Robot-Assisted Radical Prostatectomy Performed with the Novel Hugo™ RAS System: A Systematic Review and Pooled Analysis of Surgical, Oncological, and Functional Outcomes.

Background/Objectives: to assess surgical, oncological, and functional outcomes of robot-assisted radical prostatectomy (RARP) performed using the novel Hugo™ RAS system. Methods: A systematic review was conducted following the PRISMA guidelines, using PubMed, Web of Science, Scopus, and Embase databases. Eligible papers included studies involving adult males undergoing RARP with the Hugo™ RAS platform, with at least ten patients analyzed. The pooled analysis was performed using a random-effect model. Results: Quantitative analysis was conducted on 12 studies including 579 patients. The pooled median docking time, console time, and operative time were 11 min (95% CI 7.95-14.50; I2 = 98.4%, ten studies), 142 min (95% CI 119.74-164.68; I2 = 96.5%, seven studies), and 176 min (95% CI 148.33-203.76; I2 = 96.3%, seven studies), respectively. The pooled median estimated blood loss was 223 mL (95% CI 166.75-280.17; I2 = 96.5%, eleven studies). The pooled median length of hospital stay and time to catheter removal were 2.8 days (95% CI 1.67-3.89; I2 = 100%, ten studies) and 8.3 days (95% CI 5.53-11.09; I2 = 100%, eight studies), respectively. The pooled rate of postoperative CD ≥ 2 complications was 4.1% (95% CI 1-8.5; I2 = 63.6%, eleven studies). The pooled rate of positive surgical margins and undetectable postoperative PSA were 20% (95% CI 12.6-28.5; I2 = 71.5%, nine studies) and 94.2% (95% CI 87.7-98.6; I2 = 48.9%, three studies), respectively. At three months, a pooled rate of social continence of 81.9% (95% CI 73.8-88.9; I2 = 66.7%, seven studies) was found. Erectile function at six months was 31% in one study. Conclusions: despite the preliminary nature of the evidence, this systematic review and pooled analysis underscores the feasibility, safety, and reproducibility of the Hugo™ RAS system in the context of RARP.

Assessing Trifecta and Pentafecta Success Rates between Robot-Assisted vs. Open Radical Cystectomy: A Propensity Score-Matched Analysis.

BACKGROUND: This study aimed to evaluate the surgical and oncological outcomes of robot-assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) using trifecta and pentafecta parameters. METHODS: The clinical data of 41 patients who underwent RARC between 2018 and 2022 were prospectively collected and retrospectively compared to those of 330 patients undergoing ORC using 1:1 propensity score matching. Trifecta was defined as simultaneous negative surgical margins (SMs), a lymph node (LN) yield ≥ 16, and the absence of major complications (Clavien-Dindo grade III-V) within 90 days postoperatively. Pentafecta additionally included a 12-month recurrence-free rate and a time between the transurethral resection of a bladder tumor (TURBT) and radical cystectomy (RC) ≤ 3 months. The continuous variables were compared using the Mann-Whitney U test, and the categorical variables were analyzed using the chi-squared test. RESULTS: No statistically significant differences in trifecta and pentafecta success rates were observed between the RARC and ORC cohorts after propensity score matching. However, the RARC group exhibited significantly reduced blood loss (RARC: 317 mL vs. ORC: 525 mL, p = 0.01). CONCLUSIONS: RARC offers distinct advantages over ORC in terms of reduced blood loss, while trifecta and pentafecta success rates do not differ significantly between the two surgical approaches.

Comparison of PIV and Other Immune Inflammation Markers of Oncological and Survival Outcomes in Patients Undergoing Radical Cystectomy.

