Not-so-simple nephrectomy: Comparative analysis of radical and simple nephrectomy in a high-volume tertiary referral center.

OBJECTIVES: Simple nephrectomies can be challenging with significant morbidity. To prove the hypothesis of "not-so-simple" nephrectomy, we compared demographics, perioperative outcomes, and complications between simple and radical nephrectomy in a tertiary referral center. METHODS: We analyzed 473 consecutive radical nephrectomies (January 2018-October 2020) and simple nephrectomies (January 2016-October 2020). Univariate and multivariate analysis of perioperative outcomes utilized the Mann-Whitney U test, Chi-squared test, Mantel-Haenszel test of trend, and multiple linear regression. Radical nephrectomies were classified in cT1, cT2a, and cT2b-T3 subgroups and compared to simple nephrectomies. Minimally invasive and open techniques were compared between the two groups. Infected versus non-infected simple nephrectomies were compared. RESULTS: A total of 344 radical and 129 simple nephrectomies were included. Simple nephrectomy was an independent predictor of increased operative time (p = 0.001), length of stay (p = 0.049), and postoperative complications (p < 0.001). Simple nephrectomies had higher operative time (p < 0.001), length of stay (p = 0.014), and postoperative morbidity (p < 0.001) than cT1 radical nephrectomies and significantly more Clavien 1-2 complications than cT2a radical nephrectomies (p = 0.001). The trend was similar in minimally invasive operations. However, conversion to open rates was not significantly different. Infected simple nephrectomies had increased operative time (p < 0.001), length of stay (p = 0.005), blood loss (p = 0.016), and intensive care stay (p = 0.019). CONCLUSIONS: Patients undergoing simple nephrectomy experienced increased operative time and morbidity. Simple nephrectomy carries higher morbidity than radical nephrectomy in tumors ≤10 cm. Robotic simple nephrectomies may reduce open conversion rates. Postoperative intensive care and enhanced recovery may be essential in simple nephrectomy planning with infected pathology.

Reducing last-minute cancellations of elective urological surgery-effectiveness of specialist nurse preoperative assessment.

Last-minute cancellations in urological surgery are a global issue, resulting in the wastage of resources and delays to patient care. In addition to non-cessation of anticoagulants and inadequately treated medical comorbidities, untreated urinary tract infections are a significant cause of last-minute cancellations. This study aimed to ascertain whether the introduction of a specialist nurse clinic resulted in a reduction of last-minute cancellations of elective urological surgery as part of our elective recovery plan following the Coronavirus disease 2019, the contagious disease caused by severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 pandemic. A specialist urology nurse-led clinic was introduced to review urine culture results preoperatively. Specialist nurses contacted patients with positive urine cultures and their general practitioners by telephone and email to ensure a minimum of 2 days of 'lead-in' antibiotics were given prior to surgery. Patients unfit for surgery were postponed and optimized, and vacant slots were backfilled. A new guideline was created to improve the timing and structure of the generic preassessment. Between 1 January 2021 and 30 June 2021, a mean of 40 cases was booked each month, with average cancellations rates of 9.57/40 (23.92%). After implementing changes on 1 July 2021, cancellations fell to 4/124 (3%) for the month. On re-audit, there was a sustained and statistically significant reduction in cancellation rates: between 1 July 2021 and 31 December 2021 cancellations averaged 4.2/97.5 (4.3%, P < .001). Two to nine (2%-16%) patients were started on antibiotics each month, while another zero to two (0%-2%) were contacted for other reasons. The implementation of a specialist urology nurse-led preassessment clinic resulted in a sustained reduction in cancellations of last-minute elective urological procedures.

The 2022 Updated European Association of Urology Guidelines on the Use of Adjuvant Immune Checkpoint Inhibitor Therapy for Renal Cell Carcinoma.

