Urinary Tract Cancer Research Articles

Urological Cancers in Douala (Cameroon): Epidemiological and Histological Profile

<i>Background: </i>According to Globocan 2020, the global burden of cancer has increased to 19.3 million cases and 10 million cancer deaths. The International Agency for Research on Cancer estimates that, in the world, one in five people develop cancer during their lifetime. Urinary tract cancers are common in urology. They are most often of a bad prognosis. While the epidemiology of urological cancers is well known in the Northern Countries, data on these conditions are little available or insufficient. The purpose of this study was to determine the frequency of urological cancers, describe their clinical presentation and classification. <i>Methodology: </i>We conducted a transversal study in the urology, oncology and pathology anatomy departments of the Douala General Hospital (DGH) and the Douala Laquintinie Hospital (DLH). Medical records and pathology reports of biopsies carried out on patients with urological cancer and hospitalized over a period of 10 years from January 1, 2010 to December 31, 2019 were included. <i>Results</i>: A total of 93 cases were selected. The sex ratio of 8:1. The average age was 64.7±11.51 years for men and 45.8±23 years for women (p=0.030). Smoking was the main comorbidity (30.1%). Low back pain, hematuria and urine retention were the main modes of revelation. Prostate cancer was found in 75.3%. Prostate adenocarcinoma was the most found histological type (94.1%) Kidney, bladder and penis cancer were found in 16.1%; 7.5% and 1% of cases. More than half of patients with prostate cancer (68.6%) had metastasis at the time of diagnosis. <i>Conclusion</i>: urological cancers affect men more. The symptomatology is dominated by the signs of the upper and lower urinary tract. Prostate adenocarcinoma is the most found histological type.

Kidney-Sparing Management of UTUC in Solitary Kidney Patients: A Retrospective Analysis and Narrative Review.

Background/Objectives: The aim of this study is the presentation of an endoscopic therapeutic approach for three patients with a solitary kidney who were diagnosed with urothelial cancer of the upper tract. Methods: This retrospective analysis included patients with solitary kidneys who suffered from high-grade UTUC (urothelial cancer of the upper urinary tract) and underwent conservative treatment. Results: The first patient was a 67-year-old male who had a prior history of a nephroureterectomy due to UTUC six years ago. The patient was diagnosed with high-grade UTUC in the contralateral kidney. The tumor has been managed with endoscopic ablation. The second patient was a 74-year-old male with a non-functional kidney and high-grade UTUC diagnosed in the contralateral side. The patient underwent endoscopic ablation for the tumor. The third case was a 68-year-old female patient who had a history of a nephroureterectomy due to UTUC. Afterward, she was diagnosed with high-grade UTUC in the contralateral kidney. The patient was treated with percutaneous tumor resection and the placement of a nephrostomy tube. The first patient was included in an immunotherapy program based on an oncologist consultation after laser ablation treatment for Ta high-grade UTUC, followed by the endoscopic management of two recurrences. Afterward, no recurrence was detected. The remaining two patients followed up without the detection of a new recurrence. Conclusions: The kidney-sparing approach (tumor laser ablation or resection) for high-risk UTUC treatment in selected patients with solitary kidneys seems to provide adequate early outcomes in relation to preserving renal function and effective disease management. It is important to personalize the way of treatment in every case after a thorough examination of the patient's data.

An Artificial Intelligence-assisted Diagnostic System Improves Upper Urine Tract Cytology Diagnosis.

