renal masses. While surgery is still the standard of care, there is a growing interest in minimally invasive methods. Ultrasound (US)-guided percutaneous ablation is particularly attractive because it is a safe and relatively simple procedure. In this study, we investigated the results of US-guided percutaneous radiofrequency ablation (RFA) and partial nephrectomy (PN) in the treatment of cT1a renal cancers. Between August 2016 and February 2022, 271 patients with renal tumours underwent percutaneous RFA as initial treatment in our institution. In the same period, 396 patients with renal tumours underwent surgical tumour excision. For the purpose of this study, only patients with confirmed renal cancer with matched age and tumour characteristics (size, location) were selected for both groups. Thus, a group of 44 PN patients and 41 RFA patients were formed with the same qualification criteria for both groups. Parameters such as procedure length, blood loss, hospital stay, analgesics used, and pre- and post-procedural serum creatinine were compared between these groups. Patients followed up with contrast-enhanced CT. There was no significant difference in age, tumour size, tumour location, and creatinine levels between these groups. All procedures were generally well tolerated. During a median follow-up of 28 months, two cases of recurrence/residual disease were found in each group. The overall survival was 100% in both groups, and all patients were disease-free at the end of observation. Percutaneous RFA was associated with a significantly shorter procedure length and hospital stay, lower blood loss, and lower analgesics used than PN. In the selected group of renal cancer patients, US-guided percutaneous RFA was associated with a shorter hospital stay, less analgesics used, and a shorter procedure length than PN, without differences in the oncological results or kidney function.

Evaluation of tumor response to immune checkpoint inhibitors by a 3D immunotumoroid model.

Only 20 percent of renal and bladder cancer patients will show a significant response to immune checkpoint inhibitor (ICI) therapy, and no test currently available accurately predicts ICI response. We developed an "immunotumoroid" cell model system that recapitulates the tumor, its microenvironment, and necessary immune system components in patient-derived spheroids to enable ex vivo assessment of tumor response to ICI therapy. Immunotumoroids were developed from surgically resected renal cell carcinomas and bladder carcinomas selected for high tumor-infiltrating lymphocytes (TILs) and survived more than a month without media exchange. Immunohistochemistry was used to detect immune and non-immune cells in cryopreserved source tumors and the resulting immunotumoroids. Immunotumoroid response to ICIs (nivolumab, pembrolizumab, and durvalumab) and chemotherapy (cisplatin, gemcitabine, and paclitaxel) was monitored in real-time with Cytotox Red staining in an Incucyte device, and the immunotumoroid response was compared to retrospective clinical drug responses. Six of the 13 cases tested grew viable immunotumoroid models, with failed cases attributed to extensive tumor tissue necrosis or excess lymphocytes preventing spheroid formation. One successfully cultured case was excluded from the study due to low TIL infiltration (<5%) in the primary tumor sample. The five remaining models contained immune cells (CD4+ and CD8+ T cells, and macrophages), non-immune cells (fibroblasts), and tumor cells. Chemotherapy and ICI drugs were tested in immunotumoroids from 5 cases and compared to clinical outcomes where data was available. Four/five models showed cell killing in response to chemotherapy and two/five showed sensitivity to ICI. In three cases, the immunotumoroid model accurately predicted the patient's clinical response or non-response to ICIs or chemotherapy. Our immunotumoroid model replicated the multicellular nature of the tumor microenvironment sufficiently for preclinical ICI screening. This model could enable valuable insights into the complex interactions between cancer cells, the immune system, and the microenvironment. This is a feasibility study on a small number of cases, and additional studies with larger case numbers are required including correlation with clinical response.