In KEYNOTE-564, adjuvant pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) in localised clear-cell renal cell carcinoma (ccRCC) with a high risk of relapse. In 2021, the European Association of Urology RCC Guidelines Panel issued a weak recommendation for adjuvant pembrolizumab for high-risk ccRCC as defined by the trial until final overall survival data and results from other trials were available. Meanwhile, the primary DFS endpoints were not met for adjuvant atezolizumab (PD-L1 inhibitor; IMmotion010), adjuvant nivolumab plus ipilimumab (CheckMate 914), or perioperative nivolumab (PROSPER). Owing to heterogeneity, a meta-analysis is not recommended. Pembrolizumab remains the only immune checkpoint inhibitor currently recommended in this setting. Overall survival data are immature and biomarkers to predict outcome are lacking. Uncertainty exists and overtreatment is occurring. Treatment decisions should be made with caution and with the involvement of each patient. PATIENT SUMMARY: New results from three trials of immunotherapy after surgery for kidney cancer to reduce the risk of recurrence showed no improvement with these treatments. These results are in contrast to an earlier study that showed that the antibody pembrolizumab did extend the time before kidney cancer recurrence, even though it is not yet clear if overall survival is longer. Thus, we cautiously recommend pembrolizumab as additional treatment in high-risk kidney cancer after surgery, but patient preference should be carefully considered and the risk of overtreatment should be discussed.

European Association of Urology Guidelines Panel on Renal Cell Carcinoma Update on the New World Health Organization Classification of Kidney Tumours 2022: The Urologist's Point of View.

The fifth edition of the World Health Organization (WHO) classification of urogenital tumours published in 2022 will be implemented in the European Association of Urology guidelines on renal cell carcinoma for 2023. Here we provide an update summarising changes in the new WHO classification of renal tumours from a clinician perspective.

A Renewal of the TNM Staging System for Patients with Renal Cancer To Comply with Current Decision-making: Proposal from the European Association of Urology Guidelines Panel.

Over the past decade, only minor changes have been introduced in the TNM staging system for renal cancer. Conversely, many milestones and modifications in management of the disease have been achieved, especially for patients with locally advanced and metastatic cancers. The European Association of Urology guidelines panel proposes a new TNM classification scheme for staging of renal cell carcinoma to reflect these breakthrough clinical improvements.

Factors Predicting Outcomes of Supine Percutaneous Nephrolithotomy: Large Single-Centre Experience.

Objective: Percutaneous nephrolithotomy (PCNL) is the treatment of choice for large renal calculi. The prone position has been considered the preferred position to obtain renal access. However, the supine position has recently gained popularity, which confers several potential advantages. The current study analyses the prognostic factors for successful supine PCNL procedures in a larger tertiary centre. Subjects: Prospective data were collected from all patients undergoing PCNL in the Galdako modified Valdivia position at our institution between February-2007 and September-2020. Surgical outcomes variables collected included: the rate of Endoscopic-combined intra-renal surgery (ECIRS), operative times, surgical effectiveness (no residuals <2 mm stone fragments) and complications. Results: A total of 592 patients underwent PCNL with a median age of 56 years (IQR: 42−67). The median stone size was 17 mm (IQR: 13−23). Of those, 79% of patients had an effective procedure. Stone size (p < 0.001), location (p < 0.001) and Guys-Stone Score (GSS) (p < 0.001) were associated with effectiveness. A Percutaneous nephrostomy tube was sited at the completion of the procedure in 97.3% of patients and a simultaneous double-J stent in 45.3%. Stent insertion was associated with larger stones (p < 0.001), the performance of ECIRS (p < 0.001) and higher GSS (p < 0.001). The overall complication rate was 21.7%. The main type of complication was an infection in 26.2 of the cases followed by the need for repeated nephrostogram in 12.7%. Conclusions: We demonstrate that PCNL in a high-volume centre is safe and efficacious in the Galdalko modified Valdivia position. Patients with smaller stones in the renal pelvis and a low GSS have the highest chance of a successful procedure.

Primary Definitive Treatment versus Ureteric Stenting in the Management of Acute Ureteric Colic: A Cost-Effectiveness Analysis.

Objectives: To analyze the differences in cost-effectiveness between primary ureteroscopy and ureteric stenting in patients with ureteric calculi in the emergency setting. Patients and Methods: Patients requiring emergency intervention for a ureteric calculus at a tertiary centre were analysed between January and December 2019. The total secondary care cost included the cost of the procedure, inpatient hospital bed days, emergency department (A&E) reattendances, ancillary procedures and any secondary definitive procedure. Results: A total of 244 patients were included. Patients underwent ureteric stenting (62.3%) or primary treatment (37.7%), including primary ureteroscopy (URS) (34%) and shock wave lithotripsy (SWL) (3.6%). The total secondary care cost was more significant in the ureteric stenting group (GBP 4485.42 vs. GBP 3536.83; p = 0.65), though not statistically significant. While mean procedural costs for primary treatment were significantly higher (GBP 2605.27 vs. GBP 1729.00; p < 0.001), costs in addition to the procedure itself were significantly lower (GBP 931.57 vs. GBP 2742.35; p < 0.001) for primary treatment compared to ureteric stenting. Those undergoing ureteric stenting had a significantly higher A&E reattendance rate compared with primary treatment (25.7% vs. 10.9%, p = 0.02) and a significantly greater cost per patient related to revisits to A&E (GBP 61.05 vs. GBP 20.87; p < 0.001). Conclusion: Primary definitive treatment for patients with acute ureteric colic, although associated with higher procedural costs than ureteric stenting, infers a significant reduction in additional expenses, notably related to fewer A&E attendances. This is particularly relevant in the COVID-19 era, where it is crucial to avoid unnecessary attendances to A&E and reduce the backlog of delayed definitive procedures. Primary treatment should be considered concordance with clinical judgement and factors such as patient preference, equipment availability and operator experience.

