Short-term psychosocial outcomes of adding a non-contrast abdominal computed tomography (CT) scan to the thoracic CT within lung cancer screening.

OBJECTIVES: To evaluate psychological, social, and financial outcomes amongst individuals undergoing a non-contrast abdominal computed tomography (CT) scan to screen for kidney cancer and other abdominal malignancies alongside the thoracic CT within lung cancer screening. SUBJECTS AND METHODS: The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding a non-contrast abdominal CT scan to the thoracic CT within lung cancer screening. A total of 500 participants within the YKST, comprising all who had an abnormal CT scan and a random sample of one-third of those with a normal scan between 14/03/2022 and 24/08/2022 were sent a questionnaire at 3 and 6 months. Outcomes included the Psychological Consequences Questionnaire (PCQ), the short-form of the Spielberger State-Trait Anxiety Inventory, and the EuroQoL five Dimensions five Levels scale (EQ-5D-5L). Data were analysed using regression adjusting for participant age, sex, socioeconomic status, education, baseline quality of life (EQ-5D-5L), and ethnicity. RESULTS: A total of 380 (76%) participants returned questionnaires at 3 months and 328 (66%) at 6 months. There was no difference in any outcomes between participants with a normal scan and those with abnormal scans requiring no further action. Individuals requiring initial further investigations or referral had higher scores on the negative PCQ than those with normal scans at 3 months (standardised mean difference 0.28 sd, 95% confidence interval 0.01-0.54; P = 0.044). The difference was greater in those with anxiety or depression at baseline. No differences were seen at 6 months. CONCLUSION: Screening for kidney cancer and other abdominal malignancies using abdominal CT alongside the thoracic CT within lung cancer screening is unlikely to cause significant lasting psychosocial or financial harm to participants with incidental findings.

Diagnosis, treatment, and survival from kidney cancer: real-world National Health Service England data between 2013 and 2019.

OBJECTIVES: To report the NHS Digital (NHSD) data for patients diagnosed with kidney cancer (KC) in England. We explore the incidence, route to diagnosis (RTD), treatment, and survival patterns from 2013 to 2019. MATERIALS AND METHODS: Data was extracted from the Cancer Data NHSD portal for International Classification of Diseases, 10th edition coded KC; this included Cancer Registry data, Hospital Episode Statistics, and cancer waiting times data. RESULTS: Registrations included 66 696 individuals with KC. Incidence of new KC diagnoses increased (8998 in 2013, to 10 232 in 2019), but the age-standardised rates were stable (18.7-19.4/100 000 population). Almost half of patients (30 340 [45.5%]) were aged 0-70 years and the cohort were most frequently diagnosed with Stage 1-2 KC (n = 26 297 [39.4%]). Most patients were diagnosed through non-urgent general practitioner referrals (n = 16 814 [30.4%]), followed by 2-week-wait (n = 15 472 [28.0%]) and emergency routes (n = 11 796 [21.3%]), with older patients (aged ≥70 years), Stage 4 KCs, and patients with non-specified renal cell carcinoma being significantly more likely to present through the emergency route (all P < 0.001). Invasive treatment (surgery or ablation), radiotherapy, or systemic anti-cancer therapy use varied with disease stage, patient factors, and treatment network (Cancer Alliance). Survival outcomes differed by Stage, histological subtype, and social deprivation class (P < 0.001). Age-standardised mortality rates did not change over the study duration, although immunotherapy usage is likely not captured in this study timeline. CONCLUSION: The NHSD resource provides useful insight about the incidence, diagnostic pathways, treatment, and survival of patients with KC in England and a useful benchmark for the upcoming commissioned National Kidney Cancer Audit. The RTD data may be limited by incidental diagnoses, which could confound the high proportion of 'emergency' diagnoses. Importantly, survival outcomes remained relatively unchanged.

Long-term outcomes of image-guided ablation and laparoscopic partial nephrectomy for T1 renal cell carcinoma.