The initial experience of robot-assisted nephron-sparing surgery in patients with renal cell cancer

Purpose of the study: analysis of our experience in performing robotic-assisted nephron-sparing surgeries using the da robotic system. Material and Methods. The retrospective study included the first 37 consecutive patients who underwent robot-assisted partial nephrectomy from May 2020 to december 2022. Results. To assess the surgical outcomes in patients undergoing partial nephrectomy, three parameters associated with trifecta achievement were analyzed. The trifecta was assessed according to the standard criteria, whereas the quadfecta, which in addition to the trifecta included preservation of &gt;90 % of the glomerular filtration rate (calculated according to Cockroft–Gault) in the postoperative period (3–7 days), did not assess the stage of chronic renal failure one year after surgery, thus probably demonstrating the high percentage of its achievement (54.1 %). A positive surgical margin was observed in 1 (2.7 %) patients. Warm ischemia time of more than 25 minutes was used in 8 patients (21.6 %). Complications in the postoperative period (Clavien–dindo II and higher) were observed in 1 (2.7 %) patient. Trifecta and quadfecta rates were 78.4 % and 54.1 %, respectively. To analyze the surgeons’ experience, 37 renal cell cancer patients were divided into two subgroups with first 20 and subsequent robotic partial nephrectomies. There were no differences in gender, age and calculated RENAL value between 2 subgroups. depending on the surgeons’ experience, statistically significant differences in the duration of surgery (p=0.035) and blood loss during surgery (p=0.007) were found. Conclusion. Considering the extensive experience of surgeons in the field of laparoscopic surgery for tumors of the renal parenchyma, the outcomes of robotic partial nephrectomies performed in 37 patients seem to be satisfactory and successful. The accumulated experience of surgeons after 20 robotic-assisted nephron-sparing surgeries makes it possible to significantly reduce surgery time and blood loss. The technique of robotic-assisted partial nephrectomy requires further improvements.

Abstract 2463: Targeting CXCR4 impaired T regulatory function through PTEN in renal cancer patients

Abstract Purpose: In Renal Cell Carcinoma (RCC) a crucial role is played by tumor microenvironment (TME). The high presence of T regulatory cells (Tregs) in TME cause a suppressive environment that promotes the tumor growth and its treatments failure. Tregs trafficking is controlled by CXCR4. In RCC, the new CXCR4 antagonist R54 was explored in peripheral blood Tregs isolated from primary RCC patients. Experimental Design: To investigate the mechanism by which the new CXCR4 antagonist R54 impairs Tregs activity, peripheral blood (PB) Tregs were explored on primary RCC patients. PB-Tregs were isolated from 77 RCC patients and 38 healthy donors-(HD) and CFSE-Tregs suppression assay, IL-35 secretion and Nrp-1+Tregs frequency was conducted. PB-Tregs were analyzed for PTEN, CD25, TGF-β1, FOXP3, DNMT1 expression. PTEN-pAKT signaling was evaluated in the presence of R54 and/or triciribine (TCB), Akt inhibitor. TSDR (Treg-specific Demethylated Region) methylation analysis was conducted. Result: Ex vivo R54 impaired PB-RCC-Tregs function, reduced IL-35 release and Nrp-1+Tregs. As PTEN and CD25 expression significantly decreased in R54-PB-RCC-Tregs, PTEN signaling was evaluated. While CXCL12 recruited PTEN+CD25+Tregs cells, R54 significantly reduced it in PB-RCC-Tregs. Tregs activation through IL-2/PMA impaired pAKT+Tregs while R54 increased it. The Akt inhibitor, triciribine, prevented the pAKT+Tregs R54 induction. As active Tregs present demethylated Treg-specific region (TSDR), a significant decrease in demethylation rate (DMR) of Foxp3-TSDR was observed in R54 treated PB-RCC-Tregs. As consequence of TSDR modulation, the expression of Tregs regulating genes was evaluated with significant reduction in DNMT1 and FOXP3 expression. Taken together, our findings demonstrated that R54 causes an impairment of peripheral Tregs functionality in primary RCC patients through regulation of PTEN/PI3K/AKT pathway, resulting in impaired Tregs activity. Conclusion: The CXCR4 antagonist R54 affects Tregs function in primary RCC patients through regulation of PTEN/PI3K/AKT pathway, reduction in TSDR demethylation and Foxp3 and DNMT1 expression. CXCR4 targeting is thus a strategy to inhibit Tregs activity contributing to the CXCR4 function in RCC tumor microenvironment. Citation Format: Giuseppina Rea, Sara Santagata, Anna Maria Bello, Anna Capiluongo, Maria Napolitano, Sonia Desicato, Alessandra Fragale, Crescenzo D'Alterio, Anna Maria Trotta, Caterina Ieranò, Luigi Portella, Marilena Di Napoli, Salvatore Di Maro, Florinda Feroce, Rosa Azzaro, Lucia Gabriele, Nicola Longo, Sandro Pignata, Sisto Perdonà, Stefania Scala. Targeting CXCR4 impaired T regulatory function through PTEN in renal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2463.

