Effects of intravesical BCG maintenance therapy duration on recurrence rate in high-risk non-muscle invasive bladder cancer (NMIBC): Systematic review and network meta-analysis according to EAU COVID-19 recommendations.

PURPOSE: During the coronavirus disease 2019 (COVID-19) pandemic, the European Association of Urology (EAU) recommended that courses of intravesical bacillus Calmette-Guérin (BCG) therapy lasting more than 1 year could be safely terminated for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Thus, we conducted a systematic review and network meta-analysis according to EAU's COVID-19 recommendations. MATERIALS AND METHODS: A systematic review was performed following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We conducted a network meta-analysis of recurrence rate in patients with NMIBC receiving induction therapy (M0) and those receiving maintenance therapy lasting 1 year (M1) and more than 1 year (M2). RESULTS: Nineteen studies of 3,957 patients were included for the network meta-analysis. In a node-split forest plot using Bayesian Markov Chain Monte Carlo (MCMC) modeling, there were no differences between the M1 and M2 groups in recurrence rate [odds ratio (OR) 0.95 (0.73-1.2)]. However, recurrence rate in the M0 group was higher than that in the M1 [OR 1.9 (1.5-2.5)] and M2 [OR 2.0 (1.7-2.4)] groups. P-score tests using frequentist inference to rank the treatments in the network demonstrated that the therapy used in the M2 group (P-score 0.8701) was superior to that used in the M1 (P-score 0.6299) and M0 groups (P-score 0). In rank-probability tests using MCMC modeling, the M2 group showed the highest rank, followed by the M1 and M0 groups. CONCLUSION: In the network meta-analysis, there were no differences between those receiving BCG maintenance therapies in terms of recurrence rate. In the rank tests, therapy lasting more than 1-year appears to be most effective. During the COVID-19 pandemic, 1-year maintenance therapy can be used, but after the COVID-19 pandemic, therapy lasting more than 1-year could be beneficial.

The Impact of Covid-19 Pandemic on Genitourinary Cancers Stage and Grade.

INTRODUCTION: Our study aims to evaluate the impact of the COVID-19 pandemic on the number of uro-oncological surgeries (cystectomy, nephrectomy, prostatectomy, orchiectomy, and transurethral resection of bladder tumor (TURBT)) and pathological staging and grading. MATERIALS AND METHODS: The present study is a retrospective study on patients with genitourinary cancers treated from 2018 to 2021 in a referral tertiary center. The data were obtained from the hospital records with lengths of 22 and 23 months, labeled hereafter as non-COVID and COVID pandemic, respectively (2018/3/21-2020/1/20 and 2020/1/21-2021/12/21). The total number of registered patients, gender, age, stage, and grade were compared in the targeted periods. Moreover, all the pathologic slides were reviewed by an expert uropathologist before enrolling in the study. The continuous and discrete variables are reported as mean (standard deviation (SD)) and number (percent) and the χ2 test for the comparison of the discrete variables' distribution. RESULTS: In this study total number of 2077 patients were enrolled. The number of procedures performed decreased during the Covid pandemic. The tumors' distribution stage and grade and patients' baseline characteristics were not significantly different in non-COVID and COVID pandemic periods for Radical Nephrectomy, Radical Cystectomy, Radical Prostatectomy, and orchiectomy. For TURBT only, the tumor stage was significantly different (P-value<.001) from the higher stages in the COVID pandemic period. CONCLUSION: Among urinary tract cancers, staging of bladder cancer and TURBT are mainly impacted by the COVID-19 pandemic with higher stages compared to the non-COVID period. We evaluate the impact of the COVID-19 pandemic on the number of uro-oncological surgeries based on pathological staging and grading. Total number of 2077 patients were enrolled. Among urinary tract cancers, staging of bladder cancer and TURBT are mainly impacted by the COVID-19 pandemic with higher stages compared to the non-COVID period.

The delay in the diagnosis and treatment of newly diagnosed bladder cancer patients during COVID 19 pandemic.