OBJECTIVE: To compare long-term outcomes and peri-operative outcomes of image-guided ablation (IGA) and laparoscopic partial nephrectomy (LPN). MATERIAL AND METHODS: This is a retrospective cohort study of localised RCC (T1a/bN0M0) patients undergoing cryoablation (CRYO), radio-frequency ablation (RFA), or LPN at our institution from 2003 to 2016. Oncological outcomes were compared using Cox regression and log-rank analysis. eGFR changes were compared using Kruskal-Wallis and Wilcoxon-rank tests. RESULTS: A total of 296 (238 T1a, 58 T1b) consecutive patients were identified; 103, 100, and 93 patients underwent CRYO, RFA, and LPN, respectively. Median follow-up time was 75, 98, and 71 months, respectively. On univariate analysis, all oncological outcomes were comparable amongst CRYO, RFA, and LPN (p > 0.05). On multivariate analysis, T1a patients undergoing RFA had improved local recurrence-free survival (LRFS) (HR 0.002, 95% CI 0.00-0.11, p = 0.003) and metastasis-free survival (HR 0.002, 95% CI 0.00-0.52, p = 0.029) compared to LPN. In T1a and T1b patients combined, both CRYO (HR 0.07, 95% CI 0.01-0.73, p = 0.026) and RFA (HR 0.04, 95% CI 0.03-0.48, p = 0.011) had improved LRFS rates. Patients undergoing CRYO and RFA had a significantly smaller median decrease in eGFR post-operatively compared to LPN (T1a: p < 0.001; T1b: p = 0.047). Limitations include retrospective design and limited statistical power. CONCLUSIONS: IGA is potentially as good as LPN in oncological durability. IGA preserves kidney function significantly better than LPN. More studies with larger sample size should be performed to establish IGA as a first-line treatment alongside LPN. KEY POINTS: • Ablative therapies are alternatives to partial nephrectomy for managing small renal cell carcinomas. • This study reports long-term outcomes of image-guided ablation versus partial nephrectomy. • Ablative therapies have comparable oncological durability and better renal function preservation compared to partial nephrectomy.

Irreversible electroporation (IRE) in renal cell carcinoma (RCC): a mid-term clinical experience.

OBJECTIVES: To evaluate the safety and efficacy of CT-guided IRE of clinical T1a (cT1a) renal tumours close to vital structures and to assess factors that may influence the technical success and early oncological durability. METHODS: CT-guided IRE (2015-2020) was prospectively evaluated. Patients' demographics, technical details/success, Clavien-Dindo (CD) classification of complications (I-V) and oncological outcome were collated. Statistical analysis was performed to determine variables associated with complications. The overall 2- and 3-year cancer-specific (CS), local recurrence-free (LRF) and metastasis-free (MF) survival rates are presented using the Kaplan-Meier curves. RESULTS: Thirty cT1a RCCs (biopsy-proven/known VHL disease) in 26 patients (age 32-81 years) were treated with IRE. The mean tumour size was 2.5 cm and the median follow-up was 37 months. The primary technical success rate was 73.3%, where 22 RCCs were completely IRE ablated. Seven residual diseases were successfully ablated with cryoablation, achieving an overall technical success rate of 97%. One patient did not have repeat treatment as he died from unexpected stroke at 4-month post-IRE. One patient had CD-III complication with a proximal ureteric injury. Five patients developed > 25% reduction of eGFR immediately post-IRE. All patients have preservation of renal function without the requirement for renal dialysis. The overall 2- and 3-year CS, LRF and MF survival rates are 89%, 96%, 91% and 87%. CONCLUSION: CT-guided IRE in cT1a RCC is safe with acceptable complications. The primary technical success rate was suboptimal due to the early operator's learning curve, and long-term follow-up is required to validate the IRE oncological durability. KEY POINTS: • Irreversible electroporation should only be considered when surgery or image-guided thermal ablation is not an option for small renal cancer. • This non-thermal technique is safe in the treatment of small renal cancer and the primary technical success rate was 73.3%. • This can be used when renal cancer is close to important structure.

Radiofrequency ablation (RFA) of renal cell carcinoma (RCC): experience in 200 tumours.