To evaluate efficacy of the AIxURO system, a deep learning-based artificial intelligence (AI) tool, in enhancing the accuracy and reliability of urine cytology for diagnosing upper urinary tract cancers. One hundred and eighty-five cytology samples of upper urine tract were collected and categorized according to The Paris System for Reporting Urinary Cytology (TPS), yielding 168 negative for High-Grade Urothelial Carcinoma (NHGUC), 14 atypical urothelial cells (AUC), 2 suspicious for high-grade urothelial carcinoma (SHGUC), and 1 high-grade urothelial carcinoma (HGUC). The AIxURO system, trained on annotated cytology images, was employed to analyze these samples. Independent assessments by a cytotechnologist and a cytopathologist were conducted to validate the initial AIxURO assessment. AIxURO identified discrepancies in 37 of the 185 cases, resulting in a 20% discrepancy rate. The cytotechnologist achieved an accuracy of 85% for NHGUC and 21.4% for AUC, whereas the cytopathologist attained accuracies of 95% for NHGUC and 85.7% for AUC. The cytotechnologist exhibited overcall rates of roughly 15% and undercall rates of greater than 50%, while the cytopathologist showed profoundly lower miscall rates from both undercall and overcall. AIxURO significantly enhanced diagnostic accuracy and consistency, particularly in complex cases involving atypical cells. AIxURO can improve the accuracy and reliability of cytology diagnosis for upper urine tract urothelial carcinomas by providing precise detection on atypical urothelial cells and reducing subjectivity in assessments. The integration of AIxURO into clinical practice can significantly ameliorate diagnostic outcomes, highlighting the synergistic potential of AI technology and human expertise in cytology.

Relation between Urine Cytological Findings and Renal Function in Patients with Kidney Stones in Taif, Saudi Arabia

Background and Objectives: Urine serves as a vital diagnostic fluid, and urine cytology analysis plays a crucial role in identifying urinary system illnesses such as bladder cancer and kidney stones. The Paris System for Reporting Urinary Cytology establishes a uniform method for diagnosing urinary tract cancer. This study aimed to provide valuable insights that can inform diagnostic strategies related to kidney stones and ultimately improve patient outcomes via the early detection of the cellular changes associated with kidney stones and their relation to kidney function tests. Materials and Methods: A comparative study was conducted and comprised two groups: group 1, consisting of 50 patients diagnosed with kidney stones, and group 2, comprising 50 patients diagnosed with other kidney diseases. Renal function tests and urinalysis (via the PAP staining of urine cellular deposits to detect nuclear changes) were performed, and the results were analyzed. Results: There was a statistically significant increase in urinary red blood cells, white blood cells, and nuclear reactive atypical changes in urinary sediments of kidney stone patients compared to the patients without stones, while there was a decrease in the estimated glomerular filtration rate (eGFR). eGFR showed a 96.7% specificity in detecting cases with nuclear reactive atypia. Conclusions: eGFR emerges as a reliable diagnostic marker for the comprehensive assessment of kidney stones, particularly when associated with nuclear atypia. The significant correlation between the indicators of chronic kidney disease, such as decreased eGFR, and the presence of kidney stones emphasizes the urgent need for efficient diagnostic practices.

226 - A low Incidence of urinary tract cancers among patients with overactive bladder

226 - A low Incidence of urinary tract cancers among patients with overactive bladder

Artificial intelligence algorithm for neoplastic cell percentage estimation and its application to copy number variation in urinary tract cancer.

Bladder cancer is characterized by frequent mutations, which provide potential therapeutic targets for most patients. The effectiveness of emerging personalized therapies depends on an accurate molecular diagnosis, for which the accurate estimation of the neoplastic cell percentage (NCP) is a crucial initial step. However, the established method for determining the NCP, manual counting by a pathologist, is time-consuming and not easily executable. To address this, artificial intelligence (AI) models were developed to estimate the NCP using nine convolutional neural networks and the scanned images of 39 cases of urinary tract cancer. The performance of the AI models was compared to that of six pathologists for 119 cases in the validation cohort. The ground truth value was obtained through multiplexed immunofluorescence. The AI model was then applied to 41 cases in the application cohort that underwent next-generation sequencing testing, and its impact on the copy number variation (CNV) was analyzed. Each AI model demonstrated high reliability, with intraclass correlation coefficients (ICCs) ranging from 0.82 to 0.88. These values were comparable or better to those of pathologists, whose ICCs ranged from 0.78 to 0.91 in urothelial carcinoma cases, both with and without divergent differentiation/ subtypes. After applying AI-driven NCP, 190 CNV (24.2%) were reclassified with 66 (8.4%) and 78 (9.9%) moved to amplification and loss, respectively, from neutral/minor CNV. The neutral/minor CNV proportion decreased by 6%. These results suggest that AI models could assist human pathologists in repetitive and cumbersome NCP calculations.

