BACKGROUND: Renal cell carcinoma (RCC) is a prevalent kidney malignancy known for its aggressive nature and potential to extend into the renal vein or inferior vena cava (IVC), affecting patient prognosis and treatment strategies. OBJECTIVE: To assess the long-term outcomes and effectiveness of radical nephrectomy with IVC thrombectomy in patients with RCC presenting with level I-IV IVC thrombus. METHODS: A retrospective analysis was conducted on 164 adult patients treated for RCC with IVC thrombectomy at a tertiary care center from January 2004 to December 2023. Data including demographics, clinical characteristics, tumor specifics, surgical details, complications, and survival rates were meticulously reviewed. RESULTS: Among the patients, the mean age was 63.7 years, predominantly male (69.5%). The histological profile showed a majority of clear cell carcinoma (95.7%), with most tumors located on the right side (71.3%). Thrombus levels were distributed across I-IV, with 41 (25%) patients presenting with level I, 33 (20.1%) with level II, 55 (33.5%) with level III, and 35 (21.4%) with level IV thrombi. The mean operation time and blood loss increased with thrombus level. Perioperative complications were recorded in 57.3% of patients, and over half of the patients experienced disease recurrence (54.9%). The overall 5-year survival rate stood at 42.1%, with notably better survival in patients with level I thrombi. CONCLUSION: Radical nephrectomy with IVC thrombectomy provides a potential for long-term control in patients with RCC and IVC thrombus, although it is associated with significant morbidity. Multidisciplinary care and expert surgical intervention are crucial for improving patient outcomes. The variability in survival rates across thrombus levels underscores the need for individualized treatment approaches.

• Keywords
• Inferior Vena Cava, Radical nephrectomy, Renal cell carcinoma, Thrombectomy,
• MeSH
• Time Factors MeSH
• Adult MeSH
• Carcinoma, Renal Cell * surgery   pathology   complications   MeSH
• Middle Aged MeSH
• Humans MeSH
• Kidney Neoplasms * surgery   pathology   complications   MeSH
• Nephrectomy * methods   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Thrombectomy * methods   MeSH
• Vena Cava, Inferior * surgery   MeSH
• Treatment Outcome MeSH
• Venous Thrombosis * surgery   etiology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

INTRODUCTION: Renal cell carcinoma (RCC) is one of the most prevalent cancers in kidney transplant recipients (KTR). The hereditary background of RCC in native kidneys has been determined, implicating its clinical importance. MATERIALS AND METHODS: This retrospective single-center pilot study aimed to identify a potential genetic predisposition to RCC of the transplanted kidney and outcome in KTR who underwent single kidney transplantation between January 2000 and December 2020 and manifested RCC of the transplanted kidney. Next-generation sequencing (NGS) based germline genetic analysis from peripheral blood-derived genomic DNA (gDNA) was performed in both the recipient and donor using a gene panel targeting 226 cancer predisposition genes. RESULTS: The calculated incidence of RCC of the transplanted kidney among 4146 KTR was 0.43%. In fifteen KTR and donors, NGS was performed. The mean KTR age at transplantation and the diagnosis of RCC was 50.3 years (median 54; 5-67 years) and 66 years (median 66; 24-79 years), respectively. The mean donor age at transplantation and graft age at RCC diagnosis was 39.7 years (median 42; 7-68 years) and 50.2 years (median 46; 20-83 years), respectively. The mean follow-up after RCC diagnosis was 47 months (median 39.1; 0-112 months). Papillary RCC was the most prevalent (n = 8), followed by clear cell RCC (n = 6) and unspecified RCC (n = 1). Thirteen RCCs were low-stage (pT1a/b) diseases, one was pT3, and one was of unknown stage. Most RCC was higher graded. No germline pathogenic cancer-predisposition variant was found in either KTR or donors except for several variants of uncertain significance. CONCLUSION: RCC of the transplanted kidney is very rare. Germline cancer-predisposition testing has identified several variants of uncertain significance, but no germline genetic predisposition to graft RCC in KTR. Further research is needed to assess the clinical relevance of genetic testing for cancer risk in KTR.