Emergency Primary Ureteroscopy for Acute Ureteric Colic-From Guidelines to Practice.

OBJECTIVE: To review the factors that may influence the ability to achieve the present guidelines' recommendations in a well-resourced tertiary centre. According to current National Institute for Health and Care Excellence (NICE) guidelines, definitive treatment (primary ureteroscopy (URS) or shock wave lithotripsy (ESWL)) should be offered to patients with symptomatic renal colic that are unlikely to pass the stone within 48 h of diagnosis. METHODS: Retrospective review of all patients presenting to the emergency department between January and December 2019 with a ureteric or renal stone diagnosis. The rate of emergency intervention, risk factors for intervention and outcomes were compared between patients who were treated by primary definitive surgery vs. primary symptom relief by urethral stenting alone. RESULTS: A total of 244 patients required surgical management for symptomatic ureteric colic without symptoms of urinary infection. Of those, 92 patients (37.7%) underwent definitive treatment by either primary URS (82 patients) or ESWL (9 patients). The mean time for the procedure was 25.5 h (range: 1-118). Patients who underwent primary definitive treatment were likelier to have smaller and distally located stones than the primary stenting group. Primary ureteroscopy was more likely to be performed in a supervised setting than emergency stenting. CONCLUSIONS: Although definitive treatment carries high success rates, in a high-volume tertiary referral centre, it may not be feasible to offer it to all patients, with emergency stenting providing a safe and quick interim measure. Factors determining the ability to provide definitive treatment are stone location, stone size and resident supervision in theatre.

Diagnosing Oncocytoma by Core Needle Biopsy: A Single-Center Experience.

Background: Oncocytoma is one of the most common benign kidney tumors, accounting for 3-7% of all solid renal masses. Diagnosing oncocytomas using renal biopsy remains a controversy in the uro-pathologic community. With the increasing use of biopsies for assessment of renal lesions, reaching this pathologically benign diagnosis may prevent further surgical measures and have significant clinical benefit. Objective: To demonstrate our center's results using renal biopsy to diagnose oncocytomas and to suggest that this diagnosis can be made with high success rates. Design: , Setting, and Participants. From our center's database, we retrospectively identified and retrieved all cases of oncocytoma diagnosed between the years 2011 and 2020 by renal biopsy. Medical records of those patients were then reviewed to view follow-up meetings and imaging of the lesions biopsied. Outcome Measurements and Statistical Analysis. In 21 biopsies performed on 19 patients, diagnosis was supported by subsequent follow-up averaging at 3.44 years per patient. Results and Limitations. The lesions exhibited benign behavior during follow-up after biopsy, consistent with the diagnosis of oncocytoma. Conclusions: Our study demonstrates that with good patient selection and proficient cooperation between urologists, radiologists and dedicated uro-pathologists, correctly diagnosing oncocytomas using RCB is a viable task. Patient Summary. Oncocytomas are benign lesions of the kidney. In our study, we reviewed all cases of oncocytomas pathologically diagnosed using renal biopsy from our center's database. We found that in subsequent follow-up later to biopsy, the lesions displayed benign behavior consistent with oncocytoma. The use of percutaneous biopsies to reach this diagnosis could save patients more extensive surgeries.

Metastasectomy in renal cell carcinoma: where are we now?

