Radiation toxicity grading after chemoradiotherapy of canine urinary tract carcinomas: Comparing VRTOG to VRTOG_v2.0.

Radiation toxicities may be underestimated after treatment of transitional cell carcinoma in dogs' lower urinary tract. Assessing acute and late toxicities and differentiating them from progressive disease (PD) impacts further therapeutic approach. We retrospectively assessed dogs treated with definitive-intent chemoradiotherapy (12 × 3.8 Gy, various first-line chemotherapeutics). Local tumour control, radiation toxicities and survival were evaluated. We classified radiation toxicities according to the previously published radiation toxicity scheme "VRTOG" as well as the updated version, "VRTOG_v2.0". Fourteen dogs with transitional cell carcinoma of bladder ± urethra (n = 8), +prostate (n = 3) or solely urethra (n = 3), were included. Median follow-up was 298 days (range 185-1798 days), median overall survival 305 days (95%CI = 209;402) and 28.6% deaths were tumour-progression-related. Acute radiation toxicity was mild and self-limiting with both classification systems: In VRTOG, 5 dogs showed grade 1, and 1 dog grade 2 toxicity. In VRTOG_v2.0, 2 dogs showed grade 1, 3 dogs grade 2, and 3 dogs grade 3 toxicity. Late toxicity was noted in 14.2% of dogs (2/14) with the VRTOG, both with grade 3 toxicity. With VRTOG_v2.0, a larger proportion of 42.9% of dogs (6/14) showed late toxicities: Four dogs grade 3 (persistent incontinence), 2 dogs grade 5 (urethral obstructions without PD resulting in euthanasia). At time of death, 5 dogs underwent further workup and only 3 were confirmed to have PD. With the updated VRTOG_v2.0 classification system, more dogs with probable late toxicity are registered, but it is ultimately difficult to distinguish these from disease progression as restaging remains to be the most robust determinant.

The incidence of major bleeding in adult patients with urogenital and gynecological cancer being treated with direct oral anticoagulants (DOACs): a systematic review.

BACKGROUND: Direct oral anticoagulants (DOACs) are the mainstay of treatment for venous thromboembolism (VTE) and non-valvular atrial fibrillation (AF), with or without an underlying cancer. Patients with cancer have a 2-3-fold increase in risk for bleeding complications compared to non-cancer patients taking anticoagulant therapy, however the incidence of bleeding for urogenital and gynecological cancers on DOACs are uncertain. AIMS: To assess the bleeding risk associated with the use of DOACs in patients with urogenital and/or gynecological cancers. METHOD: We conducted a systematic review of randomized controlled trials (RCTs) and prospective cohort studies to address the safety of DOACs for VTE and AF when used in patients with urogenital and/or gynecological malignancy. The primary outcomes assessed were major and clinically relevant non-major (CRNMB) bleeding, with minor bleeding considered as a secondary outcome. MEDLINE, EMBASE and COCHRANE Central Registry of Controlled Trials were searched up to and including Oct 28, 2022. The study protocol was registered in PROSPERO (CRD42022370981). Studies were independently assessed for inclusion and data extracted in duplicate. RESULT: Seven studies met our inclusion criteria (Fig. 1): 2 RCTs and 5 prospective cohort studies. A total of 676 patients treated with DOACs were included, 628 (92.8%) had VTE and 48 (7.1%) had AF. In patients with VTE treated with DOACs, the pooled major bleeding rate was 2.1%, 95% confidence intervals (CI) 0.9-3.3% (Fig. 2). Pooled estimates could not be determined for AF patients given small event and patient numbers. CONCLUSION: Major bleeding rates in urogenital and/or gynecological cancer patients treated with DOACs are similar to that of the general cancer population.

Spermatocytic tumors in 2 patients aged 50 and 77 years: 2 case reports and brief review of the literature.

Testicular cancer is predominantly diagnosed in young men aged 15-35 years. However, there are some rare tumors such as spermatocytic tumors that are seen more often in the older male population. Spermatocytic tumors have previously been known as spermatocytic seminomas in the scientific literature. We report the cases of 2 patients aged 50 and 77 years both diagnosed with spermatocytic tumors. In this paper we will discuss the ultrasound and histopathology features of these tumors and review the literature of spermatocytic tumor cases.