Mortality from prostate cancer in the years 2007–2021 in North Rhine-Westphalia, Germany

BackgroundThe crude mortality rate and the lifetime mortality risk from prostate cancer in Germany are above international average. However age-standardised mortality and years of life lost per capita from prostate cancer are declining. This study analyses the mortality-related measures for the federal state of North Rhine-Westphalia (NRW) in Germany.MethodsBased on the cause of death statistics and data from the NRW State Cancer Registry on 45,300 deaths in the years 2007–2021, mortality rates, the lifetime mortality risk from prostate cancer, median age at death and years of life lost are presented. Additionally, the 15 most frequent causes of death of 95,013 patients diagnosed with prostate cancer are reported.ResultsWith a stable lifetime mortality risk from prostate cancer, age-standardised mortality and years of life lost per capita are decreasing while crude mortality and median age at death are increasing in NRW. Less than half of the patients die from their prostate cancer. Cancers of the urinary bladder and other urinary organs also occur more frequently as a cause of death than it would be expected based on the age-specific risk in the total population.ConclusionsMore people in North Rhine-Westphalia are dying of prostate cancer over time due to demographic ageing alone. At the same time, the age-specific mortality risk has not increased and when patients die of prostate cancer, it is at an increasingly older age. However, there is a statistical association with deaths from cancers of the lower urinary tract in patients diagnosed with prostate cancer, which demands further evaluation.

Central pathology review and its prognostic value in upper tract urothelial carcinoma patients: a nationwide multi-institutional study

The prognostic value of central pathology review in upper urinary tract cancer (UTUC) remains inadequately addressed in existing literature. In this study, we conducted an extensive central pathology review and presented its influence on multi-center UTUC studies. We conducted a retrospective review of patients who underwent radical nephroureterectomy or segmental resection for UTUC to determine eligibility for central pathology review. In the Taiwan UTUC Collaboration cohort, 377 cases met the criteria for pathology review. We assessed agreement between pathologists using both the total percentage of agreement and simple kappa statistics. The prognostic implications of original and review pathology for various parameters were examined using the Cox regression model. This study included 209 female and 168 male participants. Pathology review revealed substantial interobserver variability in pT staging, with a particularly high rate of pT2 cases being upgraded to pT3 upon central review (17/70 pT2 stage made by local pathologists were finally confirmed as pT3 disease by the review pathologist). The local pathologist cohort identified fewer significant histological predictors in survival models compared to the review pathology cohort. Advanced pT stage, perineural invasion (PNI), and positive surgical margin were independent predictors of poorer overall survival and cancer-specific survival. PNI, lymphatic vascular invasion, and positive surgical margin were independent predictors of disease recurrence. Substantial interobserver variability in histological assessment underscores the importance of centralized pathology review for both multi-center studies and accurate post-operative management of UTUC patients. Advanced stage, perineural invasion, and margin status were significant histological predictors of oncological outcomes.

Occupational benzene exposure and risk of kidney and bladder cancers: a systematic review and meta-analysis.

Benzene is recognized as leukemogenic. However, the association between it and solid cancers has been the subject of less investigation. We aim to conduct a systematic review and meta-analysis to evaluate the association between occupational exposure to benzene and the risk of urinary tract cancer, including kidney and bladder. We included 41 cohort and case-control studies listed in the most recent International Agency for Research on Cancer (IARC) Monograph on benzene exposure and the result of a literature review to identify more recent studies. Forest plots of relative risk (RR) were constructed for kidney, bladder, and urinary tract cancer overall. A random-effects model was used to address heterogeneity between studies. Stratified analyses were conducted to explore effect modification. Our findings revealed an association between exposure to occupational benzene and kidney and unspecified urinary tract cancers (RR = 1.20, 95% confidence interval = 1.03-1.39), and an association of borderline statistical significance with bladder cancer (RR = 1.07, 95% confidence interval = 0.97-1.18). Publication bias was excluded for both kidney (P = 0.809) and bladder cancer (P = 0.748). Stratification analysis according to the selected study characteristics showed no difference except regarding the industry for kidney cancer (P < 0.000), with a stronger association in the chemical industry. An analysis by exposure level did not reveal any trend for kidney cancer, whereas there was a trend (P = 0.01) for bladder cancer. Our study found an association between occupational benzene exposure and kidney cancer and a dose-effect association between benzene exposure and bladder cancer.

