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1.
BJU Int ; 133(5): 539-547, 2024 May.
Article in English | MEDLINE | ID: mdl-38097529

ABSTRACT

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.


Subject(s)
Early Detection of Cancer , Lung Neoplasms , Tomography, X-Ray Computed , Humans , Male , Female , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/psychology , Middle Aged , Aged , Early Detection of Cancer/psychology , Feasibility Studies , Quality of Life , Surveys and Questionnaires , Radiography, Thoracic , Radiography, Abdominal , Anxiety , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/psychology
2.
Surgeon ; 22(1): e69-e78, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37993323

ABSTRACT

Earlier detection and screening for kidney cancer has been identified as a key research priority, however the low prevalence of the disease in unselected populations limits the cost-effectiveness of screening. Risk-stratified screening for kidney cancer may improve early detection by targeting high-risk individuals whilst limiting harms in low-risk individuals, potentially increasing the cost-effectiveness of screening. A number of models have been identified which estimate kidney cancer risk based on both phenotypic and genetic data, and while several of the former have been shown to identify individuals at high-risk of developing kidney cancer with reasonable accuracy, current evidence does not support including a genetic component. Combined screening for lung cancer and kidney cancer has been proposed, as the two malignancies share some common risk factors. A modelling study estimated that using lung cancer risk models (currently used for risk-stratified lung cancer screening) could capture 25% of patients with kidney cancer, which is only slightly lower than using the best performing kidney cancer-specific risk models based on phenotypic data (27%-33%). Additionally, risk-stratified screening for kidney cancer has been shown to be acceptable to the public. The following review summarises existing evidence regarding risk-stratified screening for kidney cancer, highlighting the risks and benefits, as well as exploring the management of potential harms and further research needs.


Subject(s)
Kidney Neoplasms , Lung Neoplasms , Humans , Early Detection of Cancer , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Cost-Benefit Analysis , Risk Factors , Kidney Neoplasms/diagnosis , Mass Screening
3.
BJU Int ; 129(4): 498-511, 2022 04.
Article in English | MEDLINE | ID: mdl-34538014

ABSTRACT

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.


Subject(s)
Biological Specimen Banks , Kidney Neoplasms , Female , Humans , Kidney Neoplasms/diagnosis , Kidney Neoplasms/epidemiology , Male , Mass Screening , Public Health , Risk Assessment , Risk Factors , United Kingdom/epidemiology
4.
BJU Int ; 130(5): 550-561, 2022 11.
Article in English | MEDLINE | ID: mdl-35460182

ABSTRACT

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.


Subject(s)
Genome-Wide Association Study , Kidney Neoplasms , Humans , Genetic Predisposition to Disease/genetics , Risk Factors , ROC Curve , Kidney Neoplasms/genetics , Polymorphism, Single Nucleotide
5.
BJU Int ; 129(3): 290-303, 2022 03.
Article in English | MEDLINE | ID: mdl-34570419

ABSTRACT

OBJECTIVES: To review urinary protein biomarkers as potential non-invasive, easily obtainable, early diagnostic tools in renal cell carcinoma (RCC). METHODS: A PubMed database search was performed up to the year 2020 to identify primary studies reporting potential urinary protein biomarkers for RCC. Separate searches were conducted to identify studies describing appropriate methods of developing cancer screening programmes and detection of cancer biomarkers. RESULTS: Several urinary protein biomarkers are under validation for RCC diagnostics, e.g. aquaporin-1, perilipin-2, carbonic anhydrase-9, Raf-kinase inhibitory protein, nuclear matrix protein-22, 14-3-3 Protein ß/α and neutrophil gelatinase-associated lipocalin. However, none has yet been validated or approved for clinical use due to low sensitivity or specificity, inconsistencies in appropriate study design, or lack of external validation. CONCLUSIONS: Evaluation of biomarkers' feasibility, sample preparation and storage, biomarker validation, and the application of novel technologies may provide a solution that maximises the potential for a truly non-invasive biomarker in early RCC diagnostics.