A1CF Binding to the p65 Interaction Site on NKRF Decreased IFN-β Expression and p65 Phosphorylation (Ser536) in Renal Carcinoma Cells.

Apobec-1 complementation factor (A1CF) functions as an RNA-binding cofactor for APO-BEC1-mediated C-to-U conversion during RNA editing and as a hepatocyte-specific regulator in the alternative pre-mRNA splicing of metabolic enzymes. Its role in RNA editing has not been clearly established. Western blot, co-immunoprecipitation (Co-IP), immunofluorescence (IF), methyl thiazolyl tetrazolium (MTT), and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to examine the role of A1CF beyond RNA editing in renal carcinoma cells. We demonstrated that A1CF interacts with NKRF, independent of RNA and DNA, without affecting its expression or nuclear translocation; however, it modulates p65(Ser536) phosphorylation and IFN-β levels. Truncation of A1CF or deletion on NKRF revealed that the RRM1 domain of A1CF and the p65 binding motif of NKRF are required for their interaction. Deletion of RRM1 on A1CF abrogates NKRF binding, and the decrease in IFN-β expression and p65(Ser536) phosphorylation was induced by A1CF. Moreover, full-length A1CF, but not an RRM1 deletion mutant, promoted cell proliferation in renal carcinoma cells. Perturbation of A1CF levels in renal carcinoma cells altered anchorage-independent growth and tumor progression in nude mice. Moreover, p65(Ser536) phosphorylation and IFN-β expression were lower, but ki67 was higher in A1CF-overexpressing tumor tissues of a xenograft mouse model. Notably, primary and metastatic samples from renal cancer patients exhibited high A1CF expression, low p65(Ser536) phosphorylation, and decreased IFN-β levels in renal carcinoma tissues compared with the corresponding paracancerous tissues. Our results indicate that A1CF-decreased p65(Ser536) phosphorylation and IFN-β levels may be caused by A1CF competitive binding to the p65-combined site on NKRF and demonstrate the direct binding of A1CF independent of RNA or DNA in signal pathway regulation and tumor promotion in renal carcinoma cells.

Abstract 110: Adoptive transfer of tumor antigen-specific T cells alters the renal tumor microenvironment in the presence and absence of immunotherapy

Abstract Immunotherapies are the standard of care for patients with renal cancer, yet their effects on renal tumor antigen-specific CD8 T cell responses and their subsequent ability to modulate the renal tumor microenvironment remain difficult to evaluate. In order to address this gap in the field, we developed a novel murine model to examine tumor-antigen specific CD8 T cell immune responses in orthotopic renal cancer utilizing a new cell line, Renca-tERK-LUC. Parental Renca cells were transduced with a lentivirus expressing the naturally-occurring, mutated tERK peptide found in CMS5 fibrosarcoma cells to create Renca-tERK-LUC tumor cells. The tERK mutation consists of a one base pair change that creates an Sfc1 site, so it can be detected by RT-PCR followed by restriction enzyme digestion. Our data show that Renca-tERK-LUC cells express tERK at high levels and grow progressively in control BALB/c mice, but are rejected in DUC Thy1.1 mice, which contain endogenous TCR transgenic CD8+ T cells specific for tERK peptide/MHC I complexes. We then performed adoptive transfers of 5 × 105 DUC Thy1.1 T cells into mice with established, orthotopic Renca-tERK-LUC tumors to evaluate: 1) the effects of immunotherapy on tumor-antigen-specific T cell responses; and 2) the effects of tumor-antigen-specific T cells on the broader renal tumor microenvironment. Our data indicate that the transfer of relatively low numbers of tumor antigen-specific CD8+ T cells induces transcriptomic and cellular changes in the tumor microenvironment in both the presence and absence of immunotherapy. Defining the parameters surrounding tumor-antigen-specific T cell responses and their ability to modulate the renal tumor microenvironment under the influence of clinically relevant immunotherapeutic intervention has the potential to increase the understanding of immunity to renal tumors, which could ultimately prove beneficial for renal cancer patients. Citation Format: Holly Stephens, Elizabeth Elkins, Francesca Dempsey, Zoey Swalley, Jing Li, Jianqing Zhang, Richard Kirkman, Bo-Ruei Chen, Zachary Roberts, Sunil Sudarshan, Barry Sleckman, Hubert Tse, Daniel L. Smith, Lyse A. Norian. Adoptive transfer of tumor antigen-specific T cells alters the renal tumor microenvironment in the presence and absence of immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 110.

