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.

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.

Epitheloid Angiomyolipomas of the Kidney: Rare Renal Tumors Associated With Poor Prognoses.

OBJECTIVE: To demonstrate the clinical spectrum and challenges associated with clinical management of epitheloid angiomyolipomas (eAML). METHODS: We retrospectively reviewed the surgical database of a high-volume tertiary kidney cancer center from 2015 to 2020 to identify cases with a final histological diagnosis of eAML. Descriptive analysis of all cases was conducted. RESULTS: Five surgical cases of eAMLs were identified. Two of which have had no tumor recurrence since surgery, and three patients passed away due to disease progression. CONCLUSION: eAML are rare renal tumors which the World Health Organisation (5th Edition, 2022) and International Classification of Diseases for Oncology classify as having unspecified, borderline, or uncertain behavior. Here, we report that can also demonstrate aggressive behavior with fatal consequences. Post-operative follow-up should be recommended for all, with shorter intervals for patients with poor prognostic factors.

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.

Comparison of Long-term Outcomes for Young and Healthy Patients with cT1a and cT3a Renal Cell Carcinoma Treated with Partial Nephrectomy.

Partial nephrectomy (PN) is recommended for renal cell carcinoma (RCC) of <4 cm. We hypothesized that there is no difference in all-cause mortality (ACM) between cT1a, cT1b, and cT3a <4 cm RCC following PN. The National Cancer Database was interrogated to identify patients aged <60 yr with a Charlson comorbidity index ≤1 diagnosed between 2004 and 2017. Cox proportional-hazard models stratified for cT stage were used to predict 10-yr ACM. A total of 30 195 patients (25 121 cT1a, 4884 cT1b, and 190 cT3a <4 cm) who underwent PN with median follow-up of 64.36 mo (interquartile range 42.91-93.77) were included. Cox analysis revealed no significant difference in 10-yr ACM between cT1a and cT3a <4 cm (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.58-1.90; p = 0.88). However, the cT1b group had higher ACM (HR 1.31, 95% CI 1.15-1.48; p < 0.01). The positive surgical margin (PSM) rate was higher for cT3a <4 cm than for cT1a tumors (14.2% vs 6.3%; p < 0.01). However, there was no difference in 10-yr ACM rate between cT1a and cT3a <4 cm (10.9% vs 9.7%; p = 0.42). Our results suggest that PN is an option for cT3a RCC <4 cm, particularly in cases in which maximum nephron preservation is essential, such as patients with chronic kidney disease or a solitary kidney, although a higher PSM risk should be appreciated. PATIENT SUMMARY: We found that partial removal of the kidney for localized advanced kidney cancer is safe. The rate of surgical margins positive for the presence of tumor is higher in localized advanced kidney cancer than for less advanced cancers, but there was no difference in 10-year predicted mortality.

A Systematic Review of Heterogeneity in Outcome Definition and Reporting in Localised Renal Cancer.

