Does the Timing of Cytoreductive Nephrectomy Impact Outcomes? Analysis of REMARCC Registry Data for Patients Receiving Tyrosine Kinase Inhibitor Versus Immune Checkpoint Inhibitor Therapy.

Background and objective: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been called into question on the basis of clinical trial data from the tyrosine kinase inhibitor (TKI) era. Comparative analyses of CN for patients treated with immuno-oncology (IO) versus TKI agents are sparse. Our objective was to compare CN timing and outcomes among patients who received TKI versus IO therapy. Methods: This was a multicenter retrospective analysis of patients who underwent CN using data from the REMARCC (Registry of Metastatic RCC) database. The cohort was divided into TKI versus IO first-line therapy groups. The primary outcome was all-cause mortality (ACM). Secondary outcomes included cancer-specific mortality (CSM). Multivariable analysis was used to identify factors predictive for ACM and CSM. The Kaplan-Meier method was used to analyze 5-yr overall survival (OS) and cancer-specific survival (CSS) with stratification by primary systemic therapy and timing in relation to CN. Key findings and limitations: We analyzed data for 189 patients (148 TKI + CN, 41 IO +CN; median follow-up 23.2 mo). Multivariable analysis revealed that a greater number of metastases (hazard ratio [HR] 1.06; p = 0.015), greater primary tumor size (HR 1.10; p = 0.043), TKI receipt (HR 2.36; p = 0.015), and initiation of systemic therapy after CN (HR 1.49; p = 0.039) were associated with worse ACM. A greater number of metastases at diagnosis (HR 1.07; p = 0.011), greater primary tumor size (HR 1.12; p = 0.018), TKI receipt (HR 5.43; p = 0.004), and initiation of systemic therapy after CN (HR 2.04; p < 0.001) were associated with worse CSM. Kaplan-Meier analyses revealed greater 5-yr rates for OS (51% vs 27%; p < 0.001) and CSS (83% vs 30%; p < 0.001) for IO +CN versus TKI + CN. This difference persisted in a subgroup analysis for patients with intermediate or poor risk, with 5-yr OS rates of 50% for IO + CN versus 30% for TKI + CN (p < 0.001). A subanalysis stratified by CN timing revealed better 5-yr rates for OS (50% vs 30%; p = 0.042) and CSS (90% vs 30%, p = 0.019) for delayed CN after IO therapy, but not after TKI therapy. Conclusions and clinical implications: For patients who underwent CN, systemic therapy before CN was associated with better outcomes. In addition, IO therapy was associated with better survival outcomes in comparison to TKI therapy. Our findings question the applicability of clinical trial data from the TKI era to CN in the IO era for mRCC. Patient summary: For patients with metastatic kidney cancer treated with surgery, better survival outcomes were observed for those who also received immunotherapy in comparison to therapy targeting specific proteins in the body (tyrosine kinase inhibitors, TKIs). Immunotherapy or TKI treatment resulted in better outcomes if it was received before rather than after surgery.

Diagnostic Biopsy for Small Renal Tumours: A Survey of Current European Practice.

Background and objective: Renal tumour biopsy (RTB) can help in risk stratification of renal tumours with implications for management, but its utilisation varies. Our objective was to report current practice patterns, experiences, and perceptions of RTB and research gaps regarding RTB for small renal masses (SRMs). Methods: Two web-based surveys, one for health care providers (HCPs) and one for patients, were distributed via the European Association of Urology Young Academic Urologist Renal Cancer Working Group and the European Society of Residents in Urology in January 2023. Key findings and limitations: The HCP survey received 210 responses (response rate 51%) and the patient survey 54 responses (response rate 59%). A minority of HCPs offer RTB to >50% of patients (14%), while 48% offer it in <10% of cases. Most HCPs reported that RTB influences (61.5%) or sometimes influences (37.1%) management decisions. Patients were more likely to favour active treatment if RTB showed high-grade cancer and less likely to favour active treatment for benign histology. HCPs identified situations in which they would not favour RTB, such as cystic tumours and challenging anatomic locations. RTB availability (67%) and concerns about delays to treatment (43%) were barriers to offering RTB. Priority research gaps include a trial demonstrating that RTB leads to better clinical outcomes, and better evidence that benign/indolent tumours do not require active treatment. Conclusions and clinical implications: Utilisation of RTB for SRMs in Europe is low, even though both HCPs and patients reported that RTB results can affect disease management. Improving timely access to RTB and generating evidence on outcomes associated with RTB use are priorities for the kidney cancer community. Patient summary: A biopsy of a kidney mass can help patients and doctors make decisions on treatment, but our survey found that many patients in Europe are not offered this option. Better access to biopsy services is needed, as well as more research on what happens to patients after biopsy.