Subject(s)
Acute Kidney Injury , Carcinoma, Renal Cell , Kidney Neoplasms , Biomarkers , Biomarkers, Tumor , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/pathology , Early Detection of Cancer , Female , Humans , Kidney Neoplasms/diagnosis , Kidney Neoplasms/pathology , Male , Urinalysis
6.
BJU Int ; 130(5): 562-579, 2022 11.
Article in English | MEDLINE | ID: mdl-34914159

ABSTRACT

OBJECTIVE: To systematically identify and compare the performance of prognostic models providing estimates of survival or recurrence of localized renal cell cancer (RCC) in patients treated with surgery with curative intent. MATERIALS AND METHODS: We performed a systematic review (PROSPERO CRD42019162349). We searched Medline, EMBASE and the Cochrane Library from 1 January 2000 to 12 December 2019 to identify studies reporting the performance of one or more prognostic model(s) that predict recurrence-free survival (RFS), cancer-specific survival (CSS) or overall survival (OS) in patients who have undergone surgical resection for localized RCC. For each outcome we summarized the discrimination of each model using the C-statistic and performed multivariate random-effects meta-analysis of the logit transformed C-statistic to rank the models. RESULTS: Of a total of 13 549 articles, 57 included data on the performance of 22 models in external populations. C-statistics ranged from 0.59 to 0.90. Several risk models were assessed in two or more external populations and had similarly high discriminative performance. For RFS, these were the Sorbellini, Karakiewicz, Leibovich and Kattan models, with the UCLA Integrated Staging System model also having similar performance in European/US populations. All had C-statistics ≥0.75 in at least half of the validations. For CSS, they the models with the highest discriminative performance in two or more external validation studies were the Zisman, Stage, Size, Grade and Necrosis (SSIGN), Karakiewicz, Leibovich and Sorbellini models (C-statistic ≥0.80 in at least half of the validations), and for OS they were the Leibovich, Karakiewicz, Sorbellini and SSIGN models. For all outcomes, the models based on clinical features at presentation alone (Cindolo and Yaycioglu) had consistently lower discrimination. Estimates of model calibration were only infrequently included but most underestimated survival. CONCLUSION: Several models had good discriminative ability, with there being no single 'best' model. The choice from these models for each setting should be informed by both the comparative performance and availability of factors included in the models. All would need recalibration if used to provide absolute survival estimates.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Prognosis
7.
Health Expect ; 25(4): 1789-1806, 2022 08.
Article in English | MEDLINE | ID: mdl-35526275

ABSTRACT

INTRODUCTION: Using risk stratification to determine eligibility for cancer screening is likely to improve the efficiency of screening programmes by targeting resources towards those most likely to benefit. We aimed to explore the implications of this approach from a societal perspective by understanding public views on the most acceptable stratification strategies. METHODS: We conducted three online community juries with 9 or 10 participants in each. Participants were purposefully sampled by age (40-79 years), sex, ethnicity, social grade and English region. On the first day, participants were informed of the potential benefits and harms of cancer screening and the implications of different ways of introducing stratification using scenarios based on phenotypic and genetic risk scores. On the second day, participants deliberated to reach a verdict on the research question, 'Which approach(es) to inviting people to screening are acceptable, and under what circumstances?' Deliberations and feedback were recorded and analysed using thematic analysis. RESULTS: Across the juries, the principle of risk stratification was generally considered to be an acceptable approach for determining eligibility for screening. Disregarding increasing capacity, the participants considered it to enable efficient resource allocation to high-risk individuals and could see how it might help to save lives. However, there were concerns regarding fair implementation, particularly how the risk assessment would be performed at scale and how people at low risk would be managed. Some favoured using the most accurate risk prediction model whereas others thought that certain risk factors should be prioritized (particularly factors considered as non-modifiable and relatively stable, such as genetics and family history). Transparently justifying the programme and public education about cancer risk emerged as important contributors to acceptability. CONCLUSION: Using risk stratification to determine eligibility for cancer screening was acceptable to informed members of the public, particularly if it included risk factors they considered fair and when communicated transparently. PATIENT OR PUBLIC CONTRIBUTION: Two patient and public involvement representatives were involved throughout this study. They were not involved in synthesizing the results but contributed to producing study materials, co-facilitated the community juries and commented on the interpretation of the findings and final report.