Context: Outcomes in renal cell carcinoma (RCC) are reported inconsistently, with variability in definitions and measurement. Hence, it is difficult to compare intervention effectiveness and synthesise outcomes for systematic reviews and to create clinical practice guidelines. This uncertainty in the evidence makes it difficult to guide patient-clinician decision-making. One solution is a core outcome set (COS): an agreed minimum set of outcomes. Objective: To describe outcome reporting, definitions, and measurement heterogeneity as the first stage in co-creating a COS for localised renal cancer. Evidence acquisition: We systematically reviewed outcome reporting heterogeneity in effectiveness trials and observational studies in localised RCC. In total, 2822 studies (randomised controlled trials, cohort studies, case-control studies, systematic reviews) up to June 2020 meeting our inclusion criteria were identified. Abstracts and full texts were screened independently by two reviewers; in cases of disagreement, a third reviewer arbitrated. Data extractions were double-checked. Evidence synthesis: We included 149 studies and found that there was inconsistency in which outcomes were reported across studies and variability in the definitions used for outcomes that were conceptually the same. We structured our analysis using the outcome classification taxonomy proposed by Dodd et al. Outcomes linked to adverse events (eg, bleeding, outcomes linked to surgery) and renal injury outcomes (reduced renal function) were reported most commonly. Outcomes related to deaths from any cause and from cancer were reported in 44% and 25% of studies, respectively, although the time point for measurement and the analysis methods were inconsistent. Outcomes linked to life impact (eg, global quality of life) were reported least often. Clinician-reported outcomes are more frequently reported than patient-reported outcomes in the renal cancer literature. Conclusions: This systematic review underscores the heterogeneity of outcome reporting, definitions, and measurement in research on localised renal cancer. It catalogues the variety of outcomes and serves as a first step towards the development of a COS for localised renal cancer. Patient summary: We reviewed studies on localised kidney cancer and found that multiple terms and definitions have been used to describe outcomes. These are not defined consistently, and often not defined at all. Our review is the first phase in developing a core outcome set to allow better comparisons of studies to improve medical care.

Cost-Utility Analysis of Major System Change in Specialist Cancer Surgery in London, England, Using Linked Patient-Level Electronic Health Records and Difference-in-Differences Analysis.

BACKGROUND: Studies have shown that centralising surgical treatment for some cancers can improve patient outcomes, but there is limited evidence of the impact on costs or health-related quality of life. OBJECTIVES: We report the results of a cost-utility analysis of the RESPECT-21 study using difference-in-differences, which investigated the reconfiguration of specialist surgery services for four cancers in an area of London, compared to the Rest of England (ROE). METHODS: Electronic health records data were obtained from the National Cancer Registration and Analysis Service for patients diagnosed with one of the four cancers of interest between 2012 and 2017. The analysis for each tumour type used a short-term decision tree followed by a 10-year Markov model with 6-monthly cycles. Costs were calculated by applying National Health Service (NHS) Reference Costs to patient-level hospital resource use and supplemented with published data. Cancer-specific preference-based health-related quality-of-life values were obtained from the literature to calculate quality-adjusted life-years (QALYs). Total costs and QALYs were calculated before and after the reconfiguration, in the London Cancer (LC) area and in ROE, and probabilistic sensitivity analysis was performed to illustrate the uncertainty in the results. RESULTS: At a threshold of £30,000/QALY gained, LC reconfiguration of prostate cancer surgery services had a 79% probability of having been cost-effective compared to non-reconfigured services using difference-in-differences. The oesophago-gastric, bladder and renal reconfigurations had probabilities of 62%, 49% and 12%, respectively, of being cost-effective at the same threshold. Costs and QALYs per surgical patient increased over time for all cancers across both regions to varying degrees. Bladder cancer surgery had the smallest patient numbers and changes in costs, and QALYs were not significant. The largest improvement in outcomes was in renal cancer surgery in ROE, making the relative renal improvements in LC appear modest, and the probability of the LC reconfiguration having been cost-effective low. CONCLUSIONS: Prostate cancer reconfigurations had the highest probability of being cost-effective. It is not clear, however, whether the prostate results can be considered in isolation, given the reconfigurations occurred simultaneously with other system changes, and healthcare delivery in the NHS is highly networked and collaborative. Routine collection of quality-of-life measures such as the EQ-5D-5L would have improved the analysis.

Inter-organisational collaboration enabling care delivery in a specialist cancer surgery provider network: A qualitative study.