Genomic ascertainment of CHEK2-related cancer predisposition.

There is clear evidence that deleterious germline variants in CHEK2 increases risk for breast and prostate cancers; there is limited or conflicting evidence for other cancers. Genomic ascertainment was used to quantify cancer risk in CHEK2 germline pathogenic variant heterozygotes. Germline CHEK2 variants were extracted from two exome-sequenced biobanks linked to the electronic health record: UK Biobank (n= 469,765) and Geisinger MyCode (n=170,503). Variants were classified as per American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) criteria. Heterozygotes harbored a CHEK2 pathogenic/likely pathogenic (P/LP) variant; controls harbored benign/likely benign CHEK2 variation or wildtype CHEK2. Tumor phenotype and demographic data were retrieved; to adjust for relatedness, association analysis was performed with SAIGE-GENE+ with Bonferroni correction. In CHEK2 heterozygotes in both MyCode and UK Biobank, there was a significant excess risk of all cancers tested, including breast cancer (C50; OR=1.54 and 1.84, respectively), male genital organ cancer (C60-C63; OR=1.61 and 1.77 respectively), urinary tract cancer (C64-C68; OR=1.56 and 1.75, respectively) and lymphoid, hematopoietic, and related tissue cancer (C81-C96; OR=1.42 and 2.11, respectively). Compared to controls, age-dependent cancer penetrance in CHEK2 heterozygotes was significantly younger in both cohorts; no significant difference was observed between the penetrance of truncating and missense variants for cancer in either cohort. Overall survival was significantly decreased in CHEK2 heterozygotes in UK Biobank but there was no statistical difference in MyCode. Using genomic ascertainment in two population-scale cohorts, this investigation quantified the prevalence, penetrance, cancer phenotype and survival in CHEK2 heterozygotes. Tailored treatment options and surveillance strategies to manage those risks are warranted.

Urothelial cancer: state of art in Ukraine and improvement pathways.

This study aims to assess the effectiveness of urothelial cancer treatment in Ukraine, utilizing population-based data from the National Cancer Registry. The primary goal is to evaluate trends and approaches to therapy, with a focus on overall survival rates in patients with urothelial tumors. A retrospective cross-sectional analysis was conducted based on the National Cancer Registry, involving 12698 patients (2008-2020) with urothelial tumors of the upper urinary tract (UTUC) and bladder cancer (BC) who underwent surgical treatment. Demographic indicators, surgical interventions, complications, and survival rates were analyzed. The average age for all patients was 70 years. The number of patients undergoing radical treatment was 1820 (15%) among BC and 573 (59%) among UTUC. The 30-day readmission rate was low for both, with a slightly higher preference for UTUC (2.3 vs. 4.6%). Whereas grade III or higher Cl-Dindo complications were seen in only 0.2% of cases. Notable findings include low frequency of neoadjuvant (7%) and adjuvant chemotherapy (28%) among patients with invasive urothelial carcinomas. Median eGFR for invasive UTUC before and after surgery was 63.2 and 51.4ml/min, respectively (P=0.00054). The directly opposite trend was seen in BC-61.2 and 68.7ml/min, respectively (P=0.0026).For BC, the overall survival rates by stages were: I-73%, II-49%, III-18%, and IV-11% (χ2=1807.207; P=0.000001). As for UTUC, the 5-year overall survival rates corresponded to the literature data, but there was a pronounced negative trend towards a decrease in this indicator after a 10-year period for all stages (χ2=146.298; P=0.000003). The study emphasizes the importance of effective systemic treatments, adherence to treatment guidelines, and the need for multidisciplinary consultations among Ukrainian patients with urothelial cancer.

Diagnostic Performance and Interobserver Agreement of Diuretic 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Diagnosis of Upper Urinary Tract Cancer.

