American College of Nuclear Medicine (ACNM) 2022 ACNM Annual Meeting Abstracts

The proceedings contain 91 papers. The topics discussed include: the new approach of COVID-19 patients with deteriorating respiratory functions using perfusion SPECT/CT imaging;increasing interest in nuclear medicine: evaluation of an educational workshop;cost-benefit analysis recommends further utilization of cardiac PET/MR for sarcoidosis evaluation;development of a nomogram model for predicting the recurrence of differentiated thyroid carcinoma patients based on a thyroid cancer database from a tertiary hospital in China;multi-center validation of radiomic models in new data using ComBat-based harmonization of features;bone scan with Tc99m-MDP, the missing link in the initial staging of muscle-invasive bladder carcinoma;and comparison of absorbed doses to kidneys calculated employing three time points and employing two time points in neuroendocrine patients undergoing Lu-177 DOTATATE therapy using planar images.

Coronavirus infection and organizational changes in the clinical process in patients with non-muscle-invasive bladder carcinoma.

The spread of the aggressive disease caused by the novel respiratory syndrome coronavirus-2 (SARS-CoV-2) has had an impact not only on the health and psyche of people, but also on the state of health systems in different countries, by complicating the treatment and diagnostic process. These changes have affected patients with cancers to a greater extent. The diagnosis, treatment, and follow-up of patients are of particular scientific and practical interest when working in conditions of special anti-epidemic control. Objective. To assess the possibility of reducing the frequency of hospitalization of patients with non-muscle-invasive bladder carcinoma (NMIBC) during the Covid-19 period. Subjects and methods. Sixty-four patients with urinary tract malignancy, including 19 (29.7%) patients with low-and high-risk re-current NMIBC, were followed up in two clinics (Saint Petersburg, Russia) in March to October 2020. All the patients were oper-ated on;the patients at high risk for recurrence received a cycle of adjuvant BCG therapy. Methods for cytological examination of urine sediment and the biomarkers UBC and Cyfra 21-1 were used for special laboratory diagnosis;the server stations of both clinics were applied for telehealth consultations (TCs). Results. TCs were used to reduce hospitalization rates: after TCs, all the patients reported a reduction in transport costs and recovery time after hospitalization. TCs could protect the followed-up patients against COVID-19 infection, by observing the rules of clinical examination, and achieve maximum individualization of treatment. The authors refused to perform diagnostic operations for low-risk NMIBC and to use laboratory tests using urinary biomarkers. At the place of their residence, outpatients underwent urinalysis for several indicators, transmitting the result to the clinic's servers or through a monitoring system. Inpatient treatment was used only in cases of gross hematuria or after recording abnormal laboratory test results. Control cystoscopy detected no re-current tumor. Conclusion. During the spread of COVID-19, the periods of endoscopic examinations and control diagnostic operations can be post-poned, by replacing face-to-face consultations with TC monitoring. Outpatient laboratory and radiation examinations are indicat-ed in patients with new-onset gross hematuria or after combination treatment. Repeated operations, including diagnostic ones, should be performed in the case of multiple NMIBCs or after incomplete excision of the primary tumor.Copyright © 2021.

Evaluation of Bladder Cancer Patients' Utilization of Urologic Telehealth Services

INTRODUCTION AND OBJECTIVE: Infection control practices and public policy in response to the COVID-19 pandemic shifted healthcare practices towards a telemedicine format. Even two years after peak onset of the pandemic, many clinics, including our own institution, maintain a working telehealth option for patient visits, with some patients even preferring this modality of care delivery. Our objective was to evaluate patient utilization of telehealth visits versus inperson visits at our institution and whether this was impacted by demographics, medical history, and socioeconomic factors. METHOD(S): Medical Record Numbers for all patients with bladder cancer were pulled via accessible billing-level data from the period 7/1/2019-2/28/2022. Chart review was conducted to pull clinical data on patients including telehealth versus in person visits, demographic data, clinical stage, comorbidities (diabetes, smoking status, BMI), rural/urban status by zip code (>50,000, <50,000 individuals) and income levels by zip code (25K-49.9K, 50K-99.9K, <100K), payor status, patient distance, and gas savings/carbon footprint. RESULT(S): 430 patients completed in person visits while 268 completed telehealth visits. There was no statistically significant difference for in person visits vs. telehealth visits regarding patients' race (p=0.541), ethnicity (p=0.394) age (p=0.862), urban/rural status (p=0.507), payor status (p=0.127), mean zip code income (p=0.175), and comorbidities (p=0.626 for diabetes, p=0.706 for smoking, p=0.459 for BMI), and clinical stage (p=0.07). There was a statistically significant difference in mean distance (14.85 miles versus 26.86 miles, p<0.01). CONCLUSION(S): Post-pandemic, telehealth usage and acceptability among patients with bladder cancer remains high. Patients' with bladder cancer receive care from their urologist via in person visits versus telehealth at similar rates irrespective of their urban/rural status, demographics, payor status, relevant comorbidities, or relative income. Patients are more likely to engage in care with their urologist via telehealth if they live farther from a large urban academic center, which produces an economical and environmental impact via gas/time savings and reduced carbon footprint.

