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Background: Sex disparity between metabolic-obesity (defined by body mass index, BMI) phenotypes and obesity-related cancer (ORC) remains unknown. Considering BMI reflecting overall obesity but not fat distribution, we aimed to systematically assess the association of our newly proposed metabolic-anthropometric phenotypes with risk of overall and site-specific ORC by sex. Methods: A total of 141,579 men (mean age: 56.37 years, mean follow-up time: 12.04 years) and 131,047 women (mean age: 56.22 years, mean follow up time: 11.82 years) from the UK Biobank was included, and designated as metabolic-anthropometric phenotypes based on metabolic status (metabolically healthy/unhealthy), BMI (non-obesity/obesity) and body shape (pear/slim/apple/wide). The sex-specific association of different phenotypes with overall and site-specific ORC was assessed by hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models. Results: We found metabolically unhealthy and/or obesity phenotypes conveyed a higher risk in men than in women for overall ORC and colorectal cancer compared with metabolically healthy non-obesity phenotype (Pinteraction < 0.05). Of note, metabolically healthy obesity phenotype contributed to increased risks of most ORC in men (HRs: 1.58 ~ 2.91), but only correlated with higher risks of endometrial (HR = 1.89, 95% CI: 1.54–2.32) and postmenopausal breast cancers (HR = 1.17, 95% CI: 1.05–1.31) in women. Similarly, even under metabolically healthy, men carrying apple and wide shapes phenotypes (metabolically healthy apple/wide and metabolically healthy non-obesity apple/wide) suffered an increased risk of ORC (mainly colorectal, liver, gastric cardia, and renal cancers, HRs: 1.20 ~ 3.81) in comparison with pear shape or non-obesity pear shape. Conclusions: There was a significant sex disparity between metabolic-anthropometric phenotypes and ORC risk. We advised future ORC prevention and control worth taking body shape and sex disparity into account. [ABSTRACT FROM AUTHOR]

Background: Kidney cancer is a prevalent malignancy with an increasing incidence worldwide. Blood cell indices and inflammation-related markers have shown huge potential as biomarkers for predicting cancer incidences, but that is not clear in kidney cancer. Our study aims to investigate the correlations of blood cell indices and inflammation-related markers with kidney cancer risk. Methods: We performed a population-based cohort prospective analysis using data from the UK Biobank. A total of 466,994 participants, free of kidney cancer at baseline, were included in the analysis. The hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney cancer risk were calculated using Cox proportional hazards regression models. Restricted cubic spline models were used to investigate nonlinear longitudinal associations. Stratified analyses were used to identify high-risk populations. The results were validated through sensitivity analyses. Results: During a mean follow-up of 12.4 years, 1,710 of 466,994 participants developed kidney cancer. The Cox regression models showed that 13 blood cell indices and four inflammation-related markers were associated with kidney cancer incidence. The restricted cubic spline models showed non-linear relationships with kidney cancer. Finally, combined with stratified and sensitivity analyses, we found that the mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelet distribution width (PDW), systemic immune-inflammation index (SII), and product of platelet count and neutrophil count (PPN) were related to enhanced kidney cancer risk with stable results. Conclusion: Our findings identified that three blood cell indices (MCHC, RDW, and PDW) and two inflammation-related markers (SII and PPN) were independent risk factors for the incidence of kidney cancer. These indexes may serve as potential predictors for kidney cancer and aid in the development of targeted screening strategies for at-risk individuals. [ABSTRACT FROM AUTHOR]

Objective: To identify the causal role of sodium‐glucose cotransporter 2 (SGLT2) inhibition on three urological cancers. Methods: Six single nucleotide polymorphisms associated with the expression level of SLC5A2, a proxy for SGLT2 inhibition, from a recent publication were extracted. Three common urological cancers, including bladder cancer, prostate cancer and kidney cancer, were analysed. The main cohort of bladder cancer was derived from UK Biobank (1279 cases and 372,016 controls). The prostate cancer cohort was from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium (79,148 cases and 61,106 controls). The kidney cancer phenotype was from the UK Biobank cohort of 463,010 individuals (1114 cases and 461,896 controls). Primary and sensitivity analysis were performed to validate the results. In vitro analysis was also incorporated to validate the Mendelian randomisation results. Results: In primary analysis, SGLT2 inhibition was associated with reduced risk of bladder cancer (OR: 0.98, 95% CI: 0.97–0.99) per unit lowering of HbA1c level. A protective association was also observed for prostate cancer with odds ratio = 0.31 (95% CI = 0.21–0.47). However, we did not discover a causal relationship between SGLT2 inhibition and kidney cancer (OR: 1.00, 95% CI: 0.99–1.00). Sensitivity analysis and in vitro validation did not support the causal role of SGLT2 inhibition in increasing cancer risk. Conclusions: We did not find any evidence that SGLT2 inhibition could increase the risk of the three cancers. Even in some analysis, SGLT2 inhibition tended to show protective effects on the three urological cancers. [ABSTRACT FROM AUTHOR]

Background: The risk of second primary cancers (SPC) is increasing after the first primary cancers (FPC) are diagnosed and treated. The underlying causal relationship remains unclear. Methods: We conducted a pan-cancer association (26 cancers) study in the Surveillance, Epidemiology, and End Results (SEER) database (non-Hispanic whites). The standardized incidence ratio (SIR) was estimated as the risk of SPCs in cancer survivors based on the incidence in the general population. Furthermore, the causal effect was evaluated by two-sample Mendelian Randomization (MR, 13 FPCs) in the UK Biobank (UKB, n=459,136, European whites) and robust analysis (radial MR and Causal Analysis Using Summary Effect estimates, CAUSE). Results: We found 11 significant cross-correlations among different cancers after harmonizing SIR and MR results. Whereas only 4 of them were confirmed by MR to have a robust causal relationship. In particular, patients initially diagnosed with oral pharyngeal cancer would have an increased risk of non-Hodgkin lymphoma (SIRSEER = 1.18, 95%Confidence Interval [CI]:1.05-1.31, ORradial-MR= 1.21, 95% CI:1.13-1.30, p=6.00 × 10-3; ORcause = 1.17, 95% CI:1.05-1.31, p=8.90 × 10-3). Meanwhile, ovary cancer was identified to be a risk factor for soft tissue cancer (SIRSEER = 1.72, 95%Confidence Interval [CI]:1.08-2.60, ORradial-MR= 1.39, 95% CI:1.22-1.58, p=1.07 × 10-3; ORcause = 1.36, 95% CI:1.16-1.58, p=0.01). And kidney cancer was likely to cause the development of lung cancer (SIRSEER = 1.28, 95%Confidence Interval [CI]:1.22-1.35, ORradial-MR= 1.17, 95% CI:1.08-1.27, p=6.60 × 10-3; ORcause = 1.16, 95% CI:1.02-1.31, p=0.05) and myeloma (SIRSEER = 1.54, 95%Confidence Interval [CI]:1.33-1.78, ORradial-MR= 1.72, 95% CI:1.21-2.45, p=0.02; ORcause = 1.49, 95% CI:1.04-2.34, p=0.02). Conclusions: A certain type of primary cancer may cause another second primary cancer, and the profound mechanisms need to be studied in the future. [ABSTRACT FROM AUTHOR]