Outcomes of penile sarcomatoid squamous cell carcinoma from a single tertiary referral centre: a matched cohort study.

OBJECTIVE: To report the oncological survival outcomes of men with penile sarcomatoid squamous cell carcinoma (sSCC). PATIENTS AND METHODS: A retrospective analysis of men with penile sSCC diagnosed between January 2010 and January 2020 in a single centre was conducted. Disease-specific (DSS), recurrence-free (RFS) and metastasis-free (MFS) survival were evaluated. Outcomes were compared with a non-sarcomatoid penile SCC cohort matched to age, type of surgery and tumour stage. Kaplan-Meier plots were used to estimate survival outcomes. RESULTS: In all, 1286 men were diagnosed with penile SCC during the study period and of these 38 (3%) men had sSCC. The median (interquartile range) age and follow-up was 70 (57-81) years and 16 (7-44) months, respectively. Operations performed included: circumcision, one (2.6%); wide local excision, four (10.5%); glansectomy, 11 (29%); partial penectomy, 10 (26%); subtotal/total penectomy, 12 (32%). The Kaplan-Meier estimated 12-, 24- and 36-month DSS was 62% (vs non-sarcomatoid, 67%), 43% (vs non-sarcomatoid, 67%) and 36% (vs non-sarcomatoid, 67%), respectively (P = 0.03). The Kaplan-Meier estimated 12- and 24-month RFS was 47% (vs non-sarcomatoid, 60%) and 28% (vs non-sarcomatoid, 55%), respectively (P = 0.01). The MFS was 52% (vs non-sarcomatoid, 62%) at 12 months and 37% (vs non-sarcomatoid, 57%) at 24 months (P = 0.04). CONCLUSIONS: Sarcomatoid differentiation was associated with a lower DSS, RFS and MFS. Due to the rarity of its incidence and aggressiveness, expert histological review and multidisciplinary management is required in a specialist penile cancer centre.

Symptoms and signs of urogenital cancer in primary care.

BACKGROUND: Urogenital cancers are common, accounting for approximately 20% of cancer incidence globally. Cancers belonging to the same organ system often present with similar symptoms, making initial management challenging. In this study, 511 cases of cancer were recorded after the date of consultation among 61,802 randomly selected patients presenting in primary care in six European countries: a subgroup analysis of urogenital cancers was carried out in order to study variation in symptom presentation. METHODS: Initial data capture was by completion of standardised forms containing closed questions about symptoms recorded during the consultation. The general practitioner (GP) provided follow-up data after diagnosis, based on medical record data made after the consultation. GPs also provided free text comments about the diagnostic procedure for individual patients. RESULTS: The most common symptoms were mainly associated with one or two specific types of cancer: 'Macroscopic haematuria' with bladder or renal cancer (combined sensitivity 28.3%), 'Increased urinary frequency' with bladder (sensitivity 13.3%) or prostatic (sensitivity 32.1%) cancer, or to uterine body (sensitivity 14.3%) cancer, 'Unexpected genital bleeding' with uterine cancer (cervix, sensitivity 20.0%, uterine body, sensitivity 71.4%). 'Distended abdomen, bloating' had sensitivity 62.5% (based on eight cases of ovarian cancer). In ovarian cancer, increased abdominal circumference and a palpable tumour also were important diagnostic elements. Specificity for 'Macroscopic haematuria' was 99.8% (99.7-99.8). PPV > 3% was noted for 'Macroscopic haematuria' and bladder or renal cancer combined, for bladder cancer in male patients. In males aged 55-74, PPV = 7.1% for 'Macroscopic haematuria' and bladder cancer. Abdominal pain was an infrequent symptom in urogenital cancers. CONCLUSIONS: Most types of urogenital cancer present with rather specific symptoms. If the GP considers ovarian cancer, increased abdominal circumference should be actively determined. Several cases were clarified through the GP's clinical examination, or laboratory investigations.