Abstract 3982: Evaluating the effects of obesity on immune responses in renal tumors

Abstract Understanding the effects of obesity on cancer progression and treatment is a critically important area of research. Obesity is reaching epidemic proportions in our country and is known to increase the risk for many cancers, including renal cell carcinoma, which is among the ten most common cancers in both men and women. Our lab has shown that obesity leads to worse outcomes in advanced renal cancer patients treated with immunotherapy as compared to lean patients, but the cause for this difference is unknown. To investigate this further, we utilized a murine model with diet-induced obese mice and lean mice that were challenged with orthotopic renal tumors. The tumors grew out over three weeks and were harvested for flow cytometry staining. We stained for markers associated with immune function to better characterize what might be causing patients with obesity to be less responsive to immunotherapy. Our preliminary findings show that DIO mice had a greater tumor burden than lean controls over time. We also found that there compositional differences in multiple subsets of T cells in DIO versus lean mice. In the future, we will expand our murine studies to evaluate the phenotype and function of both tumor cells and immune cells. Additionally, we will continue these studies in human samples to further examine associations between obesity and immunotherapy outcomes. Citation Format: Francesca Dempsey, Lyse Norian. Evaluating the effects of obesity on immune responses in renal tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3982.

A Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Effect of Topical Urea for Secondary Prophylaxis of Hand Foot Skin Reaction in Renal Cell Cancer Patients on Sunitinib Therapy

IntroductionHand foot skin reaction (HFSR) is a common dose-limiting adverse effect of multi kinase inhibitors (MKI) whose mechanism is not fully understood, and the prophylaxis is inadequate. ObjectiveIn this pilot study, a double-blind, randomized placebo-controlled trial was conducted to evaluate the effect of topical urea in secondary prevention of sunitinib-induced HFSR in renal cell cancer patients. MethodsOut of 55 screened patients, 14 were randomized to receive topical urea or placebo for four weeks. The association of HFSR with drug levels of sunitinib and its metabolite (n-desethyl sunitinib), genetic polymorphism of VEGFR2 gene, quality of life (QOL) and biochemical markers was also assessed. ResultsThe results showed that urea-based cream was not superior to placebo (P = .075). There was no change in the QOL in both the groups. Single nucleotide polymorphism was checked for two nucleotides rs1870377 and rs2305948 located in VEGFR2 gene on chromosome 4. SNP (variant T > A) at rs1870377 was associated with appearance of new HFSR as compared to the wild type, although the association was not statistically significant (OR 0.714). There was no statistically significant difference between mean plasma levels of sunitinib and N-desethyl sunitinib in urea arm as compared to placebo arm as compared to placebo. The best fit population pharmacokinetic model for sunitinib was one compartment model with first order absorption and linear elimination. The median (IQR) of population parameters calculated from the population pharmacokinetics model for Ka, V and Cl was 0.22 (0.21-0.24) h-1, 4.4 (4.09-4.47) L, 0.049 (0.042-0.12) L/hr, respectively. ConclusionThe study suggested that the urea-based cream was not superior to placebo in decreasing the appearance of new HFSR in renal cancer patients receiving 4:2 regimen of sunitinib.

Performance Prediction for Surgical Outcomes in Laparoscopic Partial Nephrectomy Using Nephrometry Scores: A Comparison of Zhongshan and Radius, Exophytic/Endophytic, Nearness, Anterior/Posterior, Location Systems.