OBJECTIVES: To evaluate our clinical experience with percutaneous image-guided radiofrequency ablation (RFA) of 200 renal tumours in a large tertiary referral university institution. PATIENTS AND METHODS: Image-guided RFA (ultrasonography or computed tomography [CT]) of 200 renal tumours in 165 patients from June 2004 to 2012 was prospectively evaluated. Institutional Review Board approval was granted. The treatment response and technical success were defined by absence of contrast enhancement within the tumour on contrast enhanced CT or magnetic resonance imaging. Both major and minor complications, glomerular filtration rate (GFR) before and after RFA, the management and outcomes of the complications, as well as oncological outcome were prospectively documented. Multivariate analysis was used to determine variables associated with major complications and also the percentage GFR change after RFA. The overall (OS), 5-year cancer-specific (CSS), local recurrence-free (LRFS) and metastasis-free survival (MFS) rates are presented using the Kaplan-Meier curves. RESULTS: In all, 200 tumours were RF ablated with a mean (range) tumour size of 2.9 (1-5.6) cm and the mean (range) patient age was 67.7 (21-88.6) years with a mean follow-up period of 46.1 months. The primary technical and overall technical success rate was 95.5% and 98.5%, respectively. Two independent predictors of successful RFA in a single sitting were tumour size (<3 cm) and exophytic location in multivariate logistic regression analysis. Major complications included ureteric injury (six patients), calyceal-cutaneous fistula (one), acute tubular necrosis (one) and abscess (two). Two independent predictors of ureteric injury were central location and lower pole position. Within this cohort of patients, only four patients developed significant renal function deterioration i.e. >25% decreased in GFR. In all, 161 (98%) patients of the 165 patients have preservation of renal function. Any change in renal function after RFA was not influenced by tumour factors or solitary kidney status. In our clinical series, this yielded a 5-year OS, CSS, LRFS and MFS rates of 75.8%, 97.9%, 93.5% and 87.7% respectively. CONCLUSIONS: Image-guided RFA is a safe, nephron sparing and effective treatment for small renal cell carcinoma (RCC) tumours with a low rate of recurrence and has good 5-year CSS and MFS rates.

Acceptability of adding a non-contrast abdominal CT scan to screen for kidney cancer and other abdominal pathology within a community-based CT screening programme for lung cancer: A qualitative study.

OBJECTIVES: The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding non-contrast abdominal CT scanning to screen for kidney cancer and other abdominal malignancies to community-based CT screening for lung cancer within the Yorkshire Lung Screening Trial (YLST). This study explored the acceptability of the combined screening approach to participants and healthcare professionals (HCPs) involved in the trial. METHODS: We conducted semi-structured interviews with eight HCPs and 25 participants returning for the second round of scanning within YLST, 20 who had taken up the offer of the additional abdominal CT scan and five who had declined. Transcripts were analysed using thematic analysis, guided by the Theoretical Framework of Acceptability. RESULTS: Overall, combining the offer of a non-contrast abdominal CT scan alongside the low-dose thoracic CT was considered acceptable to participants, including those who had declined the abdominal scan. The offer of the additional scan made sense and fitted well within the process, and participants could see benefits in terms of efficiency, cost and convenience both for themselves as individuals and also more widely for the NHS. Almost all participants made an instant decision at the point of initial invitation based more on trust and emotions than the information provided. Despite this, there was a clear desire for more time to decide whether to accept the scan or not. HCPs also raised concerns about the burden on the study team and wider healthcare system arising from additional workload both within the screening process and downstream following findings on the abdominal CT scan. CONCLUSIONS: Adding a non-contrast abdominal CT scan to community-based CT screening for lung cancer is acceptable to both participants and healthcare professionals. Giving potential participants prior notice and having clear pathways for downstream management of findings will be important if it is to be offered more widely.

Estimating the Effectiveness of Kidney Cancer Screening Within Lung Cancer Screening Programmes: A Validation in UK Biobank.