Inflammation is widely acknowledged as a significant characteristic of cancer, playing a substantial function in both the initiation and advancement of cancers. In this research, we planned to compare pan-immune inflammation markers and other well-known markers (systemic immune inflammation index and neutrophil to lymphocyte ratio) to predict prognosis in individuals treated with radical cystectomy for bladder cancer. METHODS: In this retrospective analysis, we focused on preoperative PIV, systemic immune inflammation index (SII), and neutrophil-lymphocyte ratio (NLR) in 193 individuals managed with radical cystectomy for bladder cancer between January 2016 and November 2022. Multivariable logistic regression assessments were performed to assess the predictive capabilities of PIV, SII, and NLR for infiltration of lymph nodes (N), aggressive tumor stage (pT3/pT4), and any non-organ limited disease at the time of RC. Multivariable Cox regression analyses were conducted to assess the predictive impact of PIV on Relapse-free survival (RFS), Cancer-specific survival (CSS), and Overall survival (OS). RESULTS: Our individuals were divided into high PIV and low PIV cohorts using the optimal cut-off value (340.96 × 109/L) based on receiver operating characteristic curve analysis for relapse-free survival. In multivariable preoperative logistic regression models, only SII and PIV correlated with the infiltration of lymph nodes, aggressive disease, and any non-organ confined disease. In multivariable Cox regression models considering presurgical clinicopathological variables, a higher PIV was associated with diminished RFS (p = 0.017) and OS (p = 0.029). In addition, in multivariable Cox regression models for postoperative outcomes, a high PIV correlated with both RFS (p = 0.034) and OS (p = 0.048). CONCLUSIONS: Our study suggests that PIV and SII are two very similar markers that may serve as independent and significant predictors of aggressive disease and worse survival impacts on individuals undergoing radical cystectomy for bladder neoplasm.

Efficacy of transurethral botulinum toxin A injections for bladder outlet obstruction: A systematic review and meta-analysis.

INTRODUCTION: Botulinum toxin A (BoNT-A) injections in the prostate gland have been used as a minimally invasive option for treating bladder outlet obstruction (BOO). However, the efficacy of transurethral BoNT-A injections for BOO is not well established in the literature. The aim of this study is to collect evidence on the efficacy of transurethral BoNT-A injections for the treatment of BOO. MATERIALS AND METHODS: This systematic review and meta-analyses was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. A systematic literature search was performed till December 2022. The study population consisted of adult patients diagnosed with BOO, who underwent transurethral injections of BoNT-A for the treatment of BOO. EVIDENCE SYNTHESIS: Out of 883 records, we identified seven studies enrolling 232 participants, of which only one nonrandomized controlled trial was found. Four prospective studies and two retrospective studies. Three studies included patients with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) and were included in the meta-analysis. Three studies included patients with urethral sphincter hyperactivity. One study included patients with primary bladder neck disease (PBND). All studies showed significant improvements from baseline in maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and postvoid residual (PVR) at 3 and 6 months. The adverse events were mild in all studies. Hematuria, UTI, and urinary retention were reported across all studies. CONCLUSION: In conclusion, transurethral BoNT-A injections have been shown to improve LUTS, QoL, and urodynamic parameters of individuals with BOO at 3 and 6 months after injections, and no serious adverse effects have been reported. However, data on the long-term benefits of this treatment are scarce, and more prospective, randomized studies with larger samples examining various injection techniques, dosages, and extended follow-up of recurrent injections are needed.

Staghorn Caliceal Hem-o-Lok Stone: a long-term complication of robotic partial nephrectomy: a case report and literature review.

Hem-o-Lok clips (HOLCs) are a useful tool in mini-invasive surgery, especially for renal surgery. However, in rare cases, they could migrate into the collecting system and be calculogenic. We present a case of a 53 years old man with an incidental CT finding of a left staghorn caliceal stone increasing its size in the last 2 years. He had a medical history of ipsilateral robotic partial nephrectomy (RAPN) at another institution 8 years before and a previous renal colic with spontaneous stone elimination about 20 years before. The stone was located in the upper calyx. He underwent a flexible ureteroscopy. After an initial fragmentation, a Hem-o-lok was reported, partially wedged into the renal parenchyma. After removing the HOLC with a basket, a small urinary leak was observed and managed with a JJ stent placement. In the postoperative period, the patient had a fever managed with antibiotics and was discharged on the 4th postoperative day without problems. HOLC migration into the collecting system is a rare complication following robotic and laparoscopic renal surgery. HOLC could act as a nidus for stone formation. Avoiding too much tension during renal sutures using HOLC could reduce the possibility of migration. Simple knotting in particular conditions is a valuable option. However, this kind of stone can be managed endoscopically without complaints, minding the possibility that HOLC could be partially wedged into renal parenchyma leading to a urinary leak. With the widening indications for RAPN this kind of complication could be more frequent.