Objective: The aim of this study is to compare the precision and applicability of the Zhongshan (ZS) score against the radius, exophytic/endophytic, nearness, anterior/posterior, and location (RENAL) score in forecasting perioperative outcomes during laparoscopic partial nephrectomy (LPN). Materials and Methods: We retrospectively analyzed data from 99 renal cancer patients who underwent LPN between January 2017 and August 2023. Patients were scored and categorized based on both the ZS and RENAL scores. The study then compared perioperative outcomes across these groups and further investigated the correlation between ZS and RENAL scores and overall complication rates. Results: LPN was successfully accomplished in 94 patients, whereas 5 patients necessitated conversion to open or radical surgery. The high-risk group, according to the ZS score, manifested more warm ischemic time (WIT) than the low-risk group (P = .007). Furthermore, the incidence of overall complications escalated with increase in the ZS score grade (P = .045). A higher RENAL score corresponded to a greater risk of conversion to open or radical treatment (P = .012). Correlation analyses revealed associations between both ZS and RENAL scores and overall complications. The RENAL score also correlated with changes in blood creatinine values, while the ZS score was associated with WIT (all P < .05). In the univariate analysis, both ZS and RENAL scores were substantial factors for the occurrence of total complications (P = .029 and P = .027, respectively), but they were not statistically significant in the multivariate analysis. The receiver operating characteristic curves suggested that both individual and combined ZS and RENAL scores held predictive potential for the onset of overall complications (area under the curve = 0.652, 0.660, and 0.676, respectively). Conclusions: Compared with the RENAL score, the ZS score provides a more comprehensive assessment of tumor complexity in patients undergoing LPN. Integrating these two scores could potentially improve the accuracy of predicting surgical risks.

Optimal timing of delayed cytoreductive nephrectomy in metastatic renal cell carcinoma during the immunotherapy era.

403 Background: The CARMENA study found no survival benefit from cytoreductive nephrectomy (CN) in poor-risk metastatic renal cell cancer (mRCC) patients treated with first line Sunitinib. Although retrospective studies have reported survival benefits with CN following immunotherapy (IO)-based therapy, the timing remains unclear. We aimed to investigate the ideal timing of CN following IO using the National Cancer Database. Methods: 783 patients with de novo mRCC were diagnosed between 2016 and 2020 who received upfront systemic therapy and underwent CN, 343 patients met our criteria. Patients were categorized into four groups based on the timing of nephrectomy: CN ≤3 months (Group A), 4 to 6 months (Group B), 7 to 9 months (Group C) and ≥ 10 months (Group D) following the initiation of IO-based therapy. Descriptive analysis was performed to examine the demographic and clinical characteristics. Follow up time was measured from the date of surgery to reduce bias. Kaplan-Meier plots were used to analyze survival curves, and a multivariable cox regression analysis was performed to explore associations between timing and survival. Results: 343 patients who received upfront IO -based therapy were divided into four groups: 104 (30%) in A, 114 (33%) in B, 74 (22%) in C and 51 (15%) in D. 71%were male, white (90%), age 40 – 64 (62%), comorbidity index 0 (70%), clear cell histology (69%), sarcomatoid (14%). 54% were treated in academia, 57% had bone metastasis, 50% had lung, 11% had liver, and 7% had brain metastases. 66% received only IO, and 34% received IO + TKI. No significant association between CN timing and survival observed in multivariate cox regression model. (HR 0.87, 95% CI: 0.5- 1.7, p = 0.84). Compared to group A, the HR were 0.96 (95% CI, 0.73 to 1.27; p=0.78), 0.77 (95% CI, 0.53 to 1.13; p=0.19), and 0.66 (95% CI, 0.37 to 1.20; p=0.17) respectively for groups B, C and D. Conclusions: Our study did not find significant survival improvement with an optimal timing of CN following IO-based therapy, while HRs were reduced after 6 months of delay, though insignificant. This could be due to the small sample size or other confounders.

Exosomes in Renal Cell Cancer: Diagnostic and Therapeutic Nanovehicles.

Early diagnosis is crucial for enhancing the survival rate of renal cell cancer patients, and exosomes present potential advantages in this area. Their small size, high mobility, and lipid bilayer structure enable exosomes to cross biological membranes easily, protecting the bioactive cargo within from degradation. Exosomes significantly influence the invasion and metastasis of RCC, and they also contribute to tumor drug resistance and immune evasion.

Evaluating the effectiveness of the Charlson Comorbidity Index in predicting immune checkpoint inhibitor-related adverse events.

