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.

Nephron Sparing Treatment (NEST) for Small Renal Masses: A Feasibility Cohort-embedded Randomised Controlled Trial Comparing Percutaneous Cryoablation and Robot-assisted Partial Nephrectomy.

There is a paucity of high-level evidence on small renal mass (SRM) management, as previous classical randomised controlled trials (RCTs) failed to meet accrual targets. Our objective was to assess the feasibility of recruitment to a cohort-embedded RCT comparing cryoablation (CRA) to robotic partial nephrectomy (RPN). A total of 200 participants were recruited to the cohort, of whom 50 were enrolled in the RCT. In the CRA intervention arm, 84% consented (95% confidence interval [CI] 64-95%) and 76% (95% CI 55-91%) received CRA; 100% (95% CI 86-100%) of the control arm underwent RPN. The retention rate was 90% (95% CI 79-96%) at 6 mo. In the RPN group 2/25 (8%) were converted intra-operative to radical nephrectomy. Postoperative complications (Clavien-Dindo grade 1-2) occurred in 12% of the CRA group and 29% of the RPN group. The median length of hospital stay was shorter for CRA (1 vs 2 d; p = 0.019). At 6 mo, the mean change in renal function was -5.0 ml/min/1.73 m2 after CRA and -5.8 ml/min/1.73 m2 after RPN. This study demonstrates the feasibility of a cohort-embedded RCT comparing CRA and RPN. These data can be used to inform multicentre trials on SRM management. PATIENT SUMMARY: We assessed whether patients with a small kidney tumour would consent to a trial comparing two different treatments: cryoablation (passing small needles through the skin to freeze the kidney tumour) and surgery to remove part of the kidney. We found that most patients agreed and a full trial would therefore be feasible.

A Systematic Review of Patient Race, Ethnicity, Socioeconomic Status, and Educational Attainment in Prostate Cancer Treatment Randomised Trials-Is the Evidence Base Applicable to the General Patient Population?

Context: Prostate cancer (PC) disproportionately affects men of Black race, and lower educational and socioeconomic status. Guidelines are based on randomised controlled trials (RCTs); however, the representation of different races, educations, and socioeconomic backgrounds in these trials is unclear. Objective: To assess reporting of equality, diversity, and inclusion characteristics (Equality, Diversity and Inclusion [EDI]) and differences in treatment effects between different races, and educational or socioeconomic status. Evidence acquisition: We conducted a systematic review of CENTRAL, MEDLINE, and Embase in April 2020 examining RCTs investigating treatments for PC. Outcomes collected were race/ethnicity, educational attainment, and socioeconomic status. RCTs investigating PC treatment in any population or setting were included. Data extraction of characteristics was performed independently by pairs of reviewers and checked by a senior author. The Cochrane risk of bias tool assessed the quality of included papers. Evidence synthesis: A total of 265 trials were included, and 138 of these were available as full-text articles. Fifty-four trials including 19 039 participants reported any EDI data. All 54 trials reported race, 11 reported ethnicity, three reported educational attainment, and one reported socioeconomic status. Patients of White race were the majority of the recruited population (82.6%), while the minority prevalence was as follows: Black 9.8% and Asian 5.7%. Three studies reported mortality outcomes depending on the participant's race. All three studies investigated different treatments, so a meta-analysis was not performed. No studies reported outcomes stratified by the educational or socioeconomic status of participants. Conclusions: There is poor reporting of patient race, ethnicity, socioeconomic background, and educational attainment in RCTs for PC treatments between 2010 and 2020. Addressing this for future studies will help explain differences in the incidence of and mortality from PC and improve the generalisability of results. Patient summary: In this study, we reviewed prostate cancer treatment trials to see whether these reported race, education, and socioeconomic backgrounds of their patient populations. We conclude that reporting of these characteristics is poor. This needs to be improved in future to improve outcomes for patients with prostate cancer of all ethnical, racial, and socioeconomic groups.