Previous reports attempted to evaluate bladder cancer using 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) by washing out the excreted FDG with a diuretic. The purpose of this study was to evaluate the value of diuretic FDG PET/plain CT (drtPET/CT) and diuretic FDG PET/contrast-enhanced CT (drtPET/ceCT) in the assessment of upper urinary tract cancers. A total of 66 patients underwent drtPET/CTfor suspected upper urinary tract cancer (UUTC). The study targeted 29 patients who were strongly suspected of having UUTC and underwent magnetic resonance imaging (MRI) of the upper urinary tract. A total of 29 (24 male, five female) patients, with a mean ± SDage of 73 ± 3 (range, 43-84) years, had a suspected neoplasm in the upper urinary tract. They underwent FDG PET/plain and contrast-enhanced CT before and after a diuretic and MRIincluding diffusion-weighted imaging (DWI). A urologist and a physician board-certified in nuclear medicine and radiology independently interpreted the standard PET/CT (stdPET/CT), drtPET/CT, drtPET/ceCT, ceCT, and MRI with DWI images. Interobserver agreement and the diagnostic performance of each modality were evaluated. The kappa values of stdPET/CT, drtPET/CT, drtPET/ceCT, ceCT, and MRI were 0.381, 0.567, 0.7031, 0.448, and 0.185, respectively, with drtPET/ceCT showing the highest kappa value and the only one with good interobserver agreement (>60%). The area under the curve of drtPET/ceCT was 0.92, which was significantly higher than those of stdPET/CT (P=0.027) and MRI (P=0.047). In the present study, drtPET/ceCT had the best diagnostic performance and the highest interobserver agreement for detecting upper urinary tract urothelial cancers.

Efficacy of avelumab maintenance therapy for advanced urothelial carcinoma with histologic subtype and divergent differentiation: a multicenter retrospective study conducted by the Uro-Oncology Group in Kyushu.

The subtype of urothelial carcinoma (SUC) has been known to possess morphological diversity for histologic subtype or divergent differentiation. However, the efficacy of avelumab against SUC remains unclear. Therefore, the effect of the treatment as well as the survival results of avelumab monotherapy were evaluated as a first-line therapeutic maintenance in patients with advanced SUC. A retrospective analysis was conducted on consecutive patients from the Uro-Oncology Group in Kyushu study population with advanced lower and upper urinary tract cancer who underwent avelumab maintenance therapy without progression after first-line platinum-based chemotherapy. Patients with pure urothelial carcinoma (PUC) and SUC were comparatively analyzed based on objective response rate (ORR), disease control rate, progression-free survival (PFS), and overall survival (OS). Out of 49 recorded patients, 38 and 11 had PUC and SUC, respectively. The most common subtype element was glandular differentiation (n=5), followed by squamous differentiation (n=3), micropapillary (n=1), and plasmacytoid subtypes (n=1). The SUC and PUC groups had comparable ORR (0% vs. 2.6%, P>0.99) and disease control rates (54.5% vs. 44.7%, P=0.73). These patient groups also showed no significant difference in PFS (median 3.9 vs. 3.1 months, P=0.33) or OS (median 16.7 vs. 22.1 months, P=0.47). The response of SUC and PUC to avelumab was comparable in patients with advanced lower and upper urinary tract cancer, indicating that avelumab maintenance therapy is also effective for SUC.

Clinical Outcomes of Enfortumab Vedotin in Advanced Urothelial Carcinoma With Prior Avelumab Versus Pembrolizumab Therapy.