Aims: Our study aimed to evaluate the effectiveness of the Charlson Comorbidity Index (CCI) in predicting immune-related adverse events (irAEs) in solid tumor patients receiving immunotherapy. Patients & methods/materials: The CCI score at the time of initiation of immunotherapy was calculated in 164 solid tumor patients receiving immunotherapy and the correlation between the CCI score and immune toxicity was evaluated. Results: A significant relationship was found between CCI score and irAEs in lung cancer and renal cell cancer patients. In malignant melanoma, no significant relationship was found between the CCI score and the occurrence of irAEs. Conclusion: We argue that CCI can be used to predict irAEs, but we believe that a specific comorbidity index that includes autoimmune diseases should be developed.

Inpatient outcomes of metastatic epidural spinal cord compression in patients with gastric cancer compared to patients with other solid cancer.

255 Background: Metastatic epidural spinal cord compression (MESCC) is an oncologic emergency which can be associated with poor outcomes for cancer patients. Our aim was to study the differences in outcomes of MESCC in patients with gastric cancer (GC-MESCC) compared to those with other solid malignancies. Methods: Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database (2016-2020) was queried to identify all solid (breast, prostate, lung, gastrointestinal, renal and thyroid) cancer patients admitted with spinal cord compression. Multivariate logistic regression was used to evaluate differences in socio-demographics, medical comorbidities and outcomes between MESCC in gastric cancer patients and those with other solid cancers. The primary outcome included inpatient mortality, length of stay (LOS), and total hospital charges (THC). Results: 78,385 patients with the above solid cancers were admitted for spinal cord compression. Among them, 710 had gastric cancer. Patients with gastric cancer were younger (Mean age: 59.1 vs 66.3 years, p &lt; 0.001). They had higher prevalence of anemia (56 vs 41%), protein energy malnutrition (28.9 vs 18.9%, p &lt; 0.001), and lower prevalence of COPD (8.45 vs 18.5%, p =0.003), smoking (22.5 vs 33.6%, p =0.007) and CKD (9.4 vs 12.3%, p =0.03). On multivariate regression, those with GC-MESCC had two-fold higher odds of all-cause mortality (adjusted odds ratio (aOR): 2.0; 95% CI: 1.05-3.96, p = 0.034). On subgroup analysis, mortality was about four times higher for females with GC-MESCC relative to the other group (aOR = 3.8, 95% CI: 1.69-8.52, p = 0.001). There was a trend towards increased LOS (8.9 vs 7.8 days) and THC ($115, 805 vs $96, 074) but it was not statistically significant. Compared with the other cohort, GC-MESCC patients had higher rates of blood transfusion (16.2 vs 9%, p = 0.003). Conclusions: Metastatic epidural spinal cord compression is associated with increased odds of inpatient mortality in gastric cancer patients compared to those with other solid malignancies. Hence, these patients ought to have urgent intervention and close monitoring to prevent adverse outcomes. [Table: see text]

Targeting STAT3 in tumor-associated antigen-presenting cells as a strategy for kidney and bladder cancer immunotherapy.

Immune checkpoint blockade (ICB) improved clinical outcomes in renal and bladder cancer patients, but the response rates remain limited especially in metastatic disease. While STAT3 transcription factor is well-known master regulator of tumor immune evasion, little is known about the role of STAT3 in the resistance of renal or bladder cancers to immunotherapy. To better understand immune alterations associated with ICB resistance, we assessed blood biomarkers in renal cancer patients classified as responders or non-responders to first line nivolumab/ipilimumab immunotherapy. We observed that non-responders showed elevated levels of proinflammatory mediators, such as IL-1RA, IL-6, IL-8 and to lesser extent IL-10, which are associated with STAT3 activation and tumor immunosuppression. In addition, we found STAT3 activation primarily in circulating myeloid immune cells such as tolerogenic MDSCs. To assess whether STAT3 inhibition within these cell subsets can promote antitumor immune responses and/or enhance sensitivity to ICB in vivo, we used an original antisense oligonucleotide (ASO) strategy for myeloid-cell selective STAT3 knockdown (CpG-STAT3ASO). Our results in syngeneic models of renal and bladder cancers in mice demonstrated potent antitumor activity of CpG-STAT3ASO alone in contrast to PD1 blockade alone in both models. The CpG-STAT3ASO/anti-PD1 combination improved therapeutic efficacy especially against bladder tumors. Therapeutic efficacy correlated with activation of dendritic cells (DCs) and M1 macrophages in the tumor microenvironment, reduced percentages of regulatory T cells (Tregs) and the expansion of CD8 T cells in both tumor models. Our study underscores the potential of using myeloid-cell targeted CpG-STAT3 inhibitors for genitourinary cancer therapy to disrupt tolerogenic signaling, restore immune cell activity and sensitivity to immune checkpoint inhibitors and/or T cell-based immunotherapies.