Objective: To explore patient experience of follow‐up care after kidney cancer surgery and to develop recommendations for best practice. Methods: We conducted two focus groups, including 14 participants with experience of kidney cancer follow‐up after surgery, to elicit patient views on current follow‐up care. Thematic analysis was used to identify unifying themes to describe the patient experience of follow‐up, and the results were then used to develop a set of recommendations for best practice. Results: We identified six themes (feelings of abandonment; uncertainty about the plan; anxiety about appointments; variation in care; a need for information; and a need for emotional support) that described current patient experience and areas in which current care could be improved. In particular, while most of the participants felt that their physical needs had been met, many had struggled with unmet emotional needs and a lack of information and resources. This was especially noted in the period immediately following surgery, when feelings of abandonment were common, and around follow‐up scans and routine appointments, which were a source of anxiety. Our participants also described concerns about the lack of consistency between different hospitals and centres around the United Kingdom, with differences in the content and quality of follow‐up care. Based on the results, we developed a list of recommendations to address some of the challenges described through relatively minor changes to the care pathway. Conclusions: We identified gaps and variability in current follow‐up care after kidney cancer surgery, and have developed a set of recommendations that, if implemented, would improve the follow‐up care experience for these patients. [ABSTRACT FROM AUTHOR]

It is proposed that, through restriction to individuals delineated as high risk, polygenic risk scores (PRSs) might enable more efficient targeting of existing cancer screening programmes and enable extension into new age ranges and disease types. To address this proposition, we present an overview of the performance of PRS tools (ie, models and sets of single nucleotide polymorphisms) alongside harms and benefits of PRS-stratified cancer screening for eight example cancers (breast, prostate, colorectal, pancreas, ovary, kidney, lung, and testicular cancer). For this modelling analysis, we used age-stratified cancer incidences for the UK population from the National Cancer Registration Dataset (2016–18) and published estimates of the area under the receiver operating characteristic curve for current, future, and optimised PRS for each of the eight cancer types. For each of five PRS-defined high-risk quantiles (ie, the top 50%, 20%, 10%, 5%, and 1%) and according to each of the three PRS tools (ie, current, future, and optimised) for the eight cancers, we calculated the relative proportion of cancers arising, the odds ratios of a cancer arising compared with the UK population average, and the lifetime cancer risk. We examined maximal attainable rates of cancer detection by age stratum from combining PRS-based stratification with cancer screening tools and modelled the maximal impact on cancer-specific survival of hypothetical new UK programmes of PRS-stratified screening. The PRS-defined high-risk quintile (20%) of the population was estimated to capture 37% of breast cancer cases, 46% of prostate cancer cases, 34% of colorectal cancer cases, 29% of pancreatic cancer cases, 26% of ovarian cancer cases, 22% of renal cancer cases, 26% of lung cancer cases, and 47% of testicular cancer cases. Extending UK screening programmes to a PRS-defined high-risk quintile including people aged 40–49 years for breast cancer, 50–59 years for colorectal cancer, and 60–69 years for prostate cancer has the potential to avert, respectively, a maximum of 102, 188, and 158 deaths annually. Unstratified screening of the full population aged 48–49 years for breast cancer, 58–59 years for colorectal cancer, and 68–69 years for prostate cancer would use equivalent resources and avert, respectively, an estimated maximum of 80, 155, and 95 deaths annually. These maximal modelled numbers will be substantially attenuated by incomplete population uptake of PRS profiling and cancer screening, interval cancers, non-European ancestry, and other factors. Under favourable assumptions, our modelling suggests modest potential efficiency gain in cancer case detection and deaths averted for hypothetical new PRS-stratified screening programmes for breast, prostate, and colorectal cancer. Restriction of screening to high-risk quantiles means many or most incident cancers will arise in those assigned as being low-risk. To quantify real-world clinical impact, costs, and harms, UK-specific cluster-randomised trials are required. The Wellcome Trust. [ABSTRACT FROM AUTHOR]

Background: Many observational epidemiology studies discovered that kidney cancer and impaired kidney function have a bidirectional relationship. However, it remains unclear whether these two kinds of traits are causally linked. In this study, we aimed to investigate the bidirectional causal relation between kidney cancer and kidney function biomarkers (creatinine‐based estimated glomerular filtration rate (eGFRcrea), cystatin C‐based estimated glomerular filtration rate (eGFRcys), blood urea nitrogen (BUN), serum urate, and urinary albumin‐to‐creatinine ratio (UACR)). Methods: For both directions, single‐nucleotide polymorphisms (SNPs), as genetic instruments, for the five kidney function traits were selected from up to 1,004,040 individuals, and SNPs for kidney cancer were from 408,786 participants(1338 cases). In the main analysis, we applied two state‐of‐the‐art MR methods, namely, contamination mixture and Robust Adjusted Profile Score to downweight the effect of weak instrument bias, pleiotropy, and extreme outliers. We additionally conducted traditional MR analyses as sensitivity analyses. Summary‐level data of European ancestry were extracted from UK Biobank, Chronic Kidney Disease Genetics Consortium, and Kaiser Permanente. Results: Based on 99 SNPs, we found that the eGFRcrea had a significant negative causal effect on the risk of kidney cancer (OR = 0.007, 95% CI:2.6 × 10−4–0.569, p = 0.041). After adjusting for body composition or diabetes, urate had a significant negative causal effect on kidney cancer (OR <1, p < 0.05). For UACR, it showed a strong causal effect on kidney cancer, after adjusting for body composition (OR = 14.503, 95% CI: 2.546–96.001, p = 0.032). Due to lacking significant signals and effect power for the reverse MR, further investigations are warranted. Conclusions: Our study suggested a potential causal effect of damaged kidney function on kidney cancer. EGFRcrea and UACR might be causally associated with kidney cancer, especially when patients were comorbid with obesity or diabetes. We called for larger sample‐size studies to further unravel the underlying causal relationship and the exact mechanism. [ABSTRACT FROM AUTHOR]

Objective: To review the current state of genetic risk models for predicting the development of kidney cancer, by identifying and comparing the performance of published models. Methods: Risk models were identified from a recent systematic review and the Cancer‐PRS web directory. A narrative synthesis of the models, previous validation studies and related genome‐wide association studies (GWAS) was carried out. The discrimination and calibration of the identified models was then assessed and compared in the UK Biobank (UKB) cohort (cases, 452; controls, 487 925). Results: A total of 39 genetic models predicting the development of kidney cancer were identified and 31 were validated in the UKB. Several of the genetic‐only models (seven of 25) and most of the mixed genetic‐phenotypic models (five of six) had some discriminatory ability (area under the receiver operating characteristic curve >0.5) in this cohort. In general, models containing a larger number of genetic variants identified in GWAS performed better than models containing a small number of variants associated with known causal pathways. However, the performance of the included models was consistently poorer than genetic risk models for other cancers. Conclusions: Although there is potential for genetic models to identify those at highest risk of developing kidney cancer, their performance is poorer than the best genetic risk models for other cancers. This may be due to the comparatively small number of genetic variants associated with kidney cancer identified in GWAS to date. The development of improved genetic risk models for kidney cancer is dependent on the identification of more variants associated with this disease. Whether these will have utility within future kidney cancer screening pathways is yet to determined. [ABSTRACT FROM AUTHOR]

