Bladder Cancer - Volume 7, issue 2

Authors: Noval Rivas, Magali | Rosser, Charles J. | Arditi, Moshe

Article Type: Review Article

Abstract: Despite the implementation of mitigation measures, Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still spreading worldwide, and has caused more than 1 million deaths so far. Although recent reports indicate that three vaccine candidates are effective against SARS-CoV-2, more time is needed to generate enough doses for the general population. Meanwhile, frontline healthcare workers are at high risk of SARS-CoV-2 exposure. To avoid collapse of the medical care system, there is a need to develop novel approaches to limit SARS-CoV-2 spread. Through a process called trained immunity, the Bacillus Calmette-Guerin (BCG) vaccine boosts …the action of innate immune cells, resulting in a nonspecific reduction in the incidence of viral infections. Due to this immunomodulatory action, the BCG vaccine is currently used as a therapeutic in bladder cancer. Data collected from epidemiological and observational studies indicate that BCG vaccination might provide protection against COVID-19. While these observations do not provide evidence of causality and are limited by cofounding and intrinsic biases, it is crucial to explore the hypothesis that BCG vaccination may provide a nonspecific innate immune boost and therefore protect against COVID-19 in randomized controlled clinical trials, particularly for people at higher risk of developing COVID-19, such as frontline healthcare workers. Show more

Keywords: BCG, SARS-COV-2, COVID-19, clinical trials

DOI: 10.3233/BLC-201529

Citation: Bladder Cancer, vol. 7, no. 2, pp. 121-131, 2021

Authors: Zhang, Dingguo | Tian, Jinjun | Xia, Qier | Yang, Zhenyu | Gu, Bin

Article Type: Research Article

Abstract: BACKGROUND: Bladder cancer is still a disease of significant morbidity and mortality. In bladder cancer, RB1 is one of the most common mutant genes. METHODS: In this study, we explored the Genomics of Drug Sensitivity in Cancer (GDSC) database for drug sensitivity. The latest TCGA data were downloaded for analysis. To deal with functional enrichment analysis, GSEA, KEGG and GO were used. Prognostic analyses have been carried out using the GEPIA online tool. RESULTS: Results from the GDSC database showed that bladder cancer cells with RB1 mutation are more resistant to Dactolisib, MK-2206 and …GNE-317. RB1 mutation was found in 25%bladder cancer patients. Patients with RB1 mutation often had lower RB1 mRNA expression level and higher histologic grade. In addition, we identified 999 differentially expressed genes in both groups. Functional enrichment analysis suggested that DEGs were primarily enriched in multiple metabolic progressions, cell proliferation and cancer related pathways. There were strong correlations between WT1, GPR37, CHRM2 and EZH2 expression levels and the prognosis. CONCLUSIONS: In all, the significance of RB1 mutation in disease progression and drug selection in bladder cancer was suggested by our results, and multiple genes and pathways related to such a program were identified. Show more

Keywords: Bladder cancer, RB1 mutation, TCGA, RNA sequencing, bioinformatics analysis, drug selection

DOI: 10.3233/BLC-200368

Citation: Bladder Cancer, vol. 7, no. 2, pp. 133-142, 2021

Authors: Grivas, Petros | Kiedrowski, Lesli A. | Sonpavde, Guru P. | Gupta, Sumati V. | Thomas, Roby A. | Gourdin, Theodore S. | Hardin, Aaron I. | Hamann, Kimberly M. | Faltas, Bishoy M. | Vogelzang, Nicholas J.

Article Type: Short Communication

Abstract: Detecting genomic alterations (GAs) in advanced urothelial carcinoma (aUC) can expand treatment options by identifying candidates for targeted therapies. Erdafitinib is FDA-approved for patients with platinum-refractory aUC with activating mutation or fusion in FGFR2/3 . We explored the prevalence and spectrum of FGFR2/3 GAs identified with plasma cfDNA NGS testing (Guardant360) in 997 patients with aUC. FGFR2/3 GAs were detected in 201 patients (20%) with characterized activating GAs in 141 (14%). Our results indicate the Guardant360-based FGFR2/3 GA detection rate is similar to those described from previous studies employing tumor tissue testing, suggesting that plasma-based cfDNA NGS …may non-invasively identify candidates for anti-FGFR targeted therapies. Show more

DOI: 10.3233/BLC-201517

Citation: Bladder Cancer, vol. 7, no. 2, pp. 143-148, 2021

Authors: Richards, Helen L. | Sweeney, Paul | Corscadden, Rebekah | Carr, Chelsea | Rukundo, Aphie | Fitzgerald, Jill | O’Connor, Charles | Fortune, Dónal G.

