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.

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.

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.

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).

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.

Atezolizumab for the treatment of advanced recurrent basal cell carcinoma and urothelial carcinoma of bladder: a case report.

BACKGROUND: The use of checkpoint inhibitors has become increasingly important in the treatment of different cancers, including advanced muscle-invasive urothelial cancer and even in basal cell carcinoma. We present the case of a patient with advanced basal cell carcinoma and metastatic muscle-invasive urothelial cancer, who was treated with the programmed death-ligand 1 inhibitor, atezolizumab for both cancers. CASE PRESENTATION: A 72-year-old Caucasian female patient, with a history of smoking without any comorbidities developed periocular basal cell carcinoma, which was surgically removed but relapsed 4 years later. Surgical excision was carried out twice, but with positive margins, therefore definitive radiotherapy was given. Subsequently, the patient developed non-muscle-invasive papillary urothelial carcinoma, which was removed by transurethral resection. Follow-up was irregular owing to the patient's inadequate compliance, and within 2 years, the patient's cancer relapsed and histology confirmed muscle-invasive urothelial carcinoma. Definitive radiochemotherapy was not accepted by the patient. Meanwhile, the patient's basal cell carcinoma had also progressed, despite receiving vismodegib therapy. Therefore, the patient was administered epirubicin-cisplatin. Having reached the maximum cumulative dose of epirubicin, treatment with this chemotherapeutic agent could not be continued. The patient developed bladder cancer metastasis in her left suprainguinal lymph nodes. Owing to the presence of both types of tumors, programmed death-ligand 1 inhibitor atezolizumab treatment was chosen. In just over 1 year, the patient received 17 cycles of atezolizumab altogether, which was tolerated well without any adverse or side effects. Follow-up imaging scans indicated complete remission of the metastatic bladder cancer and stable disease of the basal cell carcinoma. The patient subsequently passed away in hospital due to a complication of COVID-19 infection. CONCLUSIONS: Our patient attained stable disease in advanced basal cell carcinoma and complete remission in metastatic muscle-invasive urothelial cancer after receiving programmed death-ligand 1 inhibitor, atezolizumab, therapy. To our knowledge, this is the first paper to report the use of programmed death-ligand 1 inhibitor, atezolizumab, as treatment for advanced basal cell carcinoma. This case may also be of interest for clinicians when treating patients with two synchronous cancers.

Impact of the time of surgical delay on survival in patients with muscle-invasive bladder cancer.

Background and objectives: Patients with muscle-invasive bladder cancer (MIBC) often experience a waiting period before radical surgery for numerous reasons; however, the COVID-19 outbreak has exacerbated this problem. Therefore, it is necessary to discuss the impact of the unavoidable time of surgical delay on the outcome of patients with MIBC. Methods: In all, 165 patients from high-volume centers with pT2-pT3 MIBC, who underwent radical surgery between January 2008 and November 2020, were retrospectively evaluated. Patients' demographic and pathological information was recorded. Based on the time of surgical delay endured, patients were divided into three groups: long waiting time (> 90 days), intermediate waiting time (30-90 days), and short waiting time (≤ 30 days). Finally, each group's pathological characteristics and survival rates were compared. Results: The median time of surgical delay for all patients was 33 days (interquartile range, IQR: 16-67 days). Among the 165 patients, 32 (19.4%) were classified into the long waiting time group, 55 (33.3%) into the intermediate waiting time group, and 78 (47.3%) into the short waiting time group. The median follow-up period for all patients was 48 months (IQR: 23-84 months). The median times of surgical delay in the long, intermediate, and short waiting time groups were 188 days (IQR: 98-367 days), 39 days (IQR: 35-65 days), and 16 days (IQR: 12-22 days), respectively. The 5-year overall survival (OS) rate for all patients was 58.4%, and that in the long, intermediate, and short waiting time groups were 35.7%, 61.3%, and 64.1%, respectively (P = 0.035). The 5-year cancer-specific survival (CSS) rates in the long, intermediate, and short waiting time groups were 38.9%, 61.5%, and 65.0%, respectively (P = 0.042). The multivariate Cox regression analysis identified age, time of surgical delay, pT stage, and lymph node involvement as independent determinants of OS and CSS. Conclusion: In patients with pT2-pT3 MIBC, the time of surgical delay > 90 days can have a negative impact on survival.