OBJECTIVE: To explore the processes, challenges and strategies used to govern and maintain inter-organisational collaboration between professionals in a provider network in London, United Kingdom, which implemented major system change focused on the centralisation of specialist cancer surgery. METHODS: We used a qualitative design involving interviews with stakeholders (n = 117), non-participant observations (n = 163) and documentary analysis (n = 100). We drew on an existing model of collaboration in healthcare organisations and expanded this framework by applying it to the analysis of collaboration in the context of major system change. RESULTS: Network provider organisations established shared goals, maintained central figures who could create and sustain collaboration, and promoted distributed forms of leadership. Still, organisations continued to encounter barriers or challenges in relation to developing opportunities for mutual acquaintanceship across all professional groups; the active sharing of knowledge, expertise and good practice across the network; the fostering of trust; and creation of information exchange infrastructures fit for collaborative purposes. CONCLUSION: Collaborative relationships changed over time, becoming stronger post-implementation in some areas, but continued to be negotiated where resistance to the centralisation remained. Future research should explore the sustainability of these relationships and further unpack how hierarchies and power relationships shape inter-organisational collaboration.

Perioperative impact of body mass index on upper urinary tract and renal robot-assisted surgery: a single high-volume centre experience.

To assess the impact of body mass index (BMI) on peri-operative outcomes of kidney and upper tract robot-assisted surgery. Medical audit of patients who underwent robot-assisted kidney and upper tract cancer surgery at a single institution between 2017 and 2019, categorized on BMI into obese patients with a BMI ≥ 30 kg/m2 and a control group with BMI < 25 kg/m2. Patient and tumour characteristics, surgery time, intraoperative blood loss, intraoperative adverse events (AE) according to the European Association of Urology Intraoperative Adverse Incidents Classification (EAUiaiC), conversion- to-open/radical rate as well as 30-day postoperative AE according to Clavien-Dindo (CD) and length of inpatient stay were analyzed. 366 patients were identified, 141 with a BMI < 25 (normal-weight) and 225 BMI ≥ 30 (obesity). There were no significant differences between the groups in terms of age, gender, comorbidities, tumour size, TNM stage and type of surgery. Obese patients had a higher estimated blood loss (198.05 ml), surgery time (171.75 min), intraoperative AE (all grades) (14.67%, 95% CI (0.10-0.19) as well as adherent perinephric fat (APF) (14.22%, 95% CI (0.09-0.19)) in contrast to the control group (86.85 ml, 148.29 min, 7.04% and 2.12%, respectively). Hospital stay, major intraoperative AE (≥ 3) and major postoperative AE (CD > 2) distributed equally between groups. Robotic kidney and upper tract surgery in obese patients showed an increase in surgery time and blood loss potentially related to APF. However, obesity was not associated with conversion to open surgery or radical nephrectomy in nephron-sparing procedures, length of stay, major intraoperative AE or postoperative complications.

The Current Evidence for Factors that Influence Treatment Decision Making in Localized Kidney Cancer: A Mixed Methods Systematic Review.

PURPOSE: With a growing number of treatment options for localized kidney cancer, patients and health care professionals have both the opportunity and the burden of selecting the most suitable management option. This mixed method systematic review aims to understand the barriers and facilitators of the treatment decision making process in localized kidney cancer. MATERIALS AND METHODS: We searched PubMed®, Embase® and Cochrane Central databases between January 1, 2004 and April 23, 2020 using the Joanna Briggs Manual for Evidence Synthesis and the Preferred Reporting Items for Systematic Review and Meta-analysis statement. We identified 553 unique citations; of these, 511 were excluded resulting in 42 articles included for synthesis. The Purpose, Respondents, Explanation, Findings and Significance and the Strengthening the Reporting of Observational Studies in Epidemiology checklist was applied. RESULTS: The key themes describing barriers and facilitators to treatment decision making were identified and categorized into 3 domains: 1) kidney cancer specific characteristics, 2) decision maker related criteria and 3) contextual factors. The main facilitators identified within these domains were size at diagnosis, age, comorbidities, body mass index, gender, nephrometry scoring systems, biopsy, socioeconomic status, family history of cancer, year of diagnosis, geographic region and practice pattern. The key barriers were race, gender, patient anxiety, low confidence in diagnostic and treatment options, cost of procedure, and practice patterns. CONCLUSIONS: Future interventions designed to improve the decision making process for localized kidney cancer should consider these barriers and facilitators to ensure a better patient experience.

