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.

Resection Techniques During Robotic Partial Nephrectomy: A Systematic Review.

Context: The resection technique used to excise tumor during robotic partial nephrectomy (RPN) is of paramount importance in achieving optimal clinical outcomes. Objective: To provide an overview of the different resection techniques used during RPN, and a pooled analysis of comparative studies. Evidence acquisition: The systematic review was conducted according to established principles (PROSPERO: CRD42022371640) on November 7, 2022. A population (P: adult patients undergoing RPN), intervention (I: enucleation), comparator (C: enucleoresection or wedge resection), outcome (O: outcome measurements of interest), and study design (S) framework was prespecified to assess study eligibility. Studies reporting a detailed description of resection techniques and/or evaluating the impact of resection technique on outcomes of surgery were included. Evidence synthesis: Resection techniques used during RPN can be broadly classified as resection (non-anatomic) or enucleation (anatomic). A standardized definition for these is lacking. Out of 20 studies retrieved, nine compared "standard" resection versus enucleation. A pooled analysis did not reveal significant differences in terms of operative time, ischemia time, blood loss, transfusions, or positive margins. Significant differences favoring enucleation were found for clamping management (odds ratio [OR] for renal artery clamping 3.51, 95% confidence interval [CI] 1.13-10.88; p = 0.03), overall complications (OR for occurrence 0.55, 95% CI 0.34-0.87; p = 0.01) major complications (OR for occurrence 0.39, 95% CI 0.19-0.79; p = 0.009), length of stay (weighted mean difference [WMD] -0.72 d, 95% CI -0.99 to -0.45; p < 0.001), and decrease in estimated glomerular filtration rate (WMD -2.64 ml/min, 95% CI -5.15 to -0.12; p = 0.04). Conclusions: There is heterogeneity in the reporting of resection techniques used during RPN. The urological community must improve the quality of reporting and research produced accordingly. Positive margins are not specifically related to the resection technique. Focusing on studies comparing standard resection versus enucleation, advantages with tumor enucleation in terms of avoidance of artery clamping, overall/major complications, length of stay, and renal function were found. These data should be considered when planning the RPN resection strategy. Patient summary: We reviewed studies on robotic surgery for partial kidney removal using different techniques to cut away the kidney tumor. We found that a technique called "enucleation" was associated with similar cancer control outcomes in comparison to the standard technique and had fewer complications, better kidney function after surgery, and a shorter hospital stay.

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.

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.

PSMA PET/CT in Renal Cell Carcinoma: An Overview of Current Literature.

Although the vast majority of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging occurs in the field of prostate cancer, PSMA is also highly expressed on the cell surface of the microvasculature of several other solid tumors, including renal cell carcinoma (RCC). This makes it a potentially interesting imaging target for the staging and monitoring of RCC. The objective of this review is to provide an overview of the current evidence regarding the use of PSMA PET/Computed Tomography in RCC patients.

Expanding the Role of Ultrasound for the Characterization of Renal Masses.

The incidental detection of renal masses has been steadily rising. As a significant proportion of renal masses that are surgically treated are benign or indolent in nature, there is a clear need for better presurgical characterization of renal masses to minimize unnecessary harm. Ultrasound is a widely available and relatively inexpensive real-time imaging technique, and novel ultrasound-based applications can potentially aid in the non-invasive characterization of renal masses. Evidence acquisition: We performed a narrative review on novel ultrasound-based techniques that can aid in the non-invasive characterization of renal masses. Evidence synthesis: Contrast-enhanced ultrasound (CEUS) adds significant diagnostic value, particularly for cystic renal masses, by improving the characterization of fine septations and small nodules, with a sensitivity and specificity comparable to magnetic resonance imaging (MRI). Additionally, the performance of CEUS for the classification of benign versus malignant renal masses is comparable to that of computed tomography (CT) and MRI, although the imaging features of different tumor subtypes overlap significantly. Ultrasound molecular imaging with targeted contrast agents is being investigated in preclinical research as an addition to CEUS. Elastography for the assessment of tissue stiffness and micro-Doppler imaging for the improved detection of intratumoral blood flow without the need for contrast are both being investigated for the characterization of renal masses, though few studies have been conducted and validation is lacking. Conclusions: Several novel ultrasound-based techniques have been investigated for the non-invasive characterization of renal masses. CEUS has several advantages over traditional grayscale ultrasound, including the improved characterization of cystic renal masses and the potential to differentiate benign from malignant renal masses to some extent. Ultrasound molecular imaging offers promise for serial disease monitoring and the longitudinal assessment of treatment response, though this remains in the preclinical stages of development. While elastography and emerging micro-Doppler techniques have shown some encouraging applications, they are currently not ready for widespread clinical use.

Neoadjuvant sorafenib treatment of clear cell renal cell carcinoma and release of circulating tumor fragments.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is characterized by high constitutive vascular endothelial growth factor A (VEGF-A) production that induces a specific vascular phenotype. We previously reported that this phenotype may allow shedding of multicellular tumor fragments into the circulation, possibly contributing to the development of metastasis. Disruption of this phenotype through inhibition of VEGF signaling may therefore result in reduced shedding of tumor fragments and improved prognosis. To test this hypothesis, we investigated the effect of neoadjuvant sorafenib treatment on tumor cluster shedding. PATIENTS AND METHODS: Patients with renal cancer (n = 10, of which 8 have ccRCC) received sorafenib for 4 weeks before tumor nephrectomy. The resection specimens were perfused, and the perfundate was examined for the presence of tumor clusters. Effects of the treatment on the tumor morphology and overall survival were investigated (follow-up of 2 years) and compared with a carefully matched control group. RESULTS: Neoadjuvant sorafenib treatment induced extensive ischemic tumor necrosis and, as expected, destroyed the characteristic ccRCC vascular phenotype. In contrast to the expectation, vital groups of tumor cells with high proliferation indices were detected in postsurgical renal venous outflow in 75% of the cases. Overall survival of patients receiving neoadjuvant treatment was reduced compared to a control group, matched with regard to prognostic parameters. CONCLUSIONS: These results suggest that neoadjuvant sorafenib therapy for ccRCC does not prevent shedding of tumor fragments. Although this is a nonrandomized study with a small patient group, our results suggest that neoadjuvant treatment may worsen survival through as yet undefined mechanisms.

Molecular imaging and carbonic anhydrase IX-targeted radioimmunotherapy in clear cell renal cell carcinoma.

Conventional imaging is suboptimal at evaluating disease status in renal cell carcinoma (RCC) because of poor sensitivity. Furthermore, there is an unmet need for the treatment of metastatic RCC, both in terms of improvement of progression-free survival and limitation of toxicity. For this reason, radionuclide imaging and radionuclide therapy are extensively investigated. This review provides an overview of the current progress in molecular imaging and radionuclide therapy in clear cell RCC and will focus on promising detection and therapy strategies targeting the carbonic anhydrase IX antigen, which is expressed in clear cell RCC.