This study retrospectively evaluated whether enfortumab vedotin (EV) monotherapy is effective as a late-line treatment according to prior treatment type in patients with advanced urothelial carcinoma (UC). We assessed consecutive patients from the Uro-Oncology Group in the Kyushu study population with lower and upper urinary tract cancer treated with EV monotherapy after platinum-based chemotherapy and immune checkpoint inhibitor therapy failure between December 2021 and March 2024. In particular, patients receiving avelumab maintenance or pembrolizumab therapy before EV for advanced UC were analyzed and compared according to the response rate, progression-free survival (PFS), and overall survival (OS). Of the 80 enrolled patients, 31 and 49 received avelumab and pembrolizumab before EV therapy, respectively. The avelumab and pembrolizumab groups had comparable objective response rates (48.4% vs. 44.9%, p=0.820) and disease control rates (77.4% vs. 67.3%, p=0.448). These two groups showed no significant difference in PFS from the initiation of EV (median: 6.4 months vs. 4.2 months, p=0.184); meanwhile, the avelumab group had better OS from the initiation of EV than the pembrolizumab group (median: 16.0 months vs. 10.2 months, p=0.019). Moreover, the median OS after first-line chemotherapy initiation was longer in the avelumab group than in the pembrolizumab group (40.3 months vs. 24.7 months, p=0.054). On multivariate analysis, avelumab maintenance therapy before EV reduced the mortality risk by 47% (95% confidence interval=0.27-1.03; p=0.059). EV monotherapy after avelumab maintenance therapy provides favorable survival outcomes in patients with advanced UC.

Urine microbiota in non-muscle-invasive bladder cancer and approaches to its detection

Introduction. There is evidence of a connection between infectious and inflammatory lesions of the lower urinary tract and bladder cancer (BCa). However, there is virtually no data on the urine microbiota of middle-aged and elderly men with suspected BCa. This knowledge is extremely important from the point of view of studying the role of the infectious-inflammatory hypothesis in the genesis of BCa.Objective. To conduct a comparative assessment of the microbiota of bladder urine obtained during natural urination and bladder catheterization through standard and extended cultural studies in men with a presumptive diagnosis of non-muscle-invasive bladder cancer (NMIBC).Materials &amp; methods. The prospective comparative study with consecutive patient recruitment included 23 men older than 45 years with suspected NMIBC based on clinical, laboratory and sonographic data, as well as with no history of infectious and inflammatory diseases of the kidneys and urinary tract, including sexually transmitted infections and recurrent infections of other organs and systems. A midstream urine samples and catheter-drained urine immediately before urethrocystoscopy were subjected to bacteriological analysis. Urine culture study was carried out using a standard set of nutrient media under aerobic cultivation conditions and an expanded set of nutrient media under aerobic and anaerobic cultivation conditions.Results. An anaerobic spectrum of microorganisms was predominantly detected in the urine of patients with suspected NMIBC. Moreover, Peptococcus spp. was more often found among anaerobic taxa. (70%), Eubacterium spp., Propionibacterium spp. (45% each, respectively), among representatives of the aerobes — Corynebacterium spp. (60%), S. lentus (up to 45%), S. haemolyticus (35%) and E. faecalis (30%). Data from a comparative analysis of the detection frequencies of microorganisms depending on the method of collecting material and the set of media for cultivation showed that more isolates are isolated in the midstream urine samples than in the study of catheter urine (2.9- and 1.9-fold with the standard and extended sets of media, respectively). In addition, when performing an extended bacteriological study compared to the standard method, the detection of microorganisms is 3.5-fold higher when examining an average portion of urine and 5.1-fold higher when examining catheter urine. The average number of microorganisms per one patient is also higher when using the extended method (midstream portion — 4.7 ± 1.9; catheterised urine — 2.3 ± 1.0) in comparison with the standard one (midstream portion — 1.3 ± 0.9; catheterised urine — 0.3 ± 0.5).Conclusion. Middle-aged and older men with NMIBC are characterized by asymptomatic bacteriuria in the form of a wide range of aerobic and anaerobic microorganisms. The urine pattern obtained with a urethral catheter contains a significantly narrower range of bacteria compared to the sample obtained through natural urination. It is advisable to carry out an extended cultural urine examination to study the characteristics of the microbiota / microbiome of the urine of the bladder immediately before the urethrocystoscopy procedure by collecting urine with a urethral catheter.

Urological cancer statistics on incidence from 1975 to 2019 and mortality from 1958 to 2022 in Japan.