Background: To evaluate the newly diagnosed bladder cancer(BC) patients during the pandemic period and compare them with the corresponding last4 years. Objectives: To document the time schedules of BC patient evaluation and define the possible delays and investigate the reasons. Methods: Newly diagnosed BC patients who underwent transurethral resection of bladder tumour in the last5 years were retrospectively included to study. The patients were divided into 5 groups. Group-1 was composed of patients diagnosed betweenMarch, 1,2016 -March-1,2017. The patients who were diagnosed in the further corresponding years formed group 2,3 and 4. The last group(Group-5) was composed of patients who were diagnosed during the pandemic period which was between March,1,2020 and March,1,2021. The clinicodemographic properties and diagnostic time schedules of the patients were compared between the groups. Results: There were56 patients in Group-1,60 patients in Group-2,61 patients in Group-3,68 patients in Group-4, and 58 patients inGroup-5. The mean hospital admission period was102.5±179.0days during the pandemic period which ranged between24.5± 32.0 and38.3±69.1days before thepandemic.(p=0.002)The diagnosis-anesthesia period was significantly higher during the pandemic pandemic period.(p=0.034). Conclusions: The pandemic period has caused some delays in the diagnosis and treatment of BC patients. Telemonitoring systems may be useful to prevent the possible diagnostic and treatment delays for newly diagnosed BC patients.

A global, regional, and national survey on burden and Quality of Care Index (QCI) of bladder cancer: The global burden of disease study 1990-2019.

INTRODUCTION: Bladder cancer (BCa) is the second most common genitourinary cancer and among the leading causes of cancer-related deaths. We aimed to assess BCa quality of care (QOC) utilizing a novel multi-variable quality of care index (QCI). MATERIALS AND METHODS: Data were retrieved from the Global Burden of Disease 1990-2019 database. QCI scores were calculated using four indices of prevalence-to-incidence ratio, Disability-Adjusted Life Years-to-prevalence ratio, mortality-to-incidence ratio, and Years of Life Lost-to-Years Lived with Disability ratio. We used principal component analysis to allocate 0-100 QCI scores based on region, age groups, year, and gender. RESULTS: Global burden of BCa is on the rise with 524,305 (95% UI 475,952-569,434) new BCa cases and 228,735 (95% UI 210743-243193) deaths in 2019, but age-standardized incidence and mortality rates did not increase. Global age-standardized QCI improved from 75.7% in 1990 to 80.9% in 2019. The European and African regions had the highest and lowest age-standardized QCI of 89.7% and 37.6%, respectively. Higher Socio-demographic index (SDI) quintiles had better QCI scores, ranging from 90.1% in high SDI to 30.2% in low SDI countries in 2019; however, 5-year QCI improvements from 2014 to 2019 were 0.0 for high and 4.7 for low SDI countries. CONCLUSION: The global QCI increased in the last 30 years, but the gender disparities remained relatively unchanged despite substantial improvements in several regions. Higher SDI quintiles had superior QOC and less gender- and age-based inequalities compared to lower SDI countries. We encourage countries to implement the learned lessons and improve their QOC shortcomings.

First-in-human Intravesical Delivery of Pembrolizumab Identifies Immune Activation in Bladder Cancer Unresponsive to Bacillus Calmette-Guérin.

BACKGROUND: Intravenous immune checkpoint inhibition is an effective anticancer strategy for bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) but may be associated with greater systemic toxicity compared with localized therapies. OBJECTIVE: We assessed the safety and antitumor activity of intravesical pembrolizumab combined with BCG. DESIGN, SETTING, AND PARTICIPANTS: A 3 + 3 phase 1 trial of pembrolizumab + BCG was conducted in patients with BCG-unresponsive NMIBC (NCT02808143). INTERVENTION: Pembrolizumab was given intravesically (1-5 mg/kg for 2 h) beginning 2 weeks prior to BCG induction until recurrence. Urine profiling during treatment and spatial transcriptomic profiling of pre- and post-treatment tumors were conducted to identify biomarkers that correlated with response. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Safety and tolerability of immune checkpoint inhibition were assessed, and Kaplan-Meier survival analysis was performed. RESULTS AND LIMITATIONS: Nine patients completed therapy. Median follow-up was 35 months for five patients still alive at the end of the trial. The trial was closed due to the COVID-19 pandemic. Grade 1-2 urinary symptoms were common. The maximum tolerated dose was not reached; however, one dose-limiting toxicity was reported (grade 2 diarrhea) in the only patient who reached 52 weeks without recurrence. One death occurred from myasthenia gravis that was deemed potentially related to treatment. The 6-mo and 1-yr recurrence-free rates were 67% (95% confidence interval [CI]: 42-100%) and 22% (95% CI: 6.5-75%), respectively. Pembrolizumab was detected in the urine and not in blood. CD4+ T cells were significantly increased in the urine after treatment, and a transcriptomic analysis identified decreased expression of T-cell exhaustion markers in late recurrences. CONCLUSIONS: We demonstrate that intravesical pembrolizumab is safe, feasible, and capable of eliciting strong immune responses in a clinical setting and should be investigated further. PATIENT SUMMARY: Direct application of pembrolizumab to the bladder is a promising alternative for non-muscle-invasive bladder cancer unresponsive to Bacillus Calmette-Guérin and should be investigated further.