Subject(s)
Early Detection of Cancer , Neoplasms , Adult , Aged , Early Detection of Cancer/methods , Humans , Mass Screening , Middle Aged , Neoplasms/diagnosis , Risk Assessment
8.
Health Expect ; 24(2): 341-351, 2021 04.
Article in English | MEDLINE | ID: mdl-33264472

ABSTRACT

BACKGROUND: Using risk stratification approaches to determine eligibility has the potential to improve efficiency of screening. OBJECTIVES: To compare the public acceptability and potential impact on uptake of using different approaches to determine eligibility for screening. DESIGN: An online population-based survey of 668 adults in the UK aged 45-79 including a series of scenarios in the context of a potential kidney cancer screening programme in which eligibility was determined by age, sex, age and sex combined, a simple risk score (age, sex, body mass index, smoking status), a complex risk score additionally incorporating family history and lifestyle, or a genetic risk score. OUTCOME MEASURES: We used multi-level ordinal logistic regression to compare acceptability and potential uptake within individuals and multivariable ordinal logistic regression differences between individuals. RESULTS: Using sex, age and sex, or the simple risk score were less acceptable than age (P < .0001). All approaches were less acceptable to women than men. Over 70% were comfortable waiting until they were older if the complex risk score or genetics indicated a low risk. If told they were high risk, 85% would be more likely to take up screening. Being told they were low risk had no overall influence on uptake. CONCLUSIONS: Varying the starting age of screening based on estimated risk from models incorporating phenotypic or genetic risk factors would be acceptable to most individuals and may increase uptake. PATIENT OR PUBLIC CONTRIBUTION: Two members of the public contributed to the development of the survey and have commented on this paper.


Subject(s)
Early Detection of Cancer , Mass Screening , Adult , Female , Humans , Logistic Models , Male , Risk Assessment , Surveys and Questionnaires
9.
BMC Urol ; 20(1): 170, 2020 Oct 28.
Article in English | MEDLINE | ID: mdl-33115457

ABSTRACT

BACKGROUND: Kidney cancer is often asymptomatic, leading to proposals for a screening programme. The views of the public towards introducing a new screening programme for kidney cancer are unknown. The aim of this study was to explore attitudes towards kidney cancer screening and factors influencing intention to attend a future screening programme. METHODS: We conducted an online population-based survey of 1021 adults aged 45-77 years. The main outcome measure was intention to attend four possible screening tests (urine, blood, ultrasound scan, low-dose CT) as well as extended low-dose CT scans within lung cancer screening programmes. We used multivariable regression to examine the association between intention and each screening test. RESULTS: Most participants stated that they would be 'very likely' or 'likely' to undergo each of the screening tests [urine test: n = 961 (94.1%); blood test: n = 922 (90.3%); ultrasound: n = 914 (89.5%); low-dose CT: n = 804 (78.8%); lung CT: n = 962 (95.2%)]. Greater intention to attend was associated with higher general cancer worry and less perceived burden/inconvenience about the screening tests. Less worry about the screening test was also associated with higher intention to attend, but only in those with low general cancer worry (cancer worry scale ≤ 5). Compared with intention to take up screening with a urine test, participants were half as likely to report that they intended to undergo blood [OR 0.56 (0.43-0.73)] or ultrasound [OR 0.50 (0.38-0.67)] testing, and half as likely again to report that they intended to take part in a screening programme featuring a low dose CT scan for kidney cancer screening alone [OR 0.19 (0.14-0.27)]. CONCLUSION: Participants in this study expressed high levels of intention to accept an invitation to screening for kidney cancer, both within a kidney cancer specific screening programme and in conjunction with lung cancer screening. The choice of screening test is likely to influence uptake. Together these findings support on-going research into kidney cancer screening tests and the potential for combining kidney cancer screening with existing or new screening programmes.


Subject(s)
Attitude to Health , Early Detection of Cancer , Intention , Kidney Neoplasms/diagnosis , Public Opinion , Aged , Female , Humans , Internet , Male , Middle Aged , Surveys and Questionnaires
11.
Value Health ; 22(9): 981-987, 2019 09.
Article in English | MEDLINE | ID: mdl-31511187