• MeSH
• Tissue Donors MeSH
• Child MeSH
• Adult MeSH
• Genetic Predisposition to Disease MeSH
• Carcinoma, Renal Cell * genetics   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Kidney Neoplasms * genetics   MeSH
• Pilot Projects MeSH
• Child, Preschool MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Kidney Transplantation * adverse effects   MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

INTRODUCTION: Systemic targeted therapy options are commonly used in patients with metastatic renal cell carcinoma (mRCC). Histological verification is crucial for treatment of mRCC. AIM: Our aim was to evaluate an optimal location for percutaneous computed tomography‑guided biopsy in a diagnosis of suspected mRCC. MATERIALS AND METHODS: A total of 138 percutaneous biopsies for tumors ranging from 21 to 133 mm in diameter (median, 72 mm) were carried out in 134 patients with suspected mRCC over a 5‑year period. The biopsy location was variable, with kidney biopsy performed in 77 cases (55.8%), and other localizations (retroperitoneum, peritoneal cavity, liver, pelvis, pleural space, lung, mediastinum, chest or abdominal wall, and pancreas) in 61 cases (44.2%). RESULTS: As many as 288 biopsies (97.1%), yielded truepositive results, and 4 procedures (2.9%) yielded histologically falsenegative results that required confirmation through extended rebiopsy. RCC was the most common individual diagnosis (85.5%), with non‑RCC histology verified in 14.5% of cases. In total, 32 complications (23.2%) were confirmed, 2 of which were pneumothoraces, 29 were minor bleeding that needed only conservative management, and 1 case required angiography and embolization for hemorrhage treatment. While no significant relationship between the biopsy success and lesion localization (renal vs other) was found (P = 0.13), the relationship between complication rate and biopsy localization (renal vs other) was significant (P = 0.01). CONCLUSIONS: Lesion localization (renal vs other) was not relevant to histological accuracy of the biop‑ sies performed in patients with suspected mRCC. However, the biopsies of lesions outside the kidney had a lower complication rate.

• Keywords
• biopsy location, complication rate, computed tomography guidance, metastatic disease, renal cell carcinoma,
• Publication type
• Journal Article MeSH

CONTEXT: Surgery is the gold standard for the local treatment of primary renal cell carcinoma (RCC), but alternatives are emerging. We conducted a systematic review and meta-analysis to assess the results of prospective studies using definitive stereotactic body radiotherapy (SBRT) to treat primary localised RCC. EVIDENCE ACQUISITION: This review was prospectively registered in PROSPERO (CRD42023447274). We searched PubMed, Embase, Scopus, and Google Scholar for reports of prospective studies published since 2003, describing the outcomes of SBRT for localised RCC. Meta-analyses were performed for local control (LC), overall survival (OS), and rates of adverse events (AEs) using generalised linear mixed models (GLMMs). Outcomes were presented as rates with corresponding 95% confidence intervals (95% CIs). Risk-of-bias was assessed using the ROBINS-I tool. EVIDENCE SYNTHESIS: Of the 2983 records, 13 prospective studies (n = 308) were included in the meta-analysis. The median diameter of the irradiated tumours ranged between 1.9 and 5.5 cm in individual studies. Grade ≥ 3 AEs were reported in 15 patients, and their estimated rate was 0.03 (95%CI: 0.01-0.11; n = 291). One- and two-year LC rates were 0.98 (95%CI: 0.95-0.99; n = 293) and 0.97 (95%CI: 0.93-0.99; n = 253), while one- and two-year OS rates were 0.95 (95%CI: 0.88-0.98; n = 294) and 0.86 (95%CI: 0.77-0.91; n = 224). There was no statistically significant heterogeneity, and the estimations were consistent after excluding studies at a high risk of bias in a sensitivity analysis. Major limitations include a relatively short follow-up, inhomogeneous reporting of renal function deterioration, and a lack of prospective comparative evidence. CONCLUSIONS: The short-term results suggest that SBRT is a valuable treatment method for selected inoperable patients (or those who refuse surgery) with localised RCC associated with low rates of high-grade AEs and excellent LC. However, until the long-term data from randomised controlled trials are available, surgical management remains a standard of care in operable patients.