Steroid Hormones as Modulators of Emotional Regulation in Male Urogenital Cancers.

BACKGROUND: Tumors develop within an organism operating in a specific social and physical environment. Cortisol and dehydroepiandrosterone (DHEA), two of the most abundant steroid hormones in humans, are involved in both emotional regulation and the tumor progression. Several studies reported preclinical findings that DHEA can have preventive and therapeutic efficacy in treating major age-associated diseases, including cancer, although the mechanisms of action are not yet defined. The main aim of current study was to investigate the relationship between psychological and physiological emotional regulation and cancer development. METHOD: This study assessed the quality of life of urogenital cancer male patients using several validated tools, including the Functional Assessment of Cancer Therapy-General and the Profile of Mood States. Saliva samples were collected to monitor peripheral activity of both cortisol and DHEA. It was hypothesized that patients with a better quality of life would have higher levels of the DHEA/cortisol ratios. RESULTS: We found that the quality of life was positively related to DHEA, but not cortisol levels. Negative mood increases were related to lower levels of DHEA. Logistic regression of the predictors of metastases indicated three main independent factors involved: DHEA, age, and cortisol. In other words, the higher the DHEA levels in comparison to cortisol levels, controlling for age, the lower the probability of metastases. CONCLUSION: Our results appear to support the hypothesis that emotional dysregulation mediated by DHEA/cortisol activity is a key factor in the probability of metastasis in urogenital cancers.

The role of miRNA-128 in the development and progression of gastrointestinal and urogenital cancer.

Increasing data have shown the significance of various miRNAs in malignancy. In this regard, parallel to its biological role in normal tissues, miRNA-128 (miR-128) has been found to play an essential immunomodulatory function in the process of cancer initiation and development. The occurrence of the aberrant expression of miR-128 in tumors and the unique properties of miRNAs raise the prospect of their use as biomarkers and the next generation of molecular anticancer therapies. The function of miR-128 in malignancies such as breast, prostate, colorectal, gastric, pancreatic, esophageal, cervical, ovarian and bladder cancers and hepatocellular carcinoma is discussed in this review. Finally, the effect of exosomal miR-128 on cancer resistance to therapeutics and cancer immunotherapy in certain malignancies is highlighted.

Association Between Bleeding and New Cancer Detection and the Prognosis in Patients With Myocardial Infarction.

Background Antithrombotic agents to treat patients with acute myocardial infarction can cause bleeding, which may reveal undiagnosed cancer. However, the relationship between bleeding and new cancer diagnosis and the prognostic impact is still unclear. Methods and Results We analyzed the new cancer diagnosis, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and all-cause death of 10 364 patients with acute myocardial infarction without a history of previous cancer in a multicenter acute myocardial infarction registry. During a median of 4.9 years, 1109 patients (10.7%) experienced Bleeding Academic Research Consortium 2, 3, or 5 bleeding, and 338 patients (3.3%) were newly diagnosed with cancer. Bleeding Academic Research Consortium 2, 3, or 5 bleeding was associated with an increased risk of new cancer diagnosis (subdistribution hazard ratio [sHR] 3.29 [95% CI, 2.50-4.32]). In particular, there were robust associations between gastrointestinal bleeding and new gastrointestinal cancer diagnosis (sHR, 19.96 [95% CI, 11.30-29.94]) and between genitourinary bleeding and new genitourinary cancer diagnosis (sHR, 28.95 [95% CI, 14.69-57.07]). The risk of all-cause death was not lower in patients diagnosed with new gastrointestinal cancer after gastrointestinal bleeding (hazard ratio [HR], 4.05 [95% CI, 2.04-8.02]) and diagnosed with new genitourinary cancer after genitourinary bleeding (HR, 2.79 [95% CI, 0.81-9.56]) than in patients newly diagnosed with cancer without previous bleeding. Conclusions Clinically significant bleeding, especially gastrointestinal and genitourinary bleeding, in patients with AMI was associated with an increased risk of new cancer diagnoses. However, the bleeding preceding new cancer detection was not associated with better survival. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02385682 and NCT02806102.