ABSTRACT

BACKGROUND: Population screening for renal cell carcinoma (RCC) using ultrasound has the potential to improve survival outcomes; however, a cost-effectiveness analysis (CEA) has yet to be performed. Owing to the lack of existing evidence, we performed structured expert elicitation to derive unknown quantities to inform the CEA. OBJECTIVE: To elicit the cancer stage distribution (proportion of individuals with each stage of cancer) for different RCC screening scenarios and the annual transition probabilities for undiagnosed disease becoming diagnosed in the National Health Service. METHODS: The study design and reporting adhered to the Reporting Guidelines for the Use of Expert Judgement in Model-Based Economic Evaluations. The elicitation was conducted face-to-face or via telephone between each individual expert and the facilitator, aided by online material. For multinomial data, Connor-Mosimann and modified Connor-Mosimann distributions were fitted for each expert and for all experts combined using mathematical linear pooling. RESULTS: A total of 24 clinical experts were invited, and 71% participated (7 urologists, 6 oncologists, 4 radiologists). The modified Connor-Mosimann distribution provided the best fit for most elicited quantities. Greater uncertainty was noted for the elicited transition probabilities compared with the elicited stage distributions. CONCLUSION: We performed the first expert elicitation of RCC screening parameters, crucial information that will inform the CEA of screening. In addition, the elicited quantities may enable future health economic evaluations assessing the value of diagnostic tools and pathways in RCC.


Subject(s)
Carcinoma, Renal Cell/diagnosis , Cost-Benefit Analysis/methods , Early Detection of Cancer/economics , Kidney Neoplasms/diagnosis , Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/pathology , Early Detection of Cancer/methods , False Negative Reactions , Humans , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Models, Economic , Neoplasm Staging , State Medicine , Technology Assessment, Biomedical , Uncertainty , United Kingdom
12.
World J Urol ; 36(12): 1961-1972, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30051264

ABSTRACT

PURPOSE: Patients with localised renal cell carcinoma (RCC) can expect excellent oncologic outcomes. As such, there has been a shift towards maximising health-related quality of life (HRQoL). A greater understanding of HRQoL outcomes associated with different treatment options for RCC can facilitate patient-centred care, shared decision-making and enable cost utility analyses to guide health policies. The aim of this literature review was to evaluate the evidence regarding HRQoL following different management strategies for localised RCC. METHODS: Three databases were searched to identify studies reporting HRQoL in patients with localised renal cancer, including Medline, the Tuft's Medical Centre Cost Effectiveness Analysis registry and the EuroQol website. RESULTS: Considerable methodological heterogeneity was noted. Laparoscopic nephrectomy was associated with significantly better short-term physical function compared to open surgery, although the effect on mental function was inconclusive. Nephron-sparing surgery was associated with better physical function compared to radical surgery. Patients' perception of remaining renal function was a significant independent predictor of HRQoL, rather than surgery type. Tumour size, stage, post-operative complications, age, body mass index, occupational status, educational level and comorbidities were significant predictors of HRQoL. Only three studies were available regarding non-surgical management options and very little data were available regarding the impact of follow-up protocols and long-term effects of "cancer survivorship." CONCLUSION: There is a need for validated and reproducible RCC-specific HRQoL instruments and standardisation amongst studies to enable comparisons. Increased awareness regarding determinants of poor HRQoL may enable high-risk patients to receive tailored support.


Subject(s)
Carcinoma, Renal Cell/physiopathology , Health Status , Kidney Neoplasms/physiopathology , Quality of Life , Age Factors , Body Mass Index , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/psychology , Carcinoma, Renal Cell/therapy , Comorbidity , Cost-Benefit Analysis , Decision Making , Educational Status , Employment , Health Policy , Humans , Kidney Neoplasms/pathology , Kidney Neoplasms/psychology , Kidney Neoplasms/therapy , Neoplasm Staging , Nephrectomy , Nephrons , Organ Sparing Treatments , Patient Reported Outcome Measures , Patient-Centered Care , Postoperative Complications/epidemiology , Tumor Burden
13.
World J Urol ; 36(12): 1899-1911, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30099580

ABSTRACT

PURPOSE: Clear cell, papillary cell, and chromophobe renal cell carcinomas (RCCs) have now been well characterised thanks to large collaborative projects such as The Cancer Genome Atlas (TCGA). Not only has knowledge of the genomic landscape helped inform the development of new drugs, it also promises to fine tune prognostication. METHODS: A literature review was performed summarising the current knowledge on the genetic basis of RCC. RESULTS: The Von Hippel-Lindau (VHL) tumour suppressor gene undergoes bi-allelic knockout in the vast majority of clear cell RCCs. The next most prevalent aberrations include a cohort of chromatin-modifying genes with diverse roles including PBRM1, SETD2, BAP1, and KMD5C. The most common non-clear cell renal cancers have also undergone genomic profiling and are characterised by distinct genomic landscapes. Many recurrent mutations have prognostic value and show promise in aiding decisions regarding treatment stratification. Intra-tumour heterogeneity appears to hamper the clinical applicability of sparsely sampled tumours. Ways to abrogate heterogeneity will be required to optimise the genomic classification of tumours. CONCLUSION: The somatic mutational landscape of the more common renal cancers is well known. Correlation with outcome needs to be more comprehensively furnished, particularly for small renal masses, rarer non-clear cell renal cancers, and for all tumours undergoing targeted therapy.