Efficacy and safety of atezolizumab concurrent with radiotherapy in patients with muscle-invasive bladder cancer: An interim analysis of the ATEZOBLADDERPRESERVE phase II trial (SOGUG-2017-A-IEC(VEJ)-4)

Background: Combined-modality treatments are bladder-preserving alternatives for patients (pts) who are not candidates for radical cystectomy by medical reasons, refusal, or patientś choice. Immune therapies seem to potentiate tumor-specific immune response induced by radiotherapy (RT). Combination of RT with anti-PD-1/PD-L1 therapy appears safe and there are signs of promising activity. The aim of this study is to assess the efficacy and safety of atezolizumab (ATZ) concurrent with external beam radiotherapy (EBRT) for the treatment of muscle-invasive bladder cancer (MIBC) with bladder preservation intent. Here we present an interim analysis. Methods: This is an open, multicenter, and phase II trial, sponsored by SOGUG, in pts with confirmed diagnosis of MIBC in clinical stages cT2-T4a N0 M0 who are not candidates for radical cystectomy. Treatment consists of 6 doses of ATZ 1200 mg IV every 3 weeks, starting on day 1 of EBRT, and 60 Gy of RT in 30 fractions over 6 weeks at 2 Gy/day. The primary endpoint of the study is pathological complete response (pCR) defined as a response of grade 5 according to Miller and Payne criteria, 1 to 2 months after the last dose of ATZ. A planned interim analysis has been performed (data cut-off date: November 2021) on the primary endpoint to avoid exposure to ineffective treatment according to the minimax two-stages Simon's design (stopping rule: 9 out of the first 13 evaluable pts should achieve pCR). Incidence of adverse events (AE) and serious AE (SAE) has been also secondarily assessed. Results: From September 2019 to November 2021, 39 pts were screened, of whom 13 were excluded due to non-compliance with eligibility criteria. Thus, the evaluable population consisted of 26 pts. The safety analysis was performed in 22 pts who had received at least one dose of ATZ. 14 pts were assessed pathologically and, thus, included in interim efficacy analysis (median age: 78.6 years;clinical stage: 71.4% T2a, 14.3% T2b, 7.1% T3a, 7.1% T3b). All 14 pts had achieved pCR at the cut-off date. 20/22 (91%) pts experienced at least one AE, with asthenia (11 pts), diarrhea (9 pts), and urinary tract infection (4 pts) being the most common. 9 SAEs were reported in 7 (32%) pts (bacteriemia, COVID-19 infection, depressed LVEF, unknown origin fever, hepatic toxicity, kidney failure, rectorrhagia, respiratory infection, and urinary sepsis). 6 (27%) pts suffered AEs leading to treatment discontinuation. No AEs leading to death occurred. 17 pts with available data on survival were alive at the cut-off date. Conclusions: Interim results suggest that ATZ combined with EBRT is a feasible and effective treatment in terms of pCR, with a manageable safety profile. The final results from this trial will provide information about its effects on clinical outcome, including survival and updated safety findings.

ICONIC: Impact of Covid-19 on Outcomes iN muscle Invasive bladder Cancer - preliminary Results from a prospective IBUS (International British Urological Society) led multicentre collaborative study

Introduction: The Covid-19 pandemic in the UK led to much un-certainty about the delivery of cancer services. A shift from established therapy (and its timing) in patients with Muscle invasive Bladder Cancer (MIBC) has potential deleterious consequences. To understand outcomes, we formed a collaborative to measure overall and diseasefree survival at 3-years in patients with non-metastatic MIBC (Figure 1) treated during the UK's first wave of Covid-19. Secondary aims included comparison between treatment modalities and pre-Covid controls. Patients and Methods: The collaborative included clinicians from 13 major centres, representing 3 UK nations. A prospective clinical audit, endorsed by the National Cancer Research Institute, was started to collect comprehensive data. MIBC patients discussed at the multidisciplinary meeting (MDM) between 1/3/2020-30/06/2020 were included. Results: At submission, data were available from 12 centres for 299 patients. The mean age was 69.3 years (27- 90), and there were 72 female and 227 male patients. Mean Charlson Co-morbidity Index was 5 (1-12). Preliminary analysis of available data indicate the following: MDM recommendations for (at least) 1 in 4 patients were deemed as being modified from standard practice. Twenty six patients received neoadjuvant chemotherapy. In total (from available data), 99 received radical radiotherapy and 146 underwent radical cystectomy (65 and 74 specified as open and robotic assisted, respectively). Preliminary analysis suggests that 1 in 3 patients had died within 1 year. Conclusions: Preliminary Results indicate that recommendations for MIBC patients were significantly altered consequent to the pandemic and mortality was high. Analyses towards endpoints are awaited.