PURPOSE OF REVIEW: Metastatic RCC has a variable natural history. Treatment choice depends on disease and patient factors, but most importantly disease burden and site of metastasis. This article highlights key variables to consider when contemplating metastasectomy for RCC and provide a narrative review on the evidence for metastasectomy in these patients. RECENT FINDINGS: Tumour subtype is associated with differing patterns of recurrence. Patients with single or few metastatic sites have better outcomes, and those with greater time interval from initial nephrectomy. Local recurrence is particularly amenable to minimally invasive surgical resection and is oncologically sound. Very well selected cases of liver or brain metastases may benefit from metastectomy, although lung and endocrine metastases have more favourable outcomes. Although site and burden of disease is important, the key determinate of outcome in metastasectomy depends mostly on the ability to achieve a complete resection. Adjuvant treatment is not currently advocated. SUMMARY: Metastasectomy should be generally reserved for cases where complete resection is achievable, unless the goal of treatment is to palliate symptoms. This field warrants ongoing research, particularly as systemic therapy and minimally invasive surgical techniques evolve. Elucidating tumour biology to inform patient selection will be important in future research.

European Association of Urology Guidelines on Renal Cell Carcinoma: The 2022 Update.

CONTEXT: The European Association of Urology (EAU) Renal Cell Carcinoma (RCC) Guideline Panel has prepared evidence-based guidelines and recommendations for the management of RCC. OBJECTIVE: To present a summary of the 2022 RCC guideline, which is based on a standardised methodology including systematic reviews (SRs) and provides transparent and reliable evidence for the management of RCC. EVIDENCE ACQUISITION: For the 2022 update, a new literature search was carried out with a cutoff date of May 28, 2021, covering the Medline, EMBASE, and Cochrane databases. The data search focused on randomised controlled trials (RCTs) and retrospective or controlled comparator-arm studies, SRs, and meta-analyses. Evidence synthesis was conducted using modified GRADE criteria as outlined for all the EAU guidelines. EVIDENCE SYNTHESIS: All chapters of the RCC guideline were updated on the basis of a structured literature assessment, and clinical practice recommendations were developed. The majority of the studies included were retrospective with matched or unmatched cohorts and were based on single- or multi-institution data or national registries. The exception was systemic treatment of metastatic RCC, for which there are several large RCTs, resulting in recommendations that are based on higher levels of evidence. CONCLUSIONS: The 2022 RCC guidelines have been updated by a multidisciplinary panel of experts using the highest methodological standards. These guidelines provide the most reliable contemporary evidence base for the management of RCC in 2022. PATIENT SUMMARY: The European Association of Urology panel for guidelines on kidney cancer has thoroughly evaluated the research data available to establish up-to-date international standards for the care of patients with kidney cancer.

Primary Renal Tumour Response in Patients Treated with Nivolumab and Ipilimumab for Metastatic Renal Cell Carcinoma: Real-world Data Assessment.

Following CARMENA and SURTIME, patients with metastatic renal cell carcinoma (mRCC) and International Metastatic RCC Database Consortium (IMDC) intermediate and poor risk receive systemic therapy with the primary tumour (primary) in place, with the option of deferred cytoreductive nephrectomy (CN) in responding patients. We retrospectively analysed the safety and efficacy of first-line nivolumab/ipilimumab in 71 primary mRCC patients (42.3% IMDC poor risk; 43.6% with more than three metastatic sites). The baseline mean primary diameter was 9.3 cm and median follow-up was 11.5 mo. Of 69 patients with at least one follow-up computed tomography scan, 23 (33.3 %) had a partial response (PR) of the primary after a median of 4.8 mo, which was associated with a 91.3% overall response rate at metastatic sites (MSs) and absence of progressive disease, irrespective of the IMDC risk. The complete response (CR) rate at MSs (n = 7 [10.1%]) is similar to the CR rate in CheckMate 214. Thirteen deferred CNs were performed (18.8%) after a median of 13 mo, rendering four patients disease free. Only 4.3% of primaries progressed; grade 3-4 immune-related adverse events occurred in 31.9%. Irrespective of the IMDC risk, patients with a PR in the primary had a 1-yr overall survival rate of 89% versus 67% in those without (p = 0.012). PATIENT SUMMARY: Patients with metastatic kidney cancer receiving immunotherapy with nivolumab and ipilimumab had superior response at metastatic sites and better survival irrespective of International Metastatic RCC Database Consortium (IMDC) risk.

Cytoreductive nephrectomy and exposure to sunitinib - a post hoc analysis of the Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME) trial.