The prognostic role of histomorphological subtyping in nonmetastatic papillary renal cell carcinoma after curative surgery: is subtype really irrelevant? A propensity score matching analysis of a multi-institutional real life data.

BACKGROUND AND AIM: The role of histomorphological subtyping is an issue of debate in papillary renal cell carcinoma (papRCC). This multi-institutional study investigated the prognostic role of histomorphological subtyping in patients undergoing curative surgery for nonmetastatic papRCC. PATIENTS AND METHODS: A total of 1,086 patients undergoing curative surgery were included from a retrospectively collected multi-institutional nonmetastatic papRCC database. The patients were divided into 2 groups based on histomorphological subtyping (type 1, n = 669 and type 2, n = 417). Furthermore, a propensity score-matching (PSM) cohort in 1:1 ratio (n = 317 for each subtype) was created to reduce the effect of potential confounding variables. The primary outcome of the study, the predictive role of histomorphological subtyping on the prognosis (recurrence free survival [RFS], cancer specific survival [CSS] and overall survival [OS]) in nonmetastatic papRCC after curative surgery, was investigated in both overall and PSM cohorts. RESULTS: In overall cohort, type 2 group were older (66 vs. 63 years, P = 0.015) and more frequently underwent radical nephrectomy (37.4% vs. 25.6%, P < 0.001) and lymphadenectomy (22.3% vs. 15.1%, P = 0.003). Tumor size (4.5 vs. 3.8 cm, P < 0.001) was greater, and nuclear grade (P < 0.001), pT stage (P < 0.001), pN stage (P < 0.001), VENUSS score (P < 0.001) and VENUSS high risk (P < 0.001) were significantly higher in type 2 group. 5-year RFS (89.6% vs. 74.2%, P < 0.001), CSS (93.9% vs. 84.2%, P < 0.001) and OS (88.5% vs. 78.5%, P < 0.001) were significantly lower in type 2 group. On multivariable analyses, type 2 was a significant predictor for RFS (HR:1.86 [95%CI:1.33-2.61], P < 0.001) and CSS (HR:1.91 [95%CI:1.20-3.04], P = 0.006), but not for OS (HR:1.27 [95%CI:0.92-1.76], P = 0.150). In PSM cohort balanced with age, gender, symptoms at diagnosis, pT and pN stages, tumor grade, surgical margin status, sarcomatoid features, rhabdoid features, and presence of necrosis, type 2 increased recurrence risk (HR:1.75 [95%CI: 1.16-2.65]; P = 0.008), but not cancer specific mortality (HR: 1.57 [95%CI: 0.91-2.68]; P = 0.102) and overall mortality (HR: 1.01 [95%CI: 0.68-1.48]; P = 0.981) CONCLUSIONS: This multiinstitutional study suggested that type 2 was associated with adverse histopathologic outcomes, and predictor of RFS and CSS after surgical treatment of nonmetastatic papRCC, in overall cohort. In propensity score-matching cohort, type 2 remained the predictor of RFS. Eventhough 5th WHO classification for renal tumors eliminated histomorphological subtyping, these findings suggest that subtyping is relevant from the point of prognostic view.

Prognostic Significance of Grade Discrepancy Between Primary Tumor and Venous Thrombus in Nonmetastatic Clear-cell Renal Cell Carcinoma: Analysis of the REMEMBER Registry and Implications for Adjuvant Therapy.