The causation between lipids and renal cancer remains inconclusive. Our purpose is to explore the causal relationships between the three primary lipid metabolism‐related substances, namely triglycerides (TG), low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL) with the risk of renal cancer using Mendelian randomization (MR) methods. Genetic instruments for lipids were acquired from the UK Biobank. Outcome data were from the FinnGen study (1397 renal cancer cases and 204 070). Single‐variable MR (SVMR) and multi‐variable MR (MVMR) analyses were conducted with TwoSampleMR package based on R 4.0.3. The random‐effect inverse‐variance weighted (IVW), MR‐Egger, weighted‐median method, and weighted mode were the four main computing methods. We found that per 1 SD elevated LDL level was causally associated with renal cancer occurrence based on SVMR (OR, 1.31, 95% CI: 1.05‐1.64, P =.016). Similar significant associations were found in other methods. However, the results of SVMR did not support significant associations between TG, and HDL with renal cancer risk in all methods. The association between LDL and renal cancer was still significant in MVMR analysis (OR for IVW method: 1.22 per 1 SD higher trait (SD, 95% CI: 1.11‐1.34, P <.001; OR for MR‐Egger: 1.22 per 1 SD higher trait, 95% CI: 1.01‐1.47, P =.042) when taking TG and HDL into consideration. Our study supported that elevated serum LDL levels is causally associated with an increased risk of renal cancer independent of TG and HDL. [ABSTRACT FROM AUTHOR]

Background: The association between vitamin E and cancer risk has been widely investigated by observational studies, but the findings remain inconclusive. Here, we aimed to evaluate the causal effect of circulating vitamin E on the risk of ten common cancers, including bladder, breast, colorectal, esophagus, lung, oral and pharynx, ovarian, pancreatic, prostate, and kidney cancer. Methods: A Mendelian randomization (MR) analytic framework was applied to data from a cancer-specific genome-wide association study (GWAS) comprising a total of 297,699 cancer cases and 304,736 controls of European ancestry. Three genetic instrumental variables associated with circulating vitamin E were selected. Summary statistic-based methods of inverse variance weighting (IVW) and likelihood-based approach, as well as the individual genotyping-based method of genetic risk score (GRS) were used. Multivariable IVW analysis was further performed to control for potential confounding effects. Furthermore, the UK Biobank cohort was used as external validation, supporting 355,543 European participants (incident cases ranged from 437 for ovarian cancer to 4882 for prostate cancer) for GRS-based estimation of circulating vitamin E, accompanied by a one-sample MR analysis of dietary vitamin E intake underlying the time-to-event analytic framework. Results: Specific to cancer GWAS, we found that circulating vitamin E was significantly associated with increased bladder cancer risk (odds ratios [OR]IVW = 6.23, PIVW = 3.05×10-3) but decreased breast cancer risk (ORIVW = 0.68, PIVW = 8.19×10-3); however, the significance of breast cancer was dampened (Pmultivariable IVW > 0.05) in the subsequent multivariable MR analysis. In the validation stage of the UK Biobank cohort, we did not replicate convincing causal effects of genetically predicted circulating vitamin E concentrations and dietary vitamin E intake on the risk of ten cancers. Conclusions: This large-scale population study upon data from cancer-specific GWAS and a longitudinal biobank cohort indicates plausible non-causal associations between circulating vitamin E and ten common cancers in the European populations. Further studies regarding ancestral diversity are warranted to validate such causal associations. [ABSTRACT FROM AUTHOR]

Objectives: To externally validate risk models for the detection of kidney cancer, as early detection of kidney cancer improves survival and stratifying the population using risk models could enable an individually tailored screening programme. Methods: We validated the performance of 30 existing phenotypic models predicting the risk of kidney cancer in the UK Biobank cohort (n = 450 687). We compared the discrimination and calibration of models for men, women, and a mixed‐sex cohort. Population level data were used to estimate model performance in a screening scenario for a range of risk thresholds (6‐year risk: 0.1–1.0%). Results: In all, 10 models had reasonable discrimination (area under the receiver‐operating characteristic curve >0.60), although some had poor calibration. Modelling demonstrated similar performance of the best models over a range of thresholds. The models showed an improvement in ability to identify cases compared to age‐ and sex‐based screening. All the models performed less well in women than men. Conclusions: The present study is the first comprehensive external validation of risk models for kidney cancer. The best‐performing models are better at identifying individuals at high risk of kidney cancer than age and sex alone; however, the benefits are relatively small. Feasibility studies are required to determine applicability to a screening programme. [ABSTRACT FROM AUTHOR]

Objective: Phaeochromocytomas and paragangliomas (PPGL) are rare, but strongly heritable tumours. Variants in succinate dehydrogenase (SDH) subunits are identified in approximately 25% of cases. However, clinical and genetic information of patients with SDHC variants are underreported. Design: This retrospective case series collated data from 18 UK Genetics and Endocrinology departments. Patients: Both asymptomatic and disease‐affected patients with confirmed SDHC germline variants are included. Measurements: Clinical data including tumour type and location, surveillance outcomes and interventions, SDHC genetic variant assessment, interpretation, and tumour risk calculation. Results: We report 91 SDHC cases, 46 probands and 45 non‐probands. Fifty‐one cases were disease‐affected. Median age at genetic diagnosis was 43 years (range: 11–79). Twenty‐four SDHC germline variants were identified including six novel variants. Head and neck paraganglioma (HNPGL, n = 30, 65.2%), extra‐adrenal paraganglioma (EAPGL, n = 13, 28.2%) and phaeochromocytomas (PCC) (n = 3, 6.5%) were present. One case had multiple PPGLs. Malignant disease was reported in 19.6% (9/46). Eight cases had non‐PPGL SDHC‐associated tumours, six gastrointestinal stromal tumours (GIST) and two renal cell cancers (RCC). Cumulative tumour risk (95% CI) at age 60 years was 0.94 (CI: 0.79–0.99) in probands, and 0.16 (CI: 0–0.31) in non‐probands, respectively. Conclusions: This study describes the largest cohort of 91 SDHC patients worldwide. We confirm disease‐affected SDHC variant cases develop isolated HNPGL disease in nearly 2/3 of patients, EAPGL and PCC in 1/3, with an increased risk of GIST and RCC. One fifth developed malignant disease, requiring comprehensive lifelong tumour screening and surveillance. [ABSTRACT FROM AUTHOR]

Evidence on the association between selenium and cancer risk is inconclusive. We conducted a Mendelian randomization study to examine the associations of selenium levels with 22 site‐specific cancers and any cancer. Single nucleotide polymorphisms (SNPs) strongly associated with toenail and blood (TAB) and blood selenium levels in mild linkage disequilibrium (r2 <.3) were used as instrumental variables. Genetic associations of selenium‐associated SNPs with cancer were obtained from the UK Biobank including a total of 59 647 cancer cases and 307 914 controls. Associations with P <.1 in UK Biobank were tested for replication in the FinnGen consortium comprising more than 180 000 individuals. The inverse‐variance weighted method accounting for linkage disequilibrium was used to estimate the associations. Genetically predicted TAB selenium levels were not associated with the risk of the 22 site‐specific cancers or any cancer (all 22 site‐specific cancers). Similarly, we observed no strong association for genetically predicted blood selenium levels. However, genetically predicted blood selenium levels showed suggestive associations with risk of kidney cancer (odds ratio [OR] per one‐unit increase in log‐transformed levels: 0.83; 95% confidence interval [CI]: 0.67‐1.03) and multiple myeloma (OR: 1.40; 95% CI: 1.02‐1.93). The same direction of association for kidney cancer but not for multiple myeloma was observed in FinnGen. In the metaanalysis of UK Biobank and FinnGen, the OR of kidney cancer was 0.83 (95% CI: 0.69‐1.00). Our study suggests that high selenium status may not prevent cancer development. The associations for kidney cancer and multiple myeloma need to be verified in well‐powered studies. [ABSTRACT FROM AUTHOR]