Interpretability of radiomics models is improved when using feature group selection strategies for predicting molecular and clinical targets in clear-cell renal cell carcinoma: insights from the TRACERx Renal study.

BACKGROUND: The aim of this work is to evaluate the performance of radiomics predictions for a range of molecular, genomic and clinical targets in patients with clear cell renal cell carcinoma (ccRCC) and demonstrate the impact of novel feature selection strategies and sub-segmentations on model interpretability. METHODS: Contrast-enhanced CT scans from the first 101 patients recruited to the TRACERx Renal Cancer study (NCT03226886) were used to derive radiomics classification models to predict 20 molecular, histopathology and clinical target variables. Manual 3D segmentation was used in conjunction with automatic sub-segmentation to generate radiomics features from the core, rim, high and low enhancing sub-regions, and the whole tumour. Comparisons were made between two classification model pipelines: a Conventional pipeline reflecting common radiomics practice, and a Proposed pipeline including two novel feature selection steps designed to improve model interpretability. For both pipelines nested cross-validation was used to estimate prediction performance and tune model hyper-parameters, and permutation testing was used to evaluate the statistical significance of the estimated performance measures. Further model robustness assessments were conducted by evaluating model variability across the cross-validation folds. RESULTS: Classification performance was significant (p < 0.05, H0:AUROC = 0.5) for 11 of 20 targets using either pipeline and for these targets the AUROCs were within ± 0.05 for the two pipelines, except for one target where the Proposed pipeline performance increased by > 0.1. Five of these targets (necrosis on histology, presence of renal vein invasion, overall histological stage, linear evolutionary subtype and loss of 9p21.3 somatic alteration marker) had AUROC > 0.8. Models derived using the Proposed pipeline contained fewer feature groups than the Conventional pipeline, leading to more straightforward model interpretations without loss of performance. Sub-segmentations lead to improved performance and/or improved interpretability when predicting the presence of sarcomatoid differentiation and tumour stage. CONCLUSIONS: Use of the Proposed pipeline, which includes the novel feature selection methods, leads to more interpretable models without compromising prediction performance. TRIAL REGISTRATION: NCT03226886 (TRACERx Renal).

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.

Integrating simulation and interpretive description to explore operating room leadership: critical event continuing education.

In Obstetrics and Gynecologic operating room emergencies, the surgeon cannot both operate and lead a suddenly expanded and redirected team response. However, one of the most often used approaches to interprofessional continuing education designed to improve teams' ability to respond to unanticipated critical events still emphasizes surgeon leadership. We developed Explicit Anesthesia and Nurse Distributed (EXPAND) Leadership to imagine a workflow that might better distribute emergency leadership task responsibilities and practices. The purpose of this exploratory study was to investigate teams' responses to distributing leadership during an interprofessional continuing education simulated obstetrical emergency. We used interpretive descriptive design in a secondary analysis of teams' post-simulation reflective debriefings. One-hundred sixty providers participated, including OB-Gyn surgeons, anesthesiologists, CRNAs, scrub technicians, and nurses. Using reflective thematic analysis, we identified three core themes: 1) The surgeon is focused on the surgical field, 2) Explicit leadership initiates a nurse transition from follower to leader in a hierarchical environment, and 3) Explicit distributed leadership enhances teamwork and taskwork. Continuing education which uses distributed leadership to improve teams' ability to respond to an obstetric emergency is perceived to enhance team members' response to the critical event . The potential for nurses' career growth and professional transformation was an unexpected finding associated with this continuing education which used distributed leadership. Our findings suggest that healthcare educators should consider ways in which distributed leadership may improve teams' response to critical events in the operating room.

Protocol for a MULTI-centre feasibility study to assess the use of 99mTc-sestaMIBI SPECT/CT in the diagnosis of kidney tumours (MULTI-MIBI study).