Evaluation of Sleep Disturbances in Patients With Bladder Cancer Scheduled for Local or Loco-regional Radiochemotherapy.

BACKGROUND/AIM: Organ-sparing treatment is increasingly used for bladder cancer, particularly for patients with significant comorbidities or advanced age. The upcoming treatment can cause distress and sleep disturbances. This study investigated pre-radiotherapy sleep disturbances in these patients. PATIENTS AND METHODS: Twenty-two patients with bladder cancer scheduled for local or loco-regional radiotherapy were retrospectively evaluated. Sixteen characteristics were analyzed for sleep disturbances including age, sex, performance score, comorbidities, previous malignancy, distress score, emotional problems, physical problems, treatment situation, treatment intent, current primary tumor and nodal stage, distant metastasis, treatment volume, concurrent chemotherapy, and Coronavirus Disease 2019 pandemic. RESULTS: Eleven patients (50.0%) reported sleep disturbances that were significantly associated with distress scores ≥5 (p=0.035). Trends were found for age ≤75 years (p=0.183), ≥2 emotional problems (p=0.183), ≥5 physical problems (p=0.064), and distant metastasis (p=0.090). CONCLUSION: Half of the patients reported pre-radiotherapy sleep disturbances. Risk factors facilitate identification of patients requiring psychological support.

Different patients, different preferences: A multicenter assessment of patients' personality traits and anxiety in shared decision making.

OBJECTIVE: Patient-centered care and shared decision making (SDM) are generally recognized as the gold standard for medical consultations, especially for preference-sensitive decisions. However, little is known about psychological patient characteristics that influence patient-reported preferences. We set out to explore the role of personality and anxiety for a preference-sensitive decision in bladder cancer patients (choice of urinary diversion, UD) and to determine if anxiety predicts patients' participation preferences. METHODS: We recruited a sample of bladder cancer patients (N = 180, primarily male, retired) who awaited a medical consultation on radical cystectomy and their choice of UD. We asked patients to fill in a set of self-report questionnaires before this consultation, including measures of treatment preference, personality (BFI-10), anxiety (STAI), and participation preference (API and API-Uro), as well as sociodemographic characteristics. RESULTS: Most patients (79%) indicated a clear preference for one of the treatment options (44% continent UD, 34% incontinent UD). Patients who reported more conscientiousness were more likely to prefer more complex methods (continent UD). The majority (62%) preferred to delegate decision making to healthcare professionals. A substantial number of patients reported elevated anxiety (32%), and more anxiety was predictive of higher participation preference, specifically for uro-oncological decisions (ß = 0.207, p < 0.01). CONCLUSIONS: Our findings provide insight into the role of psychological patient characteristics for SDM. Aspects of personality such as conscientiousness influence treatment preferences. Anxiety contributes to patients' motivation to be involved in pertinent decisions. Thus, personality and negative affect should be considered to improve SDM.