This retrospective study, CERES (NCT03696407), describes early clinical experience with cabozantinib in patients with advanced renal cell carcinoma (aRCC) enrolled in the UK managed access programme (MAP). Cabozantinib demonstrated clinically meaningful activity in all patients across multiple lines of therapy. Charlson Comorbidity Index score warrants further investigation as a prognostic/predictive marker. Our results provide a benchmark for future real-world studies in aRCC. Background: Cabozantinib monotherapy is approved in the UK for patients with treatment-naïve intermediateor poor-risk advanced renal cell carcinoma (aRCC), or patients who received prior vascular endothelial growth factor-targeted therapy. Data are limited on the real-world use of cabozantinib for aRCC. Patients and Methods: CERES (NCT03696407) was a retrospective study of patients with aRCC who received cabozantinib through the UK managed access programme (MAP; August 2016-July 2017), at which time cabozantinib had European regulatory approval for second- or later-line use only. The study objectives were to characterize aRCC treatment patterns and evaluate cabozantinib effectiveness. Outcomes were stratified by cabozantinib treatment line, MAP treatment date (months 0-7 vs. 8-12) and (post hoc) Charlson Comorbidity Index (CCI; = 6 vs. < 6). Results: Of 100 patients included, 99% had stage IV disease, 63% had a CCI = 6 and 81% had an Eastern Cooperative Oncology Group Performance Status 0-1. Median (range) duration of follow-up was 10.8 (0.4-33.5) months. Cabozantinib was administered as second-line, third-line and fourth- or later-line in 41%, 31% and 28% of patients, respectively. Most patients (84%) initiated cabozantinib at 60 mg. Average (range) cabozantinib dose was 45.5 (19.6-59.8) mg/day; 66% of patients had = 1 dose reduction. Disease progression was the most common reason for discontinuation (65.1%). Median (95% confidence interval) progression-free survival (PFS) and overall survival (OS) were 6.01 (5.16-7.85) and 10.84 (7.92-16.85) months, respectively. Overall response rate was 34.5%; disease control rate 70.1% and duration of response 6.9 (1.8-26.9) months. No significant differences in survival estimates were observed between treatment line or treatment date subgroups. Total CCI score = 6 (vs. > 6) was associated with prolonged median PFS and OS. Conclusion: Cabozantinib demonstrated clinical activity in this UK real-world aRCC population. The results provide a benchmark for future real-world studies in aRCC. [ABSTRACT FROM AUTHOR]

Introduction: Grip strength is the most commonly used muscle strength proxy in clinical research. However, evidence regarding the associations of grip strength with cancer has been mainly restricted to overall cancer risk. Therefore, this study aims to evaluate the associations between grip strength relative to BMI and 15 cancer sites as well as with all-cause cancer mortality.Methods: A total of 445,555 participants (53.8% women, mean age=56.3 years) were recruited across the United Kingdom. The association of grip strength relative to BMI (expressed as 1 SD) with incidence and mortality from 15 cancer sites was investigated using Cox proportional hazard models. All analyses were conducted in April 2021.Results: Over an 8.8-year follow-up period, 37,291 patients were diagnosed with cancer, and 11,363 died of it. After covariate adjustment, higher relative grip strength per 1 SD was associated with a lower risk of incident endometrial (hazard ratio=0.76, 95% CI=0.71, 0.81), liver (hazard ratio=0.81, 95% CI=0.74, 0.88), gallbladder (hazard ratio=0.83, 95% CI=0.73, 0.94), kidney (hazard ratio=0.89, 95% CI=0.84, 0.95), and colorectal (hazard ratio=0.94, 95% CI=0.91, 0.98) cancer as well as with lower risk of gallbladder, colorectal, endometrial, liver, and all-cause cancer mortality.Conclusions: Grip strength relative to BMI was associated with incidence and mortality from endometrial, gallbladder, colorectal, liver, all-cause cancer, and breast and kidney cancer incidence, independent of major confounding factors, including comorbidity, diet, and physical activity. [ABSTRACT FROM AUTHOR]

A SP 99m sp Tc-sestamibi SPECT-CT demonstrating avid uptake therefore indicates a renal mass that could be considered as at best oncocytoma, and at worst an indolent form of RCC, which may also benefit from active monitoring, especially when considering personalised management options in the context of tumour size, patient wishes, and specific comorbidities. "Case of the Month" from the Specialist Centre for Kidney Cancer, Royal Free London Hospital, UK: 99mTc-sestamibi SPECT-CT to differentiate renal cell carcinoma from benign oncocytoma Abbreviations 99m Tc 99m technetium H&E haematoxylin and eosin ISRCTN International Standard Randomised Controlled Trial Number ROI region of interest RTB renal tumour biopsy SPECT single-photon emission CT Case Presentations Our first patient (P1) is a 69-year-old male with a 4-year history of a progressively enlarging left renal upper pole mass; contrast-enhanced CT demonstrated a 3.4-cm lesion in 2017, increasing in size on sequential cross-sectional imaging to 6.0 cm as of March 2021. [Extracted from the article]

Background: Previous large observational cohort studies showed higher blood pressure (BP) positively associated with cancer. We used Mendelian randomization (MR) to obtain less confounded estimates of BP on total and site-specific cancers.Methods: We applied replicated genetic instruments for systolic and diastolic BP to summary genetic associations with total cancer (37387 cases, 367856 non-cases) from the UK Biobank, and 17 site-specific cancers (663-17881 cases) from a meta-analysis of the UK Biobank and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging. We used inverse-variance weighting with multiplicative random effects as the main analysis, and sensitivity analyses including the weighted median, MR-Egger and multivariable MR adjusted for body mass index and for smoking. For validation, we included breast (Breast Cancer Association Consortium: 133384 cases, 113789 non-cases), prostate (Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome Consortium: 79194 cases, 61112 non-cases) and lung (International Lung and Cancer Consortium: 10246 cases, 38295 non-cases) cancer from large consortia. We used asthma as a negative control outcome.Results: Systolic and diastolic BP were unrelated to total cancer (OR 0.98 per standard deviation higher [95% confidence interval (CI) 0.89, 1.07] and OR 1.00 [95% CI 0.92, 1.08]) and to site-specific cancers after accounting for multiple testing, with consistent findings from consortia. BP was nominally associated with melanoma and possibly kidney cancer, and as expected, not associated with asthma. Sensitivity analyses using other MR methods gave similar results.Conclusions: In contrast to previous observational evidence, BP does not appear to be a risk factor for cancer, although an effect on melanoma and kidney cancer cannot be excluded. Other targets for cancer prevention might be more relevant. [ABSTRACT FROM AUTHOR]