In Japan, comprehensive cancer statistics are collected through cancer registries. However, data on urological cancers are rarely summarized or published in research papers. This retrospective study was performed using publicly available statistical data on urological cancers (prostate cancer [PCa], bladder cancer [BCa], and cancers of kidney and urinary tract [except urinary bladder]) in Japan, including a summary of the Ministry's mortality statistics, cancer incidence statistics from the Regional Cancer Registries through 2015, and the National Cancer Registry statistics from 2016. We examined the incidence and mortality rates of urological cancers stratified by age groups. The number of new cases of PCa, BCa, and cancers of kidney and urinary tract (except urinary bladder) in 2019 was 94,748, 23,383, and 30,458, respectively, and the number of deaths in 2022 was 13,439, 9,598, and 9,795, respectively. The incidence and mortality rates of urological cancers have consistently increased. Since 2000, there has been a noteworthy increase in the mortality rate of urological cancers among individuals aged > 85years. The incidence and mortality rates of BCa and cancers of kidney and urinary tract (except urinary bladder) were significantly higher in males than in females. Urological cancers in very elderly patients (> 85years) will become increasingly important in the future.

Organ-Specific Tumor Response to Enfortumab Vedotin for Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study

IntroductionTo evaluate the organ-specific therapeutic effect of enfortumab vedotin (EV) after chemotherapy and immunotherapy failed for advanced urothelial carcinoma. Materials methodsAt 6 institutions between December 2021 and July 2023, we retrospectively analyzed patients with metastatic upper and lower urinary tract cancer who received EV monotherapy after platinum-based chemotherapy and immune checkpoint blockade therapy. Objective response rate (ORR) and organ-specific response rate (OSRR) were evaluated according to the Response Evaluation Criteria in Solid Tumors, version 1.1. ResultsThis study analyzed 58 patients with 210 tumor lesions, of which 24% were females and 48% had upper urinary tract cancer. The ORR and disease control rate were 53.5% and 74.1%. Moreover, we found 15 target lesions in the primary site, 7 in local recurrence, 93 in the lymph nodes, 46 in the lung, 29 in the liver, and 20 in the bone, with OSRRs of 40%, 71.4%, 61.1%, 70.6%, 90.9%, and 18.2%, respectively. Over time from baseline, the reduction rate (median) in tumor burden was 50% or more in the lymph node, lung, and liver metastases. ConclusionThe organ-specific tumor response to EV in patients with metastatic urothelial carcinoma was almost favorable. The antitumor activity of EV monotherapy may be less in bone metastasis than in other organ sites. Conversely, EV showed remarkably high efficacy against liver metastasis.

Causal Relationship Between Kidney Function and Cancer Risk: A Mendelian Randomization Study

Rationale & ObjectivePatients treated with kidney replacement therapy experience a 1.5 to 2-fold increased risk of cancer and cancer mortality compared to the general population. Whether this excess risk extends to people with earlier stages of chronic kidney disease is unclear. This study explored the potentially causal relationship between reduced kidney function and cancer. Study DesignTwo-sample Mendelian randomization (MR). Setting & ParticipantsGenome Wide Association Study (GWAS) summary statistics for estimated glomerular filtration rate (eGFR) (n=567,460) and urinary albuminuria (UACR) (n=127,865) from the CKDGen consortium and cancer outcomes from the UK Biobank (n=407,329). ExposureseGFR and UACR. OutcomesOverall cancer incidence, cancer-related mortality, and site-specific colorectal, lung, and urinary tract cancer incidence. Analytical ApproachUnivariable and multivariable MR were conducted for all outcomes using inverse-variance weighted methods. ResultsThe mean eGFR and median UACR were 91.4 mL/min/1.73m2 and 9.32 mg/g in the CKDGen and 90.4 mL/min/1.73m2 and 9.29 mg/g in the UK Biobank. There were 98,093 cases of cancer, 6,664 colorectal, 3584 lung, and 3,271 urinary tract. There were 15,850 cases of cancer-related death, The genetic instruments for eGFR and UACR comprised 34 and 38 variants, respectively. Genetically predicted kidney function (eGFR and UACR) was not associated with overall cancer risk or cancer death. No associations of genetically predicted eGFR and UACR with overall cancer incidence were observed; odds ratio (95%CI; p-value) of 0.88 (0.40-1.97; p=0.76) and 0.90 (0.78-1.04; p=0.16), respectively. An adjusted generalized additive model for eGFR and cancer demonstrated evidence of non-linearity. There was no evidence of a causal association between eGFR and cancer in a stratified MR. LimitationsTo avoid overlapping samples a smaller GWAS for UACR was used, reducing the strength of the instrument and potentially introducing population stratification. ConclusionsThese findings did not demonstrate a causal association of kidney function with overall cancer incidence or cancer-related death.