A pan-cancer analysis of the oncogenic role of COVID-19 risk gene Leucine Zipper Transcription Factor-Like Protein 1 (LZTFL1) in human tumors (preprint)

Population-based studies showed that COVID-19 infection causes higher death rate in cancer patients. However, the molecular mechanism of COVID-19 with cancer is still largely unknown. Here we analyzed the Leucine Zipper Transcription Factor-Like Protein 1 (LZTFL1) which is the most significant gene associated with COVID-19. First, we explored the potential oncogenic roles of LZTFL1 through transcriptome data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. LZTFL1 is significantly low expressed in 11 of 34 kinds of cancers we analyzed. Consistent with the mRNA expression data, the protein expression of LZTFL1 in lung adenocarcinoma (LUAD), clear cell renal cell carcinoma (ccRCC), Uterine corpus endometrial carcinoma (UCEC), and ovarian cancer (OV) patients are significantly decreased compared to healthy tissues. The survival analysis from the Kidney renal clear cell carcinoma (KIRC), Rectum adenocarcinoma (READ), and Uveal Melanoma (UVM), the LZTFL1 high expression group have a significantly higher survival rate compared to the low expression group. Taken together, LZTFL1 acts as a cancer suppressor gene for several cancers. Moreover, LZTFL1 expression was associated with the cancer-associated fibroblast infiltration in several tumors including Bladder Urothelial Carcinoma (BLCA), Breast invasive carcinoma (BRCA), Esophageal carcinoma (ESCA), Head and Neck squamous cell carcinoma (HNSC), Lung squamous cell carcinoma (LUSC), and Pancreatic adenocarcinoma (PAAD). Gene ontology analysis showed that cilium organization, positive regulation of establishment of protein localization to telomere and SRP-dependent cotranslational protein targeting to the membrane were involved in the function mechanisms related to LZTFL1. Our studies offer a relatively comprehensive understanding of the oncogenic roles of LZTFL1 across different kinds of tumors.

Avelumab First-Line Maintenance Treatment in Advanced Bladder Cancer: Practical Implementation Steps for Infusion Nurses.

Immune checkpoint inhibitors, such as programmed cell death ligand 1 inhibitors pembrolizumab, nivolumab, atezolizumab, and avelumab, are used to treat patients with advanced urothelial carcinoma (UC). Based on data from the phase 3 JAVELIN Bladder 100 trial, avelumab first-line (1L) maintenance is now considered the standard-of-care treatment for patients with locally advanced or metastatic UC who responded or experienced disease stabilization after 1L platinum-containing chemotherapy, and it is the only category 1 preferred checkpoint inhibitor maintenance option in the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for patients with cisplatin-eligible and cisplatin-ineligible locally advanced or metastatic UC. This article reviews key considerations related to avelumab 1L maintenance therapy that infusion nurses should be familiar with, including dosing, administration, and immune-related adverse event recognition and management, to ensure safe and appropriate use of this important and impactful therapy.

Can We Predict a Higher Risk of Urothelial Bladder Cancer With a Simple Blood Test?

BACKGROUND/AIM: The COVID-19 pandemic highlighted the need to develop tools prioritizing high risk patients for urgent evaluation. Our objective was to determine whether Glasgow Prognostic Score (GPS), an inflammation-based score, can predict higher grade and stage urothelial bladder cancer in patients with gross hematuria who need urgent evaluation. PATIENTS AND METHODS: We analyzed a database of 129 consecutive patients presenting with gross hematuria. GPS was calculated using pretreatment C-reactive protein (CRP) and albumin levels. Patients with bacteriuria or other known malignancies were excluded. The relationship between GPS and final diagnosis was analyzed with multivariate logistic regression. RESULTS: A total of 101 patients were included in the study and 24 patients were identified without any pathology and 77 with a bladder tumor. Pathology demonstrated 21 with muscle invasive, 18 with high grade non-muscle invasive, and 38 with low grade superficial bladder cancer. Twenty-six of 39 (67%) patients with high grade tumors had a GPS of 1 or 2 compared to only 8 out of 62 (13%) patients with either low grade or negative findings (p<0.0001). Ten of 21 (48%) patients with muscle invasive disease had a GPS of 2 compared to 1 out of 18 (6%) with high grade non muscle invasive tumors (p=0.04). On multivariate analysis, GPS was a strong independent predictor of high grade and stage bladder cancer. CONCLUSION: GPS may serve as a highly accessible predictor of high grade, high stage, and large urothelial bladder tumors at the time of initial evaluation and can help identify patients who need urgent evaluation.

Effect of neoadjuvant chemotherapy on overall survival of patients with T2-4aN0M0 bladder cancer: A systematic review and meta-analysis according to EAU COVID-19 recommendation.