Mental Health in Urologic Oncology.

This article is a systematic review of mental health in urologic oncology patients with prostate cancer (PCa), bladder cancer (BC), renal cell carcinoma (RCC), testicular cancer (TC), or penile cancer (PeCa). For all pathologies, a focus on increasing quality of life post-treatment demonstrated a positive impact in reducing Mental Health Illness (MHI) prevalence. Cancer specific mental health care may be given to patients to reduce suicide risk in BC patients and sexual identify and masculinity counseling may improve mental health for TC or PeCa patients. In order to better accommodate patient's mental health needs when undergoing GU cancer treatment, we recommend incorporation of mental health metrics such as questionnaires to assess early treatment of MHI, a greater emphasis on psychosocial support with the patient's loved ones, peers, and healthcare team, alongside advising healthy habits such as exercise which has been shown to drastically reduce MHI incidence across all pathologies. We hope that these measures conducted by urologists and oncologists, alongside possible coordination with psychiatrists and psychologists for psychotherapy, psychopharmacology, and neuro-stimulation treatment modems may be helpful in the long term to reduce MHI incidence in urology oncology patients. Given the higher incidence of MHI in oncology patients and in the patient population after the Covid-19 pandemic, MHI awareness in the sphere of urologic oncologic treatment continues to be crucial when creating a collaborative treatment platform for patients.

Versatile Use of Mycobacterium indicus pranii (MIP) Vaccine

Mycobacterium indicus pranii (MIP) earlier known as Mw is a soil-borne, non-pathogenic, saprophytic and rapidly growing strain of mycobacteria. MIP is approved as a vaccine/ immunomodulator for various indications including mycobacterium infections like leprosy in humans. Its administration has resulted in satisfactory clinical improvement, accelerated bacillary clearance, and increased immune responses to Mycobacterium leprae antigens, thereby shortening the full recovery time of the patients. It also shares its antigens with M.tuberculosis. In the last decade, RCTs have been done establishing immunotherapeutic properties of MIP in the treatment of leprosy, tuberculosis, warts and experimently in leishmaniasis. Through its immune inducing and cytotoxic property, it has also proved beneficial for human use especially in treating lung cancer. The beneficial role of it is also being explored in breast, cervical, oral, liver, and bladder cancers. Various studies on MIP have shown that it has immune-modulating properties in humans. The curiosity of the human mind has led to it being tried in Covid treatment trials. The results have shown that administering MIP has lowered inflammatory markers in Covid 19 patients, promising us for it to be a potential treatment option. More RCTs with a larger sample size should be done to establish this. Cytokine storm seen in bacterial sepsis is also decreased with MIP administration. Considering the encouraging results in hastening recovery in various diseases it appears that MIP is perhaps not being exploited to its fullest potential. © 2023, Hind Kusht Nivaran Sangh (Indian Leprosy Association). All rights reserved.