• Keywords
• CyberKnife, clear cell carcinoma, definitive treatment, kidney cancer, non-metastatic, radiation,
• Publication type
• Journal Article MeSH
• Review MeSH

Immune checkpoint inhibitor (ICI)-based combination therapies are the recommended first-line treatment for metastatic renal cell carcinoma (mRCC). However, no head-to-head phase-3 randomized controlled trials (RCTs) have compared the efficacy of different ICI-based combination therapies. Here, we compared the efficacy of various first-line ICI-based combination therapies in patients with mRCC using updated survival data from phase-3 RCTs. Three databases were searched in June 2023 for RCTs that analyzed oncologic outcomes in mRCC patients treated with ICI-based combination therapies as first-line treatment. A network meta-analysis compared outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and complete response (CR) rate. Subgroup analyses were based on the International mRCC Database Consortium risk classification. The treatment ranking analysis of the entire cohort showed that nivolumab + cabozantinib (81%) had the highest likelihood of improving OS, followed by nivolumab + ipilimumab (75%); pembrolizumab + lenvatinib had the highest likelihood of improving PFS (99%), ORR (97%), and CR (86%). These results remained valid even when the analysis was limited to patients with intermediate/poor risk, except that nivolumab + ipilimumab had the highest likelihood of achieving CR (100%). Further, OS benefits of ICI doublets were not inferior to those of ICI + tyrosine kinase inhibitor combinations. Recommendation of combination therapies with ICIs and/or tyrosine kinase inhibitors based on survival benefits and patient pretreatment risk classification will help advance personalized medicine for mRCC.

• Keywords
• Immune checkpoint inhibitors, Metastasis, Network meta-analysis, Renal cell carcinoma,
• MeSH
• Ipilimumab MeSH
• Carcinoma, Renal Cell * drug therapy   MeSH
• Humans MeSH
• Kidney Neoplasms * drug therapy   MeSH
• Follow-Up Studies MeSH
• Nivolumab MeSH
• Pathologic Complete Response MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Network Meta-Analysis MeSH
• Systematic Review MeSH
• Names of Substances
• Ipilimumab MeSH
• Nivolumab MeSH

The role of cytoreductive nephrectomy in metastatic renal cell carcinoma (RCC) has been studied intensively over the past few decades. Interestingly, the opinion with regard to the importance of this procedure has switched from a recommendation as a standard of care to an almost complete refutation. However, no definitive agreement on cytoreductive nephrectomy, including the pros and cons of the procedure, has been reached, and the topic remains highly controversial. With the advent of immune checkpoint inhibitors, we have experienced a paradigm shift, with immunotherapy playing a crucial role in the treatment algorithm. Nevertheless, obtaining results from prospective clinical trials on the role of cytoreductive nephrectomy requires time, and once some data have been gathered, the standards of systemic therapy may be different, and we stand again at the beginning. This review summarizes current knowledge on the topic in the light of newly evolving treatment strategies. The crucial point is to recognize who could be an appropriate candidate for immediate cytoreductive surgery that may facilitate the effect of systemic therapy through tumor debulking, or who might benefit from deferred cytoreduction in the setting of an objective response of the tumor. The role of prognostic factors in management decisions as well as the technical details associated with performing the procedure from a urological perspective are discussed. Ongoing clinical trials that may bring new evidence for transforming therapeutic paradigms are listed.

• Keywords
• cytoreductive nephrectomy, deferred nephrectomy, immunotherapy, renal carcinoma, tyrosine kinase inhibitors,
• Publication type
• Journal Article MeSH
• Review MeSH

PURPOSE: To analyze and summarize the efficacy of immune checkpoint inhibitor (ICI) alone or in combination therapy for renal cell carcinoma (RCC) and urothelial carcinoma (UC) stratified by sex. METHODS: Three databases were queried in October 2022 for randomized controlled trials (RCTs) analyzing RCC and UC patients treated with ICIs. We analyzed the association between sex and the efficacy of ICIs in RCC and UC patients across several clinical settings. The outcomes of interest were overall survival (OS) and progression-free survival for the metastatic setting and disease-free survival (DFS) for the adjuvant setting. RESULTS: Overall, 16 RCTs were included for meta-analyses and network meta-analyses. In the first-line treatment of metastatic RCC (mRCC) and UC (mUC) patients, ICI-based combination therapies significantly improved OS compared to the current standard of care, regardless of sex. Adjuvant ICI monotherapy reduced the risk of disease recurrence in female patients with locally advanced RCC (pooled hazard ratio [HR]: 0.71, 95% confidence interval [CI] 0.55-0.93) but not in male patients, and, conversely, in male patients with muscle-invasive UC (pooled HR: 0.80, 95%CI 0.68-0.94) but not in female patients. Treatment ranking analyses in the first-line treatment of mRCC and mUC showed different results between sexes. Of note, regarding adjuvant treatment for RCC, pembrolizumab (99%) had the highest likelihood of improved DFS in males, whereas atezolizumab (84%) in females. CONCLUSIONS: OS benefit of first-line ICI-based combination therapy was seen in mRCC and mUC patients regardless of sex. Sex-based recommendations for ICI-based regimens according to the clinical setting may help guide clinical decision-making.