OBJECTIVE: To analyse if exposure to sunitinib in the Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME) trial, which investigated opposite sequences of cytoreductive nephrectomy (CN) and systemic therapy, is associated with the overall survival (OS) benefit observed in the deferred CN arm. PATIENTS AND METHODS: A post hoc analysis of SURTIME trial data. Variables analysed included number of patients receiving sunitinib, time from randomisation to start sunitinib, overall response rate by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, and duration of drug exposure and dose in the intention-to-treat population of the immediate and deferred arm. Descriptive methods and 95% confidence-intervals (CI) were used. RESULTS: In the deferred arm, 97.7% (95% CI 89.3-99.6%; n = 48) received sunitinib vs 80% (95% CI 66.9-88.7%, n = 40) in the immediate arm. Following immediate CN, 19.6% progressed 4 weeks after CN and the median time to start sunitinib was 39.5 vs 4.5 days in the deferred arm. At week 16, 46.0% had progressed at metastatic sites in the immediate CN arm vs 32.7% in the deferred arm. Sunitinib dose reductions, escalations and interruptions were not statistically significantly different between arms. Among patients who received sunitinib in the immediate or deferred arm the median total sunitinib treatment duration was 172.5 vs 248 days. Reduction of target lesions was more profound in the deferred arm. CONCLUSIONS: In comparison to the deferred CN approach, immediate CN impairs administration, onset, and duration of sunitinib. Starting with systemic therapy leads to early and more profound disease control and identification of progression prior to planned CN, which may have contributed to the observed OS benefit.

2021 Updated European Association of Urology Guidelines on the Use of Adjuvant Pembrolizumab for Renal Cell Carcinoma.

Adjuvant treatment of nonmetastatic high-risk renal cell carcinoma is an unmet medical need. In the past, several tyrosine kinase inhibitor trials have failed to demonstrate an improvement of disease-free survival (DFS) in this setting. Only one trial (S-TRAC) provided evidence for improved DFS with sunitinib but without an overall survival (OS) signal. Keynote-564 is the first trial of an immune checkpoint inhibitor that significantly improved DFS with adjuvant pembrolizumab, a programmed death receptor-1 antibody, in clear cell renal cell carcinoma with a high risk of relapse. The intention-to-treat population, which included a group of patients after metastasectomy and no evidence of disease (M1 NED), had a significant DFS benefit. The OS data are not mature as yet. The Renal Cell Carcinoma Guideline Panel issues a weak recommendation for the adjuvant use of pembrolizumab for high-risk clear cell renal carcinoma, as defined by the trial until final OS data are available. However, the trial reilluminates the discussion on when and in whom metastasectomy should be performed. Here, caution is necessary not to perform metastasectomy in patients with poor prognostic features and rapid progressive disease, which must be excluded by a confirmatory scan of disease status prior to planned metastasectomy. PATIENT SUMMARY: New data from the adjuvant immune checkpoint inhibitor trial with pembrolizumab (a programmed death receptor-1 antibody) for the treatment of high-risk clear cell renal cell carcinoma (ccRCC) after surgery showed that the drug prolonged the period of being cancer free significantly, although whether it prolonged survival remained uncertain. Consequently, pembrolizumab is cautiously recommended as additional (ie, adjuvant) treatment in high-risk ccRCC after kidney cancer surgery.

[ROBOT ASSISTED PYELOPLASTY IN ADULTS WITH URETERO-PELVIC JUNCTION OBSTRUCTION (UPJO)].

BACKGROUND: Robotic-pyeloplasty (RP) for uretero-pelvic-junction-obstruction (UPJO) has been performed in our institution since 2013. OBJECTIVES: To summarize the outcomes of RP in adults over 18 years of age. METHODS: Adult RP cases have been prospectively documented. Analysis included demographic data such as age, sex, American Association of Anesthesiology-ASA Score, surgical-side, pre-operative imaging. Operative time (OT), estimated blood loss (EBL), length of stay (LOS) and short-term complications were also recorded. In all cases a JJ-stent has been left in place and subsequently taken out. Complications were classified in accordance with the Clavien-Dindo classification criteria. Patients were seen periodically with repeat imaging. The renal scan was performed at least once during the post-operative follow-up. Results are given as median (inter-quartile range) or numeric values (%). RESULTS: A total of 32 patients aged 33.5 years (21-45.2) had RP between the years 2013-2020, among which 53% were females and 59% right sided. An ASA score of 1-2 has been observed in 87.5% of all cases. Skin-to-skin OT was 163 min (136-185), and EBL was 5 ml (0-30). Short-term post-operative complications were hematuria (3.1%), urinary leak/urinoma (12.5%), body temperature>38.30C (12.5%). In 2 cases (6.2%) the JJ-stent had been re-positioned in the operating-theater (Clavien-Dindo 3b). LOS was 3 days (2-4) and JJ-stent had been taken out 39 days (31.7-45.2) post-operatively. Median length of follow-up was 19.5 months (9.5-26.7). In 92.3% of cases an improvement in hydronephrosis has been observed in post-operative imaging. The renal scan did not demonstrate renal function deterioration. CONCLUSIONS: Adult robotic pyeloplasty for UPJO is safe and effective. Low complication rates and over 90% success rates have been observed. These findings are in line with those found in previous studies.