[Multimodal treatment concepts of local radiation therapy with immunotherapy : Rationale for combination therapy and possible clinical treatment strategies]. / Multimodale Therapiekonzepte lokaler Verfahren mit der Immuntherapie : Rationale für kombinatorische Ansätze und mögliche klinische Therapiestrategien.

Immunotherapy has been established in the treatment of cancer in general and specifically in uro-oncology. The rationale to combine these therapies with radiotherapy is based on the biological effects of irradiation, which exceed the "physical" properties of irradiation to kill tumor cells. Depending on radiation dose and fractionation as well as tumor model or tumor entity used, irradiation can lead to immune stimulation or immune inhibition. As immune response is not limited to the local tumor microenvironment but occurs on a systemic level, a successful anticancer immune response after irradiation of one metastasis can lead to systemic tumor control (abscopal effect). Clinical trials test combination regimens in locally advanced tumors in the curative setting to improve survival rates and in the metastatic setting to prolong survival in palliative treatment. In addition, radiotherapy is used for local treatment of oligometastases and oligoprogression under palliative systemic therapy.

Is periodontal disease a risk indicator for urogenital cancer? A systematic review and meta-analysis of cohort studies.

Objectives: The objective of the present work was to conduct a systematic review and meta-analysis to assess the association between periodontal disease (PD) and urogenital cancer (UC) risk. Materials and methods: An electronic search in PubMed, EMBASE, the Cochrane Library, and Web of Science was conducted using MeSH terms to identify cohort studies published before May 17, 2022. Cohort studies examining the association between PD and UC risk were included. We used a random-effects model to summarize the effect sizes with 95% confidence intervals (CIs) of the included studies with PD as the indicator and UC as the outcome. Results: Eleven cohort studies met the inclusion criteria. Our results suggest that PD patients increases the risk of UC by 1.24-fold (hazard ratio (HR), 1.24; 95% CI, 1.17-1.31; I2, 22.4%). The strength of the sensitivity analysis and cumulative meta-analysis confirmed the reliability of the results. Conclusion: We found that PD is a potential risk factor for UC. Our results indicate that along with the decrease in the incidence of PD,PD treatment may help prevent UC. We hope that our study will raise awareness of periodontal health, thereby reducing the incidence of UC. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021244405.

Diagnosis of urogenital cancer combining deep learning algorithms and surface-enhanced Raman spectroscopy based on small extracellular vesicles.

PURPOSE: To identify and compare the capacities of serum and serum-derived small extracellular vesicles (EV) in diagnosis of common urogenital cancer combining Surface-enhanced Raman spectroscopy (SERS) and Convolutional Neural Networks (CNN). MATERIALS AND METHODS: We collected serum samples from 32 patients with prostate cancer (PCa), 33 patients with renal cell cancer (RCC) and 30 patients with bladder cancer (BCa) as well as 35 healthy control (HC), which were thereafter used to enrich extracellular vesicles by ultracentrifuge. Label-free SERS was utilized to collect Raman spectra from serum and matched EV samples. We constructed CNN models to process SERS data for classification of malignant patients and healthy controls (HCs). RESULTS: We collected 650 and 1206 spectra from serum and serum-derived EV, respectively. CNN models of EV spectra revealed high testing accuracies of 79.3%, 78.7% and 74.2% in diagnosis of PCa, RCC and BCa, respectively. In comparison, serum SERS-based CNN model had testing accuracies of 73.0%, 71.1%, 69.2% in PCa, RCC and BCa, respectively. Moreover, CNN models based on EV SERS data show significantly higher diagnostic capacities than matched serum CNN models with the area under curve (AUC) of 0.80, 0.88 and 0.74 in diagnosis of PCa, RCC and BCa, respectively. CONCLUSION: Deep learning-based SERS analysis of EV has great potentials in diagnosis of urologic cancer outperforming serum SERS analysis, providing a novel tool in cancer screening.

Label-free optical redox ratio from urinary extracellular vesicles as a screening biomarker for bladder cancer.