Subject(s)
Carcinoma, Renal Cell/genetics , Genomics , Kidney Neoplasms/genetics , DNA-Binding Proteins , Histone-Lysine N-Methyltransferase/genetics , Humans , Mutation , Nuclear Proteins/genetics , PTEN Phosphohydrolase/genetics , Telomerase/genetics , Transcription Factors/genetics , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/genetics , Von Hippel-Lindau Tumor Suppressor Protein/genetics
14.
World J Urol ; 36(12): 1943-1952, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29713755

ABSTRACT

PURPOSE: Following curative treatment for localised renal cell carcinoma (RCC), up to 30% of patients develop tumour recurrence. Prognostic scores are essential to guide individualised surveillance protocols, patient counselling and potentially in the future to guide adjuvant therapy. In metastatic RCC, prognostic scores are routinely used for treatment selection in clinical practice as well as in all major trials. METHODS: We performed a literature review on the current evidence based on prognostic factors and models for localised and metastatic RCC. RESULTS: A number of prognostic factors have been identified, of which tumour node metastasis classification remains the most important. Multiple prognostic models and nomograms have been developed for localised disease, based on a combination of tumour stage, grade, subtype, clinical features, and performance status. However, there is poor level of evidence for their routine use. Prognostic scores for patients with metastatic RCC receiving targeted treatments are used routinely, but have limited accuracy. Molecular markers can improve the accuracy of established prognostic models, but frequently lack external, independent validation. CONCLUSION: Several factors and models predict prognosis of localised and metastatic RCC. They represent valuable tools to provide estimates of clinically important endpoints, but their accuracy should be improved further. Validation of molecular markers is a future research priority.


Subject(s)
Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Neoplasm Recurrence, Local/epidemiology , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/secondary , Carcinoma, Renal Cell/therapy , Chemotherapy, Adjuvant , Humans , Kidney Neoplasms/metabolism , Kidney Neoplasms/therapy , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Staging , Prognosis , Survival Rate , Tumor Burden
15.
World J Urol ; 36(12): 1927-1942, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29948048

ABSTRACT

PURPOSE: Imaging plays a key role throughout the renal cell carcinoma (RCC) patient pathway, from diagnosis and staging of the disease, to the assessment of response to therapy. This review aims to summarise current knowledge with regard to imaging in the RCC patient pathway, highlighting recent advances and challenges. METHODS: A literature review was performed using Medline. Particular focus was paid to RCC imaging in the diagnosis, staging and response assessment following therapy. RESULTS: Characterisation of small renal masses (SRM) remains a diagnostic conundrum. Contrast-enhanced ultrasound (CEUS) has been increasingly applied in this field, as have emerging technologies such as multiparametric MRI, radiomics and molecular imaging with 99mtechnetium-sestamibi single photon emission computed tomography/CT. CT remains the first-line modality for staging of locoregional and suspected metastatic disease. Although the staging accuracy of CT is good, limitations in determining nodal status persist. Response assessment following ablative therapies remains challenging, as reduction in tumour size may not occur. The pattern of enhancement on CT may be a more reliable indicator of treatment success. CEUS may also have a role in monitoring response following ablation. Response assessments following anti-angiogenic and immunotherapies in advanced RCC is an evolving field, with a number of alternative response criteria being proposed. Tumour response patterns may vary between different immunotherapy agents and tumour types; thus, future response criteria modifications may be inevitable. CONCLUSION: The diagnosis and characterisation of SRM and response assessment following targeted therapy for advanced RCC are key challenges which warrant further research.