Machine Learning and External Validation of the IDENTIFY Risk Calculator for Patients with Haematuria Referred to Secondary Care for Suspected Urinary Tract Cancer

BackgroundThe IDENTIFY study developed a model to predict urinary tract cancer using patient characteristics from a large multicentre, international cohort of patients referred with haematuria. In addition to calculating an individual’s cancer risk, it proposes thresholds to stratify them into very-low-risk (<1%), low-risk (1–<5%), intermediate-risk (5–<20%), and high-risk (≥20%) groups. ObjectiveTo externally validate the IDENTIFY haematuria risk calculator and compare traditional regression with machine learning algorithms. Design, setting, and participantsProspective data were collected on patients referred to secondary care with new haematuria. Data were collected for patient variables included in the IDENTIFY risk calculator, cancer outcome, and TNM staging. Machine learning methods were used to evaluate whether better models than those developed with traditional regression methods existed. Outcome measurements and statistical analysisThe area under the receiver operating characteristic curve (AUC) for the detection of urinary tract cancer, calibration coefficient, calibration in the large (CITL), and Brier score were determined. Results and limitationsThere were 3582 patients in the validation cohort. The development and validation cohorts were well matched. The AUC of the IDENTIFY risk calculator on the validation cohort was 0.78. This improved to 0.80 on a subanalysis of urothelial cancer prevalent countries alone, with a calibration slope of 1.04, CITL of 0.24, and Brier score of 0.14. The best machine learning model was Random Forest, which achieved an AUC of 0.76 on the validation cohort. There were no cancers stratified to the very-low-risk group in the validation cohort. Most cancers were stratified to the intermediate- and high-risk groups, with more aggressive cancers in higher-risk groups. ConclusionsThe IDENTIFY risk calculator performed well at predicting cancer in patients referred with haematuria on external validation. This tool can be used by urologists to better counsel patients on their cancer risks, to prioritise diagnostic resources on appropriate patients, and to avoid unnecessary invasive procedures in those with a very low risk of cancer. Patient summaryWe previously developed a calculator that predicts patients’ risk of cancer when they have blood in their urine, based on their personal characteristics. We have validated this risk calculator, by testing it on a separate group of patients to ensure that it works as expected. Most patients found to have cancer tended to be in the higher-risk groups and had more aggressive types of cancer with a higher risk. This tool can be used by clinicians to fast-track high-risk patients based on the calculator and investigate them more thoroughly.

Treatment Patterns and Outcomes by Age in Metastatic Urinary Tract Cancer: A Retrospective Tertiary Cancer Center Analysis.

Metastatic urinary tract cancer (mUTC) is challenging to treat in older adults due to comorbidities. We compared the clinical courses of younger and older (≥70 years) adults with mUTC receiving first-line (1L) systemic therapy in a tertiary cancer center. Baseline clinical characteristics, treatments received, tolerability, and survival outcomes were analyzed. Among 212 patients (103 older vs. 109 younger), the older patients had lower hemoglobin at baseline (84% vs. 71%, p = 0.03), the majority were cisplatin-ineligible (74% vs. 45%, p < 0.001), received more immunotherapy-based treatments in the 1L (52% vs. 36%, p = 0.01), received fewer subsequent lines of treatment (median 0 vs. 1, p = 0.003), and had lower clinical trial participation (30% vs. 18%, p = 0.05) compared to the younger patients. When treated with 1L chemotherapy, older patients required more dose adjustments (53.4% vs. 23%, p = 0.001) and received fewer cycles of chemotherapy (median 4 vs. 5, p= 0.01). Older patients had similar OS (11.2 months vs. 14 months, p = 0.06) and similar rates of treatment-related severe toxicity and healthcare visits, independent of the type of systemic treatment received, compared to younger patients. We conclude that select older adults with mUTC can be safely treated with immunotherapy and risk-adjusted regimens of chemotherapy with tangible survival benefits.