Background: Window-of-opportunity trials, evaluating the engagement of drugs with their biological target in the time period between diagnosis and standard-of-care treatment, can help prioritise promising new systemic treatments for later-phase clinical trials. Renal cell carcinoma (RCC), the 7th commonest solid cancer in the UK, exhibits targets for multiple new systemic anti-cancer agents including DNA damage response inhibitors, agents targeting vascular pathways and immune checkpoint inhibitors. Here we present the trial protocol for the WIndow-of-opportunity clinical trial platform for evaluation of novel treatment strategies in REnal cell cancer (WIRE).Methods: WIRE is a Phase II, multi-arm, multi-centre, non-randomised, proof-of-mechanism (single and combination investigational medicinal product [IMP]), platform trial using a Bayesian adaptive design. The Bayesian adaptive design leverages outcome information from initial participants during pre-specified interim analyses to determine and minimise the number of participants required to demonstrate efficacy or futility. Patients with biopsy-proven, surgically resectable, cT1b+, cN0-1, cM0-1 clear cell RCC and no contraindications to the IMPs are eligible to participate. Participants undergo diagnostic staging CT and renal mass biopsy followed by treatment in one of the treatment arms for at least 14 days. Initially, the trial includes five treatment arms with cediranib, cediranib + olaparib, olaparib, durvalumab and durvalumab + olaparib. Participants undergo a multiparametric MRI before and after treatment. Vascularised and de-vascularised tissue is collected at surgery. A ≥ 30% increase in CD8+ T-cells on immunohistochemistry between the screening and nephrectomy is the primary endpoint for durvalumab-containing arms. Meanwhile, a reduction in tumour vascular permeability measured by Ktrans on dynamic contrast-enhanced MRI by ≥30% is the primary endpoint for other arms. Secondary outcomes include adverse events and tumour size change. Exploratory outcomes include biomarkers of drug mechanism and treatment effects in blood, urine, tissue and imaging.Discussion: WIRE is the first trial using a window-of-opportunity design to demonstrate pharmacological activity of novel single and combination treatments in RCC in the pre-surgical space. It will provide rationale for prioritising promising treatments for later phase trials and support the development of new biomarkers of treatment effect with its extensive translational agenda.Trial Registration: ClinicalTrials.gov: NCT03741426 / EudraCT: 2018-003056-21 . [ABSTRACT FROM AUTHOR]

Abdominal size is associated positively with the risk of some cancers but the influence of body mass index (BMI) and gluteofemoral size is unclear because waist and hip circumference are strongly correlated with BMI. We examined associations of 33 cancers with A Body Shape Index (ABSI) and hip index (HI), which are independent of BMI by design, and compared these with waist and hip circumference, using multivariable Cox proportional hazards models in UK Biobank. During a mean followup of 7 years, 14,682 incident cancers were ascertained in 200,289 men and 12,965 cancers in 230,326 women. In men, ABSI was associated positively with cancers of the head and neck (hazard ratio HR = 1.14; 95% confidence interval 1.03–1.26 per one standard deviation increment), esophagus (adenocarcinoma, HR = 1.27; 1.12– 1.44), gastric cardia (HR = 1.31; 1.07–1.61), colon (HR = 1.18; 1.10–1.26), rectum (HR = 1.13; 1.04–1.22), lung (adenocarcinoma, HR = 1.16; 1.03–1.30; squamous cell carcinoma [SCC], HR = 1.33; 1.17–1.52), and bladder (HR = 1.15; 1.04–1.27), while HI was associated inversely with cancers of the esophagus (adenocarcinoma, HR = 0.89; 0.79–1.00), gastric cardia (HR = 0.79; 0.65–0.96), colon (HR = 0.92; 0.86–0.98), liver (HR = 0.86; 0.75–0.98), and multiple myeloma (HR = 0.86; 0.75– 1.00). In women, ABSI was associated positively with cancers of the head and neck (HR = 1.27; 1.10–1.48), esophagus (SCC, HR = 1.37; 1.07–1.76), colon (HR = 1.08; 1.01–1.16), lung (adenocarcinoma, HR = 1.17; 1.06–1.29; SCC, HR = 1.40; 1.20– 1.63; small cell, HR = 1.39; 1.14–1.69), kidney (clear-cell, HR = 1.25; 1.03–1.50), and post-menopausal endometrium (HR = 1.11; 1.02–1.20), while HI was associated inversely with skin SCC (HR = 0.91; 0.83–0.99), post-menopausal kidney cancer (HR = 0.77; 0.67–0.88), and post-menopausal melanoma (HR = 0.90; 0.83–0.98). Unusually, ABSI was associated inversely with melanoma in men (HR = 0.89; 0.82– 0.96) and pre-menopausal women (HR = 0.77; 0.65–0.91). Waist and hip circumference reflected associations with BMI, when examined individually, and provided biased risk estimates, when combined with BMI. In conclusion, preferential positive associations of ABSI or inverse of HI with several major cancers indicate an important role of factors determining body shape in cancer development. [ABSTRACT FROM AUTHOR]

Studies of sleep duration in relation to the risk of site‐specific cancers other than breast cancer are scarce. Furthermore, the available results are inconclusive and the causality remains unclear. We aimed to investigate the potential causal associations of sleep duration with overall and site‐specific cancers using the Mendelian randomization (MR) design. Single‐nucleotide polymorphisms associated with the sleep traits identified from a genome‐wide association study were used as instrumental variables to estimate the association with overall cancer and 22 site‐specific cancers among 367 586 UK Biobank participants. A replication analysis was performed using data from the FinnGen consortium (up to 121 579 individuals). There was suggestive evidence that genetic liability to short‐sleep duration was associated with higher odds of cancers of the stomach (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.15‐4.30; P =.018), pancreas (OR, 2.18; 95% CI, 1.32‐3.62; P =.002) and colorectum (OR, 1.48; 95% CI, 1.12‐1.95; P =.006), but with lower odds of multiple myeloma (OR, 0.47; 95% CI, 0.22‐0.99; P =.047). Suggestive evidence of association of genetic liability to long‐sleep duration with lower odds of pancreatic cancer (OR, 0.44; 95% CI, 0.25‐0.79; P =.005) and kidney cancer (OR, 0.44; 95% CI, 0.21‐0.90; P =.025) was observed. However, none of these associations passed the multiple comparison threshold and two‐sample MR analysis using FinnGen data did not confirm these findings. In conclusion, this MR study does not provide strong evidence to support causal associations of sleep duration with risk of overall and site‐specific cancers. Further MR studies are required. What's new? With the exception of breast cancer, the impact of sleep duration on site‐specific cancer risk remains largely unknown. Here, using Mendelian randomization analysis, the authors investigated the causal role of sleep duration for overall cancer and for 22 site‐specific cancers in more than 367 000 UK Biobank participants. Suggestive associations were detected between certain cancer sites and genetic liability to short or long sleep duration or genetically predicted sleep duration. However, no statistically significant associations were identified between sleep duration and overall or site‐specific cancer risk, indicating that sleep duration does not have a causal influence on cancer. [ABSTRACT FROM AUTHOR]

Background: Telomere length is an important indicator of tumor progression and survival for cancer patients. Previous work investigated the associations between genetically predicted telomere length and cancers; however, the types of cancers investigated in those studies were relatively limited or the telomere length-associated genetic variants employed often came from genome-wide association studies (GWASs) with small sample sizes. Methods: We constructed the genetic risk score (GRS) for leukocyte telomere length based on 17 associated genetic variants available from the largest telomere length GWAS up to 78,592 individuals. Then, a comprehensive analysis was undertaken to evaluate the association between the constructed GRS and the risk or mortality of a wide range of cancers [i.e., 37 cancers in the UK Biobank and 33 cancers in The Cancer Genome Atlas (TCGA)]. We further applied the two-sample Mendelian randomization (MR) to estimate the causal effect of leukocyte telomere length on UK Biobank cancers via summary statistics. Results: In the UK Biobank dataset, we found that the GRS of leukocyte telomere length was associated with a decreased risk of nine types of cancer (i.e., significant association with multiple myeloma, chronic lymphocytic leukemia, kidney/renal cell cancer, bladder cancer, malignant melanoma, basal cell carcinoma, and prostate cancer and suggestive association with sarcoma/fibrosarcoma and Hodgkin's lymphoma/Hodgkin's disease). In addition, we found that the GRS was suggestively associated with an increased risk of leukemia. In the TCGA dataset, we observed suggestive evidence that the GRS was associated with a high death hazard of rectum adenocarcinoma (READ), sarcoma (SARC), and skin cutaneous melanoma (SKCM), while the GRS was associated with a low death hazard of kidney renal papillary cell carcinoma (KIRP). The results of MR further supported the association for leukocyte telomere length on the risk of malignant melanoma, Hodgkin's lymphoma/Hodgkin's disease, chronic lymphocytic leukemia and multiple myeloma. Conclusion: Our study reveals that telomere played diverse roles in different types of cancers. However, further validations in large-scale prospective studies and deeper investigations of the biologic mechanisms are warranted. [ABSTRACT FROM AUTHOR]