Extracellular vesicles (EVs) have been studied for their potential applications in cancer screening, diagnosis, and treatment monitoring. Most studies have focused on the bulk content of EVs; however, it is also informative to investigate their metabolic status, and changes under different physiological and environmental conditions. In this study, noninvasive, multimodal, label-free nonlinear optical microscopy was used to evaluate the optical redox ratio of large EVs (microvesicles) isolated from the urine of 11 dogs in three cohorts (4 healthy, 4 transitional cell carcinoma (TCC) of the bladder, and 3 prostate cancer). The optical redox ratio is a common metric comparing the autofluorescence intensities of metabolic cofactors FAD and NAD(P)H to characterize the metabolic profile of cells and tissues, and has recently been applied to EVs. The optical redox ratio revealed that dogs with TCC of the bladder had a more than 2-fold increase in NAD(P)H-rich urinary EVs (uEVs) when compared to healthy dogs, whereas dogs with prostate cancer had no significant difference. The optical redox ratio values of uEVs kept at -20°C for 48 hours were significantly different from those of freshly isolated uEVs, indicating that this parameter is more reliable when assessing freshly isolated uEVs. These results suggest that the label-free optical redox ratio of uEVs, indicating relative rates of glycolysis and oxidative phosphorylation of parent cells and tissues, may act as a potential screening biomarker for bladder cancer.

miR-221/222 as biomarkers and targets for therapeutic intervention on cancer and other diseases: A systematic review.

Among deregulated microRNAs (miRs) in human malignancies, miR-221 has been widely investigated for its oncogenic role and as a promising biomarker. Moreover, recent evidence suggests miR-221 as a fine-tuner of chronic liver injury and inflammation-related events. Available information also supports the potential of miR-221 silencing as promising therapeutic intervention. In this systematic review, we selected papers from the principal databases (PubMed, MedLine, Medscape, ASCO, ESMO) between January 2012 and December 2020, using the keywords "miR-221" and the specific keywords related to the most important hematologic and solid malignancies, and some non-malignant diseases, to define and characterize deregulated miR-221 as a valuable therapeutic target in the modern vision of molecular medicine. We found a major role of miR-221 in this view.

Subsequent primary urogenital cancers among childhood and adolescent cancer survivors in the United States.

PURPOSE: To conduct an updated and comprehensive study on the risks of subsequent primary urogenital cancers for childhood and adolescent cancer survivors. METHODS: This longitudinal study was conducted using 9 cancer registries from the Surveillance, Epidemiology and End Results (SEER) Program with follow-up from 1975 to 2017. There were 43,991 patients diagnosed with first primary cancer from 1975 to 2016 before the age of 20 years who subsequently survived for at least 1 year. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) for urogenital cancers were calculated. RESULTS: Compared with the general population, the risk of urinary system cancer was significantly higher in both female (SIR = 5.18, 95% CI: 3.65-7.14) and male (SIR = 2.80, 95% CI: 1.94-3.92) survivors of any first cancer, with shorter median interval length between first cancer and subsequent urinary system cancer for male survivors (19.9 years) than female survivors (29.3 years). Females also had significantly higher SIR than males for subsequent urinary system cancer (SIRfemale:male=1.86, 95% CI: 1.13-3.03) and kidney cancer (SIRfemale:male = 1.97, 95% CI: 1.11-3.53). Compared with the general population, females with any first cancer had significantly higher risks for cancers of the corpus uteri (SIR = 2.32, 95% CI: 1.49-3.45) and vulva (SIR = 4.27, 95% CI: 1.38-9.95). CONCLUSIONS: Childhood and adolescent cancer survivors may have greater female susceptibility for developing subsequent urinary system and kidney cancers, and these survivors may have higher risks for specific types of reproductive system cancers. Our findings may lead to better awareness and surveillance for urogenital cancer by these cancer survivors and their physicians.

In Silico Inference of Synthetic Cytotoxic Interactions from Paclitaxel Responses.