In the absence of population-based screening, addition of screening for kidney cancer to lung cancer screening could provide an efficient and low-resource means to improve early detection. In this study, we used the UK Biobank cohort (n = 442 865) to determine the performance of the Yorkshire Lung Cancer Screening Trial (YLST) eligibility criteria for selecting individuals for kidney cancer screening. We measured the performance of two models widely used to determine eligibility for lung cancer screening (PLCO[m2012] and the Liverpool-Lung-Project-v2) and the performance of the combined YLST criteria. We found that the lung cancer models have discrimination (area under the receiver operating curve) between 0.60 and 0.68 for kidney cancer. In the UK, one in four cases (25%) of kidney cancer cases is expected to occur in those eligible for lung cancer screening, and one case of kidney cancer detected for every 200 people invited to lung cancer screening. These results suggest that adding kidney cancer screening to lung cancer screening would be an effective strategy to improve early detection rates of kidney cancer. However, most kidney cancers would not be picked up by this approach. This analysis does not address other important considerations about kidney cancer screening, such as overdiagnosis. PATIENT SUMMARY: It has been proposed that adding-on kidney cancer screening to lung cancer screening (both carried out by a computed tomography scan of the chest/abdomen) would be an easy and low-cost way of detecting cases of kidney cancer earlier, when these can be treated more easily. Lung cancer screening is usually targeted at people who are at a high risk (eg, older smokers); therefore, here we look at whether the same group of people are also at a high risk of kidney cancer. Our analysis shows that one in four people later diagnosed with kidney cancer are also at a high risk of lung cancer; hence, a combined screening programme could detect up to a quarter of kidney cancers.

The Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio for Small Renal Cell Carcinomas after Image-Guided Cryoablation or Radio-Frequency Ablation.

There is a lack of cheap and effective biomarkers for the prediction of renal cancer outcomes post-image-guided ablation. This is a retrospective study of patients with localised small renal cell cancer (T1a or T1b) undergoing cryoablation or radiofrequency ablation (RFA) at our institution from 2003 to 2016. A total of 203 patients were included in the analysis. In the multivariable analysis, patients with raised neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) pre-operatively, post-operatively and peri-operatively are associated with significantly worsened cancer-specific survival, overall survival and metastasis-free survival. Furthermore, an increased PLR pre-operatively is also associated with increased odds of a larger than 25% drop in renal function post-operatively. In conclusion, NLR and PLR are effective prognostic factors in predicting oncological outcomes and peri-operative outcomes; however, larger external datasets should be used to validate the findings prior to clinical application.

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.

Application of Genomic Sequencing to Refine Patient Stratification for Adjuvant Therapy in Renal Cell Carcinoma.

PURPOSE: Patients with resected localized clear-cell renal cell carcinoma (ccRCC) remain at variable risk of recurrence. Incorporation of biomarkers may refine risk prediction and inform adjuvant treatment decisions. We explored the role of tumor genomics in this setting, leveraging the largest cohort to date of localized ccRCC tissues subjected to targeted gene sequencing. EXPERIMENTAL DESIGN: The somatic mutation status of 12 genes was determined in 943 ccRCC cases from a multinational cohort of patients, and associations to outcomes were examined in a Discovery (n = 469) and Validation (n = 474) framework. RESULTS: Tumors containing a von-Hippel Lindau (VHL) mutation alone were associated with significantly improved outcomes in comparison with tumors containing a VHL plus additional mutations. Within the Discovery cohort, those with VHL+0, VHL+1, VHL+2, and VHL+≥3 tumors had disease-free survival (DFS) rates of 90.8%, 80.1%, 68.2%, and 50.7% respectively, at 5 years. This trend was replicated in the Validation cohort. Notably, these genomically defined groups were independent of tumor mutational burden. Amongst patients eligible for adjuvant therapy, those with a VHL+0 tumor (29%) had a 5-year DFS rate of 79.3% and could, therefore, potentially be spared further treatment. Conversely, patients with VHL+2 and VHL+≥3 tumors (32%) had equivalent DFS rates of 45.6% and 35.3%, respectively, and should be prioritized for adjuvant therapy. CONCLUSIONS: Genomic characterization of ccRCC identified biologically distinct groups of patients with divergent relapse rates. These groups account for the ∼80% of cases with VHL mutations and could be used to personalize adjuvant treatment discussions with patients as well as inform future adjuvant trial design.

Ablative therapies versus partial nephrectomy for small renal masses - A systematic review and meta-analysis.