INTRODUCTION: The incidence of renal tumours is increasing and anatomic imaging cannot reliably distinguish benign tumours from renal cell carcinoma. Up to 30% of renal tumours are benign, with oncocytomas the most common type. Biopsy has not been routinely adopted in many centres due to concerns surrounding non-diagnostic rate, bleeding and tumour seeding. As a result, benign masses are often unnecessarily surgically resected. 99mTc-sestamibi SPECT/CT has shown high diagnostic accuracy for benign renal oncocytomas and other oncocytic renal neoplasms of low malignant potential in single-centre studies. The primary aim of MULTI-MIBI is to assess feasibility of a multicentre study of 99mTc-sestamibi SPECT/CT against a reference standard of histopathology from surgical resection or biopsy. Secondary aims of the study include obtaining estimates of 99mTc-sestamibi SPECT/CT sensitivity and specificity and to inform the design and conduct of a future definitive trial. METHODS AND ANALYSIS: A feasibility prospective multicentre study of participants with indeterminate, clinical T1 renal tumours to undergo 99mTc-sestamibi SPECT/CT (index test) compared with histopathology from biopsy or surgical resection (reference test). Interpretation of the index and reference tests will be blinded to the results of the other. Recruitment rate as well as estimates of sensitivity, specificity, positive and negative predictive value will be reported. Semistructured interviews with patients and clinicians will provide qualitative data to inform onward trial design and delivery. Training materials for 99mTc-sestamibi SPECT/CT interpretation will be developed, assessed and optimised. Early health economic modelling using a decision analytic approach for different diagnostic strategies will be performed to understand the potential cost-effectiveness of 99mTc-sestamibi SPECT/CT. ETHICS AND DISSEMINATION: Ethical approval has been granted (UK HRA REC 20/YH/0279) protocol V.5.0 dated 21/6/2022. Study outputs will be presented and published nationally and internationally. TRIAL REGISTRATION NUMBER: ISRCTN12572202.

Further clinical and molecular characterization of an XLID syndrome associated with BRWD3 variants, a gene implicated in the leukemia-related JAK-STAT pathway.

BACKGROUND: Since the first description of a BRWD3-associated nonsydromic intellectual disability (ID) disorder in 2007, 21 additional families have been reported in the literature. METHODS: Using exome sequencing (ES) and international data sharing, we identified 14 additional unrelated individuals with pathogenic BRWD3 variants (12 males and 2 females, including one with skewed X-inactivation). We reviewed the 31 previously published cases in the literature with clinical data available, and describe the collective phenotypes of 43 males and 2 females, with 33 different BRWD3 variants. RESULTS: The most common features in males (excluding one patient with a mosaic variant) included ID (39/39 males), speech delay (24/25 males), postnatal macrocephaly (28/35 males) with prominent forehead (18/25 males) and large ears (14/26 males), and obesity (12/27 males). Both females presented with macrocephaly, speech delay, and epilepsy, while epilepsy was only observed in 4/41 males. Among the 28 variants with available segregation reported, 19 were inherited from unaffected mothers and 9 were de novo. CONCLUSION: This study demonstrates that the BRWD3-related phenotypes are largely non-specific, leading to difficulty in clinical recognition of this disorder. A genotype-first approach, however, allows for the more efficient diagnosis of the BRWD3-related nonsyndromic ID. The refined clinical features presented here may provide additional diagnostic assistance for reverse phenotyping efforts.

Combinatorial approaches for mitigating resistance to KRAS-targeted therapies.

Approximately 15% of all cancer patients harbor mutated KRAS. Direct inhibitors of KRAS have now been generated and are beginning to make progress through clinical trials. These include a suite of inhibitors targeting the KRASG12C mutation commonly found in lung cancer. We investigated emergent resistance to representative examples of different classes of Ras targeted therapies. They all exhibited rapid reactivation of Ras signaling within days of exposure and adaptive responses continued to change over long-term treatment schedules. Whilst the gene signatures were distinct for each inhibitor, they commonly involved up-regulation of upstream nodes promoting mutant and wild-type Ras activation. Experiments to reverse resistance unfortunately revealed frequent desensitization to members of a panel of anti-cancer therapeutics, suggesting that salvage approaches are unlikely to be feasible. Instead, we identified triple inhibitor combinations that resulted in more durable responses to KRAS inhibitors and that may benefit from further pre-clinical evaluation.

