Systematic Review of the Incidence of and Risk Factors for Urothelial Cancers and Renal Cell Carcinoma Among Patients with Haematuria

Prasad, Bhavan; Escrig, J.L. Domínguez; Vale, Luís; Kuusk, Teele; Čapoun, Otakar; Soukup, Viktor; Bruins, H.M.; Yuan, Yuhong; Violette, Philippe D.; Mostafid, Hugh; Omar, Muhammad Imran

doi:10.1016/j.eururo.2022.03.027

Cited by 32 publications

(22 citation statements)

References 53 publications

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“…Challenges arise around the 2WW pathway for suspected KC [27], as it has a broad symptom signature [28,29]. The most compelling symptom is visible haematuria, but even this only generates a pooled incidence of KC of 2% (95% CI 1-2%) [30]. Hence, it is unsurprising that only 28.0% (15 472 patients) of the patients with KC were diagnosed through the 2WW pathway and more were diagnosed through non-urgent GP routes (n = 16 814 [30.4%]).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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

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Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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“…Interestingly, it has been reported that the bladder cancer detection rate using cystoscopy improves if the urologist has been informed about a positive test result upfront [ 19 ]. A urine test stratifying for cystoscopy examination would be particularly useful among patients with gross hematuria, a patient group where the incidence rate of bladder cancer is as low as 17% [ 4 ], meaning that an unnecessary high number of cystoscopies are being performed.…”

Section: Discussionmentioning

confidence: 99%

“…However, hematuria may also be caused by a variety of other genitourinary conditions, and its specificity to detect bladder cancer is rather low [ 3 ]. Indeed, the incidence rate for bladder cancer among patients with gross hematuria has been estimated to 17% [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

BladMetrix: a novel urine DNA methylation test with high accuracy for detection of bladder cancer in hematuria patients

et al. 2022

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Background Cystoscopy is the gold standard for bladder cancer detection, but is costly, invasive and has imperfect diagnostic accuracy. We aimed to identify novel and accurate DNA methylation biomarkers for non-invasive detection of bladder cancer in urine, with the potential to reduce the number of cystoscopies among hematuria patients. Results Biomarker candidates ( n = 32) were identified from methylome sequencing of urological cancer cell lines ( n = 16) and subjected to targeted methylation analysis in tissue samples ( n = 60). The most promising biomarkers ( n = 8) were combined into a panel named BladMetrix. The performance of BladMetrix in urine was assessed in a discovery series ( n = 112), consisting of bladder cancer patients, patients with other urological cancers and healthy individuals, resulting in 95.7% sensitivity and 94.7% specificity. BladMetrix was furthermore evaluated in an independent prospective and blinded series of urine from patients with gross hematuria ( n = 273), achieving 92.1% sensitivity, 93.3% specificity and a negative predictive value of 98.1%, with the potential to reduce the number of cystoscopies by 56.4%. Conclusions We here present BladMetrix, a novel DNA methylation urine test for non-invasive detection of bladder cancer, with high accuracy across tumor grades and stages, and the ability to spare a significant number of cystoscopies among patients with gross hematuria. Supplementary Information The online version contains supplementary material available at 10.1186/s13148-022-01335-2.

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“…Considering the primary diagnostic setting, the a priori chance for urothelial cancer in microscopic hematuria is 3 versus 17-31% in patients presenting with gross hematuria [2,4,5]. Given the difference in the a priori change for urothelial cancer, the performance of a test in the microscopic and gross hematuria population should be analyzed and reported separately.…”

Section: Discussionmentioning

confidence: 99%

“…The primary symptom of bladder cancer is hematuria, and therefore, current clinical guidelines recommend to perform a cystoscopy in all patients presenting with microscopic or gross hematuria [2,3]. However, the apriori bladder cancer risk in patients with microscopic hematuria is only 3 versus 17-31% in patients with gross hematuria [3][4][5]. As a result, the vast majority of patients who undergo a cystoscopy for evaluation of microscopic hematuria, have no abnormal findings at cystoscopy [6].…”

Section: Introductionmentioning

confidence: 99%

RNA-based urinary assays for non-muscle invasive bladder cancer

Pijpers

Jong

Zuiverloon

et al. 2022

Current Opinion in Urology

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Purpose of reviewTo provide an overview of the recent literature on RNA-based molecular urine assays for the diagnosis and surveillance of non-muscle invasive bladder cancer (NMIBC).Recent findingsArticles were eligible for inclusion if performance metrics sensitivity, specificity, and negative-predictive value (NPV) were reported or could be calculated. Only prospective studies published between 2020–2022 were included. Five out of fourteen studies addressed the primary diagnostic setting; the proportion of gross hematuria patients in all study populations was >50%. Only one study reported performance metrics within a microscopic hematuria subgroup. This study evaluated Xpert Bladder and reported a sensitivity: 73%, specificity: 84%, NPV: 99%, and PPV: 12%. Ten studies assessed test performance during surveillance for NMIBC. For the detection of high-grade (HG) and high-risk (HR) NMIBC, sensitivity, specificity, NPV, and PPV varied between 78–100%, 64–89%, 97.0–99.7%, and 9.2–39%.SummaryMultiple RNA-based urine assays have been investigated for the detection of urothelial cancer in the primary or surveillance setting. However, studies included within this review have important limitations, hampering the interpretation of study results. As such, performance metrics should be interpreted with caution and further research is required to evaluate the clinical impact of RNA-based urine assays in daily practice.

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Systematic Review of the Incidence of and Risk Factors for Urothelial Cancers and Renal Cell Carcinoma Among Patients with Haematuria

Cited by 32 publications

References 53 publications

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

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

BladMetrix: a novel urine DNA methylation test with high accuracy for detection of bladder cancer in hematuria patients

RNA-based urinary assays for non-muscle invasive bladder cancer

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