To exploit negatively interacting pairs of cancer somatic mutations in chemotherapy responses or synthetic cytotoxicity (SC), we systematically determined mutational pairs that had significantly lower paclitaxel half maximal inhibitory concentration (IC50) values. We evaluated 407 cell lines with somatic mutation profiles and estimated their copy number and drug-inhibitory concentrations in Genomics of Drug Sensitivity in Cancer (GDSC) database. The SC effect of 142 mutated gene pairs on response to paclitaxel was successfully cross-validated using human cancer datasets for urogenital cancers available in The Cancer Genome Atlas (TCGA) database. We further analyzed the cumulative effect of increasing SC pair numbers on the TP53 tumor suppressor gene. Patients with TCGA bladder and urogenital cancer exhibited improved cancer survival rates as the number of disrupted SC partners (i.e., SYNE2, SON, and/or PRY) of TP53 increased. The prognostic effect of SC burden on response to paclitaxel treatment could be differentiated from response to other cytotoxic drugs. Thus, the concept of pairwise SC may aid the identification of novel therapeutic and prognostic targets.

[Prospective: How will renal, prostatic and urothelial tumours be treated in 10 years?] / Prospective : comment traitera-t-on les tumeurs rénales et prostatiques et urothéliales dans 10 ans ?

Forward thinking does not seek to predict the future, to unveil it as if it were already in existence, rather, its aim is to help us to construct it. Although today's epidemiological and therapeutic situations for urogenital tumours can evolve over the next 10 years, diagnostic and therapeutic methods, as well as the treatment and implementation of innovations, are already rapidly changing. Rather than reducing our prospective thinking to the therapeutic treatment of cancer only, we will aim at proposing a global sanitary vision that includes diagnosis, therapies, prevention, routine utilisation of technomedicine, genomics and even nanomedicine. This journey into the near future of tomorrow's cancerology holds the promise of being better adapted to the evolution of the medical thinking process. Imagining the way we will be treating renal, prostatic and urothelial tumours in 10 years' time is as much an introspection into our present day treatment system as a projection into its hoped for future evolution.

Follow-up of elderly patients with urogenital cancers: Evaluation of geriatric care needs and related actions.

OBJECTIVES: To investigate a comprehensive geriatric assessment (CGA) with subsequent investigation of healthcare patterns in older patients with urological cancers undergoing initial surgery or radiotherapy, to verify the usefulness of the incorporation of geriatric principles in future care plans. MATERIAL AND METHODS: This is a prospective cohort study. From November 2011 to March 2015, CGA was offered to all patients aged 70+ years treated with radiotherapy or surgery at seven tertiary centers. Patients were classified as fit, vulnerable, or frail according to Balducci's definition. CGA and follow-up data were collected by two trained evaluators at 6 and 12months. The information collected was not available to the caring physicians during follow-up. RESULTS: CGA was performed in 453 patients with prostate cancer (295), bladder cancer (126), or kidney cancer (32). 40% of patients with prostate cancer were fit, 47% vulnerable, and 13% frail. The corresponding values for renal cancer were 25%, 40%, and 34%, and for bladder cancer, 21%, 42%, and 37%. During follow-up, 60% of patients with cardiac diseases, 42% of those with diabetes/other metabolic disorders, 35% of those with hypertension, and 35% of those with respiratory diseases were followed by a specialist (for these severe/extremely severe comorbidities). Of 16 patients with ADL impairment and 63 with IADL impairment, only 4 (25%) and 6 (10%), respectively, were referred to a rehabilitation service. Only one case was referred to a geriatrician. CONCLUSIONS: Appropriate clinical care patterns are advisable to improve quality of survivorship in older patients with urological cancers.

Potential of sulfasalazine as a therapeutic sensitizer for CD44 splice variant 9-positive urogenital cancer.