Creating a path forward: understanding the context of sexual health and sexually transmitted infections in American Indian/Alaska Native populations – a review.

This review assessed sexual health and sexually transmitted infection (STI) burden among American Indian/Alaska Native (AI/AN) peoples within the context of current clinical and public health services. We conducted a review of published literature about sexual health and bacterial STIs among AI/AN populations in the United States using Medline (OVID), CINAHL (EbscoHost) and Scopus. Peer-reviewed journals published during 1 January 2005-2 December 2021 were included and supplemented by other publicly available literature. A total of 138 articles from reference lists met inclusion criteria, including 85 peer-review articles and 53 additional references. Results indicate a disproportionate burden of STIs is carried by AI/AN populations compared to non-Hispanic Whites. Risk for STIs in AI/AN people has origins in historical trauma and structural and social determinants of health. STI services are available for AI/AN populations, but many barriers to care exist. Community-based sexual health programming has been successful, but has thus far focused primarily on adolescents and young adults. A myriad of factors contributes to high rates of STIs among AI/AN populations. Longstanding disparities show a clear need to increase the availability of integrated, low-barrier STI prevention and treatment services. Implementation of multi-level (individual, physician, clinic, healthcare organisation, and/or community level), culturally relevant sexual health and STI interventions should be community-based and person-centred, acknowledge social determinants of health, and grounded in deep respect and understanding of AI/AN histories and cultures.

The Impact of COVID-19 on the Delivery of Educational Programs in Native American Communities: Qualitative Study.

BACKGROUND: Despite the availability of culturally responsive sexual health educational programs for American Indian and Alaska Native (AI/AN) youth, barriers to their uptake and utilization persist in tribal communities. These challenges were exacerbated by the COVID-19 pandemic, which required flexible program delivery using both in-person and virtual classrooms. OBJECTIVE: This exploratory study provides a preliminary understanding of the extent to which pre-existing challenges impact the delivery of culturally responsive sexual health education programs in Native communities and to what extent they were exacerbated by the COVID-19 pandemic. It also highlights the challenges faced by adolescent health advocates when adapting culturally responsive health curricula to online platforms. Finally, this study discloses major socioeconomic, health, and mental challenges experienced by AI/AN youth during the pandemic. METHODS: An exploratory, descriptive, qualitative design approach was adopted to carry out 5 individual and 1 collective in-depth key informant interviews. A total of 8 Native and non-Native sexual health educators served as key informants and shared their personal experiences with the delivery of sexual health education programs for youth during the COVID-19 pandemic. The interviews were conducted virtually from October to November 2020 using Zoom to reach participants dispersed across different regions of the United States. We followed the consolidated criteria for reporting qualitative research (COREQ) as a reference for the study methodology. We also used the Braun and Clarke framework (2006) to conduct a thematic analysis. RESULTS: Experts' opinions were structured according to 5 main themes: (1) competing community priorities during COVID-19; (2) moving to web-based programming: skills, training, support; (3) recruiting youth; and (4) challenges for implementation in a household environment; and (5) recommendations to overcome implementation challenges. These themes are complementary, connected, and should be considered holistically for the development, dissemination, and implementation of online sexual health programs for AI/AN youth, specifically during the COVID-19 pandemic. The results raised the following points for discussion: (1) Building partnerships with schools and community organizations facilitates program adaptation and implementation, (2) there is a need to adopt a holistic approach when addressing youth sexual health in AI/AN communities, (3) a systematic and culturally responsive adaptation approach ensures effective virtual program delivery, and (4) community and youth engagement is essential for the success of virtual sexual health programs. CONCLUSIONS: Findings can provide recommendations on actions to be taken by sexual health educators and guidelines to follow to ensure cultural sensitivity, effective adaptation, and successful implementation when setting out to advocate for online sexual health programs for AI/AN youth.