V89L(rs523349) and A49T(rs9282858) variations on SRD5A2 gene on dutasteride efficacy and safety in bladder cancer patients: A pilot study

Introduction: Human steroid 5α-reductase 2 (SRD5A2) coded by SRD5A2 gene is an enzyme that catalyzes the reduction of testosterone to dihydrotestosterone. Dutasteride, an SRD5A2 inhibitor, is a widely used antiandrogen for the treatment of benign prostate hyperplasia. Multiple variations have been identified in the SRD5Ar gene. Some of these variations may affect the efficacy and safety of SRD5A2 inhibitors. Dutasteride has also been investigated for intermediate and high-risk nonmuscle- invasive urothelial bladder cancer treatment with the combination of BCG (Bacillus Calmette-Guerin). Objectives: The study aims to evaluate the potential impact of V89L (rs523349) and A49T (rs9282858) variations on the SRD5A2 gene on dutasteride efficacy and safety in bladder cancer patients that have been enrolled in Phase 2 clinical trial entitled 'Efficacy and safety of a 5-alpha reductase inhibitor, dutasteride, added to Bacillus Calmette Guerin (BCG) immunotherapy in the prevention of recurrence and progression of intermediate and high risk non-muscle invasive bladder cancer: A single-arm, Phase 2 clinical trial' Methods: Twenty-one patients on BCG and dutasteride in the Phase 2 clinical trial were included in the study. Genomic DNA was obtained from whole blood samples, and evaluation of V89L (rs523349) (G>C) and A49T (rs9282858) (C>T) variations on the SRD5A2 gene was performed by using TaqMan SNP Genotyping Assay. The severity of the adverse events was graded by the United States National Cancer Institute- Common Terminology Criteria for Adverse Events 5.0. The causality assessment of adverse drug reactions was performed using Liverpool Causality Assessment Tool, Naranjo Algorithm, and World Health Organization-Uppsala Drug Monitoring Centre Causality Assessment System. The response to dutasteride was evaluated as the presence of bladder cancer recurrence. The Chi-Square test was used for testing the relationship between categorical variables. P values of <0.05 were considered significant. Results: All patients were homozygous GG for V89L variation on the SRD5A2 gene. Regarding the A49T variation, only one patient was homozygous CC, 8 patients were homozygous TT and 12 patients were heterozygous TC. One of the 8 patients (%12) was homozygous TT and 3 of 12 patients (%25) were heterozygous TC had bladder cancer recurrence. There was no statistically significant difference between bladder cancer recurrence and A49T variation (p=0.803). None of the adverse events were associated with dutasteride treatment whereas some of the adverse events, mostly urinary tract infections, were associated with the BCG. Other adverse events were upper respiratory tract infections, COVID-19, abdominal pain, vomiting, and loss of appetite. Serious adverse events were coronary artery disease, dyspnea, hypotension, and urethral stricture. None of the serious adverse events were associated with dutasteride or BCG treatment. Conclusion: Neither V89L nor A49T variation on the SRD5A2 gene was found to be associated with the efficacy and safety of dutasteride in medium and high-risk bladder cancer patients. Further studies of these variations with larger sample sizes and/or healthy control groups may lead to a better understanding of the impact of these variations on the efficacy and safety of dutasteride.