BACKGROUND: High quality studies and reviews on the management of small renal masses (SRM) are lacking. This review aims to compare oncological outcomes in patients undergoing ablative therapies (AT) or partial nephrectomy (PN) for T1a or T1b SRM. MATERIAL AND METHODS: Medline, EMBASE, Cochrane CENTRAL and conference proceedings were searched on the 15th July 2020 for comparative studies respective to our research question. The ROBINS-I tool and the GRADE approach were used to assess any risk of biases and certainty of evidence in the included studies. The review is registered on PROSPERO. RESULTS: 1,748 records were retrieved. 32 observational studies and 1 RCT integrating 74,946 patients were included. Patients undergoing AT patients are significantly older than PN patients (MD 5.70, 95%CI 3.83-7.58). In T1a patients, AT patients have significantly worse overall survival (HR 1.64, 95%CI 1.39-1.95). Local recurrence-free survival is similar with PN in patients with longer than five-years follow up (HR 1.54, 95%CI 0.88-2.71). AT patients also have similar cancer-specific survival (CSS), metastasis-free survival, disease-free survival, significantly fewer post-operative complications (RR 0.72, 95%CI 0.55-0.94), and a smaller decline in estimated glomerular filtration rate post-operatively (MD: -7.42, 95%CI -13.1 to -1.70) compared to those undergoing PN. Evidence contradicts in T1b patients for oncological outcomes. CONCLUSIONS: AT have similar long-term oncological durability; lower rates of complications and superior kidney function preservation compared to PN. Given the low quality of evidence, AT is a reasonable alternative to PN in frail and co-morbid patients. Long-term high-quality studies are needed to confirm the potential benefits of AT, especially in T1b patients. PROSPERO REGISTRATION: CRD42020199099.

Multimodal image-guided ablation on management of renal cancer in Von-Hippel-Lindau syndrome patients from 2004 to 2021 at a specialist centre: A longitudinal observational study.

OBJECTIVES: To analyse the safety, technical feasibility, long-term renal function and oncological outcome of multimodal technologies in image-guided ablation (IGA) for renal cancer in Von-Hippel-Lindau (VHL) patients, and to evaluate factors that may influence the outcome. METHODS: Retrospective analysis of a prospective database of VHL patients who underwent IGA at a specialist centre. Patient's demographics, treatment energy, peri-operative outcome and oncological outcomes were recorded. Statistical analysis was performed to determine factors associated with complication and renal function reduction. The overall, 5 and 10-year cancer specific (CS), local recurrence-free (LRF) and metastasis-free (MF) survival rates were presented with Kaplan-Meier Curves. RESULTS: From 2004 to 2021, 17 VHL patients (age 21-68.2) with a mean (±SD) RCC size of 2.06 ± 0.92 cm received IGA. Median (IQR) RCCs per patient was 3 (2-4) over the course of follow up. Fifty-four RCCs were treated using radiofrequency ablation (n = 11), cryoablation (n = 38) and irreversible electroporation (n = 8) in 50 sessions. Primary and overall technical success rate were 94.4% (51/54) and 98% (53/54). One CD-III complication with proximal ureteric injury. Five patients in seven treatment sessions experienced a >25% reduction of eGFR immediately post-IGA. All patients have preservation of renal function at a median follow-up of 79 (51-134) months. The 5 and 10-year CS, LRF and MF survival rates are 100%, 97.8% and 100%. Whilst, the 5 and 10-year overall survival rate are100% and 90%. CONCLUSION: Multimodal IGA of de novo RCC for VHL patients is safe and has provided long term preservation of renal function and robust oncological durability.

The Yorkshire Kidney Screening Trial (YKST): protocol for a feasibility study of adding non-contrast abdominal CT scanning to screen for kidney cancer and other abdominal pathology within a trial of community-based CT screening for lung cancer.

INTRODUCTION: Kidney cancer (renal cell cancer (RCC)) is the seventh most common cancer in the UK. As RCC is largely curable if detected at an early stage and most patients have no symptoms, there is international interest in evaluating a screening programme for RCC. The Yorkshire Kidney Screening Trial (YKST) will assess the feasibility of adding non-contrast abdominal CT scanning to screen for RCC and other abdominal pathology within the Yorkshire Lung Screening Trial (YLST), a randomised trial of community-based CT screening for lung cancer. METHODS AND ANALYSIS: In YLST, ever-smokers aged 55-80 years registered with a general practice in Leeds have been randomised to a Lung Health Check assessment, including a thoracic low-dose CT (LDCT) for those at high risk of lung cancer, or routine care. YLST participants randomised to the Lung Health Check arm who attend for the second round of screening at 2 years without a history of RCC or abdominal CT scan within the previous 6 months will be invited to take part in YKST. We anticipate inviting 4700 participants. Those who consent will have an abdominal CT immediately following their YLST thoracic LDCT. A subset of participants and the healthcare workers involved will be invited to take part in a qualitative interview. Primary objectives are to quantify the uptake of the abdominal CT, assess the acceptability of the combined screening approach and pilot the majority of procedures for a subsequent randomised controlled trial of RCC screening within lung cancer screening. ETHICS AND DISSEMINATION: YKST was approved by the North West-Preston Research Ethics Committee (21/NW/0021), and the Health Research Authority on 3 February 2021. Trial results will be disseminated at clinical meetings, in peer-reviewed journals and to policy-makers. Findings will be made available to participants via the study website (www.YKST.org). TRIAL REGISTRATION NUMBERS: NCT05005195 and ISRCTN18055040.