BACKGROUND: Further stratification of the risk of recurrence of clear-cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) will facilitate selection of candidates for adjuvant therapy. OBJECTIVE: To assess the impact of tumor grade discrepancy (GD) between the primary tumor (PT) and VTT in nonmetastatic ccRCC on disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of a multi-institutional nationwide data set for patients with pT3N0M0 ccRCC who underwent radical nephrectomy and thrombectomy. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Pathology slides were centrally reviewed. GD, a bidirectional variable (upgrading or downgrading), was numerically defined as the VTT grade minus the PT grade. Multivariable models were built to predict DFS, OS, and CSS. RESULTS AND LIMITATIONS: We analyzed data for 604 patients with median follow-up of 42 mo (excluding events). Tumor GD between VTT and PT was observed for 47% (285/604) of the patients and was an independent risk factor with incremental value in predicting the outcomes of interest (all p < 0.05). Incorporation of tumor GD significantly improved the performance of the ECOG-ACRIN 2805 (ASSURE) model. A GD-based model (PT grade, GD, pT stage, PT sarcomatoid features, fat invasion, and VTT consistency) had a c index of 0.72 for DFS. The hazard ratios were 8.0 for GD = +2 (p < 0.001), 1.9 for GD = +1 (p < 0.001), 0.57 for GD = -1 (p = 0.001), and 0.22 for GD = -2 (p = 0.003) versus GD = 0 as the reference. According to model-converted risk scores, DFS, OS, and CSS significantly differed between subgroups with low, intermediate, and high risk (all p < 0.001). CONCLUSIONS: Routine reporting of VTT upgrading or downgrading in relation to the PT and use of our GD-based nomograms can facilitate more informed treatment decisions by tailoring strategies to an individual patient's risk of progression. PATIENT SUMMARY: We developed a tool to improve patient counseling and guide decision-making on other therapies in addition to surgery for patients with the clear-cell type of kidney cancer and tumor invasion of a vein.

Off-clamp Versus On-clamp Robot-assisted Partial Nephrectomy: A Systematic Review and Quantitative Synthesis by the European Association of Urology Young Academic Urologists Renal Cancer Study Group.

Context: The superiority of off-clamp robot-assisted partial nephrectomy (RAPN) over the on-clamp technique has recently been questioned by randomized controlled trials comparing the two techniques. Objective: To systematically review the recent literature and perform a quantitative synthesis of data on the comparison of off-clamp versus off-clamp hilar control during RAPN. Evidence acquisition: A systematic search was performed in the PubMed, Embase, Web of Science, and Scopus databases for studies comparing off-clamp versus on-clamp RAPN in terms of perioperative and functional outcomes. The study protocol was registered in the PROSPERO database (CRD42023413160). Only prospective randomized controlled trials and retrospective matched observational studies were included. The primary outcome of the study was the percentage decrease in the estimated glomerular filtration rate (eGFR). Evidence synthesis: A total of 11 studies were included involving a total of 2483 patients (944 patients in the off-clamp and 1539 patients in the on-clamp group). There was no difference between the two groups in the percentage decline in eGFR (mean difference [MD] 0.04%, 95% confidence interval [CI] -3.7% to 3.86%; p = 0.98). There were so significant differences between the groups for length of hospital stay (p = 0.56), complications (p = 0.08), conversion to open or radical surgery (p = 0.18), estimated blood loss (p = 0.06), or need for blood transfusion (p = 0.07). The operative time was shorter in the off-clamp group (MD-21.89 min, 95% CI -42.5 to -1.27; p = 0.04) but after sensitivity analysis the difference was no longer statistically significant (p = 0.15). The positive surgical margin rate was significantly lower in the off-clamp group (odds ratio 0.6, 95% CI 0.39-0.91; p = 0.02). Conclusions: Our review revealed no clinically relevant differences in perioperative and functional outcomes between off-clamp and on-clamp RAPN. Patient summary: In this review, we compared the two methods of controlling the kidney blood vessels during robot-assisted surgery to remove part of the kidney. We noted that there was no difference between the two groups for outcomes such as complications and the decrease in kidney function after surgery.

Artificial Intelligence in Renal Cell Carcinoma Histopathology: Current Applications and Future Perspectives.

Renal cell carcinoma (RCC) is characterized by its diverse histopathological features, which pose possible challenges to accurate diagnosis and prognosis. A comprehensive literature review was conducted to explore recent advancements in the field of artificial intelligence (AI) in RCC pathology. The aim of this paper is to assess whether these advancements hold promise in improving the precision, efficiency, and objectivity of histopathological analysis for RCC, while also reducing costs and interobserver variability and potentially alleviating the labor and time burden experienced by pathologists. The reviewed AI-powered approaches demonstrate effective identification and classification abilities regarding several histopathological features associated with RCC, facilitating accurate diagnosis, grading, and prognosis prediction and enabling precise and reliable assessments. Nevertheless, implementing AI in renal cell carcinoma generates challenges concerning standardization, generalizability, benchmarking performance, and integration of data into clinical workflows. Developing methodologies that enable pathologists to interpret AI decisions accurately is imperative. Moreover, establishing more robust and standardized validation workflows is crucial to instill confidence in AI-powered systems' outcomes. These efforts are vital for advancing current state-of-the-art practices and enhancing patient care in the future.