Benefit from BCON? The unmet need of bladder cancer patients unsuitable for chemoradiation treated with radical radiotherapy alone: A single institution retrospective case note review

Introduction & Objectives: Bladder preservation is routinely used as an alternative to radical cystectomy in the UK and is becoming more accepted elsewhere globally. The gold standard is for patients to receive radiotherapy with a radiosensitiser most commonly concurrent chemotherapy e.g. 5FU/mitomycin C, gemcitabine or cisplatin. Patients with poor performance status or comorbidities may be unable to be offered concurrent treatment with chemotherapy but alternative treatment with concurrent carbogen +/- nicotinamide as a hypoxic modifier may be of benefit. Our aim therefore was to retrospectively review patients with bladder TCC treated with radical radiotherapy alone in the last 5 years who may have benefited from carbogen +/- nicotinamide radiosensitisation at a large cancer centre in the north of England. Material(s) and Method(s): In this single institution retrospective case note review, electronic records were reviewed for 175 patients who had received radiotherapy to the bladder for TCC between 2017-2022. Patients who had radical radiotherapy (RT) alone without radiosensitisation were scrutinised to ascertain whether they would have been candidates for carbogen and nicotinamide using the inclusion/exclusion criteria previously defined in the Bladder Carbogen Nicotinamide (BCON) Randomised Phase 3 trial. Result(s): We analysed 175 patients. Of these, 133 received had radical RT without radiosensitisation. The most common reason for not offering radiosensitisation was the presence of co-morbidities (27.8%). Of interest, the proportion of patients having chemotherapy radiosensitisation did not change after COVID19 in March 2020 (21.5% pre- vs 27.5% post;p=0.32 chi2). Conversely, the proportion of patients receiving neo-adjuvant chemotherapy reduced though failed to reach significance (12.6% pre- vs 5% post;p=0.08 chi2). After review of the notes and criteria from the original BCON trial, 106 patients (79.6%) could have benefited from carbogen +/- nicotinamide. Of these, 14 patients (13.2%) could have been offered carbogen alone due to poor renal function. The most common reason for not being eligible for BCON was respiratory disease with reduced respiratory drive (44%). Conclusion(s): The National Institute for Health and Care Excellence (NICE) state that all radical RT for bladder TCC should be with a radiosensitiser. Due to logistical and departmental issues, the BCON regimen is not currently offered as a standard alternative to radiosensitisation with chemotherapy. BCON has been demonstrated to be tolerable and, whilst updated follow-up data failed to demonstrate statistical significance for overall survival (OS), meta-analysis of hypoxia modification has shown significant improvement in OS compared to RT alone. Hypoxia modification with carbogen +/- nicotinamide should be considered for all patients unsuitable for chemotherapy radiosensitisation.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.

How has the COVID-19 pandemic affected patients with primary bladder cancer?

PURPOSE: The COVID-19-induced effects of primary bladder cancer (BC) patients have not yet been clarified. The aim of this study was to investigate the effects of the pandemic on the diagnosis, treatment, and follow-up of primary BC patients. MATERIAL AND METHODS: A retrospective single-center analysis was made of all patients who underwent diagnostic and surgical procedures due to primary BC between November 2018 and July 2021. A total of 275 patients were identified and allocated to one of the groups: Pre-COVIDBC (BC diagnosed before the COVID-19 pandemic) or COVIDBC (during the pandemic). RESULTS: The BC patients diagnosed during the pandemic were mostly at higher stages (T2) (p = 0.04), the risk of non-muscle invasive BC (NMIBC) was higher (p = 0.02), and recurrence and progression scores were increased (p = 0.001) compared to patients diagnosed before the pandemic. The time to surgery from diagnosis (p = 0.001) and symptom duration (p = 0.04) were significantly prolonged during the pandemic and the rate of follow-up significantly decreased (p = 0.03). CONCLUSIONS: The study results highlight the significant increase in muscle invasive BC and the very high risk of NMIBC in patients presenting during the COVID-19 pandemic.

ANTECEDENTES: Los efectos inducidos por la COVID-19 en pacientes con cáncer de vejiga primario no están aclarados actualmente. OBJETIVO: Investigar los efectos de la pandemia en el diagnóstico, el tratamiento y el seguimiento del cáncer de vejiga primario. MÉTODO: Se realizó un análisis retrospectivo unicéntrico de todos los pacientes que se sometieron a procedimientos diagnósticos y quirúrgicos por cáncer primario de vejiga durante noviembre de 2018 y julio de 2021. Se incluyeron 275 pacientes en el estudio. Los pacientes fueron asignados a uno de dos grupos: pre-COVIDBC (antes de la pandemia) o COVIDBC (durante la pandemia). RESULTADOS: Los pacientes con cáncer de vejiga diagnosticados durante la pandemia se encontraban en su mayoría en estadios más altos (T2) (p = 0.04), el grupo de riesgo era más alto en el cáncer de vejiga no invasivo del músculo (p = 0.02), y la recurrencia y las puntuaciones de progresión aumentaron (p = 0.001) en comparación con antes del período pandémico. Además, el tiempo hasta la cirugía desde el diagnóstico (p = 0.001) y la duración de los síntomas (p = 0.04) aumentaron considerablemente durante la pandemia, y la tasa de seguimiento disminuyó significativamente (p = 0.03). CONCLUSIONES: Destaca el aumento significativo del cáncer de vejiga invasivo del músculo y del cáncer de vejiga no invasivo del músculo de muy alto riesgo durante la pandemia.