Objective: Epidemiological evidence investigating serum uric acid and kidney cancer risk remains unclear. We conducted this study to examine the relationship between serum uric acid and the incidence and mortality of kidney cancer. Methods: This is a prospective analysis of 444 462 participants without any cancer from the UK Biobank. Serum uric acid was measured at baseline and the incidence and mortality of kidney cancer was determined through contact with the cancer and death registry. Cox regression models were fitted to estimate the hazard ratio (HR) and 95% confidence interval (95%CI), adjusting for demography, lifestyle style, comorbidities, and medication use. Results: We documented 638 incidence cases and 188 mortality cases of kidney cancer over a median of 6.5 years follow‐up. People with the highest quartile had a 45% increased risk of kidney cancer compared to those with the lowest uric acid quartile (HR 1.45, 95%CI 1.08 to 1.93). Subgroup analyses showed that serum uric acid was associated with cancer risk among females but not among males (Q1 vs Q4: females HR1.47, 95%CI 1.01 to 2.16; males HR 1.19, 95%CI 0.91 to 1.56). Although we found serum uric acid was associated with an increased risk of kidney cancer mortality in age‐stratified model (HR 2.49, 95% CI 1.61 to 3.84), this association disappeared after further adjustment for other confounders. Conclusions: High uric acid is associated with a high incidence of kidney cancer, especially in women. More research is needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: Patients with metastatic renal cell carcinoma (mRCC) treated with targeted systemic therapies have demonstrated favourable outcomes in randomised controlled trials, however real-world evidence is limited. Thus, this study aimed to determine the effectiveness of targeted systemic therapies for patients with mRCC in routine clinical practice in the UK.Methods: A retrospective, observational, longitudinal study based on chart review of newly diagnosed adult mRCC patients treated at two UK hospitals from 2008 to 2015 was conducted. Targeted systemic therapies recommended for use in mRCC patients were evaluated across first to third lines of therapy (1LOT-3LOT). Important exclusions were treatment with cytokine therapy and within non-standard of care clinical trials. Primary outcome measure was overall survival (OS); data were analysed descriptively and using Kaplan-Meyer analysis.Results: 652 patients (65.3% male, 35.0% ≥70 years) were included. In 1LOT, 98.5% of patients received sunitinib or pazopanib. In 2LOT and 3LOT, 99.0 and 94.4% received axitinib or everolimus. Median OS was 12.9, 6.5 and 5.9 months at 1LOT, 2LOT and 3LOT respectively. Estimated OS at 1-year was 52.4% (95% CI: 48.6-56.4%) in 1LOT, 31.5% (25.2-39.5%) in 2LOT and 23.8% (10.1-55.9%) in 3LOT. Median OS from 1LOT in favourable, intermediate and poor MSKCC were 39.7, 15.8 and 6.1 months respectively.Conclusions: In this study, treatment was consistent with current National Institute for Health and Care Excellence (NICE) guidelines for mRCC patients. Although the study population favoured poorer prognosis patients, outcomes were more favourable than those for England at the same time. However, overall survival in this 'real-world' population remains poor and indicates significant unmet need for effective and safe treatment options to improve survival among mRCC patients. [ABSTRACT FROM AUTHOR]

Many potential disease modifying therapies have been identified as suitable for clinical evaluation in Parkinson's disease (PD). Currently, the evaluation of compounds in phase II and phase III clinical trials in PD are set up in isolation, a process that is lengthy, costly and lacks efficiency. This review will introduce the concept of a multi-arm, multi-stage (MAMS) trial platform which allows for the assessment of several potential therapies at once, transitioning seamlessly from a phase II safety and efficacy study to a phase III trial by means of an interim analysis. At the interim checkpoint, ineffective arms are dropped and replaced by new treatment arms, thereby allowing for the continuous evaluation of interventions. MAMS trial platforms already exist for prostate, renal and oropharyngeal cancer and are currently being developed for progressive multiple sclerosis (PMS) and motor neuron disease (MND) within the UK. As a MAMS trial will evaluate many potential treatments it is of critical importance that a widely endorsed core protocol is developed which will investigate outcomes and objectives meaningful to patients. This review will discuss the challenges of drug selection, trial design, stratification and outcome measures and will share strategies implemented in the planned MAMS trials for MND and PMS that may be of interest to the PD field. [ABSTRACT FROM AUTHOR]

Background: The combination of nivolumab, a programmed death-1 (PD-1) targeted monoclonal antibody, with the cytotoxic T-lymphocyte antigen-4 (CTLA-4) targeted antibody, ipilimumab, represents a new standard of care in the first-line setting for patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC) based on recent phase III data. Combining ipilimumab with nivolumab increases rates of grade 3 and 4 toxicity compared with nivolumab alone, and the optimal scheduling of these agents when used together remains unknown. The aim of the PRISM study is to assess whether less frequent dosing of ipilimumab (12-weekly versus 3-weekly), in combination with nivolumab, is associated with a favourable toxicity profile without adversely impacting efficacy.Methods: The PRISM trial is a UK-based, open label, multi-centre, phase II, randomised controlled trial. The trial population consists of patients with untreated locally advanced or metastatic clear cell RCC, and aims to recruit 189 participants. Participants will be randomised on a 2:1 basis in favour of a modified schedule of 4 doses of 12-weekly ipilimumab versus a standard schedule of 4 doses of 3-weekly ipilimumab, both in combination with standard nivolumab. The proportion of participants experiencing a grade 3 or 4 adverse reaction within 12 months forms the primary endpoint of the study, but with 12-month progression free survival a key secondary endpoint. The incidence of all adverse events, discontinuation rates, overall response rate, duration of response, overall survival rates and health related quality of life will also be analysed as secondary endpoints. In addition, the potential of circulating and tissue-based biomarkers as predictors of therapy response will be explored.Discussion: The combination of nivolumab with ipilimumab is active in patients with mRCC. Modifying the frequency of ipilimumab dosing may mitigate toxicity rates and positively impact quality of life without compromising efficacy, a hypothesis being explored in other tumour types such as non-small cell lung cancer. The best way to give this combination to patients with mRCC must be similarly established.Trial Registration: PRISM is registered with ISRCTN (reference ISRCTN95351638, 19/12/2017).Trial Status: At the time of submission, PRISM is open to recruitment and data collection is ongoing. [ABSTRACT FROM AUTHOR]