[CLINICAL OUTCOMES FOLLOWING ROBOT-ASSISTED PARTIAL NEPHRECTOMY (RAPN)].

BACKGROUND: Partial nephrectomy is the gold standard treatment for renal tumors less than 7 cm. OBJECTIVES: To describe surgical techniques and trends of treating renal tumors less than 7 cm at our department and present the clinical outcomes of our experience with Robot-Assisted Partial Nephrectomy (RAPN). METHODS: Out of an established prospective RAPN database, we retrieved demographic, clinical, surgical and pathological parameters. Operation length was defined as the time between the first surgical incision and the last suture (skin to skin). Warm ischemia time (WIT) was defined as the time between the renal artery clamping and clamp releasing. Data is presented as mean (range, standard deviation) or numeric value (%). RESULTS: Overall, 250 RAPN cases were recorded between the years 2013-2020. Mean tumor size was 32 mm. Mean operation length was 153 minutes. Mean warm ischemia time was 17.5 minutes. Intra-operative complication rates, including converting the surgery to an open approach or to radical nephrectomy, was low. Mean estimated blood loss was 359 cc. An increase in the utilization of the robotic approach has been recorded throughout the years, with a concurrent decrease in the open and laparoscopic approaches. CONCLUSIONS: RAPN is associated with lower complication rates and superior perioperative outcomes, therefore considered a good alternative to the open and laparoscopic approaches. Thus, RAPN is the gold standard treatment for renal tumors less than 7 cm at our institute.

[FOCAL TREATMENT OF PROSTATE CANCER - LEADING AND FUTURE TECHNIQUES, OUTCOMES AND COMPLICATIONS].

INTRODUCTION: Focal treatment for prostate cancer has been proposed as an innovative strategy that aims to achieve oncological benefit while reducing treatment-related morbidity. This treatment is suitable for patients with low and intermediate risk, organ-confined disease. Focal therapy can be categorized as follows: unifocal index lesion ablation, multifocal ablation, hemi-gland ablation or subtotal gland ablation. Different types of energies are applied in focal therapy including high intensity focal ultrasound (HIFU), cryotherapy, focal laser ablation (FLA), irreversible electroporation (IRE) and Photodynamic therapy (PDT). In this review we will briefly present a summary of leading techniques and the available data regarding their oncological outcomes and adverse events. Whole-gland therapies were excluded from this review.

The 2021 Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibitor-based Combination Therapies for Treatment-naive Metastatic Clear-cell Renal Cell Carcinoma Are Standard of Care.

The recent randomized controlled phase III CLEAR trial results are the last to complement immune checkpoint inhibitor (ICI)-based doublet combination therapies for treatment-naïve metastatic clear-cell renal cell carcinoma. The CLEAR trial demonstrated an improved progression-free survival (PFS), overall survival (OS), and an objective response rate (ORR) benefit for the combination of lenvatinib plus pembrolizumab over sunitinib. The CheckMate-9ER trial update demonstrated an ongoing PFS, OS, and quality-of-life benefit for cabozantinib plus nivolumab over sunitinib as did the update of Keynote-426 for axitinib plus pembrolizumab in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups. In the IMDC intermediate- and poor-risk groups, the CheckMate-214 trial of ipilimumab plus nivolumab confirmed the OS benefit with a PFS plateauing after 30 months. The RCC Guidelines Panel recommends three tyrosine kinase inhibitors + ICI combinations of axitinib plus pembrolizumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab across all IMDC risk groups in advanced first-line RCC, and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate- and poor-risk groups. PATIENT SUMMARY: New data from combination trials with immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit for lenvatinib plus pembrolizumab, cabozantinib plus nivolumab (with improved quality-of-life), axitinib plus pembrolizumab, and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.