Effect of smoking, hypertension and lifestyle factors on kidney cancer - perspectives for prevention and screening programmes.

Renal cell carcinoma (RCC) incidence has doubled over the past few decades. However, death rates have remained stable as the number of incidental renal mass diagnoses peaked. RCC has been recognized as a European health care issue, but to date, no screening programmes have been introduced. Well-known modifiable risk factors for RCC are smoking, obesity and hypertension. A direct association between cigarette consumption and increased RCC incidence and RCC-related death has been reported, but the underlying mechanistic pathways for this association are still unclear. Obesity is associated with an increased risk of RCC, but interestingly, improved survival outcomes have been reported in obese patients, a phenomenon known as the obesity paradox. Data on the association between other modifiable risk factors such as diet, dyslipidaemia and physical activity with RCC incidence are conflicting, and potential mechanisms underlying these associations remain to be elucidated.

Single-port robotic partial nephrectomy: impact on perioperative outcomes and hospital stay.

Single-port (SP) robotic surgery is a novel technology and is at the beginning of its adoption curve in urology. The goal of this narrative review is to provide an overview of SP-robotic partial nephrectomy (PN) 4 years after the introduction of the da Vinci SP dedicated platform, focusing on perioperative outcomes, length of stay, and surgical technique. A nonsystematic review of the literature was conducted. The research included the most updated articles that referred to SP robotic PN. Since its commercial release in 2018, several institutions have reproduced robotic PN by using the SP platform, both via a transperitoneal and a retroperitoneal approach. The published SP-robotic PN series are generally based on preliminary experiences by surgeons who had previous experience with conventional multi-arms robotic platforms. The reported outcomes are encouraging. Overall, three studies reported that SP-robotic PN cases had nonsignificantly different operative time, estimated blood loss, overall complications rate, and length of stay compared to the conventional 'multi-arms' robotic PN. However, in all these series, renal masses treated by SP had overall lower complexity. Moreover, two studies underlined decreased postoperative pain as a major pro of adopting the SP system. This should reduce/avoid the need for opioids after surgery. No study compared SP-robotic versus multi-arms robotic PN in cost-effectiveness. Published experience with SP-robotic PN has reported the feasibility and safety of the approach. Preliminary results are encouraging and at least noninferior with respect to those from the multi-arms series. Prospective comparative studies with long-term oncologic and functional results are awaited to draw more definitive conclusions and better establish the more appropriate indications of SP robotics in the field of PN.

Surgical and oncological management of renal medullary carcinoma in a young patient: a case report.

Renal medullary carcinoma (RMC) is a rare form of renal cell carcinoma that has a poor prognosis. It is known to be associated with sickle cell trait or disease, although the exact underlying mechanisms are still unclear. The diagnosis is made through immunochemical staining for SMARCB1 (INI1). In this report, we present a case of a 31-year-old male patient with sickle cell trait who was diagnosed with stage III right RMC. Despite the poor prognosis, the patient survived for a remarkable duration of 37 months. Radiological assessment and follow-up were primarily performed using 18F-FDG PET/MRI. The patient underwent upfront cisplatin-based cytotoxic chemotherapy before surgical removal of the right kidney and retroperitoneal lymph node dissection. Identical adjuvant chemotherapy was administered post-surgery. Disease relapses were detected in the retroperitoneal lymph nodes; these were managed with chemotherapy and surgical rechallenges. We also discuss the oncological and surgical management of RMC, which currently relies on perioperative cytotoxic chemotherapy strategies, as there are no known alternative therapies that have been shown to be superior to date.

Screening programs for renal cell carcinoma: a systematic review by the EAU young academic urologists renal cancer working group.