Interruption of BCG Therapy for NMIBC During COVID-19 Crisis, Dilemma in Its Continuation: a Review of Available Evidence and Suggested Management Strategies.

The COVID-19 disease, caused by SARS-CoV-2 virus, has been one of the worst pandemics ever to hit the human mankind. Undoubtedly the start of the second wave of COVID-19 has literally ripped apart the hearts of millions of people. Cancer patients have been left of the beaten track to their fate, with no access to treatments. Intravesical BCG instillation is the standard of care for patients with non-muscle invasive bladder cancer (NMIBC). Several patients were in the middle of their treatment regimen when this pandemic struck. As slowly the word is recuperating from concussion effect of this pandemic and routine health services are being restored, uro-oncologist will face a unique scenario with respect to intravesical BCG therapy i.e., whether to restart the course of BCG therapy or to continue course from where it was interrupted. There are no studies in literature to directly answer this peculiar question and to resolve this dilemma. So, we in this review article propose to explore the literature for the most appropriate therapeutic regimen for these patients with interruption of intravesical BCG therapy. We plan to divide the patients with interruption to BCG therapy into the following three groups:Group 1: Patients who had interruption during the induction period.Group 2: Patients who completed the induction course but maintenance course could not be started.Group 3: Patients who had interruption during maintenance phase of BCG therapy. We will compile the recent recommendations by NCCN, AUA, and EAU for the administration of intravesical BCG in non-muscle invasive bladder cancer. We herein want to review the literature to propose the most appropriate strategy, its safety profile for these subsets of patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01742-8.

COVID-19 vaccination behavior and outcomes in patients with genitourinary cancer in comparison with other cancer types

Background: Cancer(ca) and old age are risk factors for developing severe COVID-19 (C19+) disease, related morbidity and mortality. These patients (pts) were excluded from clinical trials evaluating the safety and efficacy of 3 FDA approved C19 vaccines (vax). Genitourinary (GU) ca-prostate, bladder and kidney ca contribute to the majority of non-skin ca and median age of these pts range from 65-75 yrs. We aimed to study these highly vulnerable pts behavior and outcomes regarding C19 vax in comparison to non-GU ca pts (18-89 years). Method(s): A prospective and observational single center study. Adult ca pts seen in clinics from Nov 2021-Sept 2022 were randomly interviewed using telephone surveys after a verbal consent. Type of ca and therapy data were collected from pts' medical records. The survey included C19 disease status, vax status positive (+) or negative (-), reason for vax status, side effects (s.e), impact on ca Rx or ca progression. Data was entered on REDCap. The primary end point was rate of vaccination in adult ca pts. Secondary end points were to quantify C19 vax acceptance vs. hesitance, identify s.e of C19 vax and effect of C19 vax on outcomes in GU and non-GU Ca pts. Result(s): N=172;GU ca 21 (12.2%) and non-GUca 151 (87.8%). Among GU ca pts- 9 had prostate ca, 7 had bladder ca and 5 had renal ca. C19+ in 4 (19%) GU and 45 (30.2%) non-GU pts. GU pts: 90.5% received C19 vax (Pfizer 47.6%;Moderna 42.9%, J & J 0%);9.5% were not vaxed. Non-GU pts: 85.2% received C19 vax (Pfizer 39.1%;Moderna 43%, J & J 2.6%);14.8% were not vaxed. The top 3 risk factors for serious C19+ were age >65yr (76.2%), heart disease (61.9%) and BMI.30 (42.9%) in GU ca pts and age >65yr (46.4%), BMI.30 (35.1%) and smoking (19.9%) in non-GU ca pts. The top 3 reasons for C19 vax (+) in GU ca pts: protection against C19+ for self (81%), for others (47.6%) and provider recommendation (38.1%). The main reasons for vax hesitancy in C19 vax (-) GU ca pts: concern for allergy to the vax (4.8%) and prior C19 infection (4.8%). The common s.e of C19 vax reported in GU ca pts were injection site inflammation (19%), headache (4.8%), muscle/body aches (4.8%) but no lymphadenopathy. None of GU ca pts reported delay in Rx or progression of the disease due to C-19 vax. Conclusion(s): C19 vax were overall well tolerated and did not impact ca outcomes in pts with GU malignancies. Oncologists should discuss the importance of C19 vax in the context of ca.