Advanced Age Impacts Survival After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

INTRODUCTION: Upper tract urothelial carcinoma is rare but has a poor prognosis. Prognostic factors have been extensively studied in order to provide the best possible management for patients. We have aimed to investigate commonly available factors predictive of recurrence and survival in this patient population at high risk of death and recurrence, with an emphasis on the effects of age (using a cutoff of 70 years) on survival outcomes. PATIENTS AND METHODS: From 1387 patients with clinically nonmetastatic upper tract urothelial carcinoma treated with radical nephroureterectomy at 21 academic hospital centers between 2005 and 2021, 776 patients were eligible and included in the study. Univariable and multivariable Cox regression models were built to evaluate the independent prognosticators for intravesical and extravesical recurrence, overall survival, and cancer-specific survival according to age groups. A P value of <.05 was considered statistically significant. RESULTS: We did not find an association between groups aged <70 and >70 years old and preoperatively clinical or histopathological characteristics. Kaplan-Meier analysis was found no statistical significance between the 2 age groups in terms of intravesical or extravesical recurrence (P = .09 and P = .57). Overall survival (P = .0001) and cancer-specific survival (P = .0001) have been found to be statistically significantly associated with age as independent predictors (confounding factors: gender, tumor size, tumor side, clinical T stage, localization, preoperative hydronephrosis, tumor localization, type of surgery, multifocality of the tumor, pathological grade, lymphovascular invasion, concomitant CIS, lymph node status, necrosis, or history of previous bladder cancer). CONCLUSION: This research confirms that patients aged 70 and above who undergo radical nephroureterectomy may have worse outcomes compared to younger patients, older patients needing an improved care and management of UTUC to improve their outcomes in the setting of an increase in this aged population group.

Predictive factors of surgical complications after pelvic exenteration for gynecological malignancies: a large single-institution experience.

OBJECTIVE: To evaluate pre-operative predictors of early (<30 days) severe complications (grade Dindo 3+) in patients with gynecological malignancy submitted to pelvic exenteration (PE). METHODS: We retrospectively analyzed 129 patients submitted to surgery at Fondazione Policlinico Gemelli between 2010 and 2019. We included patients affected by primary or recurrent/persistent cervical, endometrial, or vulvar/vaginal cancers. Post-operative complications were graded according to the Dindo classification. Logistic regression was used to analyze potential predictors of complications. RESULTS: We performed 63 anterior PE, 10 posterior PE, and 56 total PE. The incidence of early severe post-operative complications was 27.9% (n=36), and the early mortality rate was 2.3% (n=3). More frequent complications were related to the urinary diversion and intestinal surgery. In univariable analysis, hemoglobin ≤10 g/dL (odds ratio [OR]=4.2; 95% confidence interval [CI]=1.65-10.7; p=0.003), low albumin levels (OR=3.9; 95% CI=1.27-12.11; p=0.025), diabetes (OR=4.15; 95% CI=1.22-14.1; p=0.022), 2+ comorbidities at presentation (OR=5.18; 95% CI=1.49-17.93; p=0.012) were predictors of early severe complications. In multivariable analysis, only low hemoglobin and comorbidities at presentation were independent predictors of complications. CONCLUSION: Pelvic exenteration is an aggressive surgery characterized by a high rate of post-operative complications. Pre-operative assessment of comorbidities and patient health status are crucial to better select the right candidate for this type of surgery.

Simultaneous surgical management of renal cancer with atrial thrombotic extension and severe chronic coronary artery disease: a case report.

BACKGROUND: Renal cell carcinoma accounts for 2-3% of all malignant cancers in adults and is characterized by the potential development of venous tumor thrombus. CASE PRESENTATION: We present a rare case of a 62-year-old Caucasian man who arrived in the emergency department for monosymptomatic hematuria. Further investigation revealed a right renal cell carcinoma with 16 cm intravascular extension through the renal vein into the inferior vena cava and right atrium associated with significant coronary artery disease based on the computed tomography scan and coronary angiography. To the best of our knowledge, after an extensive literature review, only one similar case has been reported with involvement of the contralateral kidney. Therefore, there are no applicable management recommendations. After performing coronary artery bypass graft surgery, we proceeded with an open right radical nephrectomy and inferior vena cava and right atrium thrombectomy under cardiopulmonary bypass and while the patient's heart was still beating. The postoperative course went without complications, and the patient was discharged from the hospital on the 10th postoperative day. CONCLUSIONS: Radical nephrectomy and thrombectomy with reconstruction of the inferior vena cava combined with coronary artery bypass graft can be performed safely and effectively in selected patients with renal cell carcinoma and significant coronary artery disease. Multidisciplinary teamwork and careful patient selection are essential for optimal outcomes.