Cancer stem-like cells (CSCs) with high expression of CD44 splice variant (CD44v) have an enhanced capacity for intracellular reduced glutathione synthesis and defense against reactive oxygen species, resulting in resistance to various therapeutic stresses. Sulfasalazine (SSZ), a drug used in the treatment of rheumatoid arthritis (RA), inhibits glutamate-cystine transport, and suppressed CD44v-dependent tumor growth and increased sensitivity to cytotoxic drugs in an in vivo study. Here, we present two cases of CD44v9-positive urogenital cancer with concomitant treatment with SSZ for RA. Patient 1 was a 62-year-old man who had received SSZ for RA beginning 2 months before the diagnosis of urinary bladder cancer. Although he had multiple metastases to the bladder, abdominal, left cervical and left axillary lymph nodes, and brain, complete response with multidisciplinary therapy was maintained for more than 2 years. Patient 2 was a 74-year-old man with castration-resistant prostate cancer who was diagnosed with RA during chemotherapy and a gradual increase in prostate-specific antigen (PSA) level. When SSZ was added, his PSA value (ng/mL) decreased from 12.93 to 5.58 in only 2 weeks and then quickly rebounded, whereas levels of neuron-specific enolase, a neuroendocrine differentiator and CSC marker, remained almost unchanged. We therefore speculate that SSZ treatment may represent a new adjuvant treatment option for patients with CD44v9-positive urogenital cancer.

Urinary carbonic anhydrase IX splicing messenger RNA variants in urogenital cancers.

BACKGROUND: To identify molecular biomarkers for tumor diagnosis and monitoring of disease progression, several noninvasive tests on liquid biopsy have been proposed for different cancers including those of urogenital origin. Among biomarkers, carbonic anhydrase IX (CAIX) has gained attention as it regulates extracellular pH and induces cytoplasmic alkalization contributing to malignant progression and poor treatment outcome. Works on tissues suggested the potential use of CAIX as a tumor biomarker for urogenital malignancies, but only few studies have been performed on its detection in urine. SCOPE: The aim of the present study is the measurement of CAIX messenger RNA (mRNA) in urine sediments of patients affected by kidney, prostate, and bladder cancers to evaluate the clinical sensitivity and specificity of the test. PROCEDURES: The quantification of the total CAIX mRNA concentration and of its full-length isoform (CAIX FL) have been performed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) on RNA extracted from urine sediments of patients affected by urogenital cancers. RESULTS: Urinary total CAIX mRNA expression resulted to be lower in patients with kidney and prostate cancer in comparison with the control group, but no statistically significant difference could be evidenced for bladder cancer. The evaluation of the relative percentage of FL isoform mRNA (FL%) showed a significant increase of FL% in urine from patients with cancer (median = 70.8%) in comparison with the healthy subjects (median = 2.6%) and this finding was confirmed for each cancer type separately. The comparison among receiver operating characteristic curves for total CAIX mRNA, CAIX FL mRNA, and FL% indicated that FL% shows the best diagnostic performance with 90% sensitivity and 72% specificity. Comparison of the results obtained in urine with those found in the corresponding tissues indicated 80% concordance. CONCLUSIONS: The CAIX mRNA expression in urine sediments can be considered a surrogate marker of CAIX expression in tumor tissues of urogenital origin. In particular, the analysis of FL% possesses the best characteristics to be a suitable noninvasive biomarker for urogenital cancer diagnosis.

Statistical-based approach in potential diagnostic application of urinary nucleosides in urogenital tract cancer.

AIM: We aimed at evaluation the potential diagnostic role of urinary nucleosides in urogenital tract cancer. MATERIALS & METHODS: Concentrations of 12 nucleosides determined by LC-MS/MS were subjected to correlation, association and interaction analyses. RESULTS: We identified six pairs of nucleosides differently correlated in the group of patients and controls (p < 0.05). N-2-methylguanosine (odds ratio: 4.82; 95% CI: 1.78-12.93; p = 0.002) and N,N-dimethylguanosine (odds ratio: 5.45; 95% CI: 1.78-16.44; p = 0.003), were significantly associated with the disease risk (p-corrected = 0.004). Interaction between N-2-methylguanosine and adenosine (p-interaction = 0.019) suggested their multiplicative effect on the outcome. CONCLUSION: Urinary nucleosides, namely N,N-dimethylguanosine and N-2-methylguanosine may have the potential to serve as prognostic biomarkers. Gender-specific differences in urogenital tract cancer are likely to occur.