Salvage Robot-assisted Renal Surgery for Local Recurrence After Surgical Resection or Renal Mass Ablation: Classification, Techniques, and Clinical Outcomes.

BACKGROUND: Salvage treatment for local recurrence after prior partial nephrectomy (PN) or local tumor ablation (LTA) for kidney cancer is, as of yet, poorly investigated. OBJECTIVE: To classify the treatments and standardize the nomenclature of salvage robot-assisted renal surgery, to describe the surgical technique for each scenario, and to investigate complications, renal function, and oncologic outcomes. DESIGN, SETTING, AND PARTICIPANTS: Sixty-seven patients underwent salvage robot-assisted renal surgery from October 2010 to December 2020 at nine tertiary referral centers. SURGICAL PROCEDURE: Salvage robot-assisted renal surgery classified according to treatment type as salvage robot-assisted partial or radical nephrectomy (sRAPN or sRARN) and according to previous primary treatment (PN or LTA). MEASUREMENTS: Postoperative complications, renal function, and oncologic outcomes were assessed. RESULTS AND LIMITATIONS: A total of 32 and 35 patients underwent salvage robotic surgery following PN and LTA, respectively. After prior PN, two patients underwent sRAPN, while ten underwent sRARN for a metachronous recurrence in the same kidney. No intra- or perioperative complication occurred. For local recurrence in the resection bed, six patients underwent sRAPN, while 14 underwent sRARN. For sRAPN, the intraoperative complication rate was 33%; there was no postoperative complication. For sRARN, there was no intraoperative complication and the postoperative complication rate was 7%. At 3 yr, the local recurrence-free rates were 64% and 82% for sRAPN and sRARN, respectively, while the 3-yr metastasis-free rates were 80% and 79%, respectively. At 33 mo, the median estimated glomerular filtration rates (eGFRs) were 57 and 45 ml/min/1.73 m2 for sRAPN and sRARN, respectively. After prior LTA, 35 patients underwent sRAPN and no patient underwent sRARN. There was no intraoperative complication; the overall postoperative complications rate was 20%. No local recurrence occurred. The 3-yr metastasis-free rate was 90%. At 43 mo, the median eGFR was 38 ml/min/1.73 m2. The main limitations are the relatively small population and the noncomparative design of the study. CONCLUSIONS: Salvage robot-assisted surgery has a safe complication profile in the hands of experienced surgeons at high-volume institutions, but the risk of local recurrence in this setting is non-negligible. PATIENT SUMMARY: Patients with local recurrence after partial nephrectomy or local tumor ablation should be aware that further treatment with robot-assisted surgery is not associated with a worrisome complication profile, but also that they are at risk of further recurrence.

Impact of the first surge of the COVID-19 pandemic on a tertiary referral centre for kidney cancer.

OBJECTIVE: To analyse the impact of the COVID-19 pandemic on a centralized specialist kidney cancer care pathway. MATERIALS AND METHODS: We conducted a retrospective analysis of patient and pathway characteristics including prioritization strategies at the Specialist Centre for Kidney Cancer located at the Royal Free London NHS Foundation Trust (RFH) before and during the surge of COVID-19. RESULTS: On 18 March 2020 all elective surgery was halted at RFH to redeploy resources and staff for the COVID-19 surge. Prioritizing of patients according to European Association of Urology guidance was introduced. Clinics and the specialist multidisciplinary team (SMDT) meetings were maintained with physical distancing, kidney surgery was moved to a COVID-protected site, and infection prevention measurements were enforced. During the 7 weeks of lockdown (23 March to 10 May 2020), 234 cases were discussed at the SMDT meetings, 53% compared to the 446 cases discussed in the 7 weeks pre-lockdown. The reduction in referrals was more pronounced for small and asymptomatic renal masses. Of 62 low-priority cancer patients, 27 (43.5%) were deferred. Only one (4%) COVID-19 infection occurred postoperatively, and the patient made a full recovery. No increase in clinical or pathological upstaging could be detected in patients who underwent deferred surgery compared to pre-COVID practice. CONCLUSION: The first surge of the COVID-19 pandemic severely impacted diagnosis, referral and treatment of kidney cancer at a tertiary referral centre. With a policy of prioritization and COVID-protected pathways, capacity for time-sensitive oncological interventions was maintained and no immediate clinical harm was observed.