Is Systemic Immune-Inflammation Index a Real Non-Invasive Biomarker to Predict Oncological Outcomes in Patients Eligible for Radical Cystectomy?

Background and Objectives: To assess the potential prognostic role of the systemic immune-inflammation index (SII) in predicting oncological outcomes in a cohort of patients treated with radical cystectomy (RC). Materials and Methods: From 2016 to 2022, a retrospective monocentric study enrolled 193 patients who were divided into two groups based on their SII levels using the optimal cutoff determined by the Youden index. The SII was obtained from a preoperative blood test approximately one month before RC. Univariable and multivariable logistic regression analyses were conducted to investigate the capacity of SII to predict lymph node invasion (N), advanced pT stage (pT3/pT4), and locally advanced condition at the time of RC. Multivariable Cox regression models adjusted for preoperative and postoperative features were used to analyze the prognostic effect of SII on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results: The optimal cutoff value of the SII was 640.27. An elevated SII was seen in 113 (58.5%) patients. Using the multivariable preoperative logistic regression models, an elevated SII was correlated with nodal invasion (N; p = 0.03), advanced pT stage (p = 0.04), and locally advanced disease (p = 0.005), with enhancement of AUCs for predicting locally advanced disease (p = 0.04). In multivariable Cox regression models that considered preoperative clinicopathologic factors, an elevated SII was linked to poorer RFS (p = 0.005) and OS (p = 0.01). Moreover, on multivariable Cox regression postoperative models, a high SII was linked to RFS (p = 0.004) and to OS (p = 0.01). Conclusions: In this monocentric retrospective study, higher preoperative SII values predicted worse oncological outcomes in patients with bladder cancer (BCa) who underwent RC.

Robotic surgery in ovarian cancer.

Ovarian cancer (OC) represents one of the most lethal cancers in women. The aim of surgical treatment is complete cytoreduction in advanced stages and a surgical staging in early stages. Although the guidelines still suggest laparotomy as the standard approach, in recent years minimally invasive surgery (MIS) has become increasingly popular in the treatment of OC, especially in early stages, because the 5-year relative survival exceeds 90% and the patients' quality of life cannot be overshadowed. However, MIS has been demonstrated to have a role even in advanced stages, in the prediction of optimal cytoreduction, identification patients who may benefit from neoadjuvant chemotherapy, and, more recently, in the interval debulking surgery, as in selected cases of secondary cytoreduction for recurrent ovarian cancer. The aim of this review is to describe the MIS (especially robotic surgery), with its advantages and pitfalls, in the treatment of OC.

Are ureterolysis for deep endometriosis really all the same? An anatomical classification proposal for ureterolysis: A single-center experience.

OBJECTIVE: Ureteral endometriosis has an incidence of 0.1% to 1%. The type of surgery required is either conservative (ureterolysis) or radical treatment, depending on the degree of ureter infiltration. The incidence of intraoperative and postoperative complications is heterogeneous. Thus, the aim of the current study was to propose a classification of ureterolysis based on the anatomical structure of the ureter and differing complication rates with procedures. METHODS: A total of 139 ureterolysis procedures were included in the study. Patients were divided into three groups according to the depth of ureterolysis required. Differences were recorded across the three types of ureterolysis in terms of intraoperative and postoperative complications. RESULTS: The incidence of ureteral fistula was reported in 0.7% of cases, with postoperative ureteral stenosis in 2% of type 2 ureterolysis. In the case of type 3 ureterolysis, after conservative procedures, 52.9% of patients required an ureteroneocystostomy to solve the ureteral stenosis. CONCLUSION: The risk of ureteral injury and ureteroneocystostomy after conservative procedures appears to be associated with type 3 ureterolysis, probably due to excessive devascularization, secondary to the incision of adventitia. Obviously, these data should be confirmed through a prospective study of a larger number, but our proposed classification can provide the basis for making data from future studies more comparable.