• Keywords
• Adjuvant, Advanced, Gender, Immune checkpoint inhibitors, Metastatic, Renal cell carcinoma, Sex, Urothelial carcinoma,
• MeSH
• Adjuvants, Immunologic MeSH
• Immune Checkpoint Inhibitors therapeutic use   MeSH
• Carcinoma, Transitional Cell * drug therapy   MeSH
• Carcinoma, Renal Cell * drug therapy   MeSH
• Kidney MeSH
• Humans MeSH
• Neoplasm Recurrence, Local MeSH
• Kidney Neoplasms * drug therapy   MeSH
• Urinary Bladder Neoplasms * MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Network Meta-Analysis MeSH
• Systematic Review MeSH
• Names of Substances
• Adjuvants, Immunologic MeSH
• Immune Checkpoint Inhibitors MeSH

(1) Background: The incidence of psychological distress and its impact on renal cell carcinoma (RCC) patients is unclear. Our aim was to analyze the literature regarding the prevalence of psychological distress and its impact on patients with non-metastatic or metastatic RCC; (2) Methods: A systematic search of five databases was performed. Studies were considered eligible if they included patients with RCC, had a prospective or retrospective design, and assessed anxiety, depression, or psychological distress at any time during treatment or follow-up. Exclusion criteria: no treatment for RCC, or not providing data for RCC patients; (3) Results: A total of 15 studies were included. Reported psychological distress was up to 77% and the prevalence of depressive and anxiety symptoms were up to 77.6% and 68.3% in patients with non-metastatic RCC. There was no association of depression with overall survival (OS) in patients with non-metastatic RCC treated by radical nephrectomy; on the contrary, in patients with metastatic disease, depression had an impact on OS. Limitations are related to the quality of the included studies; (4) Conclusions: Patients with RCC reported a high level of psychological distress like other cancer patients. It seems that for patients with localized disease, psychological distress does not impact OS, while it does in those with metastatic disease.

• Keywords
• anxiety, depression, metastasis, nephrectomy, psychological distress, renal cancer, survival,
• Publication type
• Journal Article MeSH
• Review MeSH

Robot-assisted partial nephrectomy (RAPN) is used more and more in present days as a therapy option for surgical treatment of cT1 renal masses. Current guidelines equally recommend open (OPN), laparoscopic (LPN), or robotic partial nephrectomy (PN). The aim of this review was to analyze the most representative RAPN series in terms of reported oncological outcomes. (2) Methods: A systematic search of Webofscience, PUBMED, Clinicaltrials.gov was performed on 1 August 2022. Studies were considered eligible if they: included patients with renal cell carcinoma (RCC) stage T1, were prospective, used randomized clinical trials (RCT) or retrospective studies, had patients undergo RAPN with a minimum follow-up of 48 months. (3) Results: Reported positive surgical margin rates were from 0 to 10.5%. Local recurrence occurred in up to 3.6% of patients. Distant metastases were reported in up to 6.4% of patients. 5-year cancer free survival (CFS) estimates rates ranged from 86.4% to 98.4%. 5-year cancer specific survival (CSS) estimates rates ranged from 90.1% to 100%, and 5-year overall survival (OS) estimates rated ranged from 82.6% to 97.9%. (4) Conclusions: Data coming from retrospective and prospective series shows very good oncologic outcomes after RAPN. Up to now, 10-year survival outcomes were not reported. Taken together, RAPN deliver similar oncologic performance to OPN and LPN.

• Keywords
• cancer-specific survival, metastasis, nephron-sparing surgery, overall survival, partial nephrectomy, renal cancer, robot-assisted,
• Publication type
• Journal Article MeSH
• Review MeSH