Background Everolimus (mammalian target of rapmaycin (mTOR) inhibitor) and dovitinib (vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) inhibitor) demonstrate activity in metastatic clear cell renal cancer. The combination of these agents has a broad spectrum of relevant activity. The combination is explored in this phase Ib study. Methods Patients with metastatic clear cell renal cancer who have failed VEGF targeted therapy were eligible. Up to four cohorts of three to six patients (3+3 design) were treated with escalating doses of everolimus and dovitinib. Dose-limiting toxicities (DLTs) were assessed to determine the maximum tolerated dose (MTD). An expansion cohort (n=15) was investigated to obtain additional efficacy information. Sequential fluorodeoxyglucose positron emission tomography (FDG-PET) was used as a surrogate marker of response. Results Overall 18 patients were recruited into the study. Fifteen patients received the MTD, which was everolimus 5mg orally (PO) once daily (OD) and dovitinib 200mg PO day 1-5/7. The MTD was associated with toxicity, which included fatigue, mucositis and diarrhoea in 73%, 53% and 53% (Common Toxicity Criteria (CTC) grade 1-4) of patients, respectively. Frequent biochemical abnormalities occurred (such as hypertriglyceridaemia in 67%). Higher doses of the combination were not tolerable due to grade 3 fatigue in 2/3 patients and grade 3 nausea in 1/3 patients within 1month of therapy. The response rate at the MDT was 1/15 (7%) while the progression free survival for the MTD was 7months (95% confidence interval (CI) 2.2-11months). Pharmacokinetic data at the MTD showed stable kinetics with time. Conclusion Dovitinib and everolimus had modest activity, but did not meet all of the planned efficacy end-points. Fatigue was the dose limiting toxicity. [ABSTRACT FROM AUTHOR]

We compare the COVID-19-specific guidelines on diagnosis and management of the main urological cancers between the UK, Europe and the US to investigate differences in approaches. B Results: b Across all major urological cancers it was found that BAUS guidance favoured more conservative management compared with Europe and that the US was more aggressive in its approach to treatment than both the UK and Europe. [Extracted from the article]

Background: Kidney cancer accounts for over 4000 UK deaths annually, and is one of the cancer sites with a poor mortality record compared with Europe. Aim: To identify and quantify all clinical features of kidney cancer in primary care. Design: Case-control study, using General Practice Research Database records. Method: A total of 3149 patients aged =40 years, diagnosed with kidney cancer between 2000 and 2009, and 14 091 age, sex and practicematched controls, were selected. Clinical features associated with kidney cancer were identified, and analysed using conditional logistic regression. Positive predictive values for features of kidney cancer were estimated. Results: Cases consulted more frequently than controls in the year before diagnosis: median 16 consultations (interquartile range 10-25) versus 8 (4-15): P<0.001. Fifteen features were independently associated with kidney cancer: visible haematuria, odds ratio 37 (95% confidence interval [CI] = 28 to 49), abdominal pain 2.8 (95% CI = 2.4 to 3.4), microcytosis 2.6 (95% CI = 1.9 to 3.4), raised inflammatory markers 2.4 (95% CI = 2.1 to 2.8), thrombocytosis 2.2 (95% CI = 1.7 to 2.7), low haemoglobin 1.9 (95% CI = 1.6 to 2.2), urinary tract infection 1.8 (95% CI = 1.5 to 2.1), nausea 1.8 (95% CI = 1.4 to 2.3), raised creatinine 1.7 (95% CI = 1.5 to 2.0), leukocytosis 1.5 (95% CI = 1.2 to 1.9), fatigue 1.5 (95% CI = 1.2 to 1.9), constipation 1.4 (95% CI = 1.1 to 1.7), back pain 1.4 (95% CI = 1.2 to 1.7), abnormal liver function 1.3 (95% CI = 1.2 to 1.5), and raised blood sugar 1.2 (95% CI = 1.1 to 1.4). The positive predictive value for visible haematuria in patients aged =60 years was 1.0% (95% CI = 0.8 to 1.3). Conclusion: Visible haematuria is the commonest and most powerful single predictor of kidney cancer, and the risk rises when additional symptoms are present. When considered alongside the risk of bladder cancer, the overall risk of urinary tract cancer from haematuria warrants referral. [ABSTRACT FROM AUTHOR]

Abstract: Renal cell cancer is the seventh most common cancer in males and ninth most common in females in the UK. Although it classically presents with haematuria, loin pain and a palpable mass, increasingly small renal cancers are being detected incidentally. Curative treatment for the disease remains surgical, with, until recently, few effective additional treatments. Recent advances in the molecular/genetic understanding of the disease have enabled the development of effective treatments for advanced disease. Surgery for renal cancer remains technically challenging and increasing detection of small tumours is necessitating the development of lower morbidity, nephron-sparing techniques. This article discusses current understanding of renal cancer, modes of diagnosis and various treatment options available. [ABSTRACT FROM AUTHOR]

Aim: To determine the follow-up protocol for interval assessment of patients following radical nephrectomy for renal cell cancer and to compare them with the recommendations proposed in the literature. Methods: Consultant urologists across Britain and Ireland completed a postal questionnaire. One follow-up mailing was used to encourage non-responders. The responses were analysed in the light of the recommendations from European Association of Urology and American guidelines. Also information was collected from the respondents on the choice of follow-up investigations for renal cell cancer and the total duration of follow-up. Results: Of the 480 urologists surveyed 292 (60.8%) responded. Most respondents recommended regular follow-up with chest radiography (CR), ultrasound and computed tomography (CT). For T1 disease CR was requested by 28, 62 and 55%; for T2 disease by 30, 66 and 51%; for T3 disease by 39, 63, and 48% at 3, 6 and 12 months, respectively. For T1 disease US was requested by 5, 23 and 30%; for T2 disease 6, 27 and 30%; for T3 disease 8, 25, and 26% at 3, 6 and 12 months, respectively. For T1 disease an abdominal CT was requested by 2, 17 and 21%; for T2 disease 3.7, 19.5 and 26%; for T3 disease 10, 31, and 33% at 3, 6 and 12 months, respectively. Only one respondent followed the guidelines suggested in the literature. Further follow-up after 12 months for 5 and 10 years was suggested by 58.2 and 21.3% for T1, 53 and 24.73% for T2, and 45.5 and 25.5% for T3, respectively. There is appreciable variation in the frequency of use and timing of imaging. Conclusions: Most respondents perform follow-up after radical nephrectomy in patients with renal cancer, with considerable variability in their practices. In the current increasingly cost-conscious healthcare industry a scientifically justified follow-up should be considered. [ABSTRACT FROM AUTHOR]

OBJECTIVE To define the current achievable outcomes from open partial nephrectomy (OPN) in the UK at a time when other treatments for small kidney tumours are increasingly being advocated. Current knowledge of the effectiveness of OPN is limited by the fact that published data are almost exclusively derived from a very few centres of established world renown. PATIENTS AND METHODS We retrospectively reviewed 100 consecutive planned OPNs in 90 patients at two UK centres; 93 operations were for suspected cancer. The median (range) tumour size was 3.8 (1.2–9) cm. In all, 42 OPNs were imperative for patients with a single kidney (14), synchronous bilateral tumours (20), or renal impairment alone (eight). In 42 patients with a tumour of ≤ 4 cm and a normal contralateral kidney the decision to do OPN was considered elective. There were 10 additional operations in seven patients with Von Hippel-Lindau (VHL) disease. In all, 21 OPNs were in the context of a single kidney. RESULTS In all, 95 OPNs were successfully completed; one operation was abandoned and there were four nephrectomies, including two for bleeding, one for a positive margin on frozen-section analysis, and one for multifocal tumours. The median warm/cold ischaemia time was 20/33 min. The intraoperative/early complication rate was 36%, including a major complication rate of 11% and re-operation rate for primary bleeding of 3%. Of 36 complications, 30 (83%) were in 23 patients with either an imperative indication or VHL. Complications were more common in the imperative/VHL group (59%) than in the elective/other group (12%). Renal function was preserved in 80 of 100 (80%) OPNs overall. Creatinine levels returned to baseline in 11 of 21 (50%) patients with renal impairment before OPN and in 12 of 20 (60%) with a single kidney, whilst five of 21 (24%) with a single kidney needed dialysis after OPN. The median (range) stay after surgery was 6 (3–50) nights. A malignant diagnosis was confirmed in 76 of 93 (82%) specimens on final histopathology. There were 11 of 100 (11%) positive margins, one managed by immediate conversion to nephrectomy and the remaining 10 managed expectantly. After a median (range) follow-up of 24 (1–69) months there were no deaths from kidney cancer, but three patients had local recurrences and two others had developed metastatic recurrence. CONCLUSION OPN is complex surgery, especially in the imperative setting, but very good results are achievable outside established centres of world renown. It provides good cancer control in the short term with low renal morbidity. These results may act as a reference point in the UK by which to compare results of new treatments for kidney cancer. [ABSTRACT FROM AUTHOR]