PURPOSE: In the context of the COVID-19 outbreak, the European Association of Urology (EAU) guidelines Rapid Reaction Group provided recommendations to manage muscle invasive bladder cancer (MIBC) based on priority levels: neoadjuvant chemotherapy (NAC) should be avoided for patients with T2-3N0M0 MIBC. This meta-analysis aims to evaluate the efficacy of NAC compared with radical cystectomy (RC) alone in improving the overall survival (OS) of patients with T2-4aN0M0 MIBC. MATERIALS AND METHODS: A systematic review was performed according to the PRISMA guidelines. The PubMed/Medline, EMBASE, and Cochrane Library databases were searched. The primary outcome was OS of patients with T2-4aN0M0 MIBC, and the secondary outcome was OS of patients with only T2N0M0 MIBC. RESULTS: Eight studies were included in this meta-analysis. Overall, the quality of all studies was relatively high, and little publication bias was demonstrated. The OS was significantly better in the NAC with RC group than in RC alone (HR, 0.79; 95% CI, 0.68-0.92; p = 0.002). A subgroup analysis was performed on only patients with T2N0M0 MIBC, and five studies were included. There was no difference in the OS between the NAC with RC and the RC alone groups (HR, 0.83; 95% CI, 0.69-1.01 p = 0.06). CONCLUSIONS: As recommended by the EAU guidelines Rapid Reaction Group, patients with T2N0M0 MIBC should strongly consider omitting NAC until the end of the COVID-19 pandemic. Whether to omit NAC in T3-4aN0M0 MIBC needs further discussion, and studies targeting only T2-3N0M0 MIBC are expected to proceed further.

Comparative Analysis of the Efficacy of Transurethral Bipolar Plasma Needle Electrode and Ring Electrode in the Treatment of Non-Muscle-Invasive Bladder Cancer.

Bladder cancer is the most prevalent tumor of the urinary tract, ranking seventh in males and seventeenth in women. The gold standard for the definitive diagnosis and initial treatment of non-muscle-invasive bladder cancer is transurethral resection (TUR) of the bladder tumor. The ability to accurately detect disease, typically in the presence of hematuria as well as to detect early recurrent tumors in patients with a history of NMIBC, is critical to the successful treatment of non-muscle-invasive bladder cancer (NMIBC). Unfortunately, the current biomarker landscape for NMIBC is still evolving. Cystoscopy remains the gold standard, but it can still miss 10% of tumors. As a result, physicians frequently employ additional diagnostic tools to aid in the diagnosis of bladder cancer. The efficacy of transurethral bipolar plasma needle electrodes and ring electrodes in the treatment of non-muscle-invasive bladder cancer was compared and analyzed in this study. During our study, 100 patients with non-muscle-invasive bladder cancer admitted to our hospital between June 2019 and June 2020 were randomly assigned to a control group and an observation group, with 50 cases in each group. The observation group was given a bipolar plasma needle electrode, while the control group was given a bipolar plasma ring. Patients continued to receive bladder irrigation chemotherapy as well as traditional Chinese medicine (TCM) treatment as part of our treatment plan, while the control group received only bladder irrigation chemotherapy. Clinical factors such as operational blood loss, catheter indention time, length of hospital stay, and others were compared between the two groups. When the risk grades in the two groups were compared, the observation group had fewer medium- and high-risk grades than the control group, but the control group had more low-risk grades, with statistical significance (P < 0.05).

Effect of active anticancer therapy on serologic response to SARS-CoV-2 BNT162b2 vaccine in patients with urothelial and renal cell carcinoma.