The Impact of the COVID-19 Pandemic on Bladder Cancer Care in the Netherlands

BACKGROUND: The COVID-19 pandemic has disrupted regular health care with potential consequences for non-COVID diseases like cancer. To ensure continuity of oncological care, guidelines were temporarily adapted. OBJECTIVE: To evaluate the impact of the COVID-19 outbreak on bladder cancer care in the Netherlands. METHODS: The number of bladder cancer (BC) diagnoses per month during 2020-2021 was compared to 2018-2019 based on preliminary data from the Netherlands Cancer Registry (NCR). Additionally, detailed data were retrieved from the NCR for the cohort diagnosed between March 1st-May 31st 2020 (first COVID wave) and 2018-2019 (reference cohort). BC diagnoses, changes in age and stage at diagnosis, and time to first-line treatment were compared between both periods. Changes in treatment were evaluated using logistic regression. RESULTS: During the first COVID wave (week 9-22), the number of BC diagnoses decreased by 14%, corresponding with approximately 300 diagnoses, but increased again in the second half of 2020. The decline was most pronounced from week 13 onwards in patients≥70 years and patients with non-muscle invasive BC. Patients with muscle-invasive disease were less likely to undergo a radical cystectomy (RC) in week 17-22 (OR=0.62, 95% CI=0.40-0.97). Shortly after the start of the outbreak, use of neoadjuvant chemotherapy decreased from 34% to 25% but this (non-significant) effect disappeared at the end of April. During the first wave, 5% more RCs were performed compared to previous years. Time from diagnosis to RC became 6 days shorter. Overall, a 7% reduction in RCs was observed in 2020. CONCLUSIONS: The number of BC diagnoses decreased steeply by 14% during the first COVID wave but increased again to pre-COVID levels by the end of 2020 (i.e. 600 diagnoses/month). Treatment-related changes remained limited and followed the adapted guidelines. Surgical volume was not compromised during the first wave. Altogether, the impact of the first COVID-19 outbreak on bladder cancer care in the Netherlands appears to be less pronounced than was reported for other solid tumors, both in the Netherlands and abroad. However, its impact on bladder cancer stage shift and long-term outcomes, as well as later pandemic waves remain so far unexamined.

EFFECT OF NEOADJUVANT CHEMOTHERAPY IN IMPROVING OVERALL SURVIVAL OF T2-4AN0M0 BLADDER CANCER PATIENTS: A SYSTEMIC REVIEW AND META-ANALYSIS ACCORDING TO EAU COVID-19 RECOMMENDATION

INTRODUCTION AND OBJECTIVE: In situation with the COVID-19 outbreak, the EAU guidelines Rapid Reaction Group provided recommendations to guide muscle invasive bladder cancer (MIBC) priorities, and they recommended that neoadjuvant chemotherapy should be considered omitted in T2/3 focal N0M0 MIBC patients. This meta-analysis aims to evaluate the efficacy of neoadjuvant chemotherapy compared to radical cystectomy alone in improving overall survival of T2-4aN0M0 MIBC patients. METHODS: Following the PRISMA guideline, PubMed, EMBASE, and Cochrane Library were searched up to September 2021. The articles were searched with keywords muscle-invasive bladder cancer, neoadjuvant chemotherapy, cystectomy, and overall survival. Participants, patients with T2-4aN0M0 MIBC;Interventions, T2- 4aN0M0 MIBC patients who underwent neoadjuvant chemotherapy;Outcomes, comparison of overall survival included for analysis. The overall survival was analyzed as hazard ratio (HR) and 95% confidence interval (CI) and presented in a forest plot. We also conducted a sub-analysis of only T2N0M0 MIBC patients. Quality assessments were performed independently by two reviewers using the Scottish Intercollegiate Guidelines Network. RESULTS: A total of 8 studies were included in the metaanalysis. 8 studies were intermediate risk for detection bias and there were no major problems. In T2-4aN0M0 MIBC patients, the overall survival was significantly better in the neoadjuvant chemotherapy + radical cystectomy group than in the radical cystectomy alone group (HR, 0.79;95% CI, 0.69-0.92;p=0.002) (Fig. 1A). A subgroup analysis was performed on only T2N0M0 MIBC patients and 5 studies were included. There was no difference in overall survival between the neoadjuvant chemotherapy + radical cystectomy group and the radical cystectomy alone group (HR, 0.83;95% CI, 0.69-1.02;p=0.06) (Fig. 1B). CONCLUSIONS: As recommended by the EAU guidelines Rapid Reaction Group, it is thought that patients with T2N0M0 MIBC should strongly consider omitting neoadjuvant chemotherapy until the end of the COVID-19 pandemic. Whether to omit neoadjuvant in T2- 4aN0M0 MIBC should be discussed further, and studies targeting only T2-3N0M0 MIBC are expected to proceed further.

Outpatient transurethral laser ablation (TULA) of non-muscle invasive bladder cancers: A safe, well tolerated and game changing procedure