Ultrasound-guided endoscopy to improve accuracy of persistent urogenital sinus (PUGS) diagnosis in adult patient: A case report.

Introduction: persistent urogenital sinus (PUGS) is a rare condition characterized by abnormal communication between the urethra and vagina, that can frequently be associated with other complex Mullerian malformation (33%). We present a case of PUGS associated with a complex Mullerian malformation diagnosed in adult age after the integration of gynecological ultrasound with hysteroscopy, both performed by expert operators. Case description: 27-year-old women was referred to our clinic because of frequent urinary tract infections and cyclic pelvic pain. She was virgo, with normal menstrual cycles and dysmenorrhea. A didelphys uterus and double vagina with bilateral hematocolpos was firstly diagnosed through transrectal and transabdominal ultrasound. An MRI was then performed and a monorenal and ipsilateral ureteral malformation were diagnosed; in addition, a complete absence of the lower third of the vagina and an abnormal origin of the urethra from the bladder were described. Patient underwent lower genital tract endoscopy: external vaginal orifice was obliterated, a PUGS was diagnosed and both vaginas' ostia were detected on the PUGS's posterior-lateral walls. The procedure was performed under transabdominal ultrasound guidance which confirmed the endoscopic anatomical suspicion, avoiding complications such as perforation and misdiagnosis. Discussion: ultrasound guided endoscopy plays an essential role in the evaluation of complex anatomic anomalies, such as persistent urogenital sinus (PUGS), leading to a dynamic one-stop diagnosis; it avoids delays and misdiagnosis in preoperative assessment possibly related to the separately application of different radiological and endoscopic techniques.

Post nephrectomy management of localized renal cell carcinoma. From risk stratification to therapeutic evidence in an evolving clinical scenario.

Standard treatment for localized non-metastatic renal cell carcinoma (RCC) is radical or partial nephrectomy. However, after radical surgery, patients with stage II-III have a substantial risk of relapse (around 35%). To date a unique standardized classification for the risk of disease recurrence still lack. Moreover, in the last years great attention has been focused in developing systemic therapies with the aim of improving the disease-free survival (DFS) of high-risk patients, with negative results from adjuvant VEGFR-TKIs. Therefore, there is still a need for developing effective treatments for radically resected RCC patients who are at intermediate/high risk of relapse. Recently, interesting results came from immune-checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway, with a significant benefit in terms of disease-free survival from adjuvant pembrolizumab. However, the conflicting results of diverse clinical trials investigating different ICI-based regimens in the adjuvant setting, together with the still immature data on the overall survival advantage of immunotherapy, requires careful considerations. Furthermore, several questions remain unanswered, primarily regarding the selection of patients who could benefit the most from immunotherapy. In this review, we have summarized the main clinical trials investigating adjuvant therapy in RCC, with a particular focus on immunotherapy. Moreover, we have analyzed the crucial issue of patients' stratification according to the risk of disease recurrence, and we have described the possible future prospective and novel agents under evaluation for perioperative and adjuvant therapies.

HPV Vaccination Adherence in Working-Age Men: A Systematic Review and Meta-Analysis.

BACKGROUND: Human papillomavirus (HPV) infection is the most common sexually transmitted viral infection in the world. HPV vaccination adherence rates in men are generally lower than in women. The aim of this systematic review and meta-analysis was to assess adherence to HPV vaccination in young working-age males (18-30 years old). METHODS: A systematic review was performed using three databases: PubMed, Scopus, and Web of Science, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: After duplicate removal, the initial search resulted in 478 eligible papers. With the exclusion of 425 papers after screening the abstracts, full texts of 53 articles were reviewed. Subsequently, 45 were excluded. Among the eight studies included, four (50%) examined the vaccination adherence in young adults through data registered in nationwide insurance or private companies' databases, three (37.5%) in young adults in different settings through data collected from surveys and questionnaires, and one (12.5%) an HPV vaccination campaign in a family medicine residency practice. CONCLUSION: Adherence to HPV vaccination in men of working age (18-30 years) does not appear to be adequate (pooled prevalence 11%). In order to achieve a higher level of compliance, it is important to place an emphasis on vaccination campaigns in schools as well as in the workplace, after consultation with and approval from local, regional, and federal public health agencies.