OBJECTIVES: To evaluate the serologic response to the BNT162b2 messenger ribonucleic acid vaccine in patients with urothelial carcinoma and renal cell carcinoma. METHODS: Between June 2021 and November 2021, we retrospectively evaluated blood samples from 60 healthy controls (control group), 57 patients with urothelial carcinoma, and 28 patients with renal cell carcinoma who had received two doses of the BNT162b2 vaccine at Hirosaki University Hospital. We determined the immunoglobulin G antibody titers against the severe acute respiratory syndrome coronavirus 2 spike receptor-binding domain. Seropositivity was defined as ≥15 U/mL. We investigate factors associated with antibody titers and seropositivity in the patients with urothelial carcinoma and renal cell carcinoma. RESULTS: Antibody titers in the control, urothelial carcinoma, and renal cell carcinoma groups were 813, 431, and 500 U/mL, respectively. Seropositivity was 100%, 90%, and 96% in the control, urothelial carcinoma, and renal cell carcinoma groups, respectively. Of the 85 patients, 37 of 57 (65%) and 21 of 28 (75%) were actively undergoing anticancer treatment for urothelial carcinoma and renal cell carcinoma, respectively. Anti-severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers and seropositivity was not significantly different between the patients with urothelial carcinoma and renal cell carcinoma. Anti-severe acute respiratory syndrome coronavirus 2 spike immunoglobulin G antibody titers were not significantly associated with active anticancer therapy or steroid treatment for immune-related adverse events. Univariable logistic regression analysis revealed that older age and metastatic disease were significantly and negatively associated with seropositivity. CONCLUSIONS: Patients with urothelial carcinoma or renal cell carcinoma exhibited an adequate antibody response to the BNT162b2 vaccine. Active anticancer therapy was not significantly associated with seropositivity following vaccination with severe acute respiratory syndrome coronavirus 2 BNT162b2 in patients with urothelial carcinoma and renal cell carcinoma.

Feasibility of a geriatric comanagement (GERICO) pilot program for patients 75 and older undergoing radical cystectomy.

BACKGROUND: Retrospective studies have shown the beneficial impact of geriatric comanagement (GERICO) on perioperative outcomes of older adults with cancer. We prospectively assessed the feasibility of perioperative GERICO for older adults with bladder cancer undergoing radical cystectomy. METHODS: We conducted a pilot study wherein all patients 75 years and older undergoing radical cystectomy between October 2019 and November 2020 were referred to the Geriatric Service preoperatively. Feasibility was defined according to the percentage of patients who received preoperative evaluation by the Geriatrics Service, who were followed for more than 80% of their inpatient days and who had their surgery rescheduled for logistical reasons. Urology advanced practice provider (APP) satisfaction with the program was measured via an 11-item survey. RESULTS: Sixty-six eligible patients underwent radical cystectomy in the stated time frame; 59 (89%; 95% confidence interval [CI], 79-97%) were referred to the Geriatric Service for evaluation. The median age of patients who had geriatric comanagement was 79 years; 40 (68%) were male. Forty-one patients (69%) were visited on at least 80% of the days in which they were not in the intensive care unit. No surgeries were rescheduled for logistical reasons. Nine of the 12 urology APPs (75%) responded to the survey; all nine "somewhat" or "strongly" agreed with statements indicating satisfaction with the program. CONCLUSION: Despite the challenges of the COVID-19 pandemic, we showed that perioperative GERICO is feasible. Fully powered prospective randomized controlled trials should be conducted to assess GERICO's impact on perioperative outcomes of older adults with cancer.

A novel liquid biopsy-based approach for highly specific cancer diagnostics: mitigating false responses in assaying patient plasma-derived circulating microRNAs through combined SERS and plasmon-enhanced fluorescence analyses.

Studies have shown that microRNAs, which are small noncoding RNAs, hold tremendous promise as next-generation circulating biomarkers for early cancer detection via liquid biopsies. A novel, solid-state nanoplasmonic sensor capable of assaying circulating microRNAs through a combined surface-enhanced Raman scattering (SERS) and plasmon-enhanced fluorescence (PEF) approach has been developed. Here, the unique localized surface plasmon resonance properties of chemically-synthesized gold triangular nanoprisms (Au TNPs) are utilized to create large SERS and PEF enhancements. With careful modification to the surface of Au TNPs, this sensing approach is capable of quantifying circulating microRNAs at femtogram/microliter concentrations. Uniquely, the multimodal analytical methods mitigate both false positive and false negative responses and demonstrate the high stability of our sensors within bodily fluids. As a proof of concept, microRNA-10b and microRNA-96 were directly assayed from the plasma of six bladder cancer patients. Results show potential for a highly specific liquid biopsy method that could be used in point-of-care clinical diagnostics to increase early cancer detection or any other diseases including SARS-CoV-2 in which RNAs can be used as biomarkers.