Background It is unknown whether relationships between lifestyle and cancer differ by genetic risk. We investigated this for 13 cancer types using prospective data from the UK Biobank. Methods In 2006-2010, participants aged 37-73 years completed an assessment and provided biological samples. Those of European ancestry with no history of malignant cancer were included in our analysis (n = 196,485). For each individual, a healthy lifestyle index (HLI) was calculated based on recommendations, and polygenic risk scores (PRSs) were computed for 13 cancer types. Relationships with cancer incidence were assessed by cox regression, adjusting for age, sex, assessment centre, birth location, and measures of socioeconomic status. Interactions between the HLI and PRSs were explored. Results For all cancer outcomes, a high genetic risk was associated with an increased cancer risk, or there was a trend in that direction. Those in the top PRS tertile had a greater than 2-fold increased risk of colorectal cancer (HR[95%CI]=2.18[1.90,2.49]), pancreatic cancer (2.39[1.71,3.32]) and lymphocytic leukemia (2.45[1.67,3.59]). An unhealthy lifestyle was associated with a higher cancer risk for 8 cancer types, with strong relationships observed for lung (3.41[2.76,4.20]), pancreatic (2.06[1.47,2.91]), bladder (1.95[1.43,2.66]) and kidney cancers (1.90[1.43,2.54]). No interactions between HLI and PRSs were detected (all interaction p-values>0.10). Conclusions Associations between lifestyle and cancer incidence did not differ by genetic risk. Key messages A healthy lifestyle can reduce the risk of several cancers, even in those who are genetically predisposed to develop cancer. [ABSTRACT FROM AUTHOR]

Objective To investigate the management of urological malignancies in the United Kingdom. Methods A postal survey of consultant urologists and general surgeons with an interest in urology was conducted to examine current clinical practice in urological malignancies. Results Completed questionnaires were received from 273 consultant surgeons who saw an estimated total of 13 241 new patients with renal, bladder or testis cancer per year; 82% had access to on-site oncology services and in general there was a consensus in the answers given. Most respondents advised active treatment of an asymptomatic primary renal cancer in the presence of metastases and a significant proportion of patients with metastases were not prescribed immunotherapy nor were offered a multidisciplinary approach for their condition. Forty-six per cent of patients with testis cancer received no advice to store sperm before chemotherapy and there were varied opinions as to the need for surgical resection of residual masses after completion of chemotherapy. Conclusion This survey showed minor variations in the management of renal, bladder and testis tumours in the UK. Consensus management guidelines for urological malignancies and a change in the working relationships between urologists and oncologists is required, to improve the outcome of patients with urological malignancy. [ABSTRACT FROM AUTHOR]

The article presents a study that validates an algorithm in estimating the individualised risk of having renal tract cancer in Great Britain. It notes that the QResearch database has been used to develop the risk prediction models that contains robust data on relevant exposures and outcomes for further use in primary care. Results confirmed that prior cancer and loss of appetite were not significant factors in males.

The authors reflect on new treatments, including bevacizumab, which are available for kidney cancer in Great Britain. They suggest that the new treatments offer hope but many of them are still waiting for regulatory approval in Great Britain. They argue that kidney cancer patients in Great Britain should not have to wait for approval of the treatments by the country's National Institute for Health and Clinical Excellence.

Focuses on the health hazards of caffeine and coffee in Great Britain. Consideration of caffeine as a carcinogenic substance; Evidence of anticarcinogenic effects of caffeine on animals exposed to known carcinogens; Correlation between coffee consumption and mortality rates for renal cancer.

Background: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor used in vascular endothelial growth factor (VEGF)-refractory metastatic renal cell carcinoma (mRCC). It acts on only part of the mTOR complex (TORC1 alone). In vitro data support the use of mTOR inhibitors with broader activity (TORC1 and TORC2)., Objective: The purpose of this study was to determine whether combined TORC1 and TORC2 inhibition with AZD2014 has superior activity to everolimus in VEGF-refractory clear cell mRCC., Design, Setting, and Participants: Patients with measurable mRCC and VEGF-refractory disease were eligible for this trial., Intervention: Starting in February 2013, patients were randomised (1:1) to AZD2014 (50 mg twice daily) or everolimus (10 mg once daily) until progression of disease at 10 centres across the United Kingdom., Outcome Measurements and Statistical Analysis: Progression-free survival (PFS) was the primary end point and was compared using the stratified log-rank test. Secondary end points included tolerability, response rates, overall survival (OS), and pharmacokinetics (PK) analysis. The study was planned to recruit 120 patients., Results and Limitations: Recruitment into the trial was stopped early (June 2014) due to lack of efficacy of AZD2014. At that point, 49 patients were randomised (26 to AZD2014 and 23 to everolimus). The PFS for AZD2014 and everolimus was 1.8 and 4.6 mo, respectively (hazard ratio: 2.8 [95% confidence interval (CI), 1.2-6.5]; p=0.01). Progression of disease as the best response to therapy was 69% for AZD2014 and 13% for everolimus (p<0.001). Grade 3-4 adverse events (AEs) occurred in 35% of AZD2014 and 48% of everolimus patients (p=0.3). Only 4% of patients stopped AZD2014 due to AEs. PK analysis suggested concentrations of AZD2014 were compatible with the therapeutic range. Final stratified OS hazard ratio at the time of trial closure (January 2015) was 3.1 (95% CI, 1.1-8.4; p<0.02)., Conclusions: The PFS and OS of AZD2014 were inferior to everolimus in this setting despite acceptable AE and PK profiles., Patient Summary: There is a strong rationale for testing mTOR inhibitors with a broader spectrum of activity than everolimus in metastatic clear cell renal cell carcinoma. AZD2014 is such an agent, but in this study, it was inferior to everolimus despite its attractive toxicity profile., (Copyright © 2015. Published by Elsevier B.V.)

The article reports on the recommendation of the United Kingdom National Institute for Health and Clinical Excellence (NICE) against funding for sunitinib, bevacizumab, sorafenib, and temsirolimus in the treatment of metastatic renal cell carcinoma. It adds the notion that the improvement in progression-free survival does not justify the high cost of the treatment.

The article offers news briefs related to medical research in Great Britain. It reveals that patients taking the drug sorafenib or Nexavar for advanced kidney cancer are at risk of developing high blood pressure. The study confirms that breast cancer patients who smoke could develop lung cancer a decade after their original diagnosis. The research informs that women who take contraceptive pill for even a short time have a reduced risk of developing ovarian cancer for several years.