Impact of COVID-19 on Uro-Oncological Patients: A Comprehensive Review of the Literature.

Background: The aim of this paper is to discuss the impact of COVID-19 on patients with urological malignancies (prostate cancer, bladder and upper tract urothelial cancer, kidney cancer, penile and testicular cancer) and to review the available recommendations reported in the literature. Methods: A review was performed, through the PubMed database, regarding available recommendations reported in the literature, to identify studies examining the impact of COVID-19 on treatment and clinical outcomes (including upstaging, recurrence, and mortality) for uro-oncological patients. Results: The COVID-19 pandemic dramatically changed the urological guidelines and patients' access to screening programs and follow-up visits. Great efforts were undertaken to guarantee treatments to high-risk patients although follow up was not always possible due to recurrent surges, and patients with lower risk cancers had to wait for therapies. Conclusions: Physically and mentally, uro-oncological patients paid a heavy price during the COVID-19 pandemic. Long term data on the "costs" of clinical decisions made during the COVID-19 pandemic are still to be revealed and analyzed.

Laparoscopic ureteroneocystostomy and round ligament bladder hitching for ureteral stenosis in parametrial deep endometriosis: Our tips for a tension-free anastomosis.

OBJECTIVE: To investigate the feasibility and the efficacy of laparoscopic ureteroneocystostomy with round ligament bladder hitching. METHODS: This is a monocentric retrospective study. Enrolled patients affected by deep endometriosis underwent laparoscopic nerve-sparing parametrectomy and monolateral ureteroneocystostomy with bladder suspension to the round ligament. Perioperative and postoperative outcomes were collected, as well as urinary and pain symptoms before and after surgery. RESULTS: Laparoscopic ureteroneocystostomy with round ligament bladder hitching was performed in nine women. The most frequent postoperative complication was post-voiding urinary retention (22.2%). No ureteral fistula or stenosis of the anastomosis was reported. CONCLUSION: In selected cases of ureteral resection and reimplantation, performing a round ligament bladder hitching allowed us to overcome the ureteral gap. This is a safe and feasible procedure to ensure stability of the anastomosis and avoid the possible disadvantages of the "standard" psoas hitch procedure.

Urological Safety and COVID-19 Vaccinations.

OBJECTIVE: To discuss the impact of COVID-19 vaccines on the urological field and to review the available data in the literature. MATERIAL AND METHODS: All the related reports and original articles discussing COVID-19 vaccines and their impact on the urological field were searched in PubMed, Scopus, and Web of Science. RESULTS: There are few published articles discussing the COVID-19 vaccine impact on urology. Vaccine safety was confirmed in this field as no major side effects were described. AKI (Acute Kidney Injury) was reported in selected populations. However, about 1% of the side effects was urological. Rare genital complications, low urinary tract symptoms, and occasional gross hematuria were reported. Fertility seems to be not impaired after vaccination. A potential misinterpretation of radiological findings in the oncological field has been reported. CONCLUSIONS: In the literature, there are few studies regarding COVID-19 vaccines and their impact on the urological and andrological fields. We need more studies and extended follow-ups after repeated vaccinations in order to have more corroborating data particularly in selected populations, such as kidney transplant recipients and oncological patients.

Targeting hypoxia-inducible factor pathways in sporadic and Von Hippel-Lindau syndrome-related kidney cancers.

Hereditary and sporadic renal cell carcinomas (RCCs) are often associated with Von Hippel-Lindau (VHL)-gene inactivation. Patients with VHL disease have an increased risk of RCC, leading to bilateral nephrectomy and dialysis. In patients with advanced RCC, no standard second-lines are available after progression to immune checkpoint inhibitors (ICIs), and new agents are required to manage progression. HIFs have emerged as a promising target for metastatic RCC patients who have progressed to ICI-based combinations, as well as for those with RCC and VHL syndrome where the goal is to delay surgery and/or and preserve kidney function and avoid dialysis. This review describes the available evidence supporting the use of the small-molecule HIF-2 alpha inhibitor, belzutifan (MK-6482), as well as other new anti-HIF molecules that have demonstrated significant efficacy in VHL disease-related RCCs as well as for sporadic RCC that has progressed after the use of ICI-based combinations.