PURPOSE: To systematically review studies focused on screening programs for renal cell carcinoma (RCC) and provide an exhaustive overview on their clinical impact, potential benefits, and harms. METHODS: A systematic review of the recent English-language literature was conducted according to the European Association of Urology guidelines and the PRISMA statement recommendations (PROSPERO ID: CRD42021283136) using the MEDLINE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases. Risk-of-bias assessment was performed according to the QUality In Prognosis Studies (QUIPS) tool. RESULTS: Overall, nine studies and one clinical trials were included. Eight studies reported results from RCC screening programs involving a total of 159 136 patients and four studies reported screening cost-analysis. The prevalence of RCC ranged between 0.02 and 0.22% and it was associated with the socio-demographic characteristics of the subjects; selection of the target population decreased, overall, the screening cost per diagnosis. CONCLUSIONS: Despite an increasing interest in RCC screening programs from patients and clinicians there is a relative lack of studies reporting the efficacy, cost-effectiveness, and the optimal modality for RCC screening. Targeting high-risk individuals and/or combining detection of RCC with other health checks represent pragmatic options to improve the cost-effectiveness and reduce the potential harms of RCC screening.

The Effects of Lateral 45° Head-Down Position and Carbon Dioxide Pneumoperitoneum on the Optic Nerve Sheath Diameter in Patients Undergoing Laparoscopic Transperitoneal Nephrectomies: A Prospective Observational Study.

Background: The aim of this study is to assess the extent of the increased intracranial pressure resulting from lateral decubitus and 45° downward positioning using sonographic optic nerve sheath diameter (ONSD) in patients undergoing laparoscopic transperitoneal nephrectomy. In addition, we evaluated the effect of the carbon dioxide pneumoperitoneum (CO2PP) on ONSD. Materials and Methods: Twenty-four adults were enrolled in this prospective observational study. Longitudinal and transverse ONSDs were measured for each eye by ocular ultrasonography. The values were noted in supine position (T0), 20 minutes after induction of anesthesia (T1), after insufflation of the abdomen in lateral 45° head-down position (T2), at 30-minute intervals during surgery (T3-T4-T5), during lateral 45° head-down position after CO2 exsufflation (T6), before awakening while supine (T7), and at postoperative 24th hour (T8). Hemodynamic and respiratory parameters were investigated at the measurement time points. Results: Average ONSD values for the lower eye was T0 = 4.27 ± 0.4 mm, T1 = 4.56 ± 0.6 mm, T2 = 4.84 ± 0.6 mm, T3 = 4.91 ± 0.4 mm, T4 = 4.99 ± 0.5 mm, T5 = 4.97 ± 0.5 mm T6 = 4.96 ± 0.5 mm, T7 = 4.76 ± 0.4 mm, T8 = 4.36 ± 0.5 mm and for the upper eye was T0 = 4.24 ± 0.4 mm, T1 = 4.39 ± 0.5 mm, T2 = 4.54 ± 0.5 mm, T3 = 4.60 ± 0.4 mm, T4 = 4.66 ± 0.4 mm, T5 = 4.72 ± 0.7 mm, T6 = 4.68 ± 0.4 mm, T7 = 4.52 ± 0.4 mm, T8 = 4.30 ± 0.4 mm (P < .001). Conclusion: In our study, we observed a significant increase in ONSD within minutes after the patient was placed in a head-down position. We also observed that the difference increased more with CO2PP and was proportional to the length of the surgery. We found that it regressed to initial levels at the postoperative 24th hour. Clinicaltrials.gov: NCT05185908.

Hot topics in renal cancer pathology: implications for clinical management.

INTRODUCTION: The updated European Association of Urology (EAU) Guidelines issued a weak recommendation for adjuvant pembrolizumab for patients with high-risk operable clear cell Renal Cell Carcinoma (ccRCC). High risk of recurrence was defined, as per protocol-criteria, as T2 with nuclear grade 4 or sarcomatoid differentiation, T3 or higher, regional lymph node metastasis, or stage M1 with no evidence of disease. Considering the heterogeneous population included in the recommendation, it has been questioned if adjuvant pembrolizumab may lead to overtreatment of some patients as well as undertreatment of patients with worse prognosis. AREAS COVERED: In this review, we discuss the issues related to the assessment of pathological features required to identify those patients harboring a high-risk tumor, highlighting the issue related to interobserver variability and discuss the currently available prognostic scoring systems in ccRCC. EXPERT OPINION: PPathologist assessment of prognostic features suffers from interobserver variability which may depend on gross sampling and the pathologist's expertise. The presence of clear cell feature is not sufficient criteria by itself to define ccRCC since clear cell can be also found in other histotypes. Application of molecular biomarkers may be useful tools in the near future to help clinicians identify patients harboring tumors with worse prognosis.

Quantitative Phosphoproteomics Analysis Uncovers PAK2- and CDK1-Mediated Malignant Signaling Pathways in Clear Cell Renal Cell Carcinoma.