Measurement of Glomerular Filtration Rate in Patients Undergoing Renal Surgery for Cancer: Estimated Glomerular Filtration Rate versus Measured Glomerular Filtration Rate in the Era of Precision Medicine.

In the era of precision medicine, determining reliable renal function assessment remains a critical and debatable issue, especially in nephrology and oncology. This paper delves into the significance of accurately measured glomerular filtration rate (mGFR) in clinical practice, highlighting its essential role in guiding medical decisions and managing kidney health, particularly in the context of renal cancer (RC) patients undergoing nephrotoxic anti-cancer drugs. The limitations and advantages of traditional glomerular filtration rate (GFR) estimation methods, primarily using serum biomarkers like creatinine and cystatin C, are discussed, emphasizing their possible inadequacy in cancer patients. Specifically, newer formulae designed for GFR estimation in cancer patients may not perform at best in RC patients. The paper explores various methods for direct GFR measurement, including the gold standard inulin clearance and alternatives like iohexol plasma clearance. Despite the logistical challenges of these methods, their implementation is crucial for accurate renal function assessment. The paper concludes by emphasizing the need for continued research and innovation in GFR measurement methodologies to improve patient outcomes, particularly in populations with complex medical needs.

A comparative study of tumor markers and dynamic contrast-enhanced CT and their combined evaluation in the diagnosis of renal cancer patients

The objectives of this study were to investigate the diagnostic efficacy of dynamic contrast-enhanced Computed Tomography (CT) and tumor markers and their combined evaluation in renal cancer patients. A total of eighty male patients with solid renal lesions were selected from our hospital and categorized into two groups based on pathological examination findings: renal cancer group and benign lesion group. A comparison was made between the findings of dynamic contrast-enhanced CT and tumor markers and the diagnostic efficacy of either mono or combined evaluation were compared. Receiver operating characteristic curves were plotted to better analyze and compare different diagnostic techniques. The serum concentrations of carcinoembryonic antigen (CEA), Cytokeratin 19 fragment (CYFRA21-1), midkine (MK) and matrix metalloproteinase 9 (MMP-9) in renal cancer patients were significantly higher than those with benign lesions (p &lt; 0.05). The Receiver Operating Characteristic (ROC) curve analysis demonstrated that the combination of dynamic contrast-enhanced CT and tumor markers had the highest area under the curve. This difference was statistically significant (p &lt; 0.05). The analysis of the overall model quality results revealed that the model values for both single and combination indicators exceeded 0.5, with the combined indicators having the highest value of (0.84). The diagnostic efficacy of dynamic contrast-enhanced CT combined with tumor markers for renal cancer is significantly higher than either the dynamic contrast-enhanced CT or tumor markers alone. The combination of dynamic contrast-enhanced CT and tumor markers has a significant therapeutic benefit in diagnosing renal cancer. We envisage that, this approach can offer valuable guidance for the clinical diagnosis and treatment of renal cancer.