Background: Management of non-muscle invasive bladder cancer (NMIBC) is expensive with negative quality-of-life effects due to requirement for multiple transurethral resection/biopsies under general/regional anaesthetic;especially in those with low-and intermediate-risk NMIBC due to their low risk of progression but high recurrence rate (>30%). Pressures on the National Health Service, which is exacerbated by the COVID-19 pandemic, means safe, efficient and cost-effective solutions are required. We present our experience of transurethral laser ablation (TULA) in a large single tertiary unit. Patients and Methods: A retrospective review of electronic records of all TULA cases with available 3-month cystoscopy follow-up results between October 2019 and February 2021 were included. Data analysed included: patient demographics, co-morbidities (Charleston comorbidity index score-CCIS), anticoagulation, initial histopathological data, tumour number/size, procedural tolerance, post-procedure complications, 3-month recurrence rate and cost savings of outpatient TULA versus inpatient bladder cancer surgery. Results: Fifty patients with a median age of 75 years (range: 55-96) were identified. Median CCIS was 4 (range: 1-7) with only 10 patients on anticoagulation which was not stopped pre-procedure. The most common initial histopathological diagnosis was low-grade G2pTa TCC (n = 32). Median number of tumours treated were 2 (range: 1-9) ranging from 0.5 to 3 cm. Only one patient did not tolerate TULA and was listed for GA bladder biopsy. No complications were noted. Three-month recurrence rate was 11/49 (22%). Outpatient TULA saved £33,600 compared to inpatient bladder cancer surgery, and this does not account for other efficiency savings such as reducing waiting lists and avoiding protracted hospital admissions in elderly co-morbid patients. Conclusion: TULA is a safe and well-tolerated procedure. It is a cost-effective option for the treatment of low-risk NMIBC patients and also those deemed unfit for general/regional anaesthesia. Larger case series are needed to assess its long-term outcomes.

Comparison of maintenance of intravesical BCG therapy between 1 year and more than 1 year therapies for recurrence rate in high-risk NMIBC: Systematic review and network meta-analysis according to EAU COVID-19 recommendation

Introduction & Objectives: During coronavirus disease 2019 (COVID-19) pandemic, EAU recommended intravesical bacillus Calmette-Guérin (BCG) therapy courses that have been ongoing for longer than 1 year can be safely terminated for high-risk non-muscle-invasive bladder cancer(NMIBC) patients. Thus, we conducted a systematic review and network meta-analysis according to EAU COVID-19 recommendation.Materials & Methods: Systematic review was performed following the PRISMA guideline. PubMed/Medline, EMBASE, and Cochrane Library weresearched up to Sep, 2021. We conducted a network meta-analysis to outcomes including only induction therapy group (No_M), 1-year (M1) andmore than 1 year (MM1) maintenance therapies groups for recurrence rate in patients with NMIBC. Participants, patients with NMIBC;Interventions,NMIBC patients who underwent intravesical BCG therapy;Outcomes, comparison of recurrence rate included for analysis. Quality assessmentswere performed independently by two reviewers using the Scottish Intercollegiate Guidelines Network.Results: Nineteen studies with a total of 3,957 patients were included for network meta-analysis. 19 studies were intermediate risk for detectionbias and there were no major problems. There was just two published studies between M1 and MM1. Five studies between No_M and M1 and 12articles between No_M and MM1 were identified. In node-split forest plot using Bayesian Markov Chain Monte Carlo (MCMC) modeling, there couldbe no difference between M1 and MM1 in recurrence rate (OR 0.95 (0.73-1.2)). However, recurrence rate in No_M group was higher than M1 (OR1.9 (1.5-2.5)) and MM1 (OR 2.0 (1.7-2.4)) groups (Fig. 1A). P-score test using frequentist method to rank treatments in network demonstrate MM1(P-score 0.8701) was superior to M1 (P-score 0.6299) and No_M groups (P-score 0). In the rank-probability test using MCMC modeling, MM1 had the highest rank, followed by M1 and No_M groups (Fig. 1B). (Figure Presented)(Figure Presented)Conclusions: In network meta-analysis, there could be no difference between 1-year and more than 1-year maintenance intravesical BCGtherapies in recurrence rate. In the rank test, more than 1-year therapy could be most effective. During COVID-19 pandemic, 1-year maintenancetherapy can be performed, however, after the COVID-19 pandemic, more than 1-year therapy will be decided