89zirconium-labelled girentuximab (89zr-tlx250) pet in urothelial cancer patients (zipup) - a phase i trial of a novel staging modality for urothelial carcinoma

Introduction & Objectives: Urothelial cancer is a lethal disease with a rising incidence. The current imaging modalities for staging, either CT of the chest, abdomen and pelvis or FDG PET/CT, have issues. CT is known to have relatively low sensitivity for detecting low volume metastatic disease, while FDG PET is predominantly renally excreted and has intense activity in the urinary tract, which limits its utility to detect bladder or upper tract lesions, or nodal metastases in close proximity to the urinary tract. Utilizing 89Zr-TLX250, which is predominantly hepatically cleared, may improve imaging in these scenarios. The aim of this study is to explore the feasibility, safety, and utility of Zirconium-89-Girentuximab (89Zr-TLX250) PET/CT in the accurate staging of bladder and urothelial cancer as compared to FDG PET. Material(s) and Method(s): ZipUp is single-arm, phase I trial examining the feasibility, safety, and utility of 89Zr-TLX250 PET/CT in patients either undergoing pre-operative staging of urothelial carcinoma or bladder cancer for curative intent, or with known metastatic urothelial carcinoma or bladder cancer. Following Ethical approval (HREC ID: RGS3940), all participants undergo 89Zr-TLX250 PET/CT and will need to have undergone recent FDG PET/CT for means of comparison (Figure 1. Trial Schema). This trial aims to recruit 10 participants undergoing pre-operative staging prior to planned cystectomy and 10 participants with known metastatic disease. The primary endpoint is feasibility defined by the ability to recruit to the target sample size within the study duration. Secondary endpoints are safety, tolerability and sensitivity/specificity in detecting lymph node metastases (pre-cystectomy group) compared with FDG PET/CT. Result(s): Since May 2021, 15 patients consented to participate, but 2 patients subsequently withdrew. 7 patients did not proceed to dose administration and imaging due to COVID-19 pandemic related supply issues of IMP which would have delayed initiation of treatment. 6 patients have been enrolled with imaging performed. . 5 pre-cystectomy staging group . 1 metastatic group Conclusion(s): If 89Zr-TLX250 PET/CT is proven to be feasible, safe, and effective in staging urothelial cancer, it could improve the appropriate selection of treatment for patients with metastatic or primary urothelial carcinoma or bladder cancer. [Figure presented]Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Perception and factors affecting compliance to intravesical bacillus calmette - guerin therapy in carcinoma bladder patients: An in-depth analysis in a tertiary care-a mix method study design

Introduction and Objective: Intravesical Bacillus Calmette-Guerin (iBCG) therapy for urinary bladder cancer (UBC) is associated with poor compliance due to various psycho-social issues unique to its treatment. The objective of this study was to identify and analyse the patient's perception and the factors that affected its adherence. Method(s): This mixed-method study was conducted on UBC patients who received/received iBCG. Following purposive sampling, patients who received at least one induction and one maintenance dose were assigned to a compliant group, and who did not were assigned to the non-compliant group. The patient's quality of life was assessed using the World Health Organization Quality of Life Instrument (WHOQOL-BREF). Semi-structured, in-depth interviews (IDI) of 35-40 minutes were conducted. The transcribed verbatim was analysed by deductive coding and content analysis. The appropriate codes, domains and themes were identified and analysed. Result(s): Demographic and socio-economic characteristics were comparable in both groups. The mean treatment expenditure was higher in the non-compliant group (1.87+/-0.75 vs 3.87+/-1.31;p=0.04). The quality of life measured was similar in both groups. IDI analysis noted that the primary reasons for non-compliance were frequent hospital commute, COVID travel restrictions, lack of knowledge, loss of daily wage, paucity at various levels in government hospitals and expensive corporate healthcare. Treatment-related severe frequency and dysuria also significantly contributed to non-compliance. Conclusion(s): Compliance can be achieved if the patients cope with the initial phase of treatment with positivity and optimism. Good symptomatic relief with proper knowledge and guidance could address the non-compliance.