Iatrogenic ureteric stricture post image guided renal cryoablation in a patient with von hippel-lindau syndrome.

A 53-year-old lady is known to have Von Hippel-Lindau syndrome with a long history of previous renal cell carcinomas (RCCs) in both kidneys. She was treated by partial nephrectomy for a right peripheral RCC and subsequently image guided radiofrequency ablation (RFA) of a left central RCC. She developed another de novo RCC adjacent to the right pelvic-ureteric junction (PUJ) 4 years after the initial RFA. Due to the close proximity to the PUJ and visibility of an ice ball with cryoablation (CRYO), the consensus from the MDT was that CRYO would be safer than RFA and she subsequently underwent percutaneous image guided CRYO to treat the small de novo RCC. Unfortunately, during the 1-month imaging follow up, she developed moderate hydronephrosis and a ureteric stricture needing long-term ureteric stent management. This case highlights the risk of ureteric injury caused by the thermal effect of the ice ball during image guided renal CRYO. Therefore, it is vital that all interventional radiologists adopt various manoeuvres to protect the ureter from the ice ball during CRYO in order to avoid the development of latent ureteric stricture.

Urinothorax following percutaneous image-guided renal cryoablation.

A 69-year-old lady with 2 renal cell carcinomas, one sited at the upper pole of her solitary right kidney, underwent percutaneous image-guided cryoablation and developed urinothorax as a complication. This was diagnosed from pleural fluid analysis and radiology imaging with computed tomography (CT). Management included image-guided chest drain and retrograde ureteric stent insertion to divert the urine from entering the pleural cavity. CT images demonstrated a fistula between the site of renal puncture and the pleural cavity, indicating that the cryoprobes traversed the diaphragm during the procedure. This case highlights urinothorax as an unusual complication of cryoablation of renal cell carcinoma. Prompt diagnosis by interventional radiologists is crucial to avert from this potentially life-threatening complication.

Challenges of early renal cancer detection: symptom patterns and incidental diagnosis rate in a multicentre prospective UK cohort of patients presenting with suspected renal cancer.

OBJECTIVES: To describe the frequency and nature of symptoms in patients presenting with suspected renal cell carcinoma (RCC) and examine their reliability in achieving early diagnosis. DESIGN: Multicentre prospective observational cohort study. SETTING AND PARTICIPANTS: Eleven UK centres recruiting patients presenting with suspected newly diagnosed RCC. Symptoms reported by patients were recorded and reviewed. Comprehensive clinico-pathological and outcome data were also collected. OUTCOMES: Type and frequency of reported symptoms, incidental diagnosis rate, metastasis-free survival and cancer-specific survival. RESULTS: Of 706 patients recruited between 2011 and 2014, 608 patients with a confirmed RCC formed the primary study population. The majority (60%) of patients were diagnosed incidentally. 87% of patients with stage Ia and 36% with stage III or IV disease presented incidentally. Visible haematuria was reported in 23% of patients and was commonly associated with advanced disease (49% had stage III or IV disease). Symptomatic presentation was associated with poorer outcomes, likely reflecting the presence of higher stage disease. Symptom patterns among the 54 patients subsequently found to have a benign renal mass were similar to those with a confirmed RCC. CONCLUSIONS: Raising public awareness of RCC-related symptoms as a strategy to improve early detection rates is limited by the fact that related symptoms are relatively uncommon and often associated with advanced disease. Greater attention must be paid to the feasibility of screening strategies and the identification of circulating diagnostic biomarkers.