Clear cell Renal Cell Carcinoma (ccRCC) is among the 10 most common cancers in both men and women and causes more than 140,000 deaths worldwide every year. In order to elucidate the underlying molecular mechanisms orchestrated by phosphorylation modifications, we performed a comprehensive quantitative phosphoproteomics characterization of ccRCC tumor and normal adjacent tissues. Here, we identified 16,253 phosphopeptides, of which more than 9000 were singly quantified. Our in-depth analysis revealed 600 phosphopeptides to be significantly differentially regulated between tumor and normal tissues. Moreover, our data revealed that significantly up-regulated phosphoproteins are associated with protein synthesis and cytoskeletal re-organization which suggests proliferative and migratory behavior of renal tumors. This is supported by a mesenchymal profile of ccRCC phosphorylation events. Our rigorous characterization of the renal phosphoproteome also suggests that both epidermal growth factor receptor and vascular endothelial growth factor receptor are important mediators of phospho signaling in RCC pathogenesis. Furthermore, we determined the kinases p21-activated kinase 2, cyclin-dependent kinase 1 and c-Jun N-terminal kinase 1 to be master kinases that are responsible for phosphorylation of many substrates associated with cell proliferation, inflammation and migration. Moreover, high expression of p21-activated kinase 2 is associated with worse survival outcome of ccRCC patients. These master kinases are targetable by inhibitory drugs such as fostamatinib, minocycline, tamoxifen and bosutinib which can serve as novel therapeutic agents for ccRCC treatment.

Current strategies to diagnose and manage positive surgical margins and local recurrence after partial nephrectomy.

Objective: No standard strategy for diagnosis and management of positive surgical margin (PSM) and local recurrence after partial nephrectomy (PN) are reported in literature. This review aims to provide an overview of the current strategies and further perspectives on this patient setting. Methods: A non-systematic review of the literature was completed. The research included the most updated articles (about the last 10 years). Results: Techniques for diagnosing PSMs during PN include intraoperative frozen section, imprinting cytology, and other specific tools. No clear evidence is reported about these methods. Regarding PSM management, active surveillance with a combination of imaging and laboratory evaluation is the first option line followed by surgery. Regarding local recurrence management, surgery is the primary curative approach when possible but it may be technically difficult due to anatomy resultant from previous PN. In this scenario, thermal ablation (TA) may have the potential to circumvent these limitations representing a less invasive alternative. Salvage surgery represents a valid option; six studies analyzed the outcomes of nephrectomy on local recurrence after PN with three of these focused on robotic approach. Overall, complication rates of salvage surgery are higher compared to TA but ablation presents a higher recurrence rate up to 25% of cases that can often be managed with repeat ablation. Conclusion: Controversy still exists surrounding the best strategy for management and diagnosis of patients with PSMs or local recurrence after PN. Active surveillance is likely to be the optimal first-line management option for most patients with PSMs. Ablation and salvage surgery both represent valid options in patients with local recurrence after PN. Conversely, salvage PN and radical nephrectomy have fewer recurrences but are associated with a higher complication rate compared to TA. In this scenario, robotic surgery plays an important role in improving salvage PN and radical nephrectomy outcomes.

Potential benefit of lymph node dissection during radical nephrectomy for kidney cancer: A review and critical analysis of current literature.

Objective: The role of lymph node dissection (LND) is still controversial in patients with renal cell carcinoma undergoing surgery. We aimed to provide a comprehensive review of the literature about the effect of LND on survival, prognosis, surgical outcomes, as well as patient selection and available LND templates. Methods: Recent literature (from January 2011 to December 2021) was assessed through PubMed and MEDLINE databases. A narrative review of most relevant articles was provided. Results: The frequencies in which LNDs are being carried out are decreasing due to an increase in minimally invasive and nephron sparing surgery. Moreover, randomized clinical trials and meta-analyses failed to show any survival advantage of LND versus no LND. However, retrospective studies suggest a survival benefit of LND in high-risk patients (bulky tumors, T3-4 stage, and cN1 patients). Moreover, extended LND might provide important staging information, which could be of interest for adjuvant treatment planning. Conclusion: No level 1 evidence of any survival advantage deriving from LND is currently available in literature. Thus, the role of LND is limited to staging purposes. However, low grade evidence suggests a possible role of LND in high-risk patients. Randomized clinical trials are warranted to corroborate these findings.