Impact of vaccination against SARS-CoV-2 on the risk of hospital admission and death among infected patients with urologic cancers: A population-based study in northern Italy

Background: Hospital admission and death of infected cancer patients were investigated according to SARS-CoV-2 vaccination status. Method(s): Population-based observational study on 1874 SARS-CoV-2 infected patients with prostate (n=1276), kidney (n=327), and bladder (n=271) cancers. Hazard ratios (HR) and their 95% confidence intervals (CI), adjusted for sex and age, were computed to assess the risk of hospital admission and death of unvaccinated patients as compared to vaccinated ones. Result(s): 24.5% of patients with prostate, 26.9%with kidney and 29.5%with bladder cancer were unvaccinated. As compared to vaccinated ones, a statistically significant excess risk of hospital admission emerged for unvaccinated ones with prostate (HR=3.33, 95% CI: 2.50-4.55), and kidney (HR=4.35, 95% CI: 2.33-8.33) cancer. The 312 unvaccinated prostate cancer patients were also at a nearly 3-fold higher risk of death than vaccinated ones (HR=2.98, 95% CI:1.89-4.70). Conclusion(s): Study findings stress the importance of SARS-CoV-2 vaccines in reducing hospital admission and death in patients with urologic cancers, particularly prostate cancer.

Intravesical administration of durvalumab to patients with high risk non muscle invasive bladder cancer after BCG failure. A phase II trial by the Hellenic GU Cancer Group

Introduction & Objectives: Patients with high risk non muscle invasive bladder cancer (NMIBC) who experience BCG failure have limited bladder preserving treatment options as radical cystectomy currently represents the standard therapeutical approach. Systematic immunotherapy (IO) has changed the landscape in advanced bladder cancer and is currently being investigated in NMIBC. Based on the hypothesis that intravesical administration will not be related with severe adverse events, we evaluated the role of intravesically administered durvalumab in NMIBC patients after BCG failure. Material(s) and Method(s): An open label, single-arm, multi-center, phase II clinical trial was conducted. A run-in phase had the objective to determine the maximum tolerated dose (MTD) of durvalumab and to exclude a detrimental effect on disease relapse by this strategy. Durvalumab was administered for a total of 6 instillations per patient at consecutive levels of 500, 750 and 1000 mg. Phase II has as primary end point the 1-year high-grade-relapse-free (HGRF)-rate. Secondary endpoints included toxicity, and high-grade progression-free rat at 1, 3 and 6 months after treatment. Result(s): Thirty patients were enrolled (run in phase: 9, phase II: 21). One patient withdrew consent prior to receiving study treatment, so 29 patients were included in efficacy and toxicity analyses. Mean age was 66.5 years. MTD of durvalumab was set at 1000 mg as no dose related toxicities (DLTs) occurred at any level studied. Three of 9 patients included in the run-in phase (33.3%) were tumor free one month after the last durvalumab instillation, therefore, the null hypothesis was rejected by the futility analysis. Western blot showed that durvalumab remained stable in urine during instillation. One patient died from Covid-19, 3 months after the last durvalumab administration. All patients concluded at least 1 year follow up. One-year HGRF rate was 34.6%. HGRF rates at 1, 3 and 6 months was 73%, 65.3% and 50% respectively. Five patients (17%) experienced a T2 or above disease relapse. Five out of the six patients who received 500mg or 750mg of durvalumab relapsed within 1 year. When efficacy analyses were restricted to patients receiving 1000mg of durvalumab, 1-year HGRF rate was 35%. Interestingly, 2 out of 2 patients with only CIS disease at baseline experienced a tumor complete response, which was durable and was maintained at least for a year. No severe adverse events were noted. The most common adverse event was Grade 1 hematuria. Conclusion(s): Intravesical IO using durvalumab was proved to be feasible with an excellent safety profile. Oncological results seem to be promising and comparable with other bladder preserving strategies in BCG failure with the advantage of a better safety profile. Further study of intravesical IO in high-risk patients with NMIBC after BCG failure is warranted.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Acute kidney injury (AKI) post-mRNA SARS-CoV-2 vaccine in patients with cancer, treated with immune check point inhibitor (ICPi): An immune double whammy!