Outcomes by time to definitive chemoradiation treatment for patients with muscle-invasive bladder cancer.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has raised concerns about delaying treatment for localized cancer and its impact on long-term outcomes. OBJECTIVE: We aimed to investigate the impact of time to chemoradiation (CRT) on recurrence and survival outcomes for patients with muscle-invasive bladder cancer (MIBC). METHODS: In the national Veterans Affairs' database, we identified patients with urothelial histology, MIBC (T2-4a/N0-3/M0) diagnosed between 2000 to 2018 and treated with definitive CRT. Time to treatment was defined as the number of days between date of diagnosis and start date of CRT. The cohort was stratified into < 90 (early) or ≥ 90 days (delayed) groups. Endpoints of locoregional failure (LRF), distant failure (DF), overall survival (OS), and bladder cancer-specific survival (BCS) were evaluated in multivariable Cox and Fine-Gray models. RESULTS: 305 patients with MIBC underwent CRT - 190 (62.3%) received early CRT, 115 (37.7%) received delayed CRT. Multivariable analysis (including success of transurethral resection of bladder tumor and type of chemotherapy) revealed no difference in recurrence between groups - LRF HR 1.12 (95%CI 0.76-1.67, P = 0.56) and DF HR 1.03 (95%CI 0.70-1.53, P = 0.88). Similarly, there were no differences in survival outcomes. The lack of association was maintained at both earlier and later time cutoffs (60-120 days). CONCLUSIONS: Our findings suggest that a short-term delay in definitive therapy may not affect long-term outcomes for patients with MIBC undergoing CRT. This study does not endorse delays in therapy, but rather provides information to aid patients and clinicians navigate the unique challenges of MIBC care in both pandemic and non-pandemic times.

Optimal Delivery of Follow-Up Care After Radical Cystectomy for Bladder Cancer.

PURPOSE OF REVIEW: To identify components representing optimal delivery of follow-up care after radical cystectomy because of bladder cancer and report the current level of evidence. METHODS: We conducted a systematic literature search of the following databases: Cochrane, MEDLINE, Embase, CINAHL, Web of Science, Physiotherapy Evidence Database and ClinicalTrials.gov. The search results were managed in Covidence Reference Manager and abstracts were screened by title. Articles relevant to the subject of interest were included and the results are reported narratively. RESULTS: Several studies have evaluated the positive impact of enhanced recovery after surgery (ERAS) on length of stay, albeit not on the further impact on 90-day postoperative complication rate, functional recovery, or mortality. Minimally invasive surgery may result in a slighter shorter length of stay compared to open surgery. Physical training combined with nutritional intervention can improve functional recovery up to one year after surgery. Nutritional supplements can preserve muscle and bone mass, and potentially improve recovery. Patient education in stoma care and prevention of infection can significantly improve self-efficacy and avoid symptoms of infection postoperatively. Moreover, specific devices like applications (apps) can support these efforts. Continued smoking increases the risk of developing postoperative complications while no evidence was found on the impact of continued alcohol drinking. Currently, there is no evidence on psychological well-being, sexual health, or shared decision making interventions with an impact on rehabilitation after radical cystectomy. CONCLUSION: Data are scarce but indicate that peri- and postoperative multi-professional interventions can reduce prevalence of sarcopenia, and improve functional recovery, physical capacity, nutritional status, and self-efficacy in stoma care (level 1 evidence). Continued smoking increases the risk of complications, but the effects of a smoking and alcohol intervention remain unclear (level 3 evidence). The results of this review provide guidance for future directions in research and further attempts to develop and test an evidence-based program for follow-up care after radical cystectomy.

Protective role of intravesical BCG in COVID-19 severity.

OBJECTIVES: To establish the role of BCG instillations in the incidence and mortality of COVID-19. PATIENTS AND METHODS: NMIBC patients in instillations with BCG (induction or maintenance) during 2019/2020 were included, establishing a COVID-19 group (with a diagnosis according to the national registry) and a control group (NO-COVID). The cumulative incidence (cases/total patients) and the case fatality rate (deaths/cases) were established, and compared with the national statistics for the same age group. T-test was used for continuous variables and Fisher's exact test for categorical variables. RESULTS: 175 patients were included. Eleven patients presented CIS (11/175, 6.3%), 84/175 (48.0%) Ta and 68/175 (38.9%) T1. Average number of instillations = 13.25 ± 7.4. One hundred sixty-seven patients (95.4%) had complete induction. Forty-three patients (cumulative incidence 24.6%) were diagnosed with COVID-19. There is no difference between COVID-19 and NO-COVID group in age, gender or proportion of maintenance completed. COVID-19 group fatality rate = 1/43 (2.3%). Accumulated Chilean incidence 70-79 years = 6.3%. Chilean fatality rate 70-79 years = 14%. CONCLUSIONS: According to our results, patients with NMIBC submitted to instillations with BCG have a lower case-fatality rate than the national registry of patients between 70 and 79 years (2.3% vs. 14%, respectively). Intravesical BCG could decrease the mortality due to COVID-19, so instillation schemes should not be suspended in a pandemic.