UK Multicenter Prospective Evaluation of the Leibovich Score in Localized Renal Cell Carcinoma: Performance has Altered Over Time.

OBJECTIVE: To examine changes in outcome by the Leibovich score using contemporary and historic cohorts of patients presenting with renal cell carcinoma (RCC) PATIENTS AND METHODS: Prospective observational multicenter cohort study, recruiting patients with suspected newly diagnosed RCC. A historical cohort of patients was examined for comparison. Metastasis-free survival (MFS) formed the primary outcome measure. Model discrimination and calibration were evaluated using Cox proportional hazard regression and the Kaplan-Meier method. Overall performance of the Leibovich model was assessed by estimating explained variation. RESULTS: Seven hundred and six patients were recruited between 2011 and 2014 and RCC confirmed in 608 (86%) patients. Application of the Leibovich score to patients with localized clear cell RCC in this contemporary cohort demonstrated good model discrimination (c-index = 0.77) but suboptimal calibration, with improved MFS for intermediate- and high-risk patients (5-year MFS 85% and 50%, respectively) compared to the original Leibovich cohort (74% and 31%) and a historic (1998-2006) UK cohort (76% and 37%). The proportion of variation in outcome explained by the model is low and has declined over time (28% historic vs 22% contemporary UK cohort). CONCLUSION: Prognostic models are widely employed in patients with localized RCC to guide surveillance intensity and clinical trial selection. However, the majority of the variation in outcome remains unexplained by the Leibovich model and, over time, MFS rates among intermediate- and high-risk classified patients have altered. These findings are likely to have implications for all such models used in this setting.

Differences in side-effect duration and related bother levels between phosphodiesterase type 5 inhibitors.

OBJECTIVE: To assess whether the longer half-life of tadalafil is associated with longer lasting or more severe side-effects than the other phosphodiesterase type 5 inhibitors (PDE-5Is), as clinical trials have shown that the efficacy and safety of the three available are similar, but tadalafil has a half-life four times longer than the other two drugs. PATIENTS AND METHODS: Treatment-naive men beginning PDE5-I therapy were recruited from a specialist clinic. Data on the type and duration of drug-associated side-effects were collected prospectively. Levels of bother were assessed with a visual analogue scale (VAS). Differences in type, duration and bother of side-effect were compared between drugs. RESULTS: In all, 409 men provided data; there were no differences between drugs in the proportion of men responding, or the overall prevalence of side-effects. The mean duration of side-effects with tadalafil was 14.9 h, compared to 3.9 and 7.7 h for sildenafil and vardenafil. Of men taking tadalafil, 30% had side-effects lasting >12 h. There were no differences in mean VAS scores between the drugs. Individual side-effects caused similar levels of bother, except for facial flushing, which was less bothersome. CONCLUSIONS: Men taking tadalafil are at risk of prolonged side-effects, although levels of bother associated with these side-effects are not significantly greater than those seen with short-acting PDE5-Is.

The feasibility of establishing a programme of adjuvant autologous vaccination for renal cell carcinoma.

OBJECTIVE: To report the results of a programme aimed at determining the feasibility of autologous renal cell carcinoma (RCC) tissue collection and vaccine preparation within the setting of a UK National Health Service Cancer Centre. PATIENTS AND METHODS: Patients undergoing nephrectomy for suspected renal tumours were identified from theatre lists between April 2005 and July 2007. Samples of tumour were freshly cut from nephrectomy specimens. If tissue collection failed the reason was recorded prospectively. Cell viability was assessed after sample sieving. Freeze-thaw lysates were prepared from viable tumour cells, and the immunogenicity tested by pulsing onto dendritic cells (DC). RESULTS: Of 84 patients, 83 had a histological diagnosis of RCC; samples were obtained from 29 of these 83 (35%). Reasons for failure in tissue collection included that the tumour was too small or haemorrhagic/necrotic, pre-surgical embolization, and difficulties with fresh tumour collection out of normal working hours. Viable tumour cells were obtained in 12 of the 29 samples (41%); no factor was able to predict the production of viable cells. Unmodified lysates did not activate DC. CONCLUSION: An autologous RCC vaccination programme might fail to generate vaccines for a substantial proportion of eligible patients in the setting of a clinical cancer centre.