Subject(s)
Carcinoma, Renal Cell/diagnostic imaging , Kidney Neoplasms/diagnostic imaging , Kidney/diagnostic imaging , Lymph Nodes/diagnostic imaging , Carcinoma, Renal Cell/therapy , Humans , Kidney Neoplasms/therapy , Magnetic Resonance Imaging , Molecular Imaging , Radiopharmaceuticals , Single Photon Emission Computed Tomography Computed Tomography , Technetium Tc 99m Sestamibi , Tomography, X-Ray Computed , Treatment Outcome , Ultrasonography
16.
World J Urol ; 36(9): 1341-1353, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29610964

ABSTRACT

PURPOSE: The widespread use of abdominal imaging has affected the epidemiology of renal cell carcinoma (RCC). Despite this, over 25% of individuals with RCC have evidence of metastases at presentation. Screening for RCC has the potential to downstage the disease. METHODS: We performed a literature review on the epidemiology of RCC and evidence base regarding screening. Furthermore, contemporary RCC epidemiology data was obtained for the United Kingdom and trends in age-standardised rates of incidence and mortality were analysed by annual percentage change statistics and joinpoint regression. RESULTS: The incidence of RCC in the UK increased by 3.1% annually from 1993 through 2014. Urinary dipstick is an inadequate screening tool due to low sensitivity and specificity. It is unlikely that CT would be recommended for population screening due to cost, radiation dose and increased potential for other incidental findings. Screening ultrasound has a sensitivity and specificity of 82-83% and 98-99%, respectively; however, accuracy is dependent on tumour size. No clinically validated urinary nor serum biomarkers have been identified. Major barriers to population screening include the relatively low prevalence of the disease, the potential for false positives and over-diagnosis of slow-growing RCCs. Individual patient risk-stratification based on a combination of risk factors may improve screening efficiency and minimise harms by identifying a group at high risk of RCC. CONCLUSION: The incidence of RCC is increasing. The optimal screening modality and target population remain to be elucidated. An analysis of the benefits and harms of screening for patients and society is warranted.


Subject(s)
Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/epidemiology , Early Detection of Cancer/methods , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/epidemiology , Age Distribution , Humans , Incidence , Sensitivity and Specificity , Sex Distribution , Tomography, X-Ray Computed/economics , Tomography, X-Ray Computed/standards , Ultrasonography/standards , United Kingdom/epidemiology
17.
Urol Int ; 101(3): 366-368, 2018.
Article in English | MEDLINE | ID: mdl-28494441

ABSTRACT

Parapelvic cysts originate in the renal parenchyma and extend into the renal sinus. A series of 3 patients with symptomatic obstructing parapelvic cysts is described, 2 with acute presentations, and 1 with chronic symptoms. In 2 of the 3 cases, there was a significant delay in establishing a diagnosis. Although one individual was successfully managed by image-guided cyst aspiration, the second patient required repeated aspiration due to cyst re-accumulation. A high index of clinical suspicion and a combination of imaging modalities, including serial ultrasound, excretory-phase CT, and MAG3 renogram, are necessary to establish the diagnosis and monitor response to treatment.


Subject(s)
Kidney Diseases, Cystic/therapy , Kidney Pelvis/pathology , Tomography, X-Ray Computed , Ultrasonography , Ureteral Diseases/therapy , Cysts/therapy , Humans , Hydronephrosis/pathology , Inflammation , Kidney/immunology , Kidney/pathology , Kidney Diseases, Cystic/diagnosis , Male , Pain/diagnosis , Radioisotope Renography , Treatment Outcome , Ureteral Diseases/diagnosis , Urography
18.
BMC Cardiovasc Disord ; 16: 70, 2016 Apr 19.
Article in English | MEDLINE | ID: mdl-27095611