Growth and renal function dynamics of renal oncocytomas in patients on active surveillance.

OBJECTIVES: To study the natural history of renal oncocytomas and address indications for intervention by determining how growth is associated with renal function over time, the reasons for surgery and ablation, and disease-specific survival. PATIENTS AND METHODS: The study was conducted in a retrospective cohort of consecutive patients with renal oncocytoma on active surveillance reviewed at the Specialist Centre for Kidney Cancer at the Royal Free London NHS Foundation Trust (2012 to 2019). Comparison between groups was performed using Mann-Whitney U-tests and chi-squared tests. A mixed-effects model with a random intercept for patient was used to study the longitudinal association between tumour size and estimated glomerular filtration rate (eGFR). RESULTS: Longitudinal data from 98 patients with 101 lesions were analysed. Most patients were men (68.3%) and the median (interquartile range [IQR]) age was 69 (13) years. The median (IQR) follow-up was 29 (26) months. Most lesions were small renal masses, and 24% measured over 4 cm. Over half (64.4%) grew at a median (IQR) rate of 2 (4) mm per year. No association was observed between tumour size and eGFR over time (P = 0.871). Nine lesions (8.9%) were subsequently treated. Two deaths were reported, neither were related to the diagnosis of renal oncocytoma. CONCLUSION: Natural history data from the largest active surveillance cohort of renal oncocytomas to date show that renal function does not seem to be negatively impacted by growing oncocytomas, and confirms clinical outcomes are excellent after a median follow-up of over 2 years. Active surveillance should be considered the 'gold standard' management of renal oncocytomas up to 7cm.

Pattern, timing and predictors of recurrence after surgical resection of chromophobe renal cell carcinoma.

PURPOSE: Currently there are no specific guidelines for the post-operative follow-up of chromophobe renal cell carcinoma (chRCC). We aimed to evaluate the pattern, location and timing of recurrence after surgery for non-metastatic chRCC and establish predictors of recurrence and cancer-specific death. METHODS: Retrospective analysis of consecutive surgically treated non-metastatic chRCC cases from the Royal Free London NHS Foundation Trust (UK, 2015-2019) and the international collaborative database RECUR (15 institutes, 2006-2011). Kaplan-Meier curves were plotted. The association between variables of interest and outcomes were analysed using univariate and multivariate Cox proportional hazards regression models with shared frailty for data source. RESULTS: 295 patients were identified. Median follow-up was 58 months. The five and ten-year recurrence-free survival rates were 94.3% and 89.2%. Seventeen patients (5.7%) developed recurrent disease, 13 (76.5%) with distant metastases. 54% of metastatic disease diagnoses involved a single organ, most commonly the bone. Early recurrence (< 24 months) was observed in 8 cases, all staged ≥ pT2b. 30 deaths occurred, of which 11 were attributed to chRCC. Sarcomatoid differentiation was rare (n = 4) but associated with recurrence and cancer-specific death on univariate analysis. On multivariate analysis, UICC/AJCC T-stage ≥ pT2b, presence of coagulative necrosis, and positive surgical margins were predictors of recurrence and cancer-specific death. CONCLUSION: Recurrence and death after surgically resected chRCC are rare. For completely excised lesions ≤ pT2a without coagulative necrosis or sarcomatoid features, prognosis is excellent. These patients should be reassured and follow-up intensity curtailed.