Analysis of the results of surgical treatment of renal cancer patients with extended venous tumor thrombosis

Analysis of the results of surgical treatment of renal cancer patients with extended venous tumor thrombosis

Deep learning-assisted survival prognosis in renal cancer: A CT scan-based personalized approach

This paper presents a deep learning (DL) approach for predicting survival probabilities of renal cancer patients based solely on preoperative CT imaging. The proposed approach consists of two networks: a classifier- and a survival- network. The classifier attempts to extract features from 3D CT scans to predict the ISUP grade of Renal cell carcinoma (RCC) tumors, as defined by the International Society of Urological Pathology (ISUP). Our classifier is a 3D convolutional neural network to avoid losing crucial information on the interconnection of slides in 3D images. We employ multiple procedures, including image augmentation, preprocessing, and concatenation, to improve the performance of the classifier. Given the strong correlation between ISUP grading and renal cancer prognosis in the clinical context, we use the ISUP grading features extracted by the classifier as the input to the survival network. By leveraging this clinical association and the classifier network, we are able to model our survival analysis using a simple DL-based network. We adopt a discrete LogisticHazard-based loss to extract intrinsic survival characteristics of RCC tumors from CT images. This allows us to build a completely parametric survival model that varies with patients' tumor characteristics and predicts non-proportional survival probability curves for different patients. Our results demonstrated that the proposed method could predict the future course of renal cancer with reasonable accuracy from the CT scans. The proposed method obtained an average concordance index of 0.72, an integrated Brier score of 0.15, and an area under the curve value of 0.71 on the test cohorts.

New Insights into the Link between SARS-CoV-2 Infection and Renal Cancer.

Cancer has been described as a risk factor for greater susceptibility to SARS-CoV-2 infection and severe COVID-19, mainly for patients with metastatic disease. Conversely, to that reported for most solid and hematological malignancies, the few available clinical studies reported that the infection did not increase the risk of death in renal cancer patients. The expression on proximal tubular renal cells of the key players in cellular viral uptake, ACE2, TMPRSS2, and NRP1, seems to be the mechanism for the direct kidney injury seen in patients with COVID-19. Interestingly, data from The Cancer Genome Atlas and experimental analyses on various renal cancer cell lines demonstrated that the above-reported receptors/cofactors are maintained by renal cancer cells. However, whether SARS-CoV-2 infection directly kills renal cancer cells or generates enhanced immunogenicity is a question worth investigating. In addition, some researchers have further addressed the topic by studying the expression and prognostic significance of gene signatures related to SARS-CoV-2 infection in renal cancer patients. The emerging data highlights the importance of better understanding the existence of a link between renal cancer and COVID-19 since it could lead to the identification of new prognostic factors and the development of new therapeutic targets in the management of renal cancer patients.

Immunotherapy in Elderly Patients-Single-Center Experience.

Cancer management faces a substantial challenge posed by the aging demographic. Aging is marked by accumulated DNA damage, and this phenomenon is implicated in the process of tumorigenesis. The concept of immunosenescence, postulated to manifest in elderly individuals, is defined by an age-related decline in T cells and a simultaneous elevation in proinflammatory status, leading to a diminished efficacy in response to immunotherapy. Notably, despite the rising prevalence of cancer in the elderly population, their underrepresentation in clinical trials persists. This underscores the unmet need to evaluate the safety and efficacy of cancer treatment in the elderly. This retrospective, single-center cohort study aimed to assess and evaluate the effectiveness and safety of immunotherapy in patients compared to younger individuals with metastatic solid tumors receiving ICI. A total of 220 patients were included, mostly males, with a median age of 64. The proportion of patients ≥ 65 years old was 56.5%. The use of ICI showed no significant differences concerning overall survival (OS) and progression-free survival (PFS) among age groups across different cancer types (melanoma, non-small-cell lung cancer (NSCLC), renal, and bladder cancer; p = 0.388). Concerning the response to treatment in renal cancer patients, a significant difference was observed (p = 0.041), suggesting a potential negative impact of age on the treatment response. In patients that presented immune-related adverse events (irAEs), oral corticosteroid therapy was marginally associated (p = 0.059) with the elderly population. When evaluating the NSCLC population alone (n = 131, 59.5%), our study revealed a strong association between the development of irAEs, patients' PFS and OS, and the duration of ICI treatment, but not directly correlated with age. The NSCLC elderly population presented a marginally greater number of irAEs, although without statistical significance (p = 0.86). ICI maintained efficacy and safety in elderly patients, challenging the notion that age alone should determine treatment decisions. The findings emphasize the necessity of a comprehensive geriatric assessment rather than relying solely on chronological age for personalized cancer treatment in the elderly population. Further prospective studies are needed to better understand immune responses in older adults and derive predictive biomarkers for cancer treatment.