Background: Immune check point inhibitors (ICPi) have become the first line treatment for most of the cancers and have shown promising results. However, they can provoke reactions, the most feared being immune related adverse events (irAE). Case presentation: We present a series of three cases, of patients recieving ICPi. All three patients developed AKI after administration of SARS-CoV-2 mRNA vaccine. Two patients had kidney-biopsy-proven acute interstitial nephritis (AIN) which responded to ICPi discontinuation and treatment with steroids. One had presumed AIN based on the high levels of CRP and urine retinol binding protein to creatinine ratio and responded to cessation of ICPi alone. Conclusion(s): These three cases demonstrate that a strong immune response from the SARS-CoV-2 mRNA vaccine combined with an uninhibited immune system under influence of ICPi led to an amplification of autoimmunity leading to AKI presenting as AIN.Copyright © The Author(s) 2022.

Role of plasma fibrinogen and D-dimer as prognostic biomarkers in patients with non-muscle invasive bladder cancer

Background: We aimed to evaluate the role of plasma fibrinogen and D-dimer as prognostic biomarkers in patients with non-muscle invasive bladder cancer (NMIBC). Method(s): The prospective study included 35 patients (30 males) with newly diagnosed NMIBC with no history of thromboembolic event or anti-coagulant intake or active infection and underwent complete trans-urethral resection between September 2020 and December 2021. Patients with deranged hepato-renal functions, refractory hypertension or diagnosed with COVID-19 infection with in one-month before surgery or routine follow-up were excluded. Follow-up was done as per NCCN guidelines. Fibrinogen and D-dimer levels were measured with in seven days of surgery or follow-up and analyzed for recurrence-free survival (RFS) and progression-free survival (PFS). Cox regression analyses were adopted to assess the influence of these two parameters on RFS and PFS. Result(s): The mean age was 53.9 years with a median follow-up of 9-months. Nine had recurrence of which six had progression. The cut-off values of fibrinogen and D-dimer were 402.5 mg/dl and 0.55 microg/ml, respectively. Kaplan-Meier analysis demonstrated that high fibrinogen and D-dimer levels were significantly related to poor RFS and PFS (p < 0.001). On multivariate analysis only fibrinogen and D-dimer retained their significance for RFS (p = 0.026 and 0.014, respectively) and PFS (p = 0.027 and 0.042, respectively). High levels of fibrinogen and D-dimer were also present in patients who had recurrence or progression at follow-up visits compared to rest of the patients. Conclusion(s): High levels of fibrinogen and D-dimer may indicate worse prognosis in patients with NMIBC, suggesting that these two can be used as prognostic biomarkers.Copyright © 2023, The Author(s).

Disease management in a patient diagnosed with COVID-19 disease during induction intravesical BCG therapy: A case report and review of the literature.

OBJECTIVE: To discuss the patient diagnosed with COVID-19 disease while receiving intravesical induction bacillus Calmette-Guérin (BCG) treatment for non-muscle-invasive bladder cancer, its management in the light of the literature. PATIENT AND METHODS: A 52-year-old male patient, who received intravesical BCG treatment for high-grade pT1 papillary urothelial carcinoma, presented 12 h after taking the fourth dose of induction therapy 38.2° fever and chills. The patient's reverse transcriptase-polymerase chain reaction test was positive, and Thorax CT imaging showed a few ground-glass pneumonic infiltrations in bilateral lung bases consistent with COVID-19 disease. RESULTS: Although international urology associations have current recommendations regarding the pandemic process, only one study has made specific recommendations regarding the patient group diagnosed with COVID-19 while receiving intravesical BCG treatment. According to this recommendation, we interrupted our patient's BCG treatment for 3 weeks and then completed the treatment for 6 weeks. A maintenance treatment not exceeding 1 year was planned. CONCLUSION: This group of patients' recommendation is to delay BCG therapy for at least 3 weeks after initial symptoms to allow for complete recovery. Although the administration schedule varies, maintenance therapy is recommended for no more than 1 year.

Hypofractionation: less is more?