ABSTRACT

BACKGROUND: We have previously described a panel of 238 urinary polypeptides specific for established severe coronary artery disease (CAD). Here we studied this polypeptide panel in patients with a wider range of CAD severity. METHODS: We recruited 60 patients who underwent elective coronary angiography for investigation of stable angina. Patients were selected for either having angiographic evidence of CAD or not (NCA) following coronary angiography (n = 30/30; age, 55 ± 6 vs. 56 ± 7 years, P = 0.539) to cover the extremes of the CAD spectrum. A further 66 patients with severe CAD (age, 64 ± 9 years) prior to surgical coronary revascularization were added for correlation studies. The Gensini score was calculated from coronary angiograms as a measure of CAD severity. Urinary proteomic analyses were performed using capillary electrophoresis coupled online to micro time-of-flight mass spectrometry. The urinary polypeptide pattern was classified using a predefined algorithm and resulting in the CAD238 score, which expresses the pattern quantitatively. RESULTS: In the whole cohort of patients with CAD (Gensini score 60 [40; 98]) we found a close correlation between Gensini scores and CAD238 (ρ = 0.465, P < 0.001). After adjustment for age (ß = 0.144; P = 0.135) the CAD238 score remained a significant predictor of the Gensini score (ß =0.418; P < 0.001). In those with less severe CAD (Gensini score 40 [25; 61]), however, we could not detect a difference in CAD238 compared to patients with NCA (-0.487 ± 0.341 vs. -0.612 ± 0.269, P = 0.119). CONCLUSIONS: In conclusion the urinary polypeptide CAD238 score is associated with CAD burden and has potential as a new cardiovascular biomarker.


Subject(s)
Angina, Stable/diagnosis , Coronary Artery Disease/diagnosis , Peptides/urine , Proteomics/methods , Angina, Stable/urine , Biomarkers/urine , Coronary Angiography , Coronary Artery Disease/urine , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Retrospective Studies , Severity of Illness Index , Urinalysis
19.
iScience ; 27(7): 110330, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39055933

ABSTRACT

Prostate cancer screening using prostate-specific antigen (PSA) has been shown to reduce mortality but with substantial overdiagnosis, leading to unnecessary biopsies. The identification of a highly specific biomarker using liquid biopsies, represents an unmet need in the diagnostic pathway for prostate cancer. In this study, we employed a method that enriches for methylated cell-free DNA fragments coupled with a machine learning algorithm which enabled the detection of metastatic and localized cancers with AUCs of 0.96 and 0.74, respectively. The model also detected 51.8% (14/27) of localized and 88.7% (79/89) of patients with metastatic cancer in an external dataset. Furthermore, we show that the differentially methylated regions reflect epigenetic and transcriptomic changes at the tissue level. Notably, these regions are significantly enriched for biologically relevant pathways associated with the regulation of cellular proliferation and TGF-beta signaling. This demonstrates the potential of circulating tumor DNA methylation for prostate cancer detection and prognostication.

20.
Eur Urol ; 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39271419

ABSTRACT

BACKGROUND AND OBJECTIVE: The Yorkshire Kidney Screening Trial (YKST) assessed the feasibility of adding abdominal noncontrast computed tomography (NCCT) to lung cancer screening to screen for kidney cancer and other abdominal pathology. METHODS: A prospective diagnostic study offered abdominal NCCT to 55-80-yr-old ever-smokers attending a UK randomised lung cancer screening trial (May 2021 to October 2022). The exclusion criteria were dementia, frailty, previous kidney/lung cancer, and computed tomography (CT) of the abdomen and thorax within previous 6 and 12 mo, respectively. Six-month follow-up was undertaken. KEY FINDINGS AND LIMITATIONS: A total of 4438 people attended lung screening, of whom 4309 (97%) were eligible for and 4019 (93%) accepted abdominal NCCT. Only 3.9% respondents regretted participating. The additional time to conduct the YKST processes was 13.3 min. Of the participants, 2586 (64%) had a normal abdominal NCCT, whilst 787 (20%) required an abdominal NCCT imaging review but no further action and 611 (15%) required further evaluation (investigations and/or clinic). Of the participants, 211 (5.3%) had a new serious finding, including 25 (0.62%) with a renal mass/complex cyst, of whom ten (0.25%) had histologically proven kidney cancer; ten (0.25%) with other cancers; and 60 (1.5%) with abdominal aortic aneurysms (AAAs). Twenty-five (0.62%) participants had treatment with curative intent. Of the participants, 1017 (25%) had nonserious findings, most commonly benign renal cysts (727 [18%]), whereas only 259 (6.4%) had nonserious findings requiring further tests. The number needed to screen to detect one serious abdominal finding was 18; it was 93 to detect one suspicious renal lesion and 402 to detect one histologically confirmed renal cancer. Limitations of the cohort were fixed age range and being prior lung cancer screening attendees. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this first prospective risk-stratified screening study of abdominal NCCT offered alongside CT thorax, uptake and participant satisfaction were high. The prevalence of serious findings, cancers, and AAAs, is in the range of established screening programmes such as bowel cancer. Longer-term outcomes and cost effectiveness should now be evaluated.

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