One third of patients with bladder cancer present with muscle invasive bladder cancer (MIBC) which has a poor prognosis. International guidelines for the management of MIBC recommend radical cystectomy or bladder-preserving treatment based on radical radiotherapy with a form of radiosensitisation. In the UK, both conventional fractionation with 64 Gy in 32 fractions and hypofractionation with 55 Gy in 20 fractions are standard of care options with the choice varying between centres. A meta-analysis of individual patients with locally advanced bladder cancer from two UK multicentre phase 3 trials was published recently. This study evaluated the non-inferiority of a hypofractionated schedule compared to a conventional regime. This analysis confirmed the non-inferiority of the hypofractionated regimen, and noted superior locoregional control. We discuss the relevance of these findings to current practice while considering the radiobiology of hypofractionation, the role of systemic therapies and radiosensitisation, as well as the socioeconomic benefits.

Drug-induced interstitial pneumonia after intravesical Bacillus Calmette-Guerin administration for bladder cancer with scleroderma.

Introduction: Intravesical Bacillus Calmette-Guerin administration is the standard therapy for high-risk nonmuscle invasive bladder cancer and is usually well tolerated. However, some patients experience severe, potentially fatal, complications including interstitial pneumonitis. Case presentation: A 72-year-old female with scleroderma was diagnosed with bladder carcinoma in situ. She developed severe interstitial pneumonitis with the first administration of intravesical Bacillus Calmette-Guerin after the cessation of immunosuppressive agents. Six days after the first administration, she experienced dyspnea at rest, and computed tomography revealed scattered frosted shadows in the upper lung. The following day, she required intubation. We suspected drug-induced interstitial pneumonia and started steroid pulse therapy for 3 days, resulting in a complete response. No exacerbation of scleroderma symptoms or recurrence of cancer was observed 9 months after Bacillus Calmette-Guerin therapy. Conclusion: For patients receiving intravesical Bacillus Calmette-Guerin therapy, close observation of the respiratory condition is necessary for early therapeutic intervention.

HSPA5 Promotes the Proliferation, Metastasis and Regulates Ferroptosis of Bladder Cancer.

Heat shock protein family A (HSP70) member 5 (HSPA5) is aberrantly expressed in various tumors and closely associated with the progression and prognosis of cancer. Nevertheless, its role in bladder cancer (BCa) remains elusive. The results of our study demonstrated that HSPA5 was upregulated in BCa and correlated with patient prognosis. Cell lines with low expression level of HSPA5 were constructed to explore the role of this protein in BCa. HSPA5 knockdown promoted apoptosis and retarded the proliferation, migration and invasion of BCa cells by regulating the VEGFA/VEGFR2 signaling pathway. In addition, overexpression of VEGFA alleviated the negative effect of HSPA5 downregulation. Moreover, we found that HSPA5 could inhibit the process of ferroptosis through the P53/SLC7A11/GPX4 pathway. Hence, HSPA5 can facilitate the progression of BCa and may be used as a novel biomarker and latent therapeutic target in the clinic.

Evaluating the Protective Effect of Intravesical Bacillus Calmette-Guerin against SARS-CoV-2 in Non-Muscle Invasive Bladder Cancer Patients: A Multicenter Observational Trial.

We aim to evaluate the potential protective role of intravesical Bacillus Calmette-Guerin (BCG) against SARS-CoV-2 in patients with non-muscle invasive bladder cancer (NMIBC). Patients treated with intravesical adjuvant therapy for NMIBC between January 2018 and December 2019 at two Italian referral centers were divided into two groups based on the received intravesical treatment regimen (BCG vs. chemotherapy). The study's primary endpoint was evaluating SARS-CoV-2 disease incidence and severity among patients treated with intravesical BCG compared to the control group. The study's secondary endpoint was the evaluation of SARS-CoV-2 infection (estimated with serology testing) in the study groups. Overall, 340 patients treated with BCG and 166 treated with intravesical chemotherapy were included in the study. Among patients treated with BCG, 165 (49%) experienced BCG-related adverse events, and serious adverse events occurred in 33 (10%) patients. Receiving BCG or experiencing systemic BCG-related adverse events were not associated with symptomatic proven SARS-CoV-2 infection (p = 0.9) nor with a positive serology test (p = 0.5). The main limitations are related to the retrospective nature of the study. In this multicenter observational trial, a protective role of intravesical BCG against SARS-CoV-2 could not be demonstrated. These results may be used for decision-making regarding ongoing and future trials.