Article Type: Research Article

Abstract: BACKGROUND: There is a paucity of data regarding patient experiences of living with non-muscle-invasive bladder cancer (NMIBC). OBJECTIVES: To investigate patients’ beliefs about NMIBC utilising both a well-established verbal/linguistic method, the Brief Illness Perception Questionnaire (B-IPQ) in addition to a novel visual/perceptual method, that is, asking patients to draw their bladder as it is now and as they perceive it will be in the future. METHODS: Cross-sectional study of patients with NMIBC. Patients completed: (i) the B-IPQ, and (ii) 2 drawings of their bladder: as they perceived it currently and as they perceived it would look …in 5 years’ time. RESULTS: A total of 118 patients completed the B-IPQ, of which 96 produced 2 bladder drawings. Forty-seven per cent of patients depicted no change in their bladder across time, 35% depicted improvements, while 18% drew their NMIBC as deteriorating between the two time points. Patients who drew their NMIBC worsening over time reported significantly stronger beliefs in the severity of current consequences from their NMIBC (F(2,94) = 9.07, p  < 0.001, m  = 5.68, 95% CI 4.38–6.88) and greater current concerns about their NMIBC (F(2,94) = 6.17, p  < 0.01, m  = 7.06, 95% CI 5.47–8.66). This was unrelated to cancer grade, cancer stage, treatment or demographic variables. CONCLUSION: This is the first study to explore beliefs about NMIBC in a sample of patients with NMIBC attending routine clinics using both a well-established and a novel method of assessing patients’ perceptions. Results highlight the usefulness of a simple non-verbal technique, in identifying patients’ concerns about the condition. Almost one fifth of patients with NMIBC may experience significant concerns about the worsening of their condition, which appear to be independent of demographic, histopathological, and treatment related variables. Further exploration of the psychological concerns of individuals with NMIBC is required in order to appropriately plan for needs led multidisciplinary approach in their care. Show more

Keywords: Non-muscle-invasive bladder cancer, illness perceptions, psychological, fear of cancer recurrence, psycho-oncology

DOI: 10.3233/BLC-201528

Citation: Bladder Cancer, vol. 7, no. 2, pp. 149-159, 2021

Authors: Jahnson, Staffan | Gårdmark, Truls | Hosseini, Abolfazl | Jerlström, Tomas | Liedberg, Fredrik | Malmström, Per-Uno | Hagberg, Oskar | Sherif, Amir | Ströck, Viveka | Söderkvist, Karin | Ullen, Anders | Häggström, Christel | Holmberg, Lars | Aljabery, Firas

Article Type: Research Article

Abstract: BACKGROUND: Routine VTE prophylaxis within 30 days of radical cystectomy (RC) for urinary bladder cancer (UBC) is used to protect from venous thromboembolism (VTE). However, randomized studies and nationwide population-based studies are lacking. OBJECTIVE: To study VTE and risk factors for VTE in muscle-invasive UBC in a nationwide population-based series, with a focus on the association with RC with and without chemotherapy. MATERIALS AND METHODS: We studied all patients with clinical stage T2-T4 UBC diagnosed 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe). Previous VTE events and risk factors for VTE were registered …from 1987. Cox regression analyses and Kaplan-Meier curves were performed to study risk factors for VTE and cumulative incidence of VTE. RESULTS: In 9720 patients (71%males) with a median age of 74 years 546 (5.6%) had VTE after diagnosis. In Cox analyses controlling for patient’s and tumour characteristics, and risk factors for VTE, VTE after diagnosis and first treatment date were associated with chemotherapy with or without RC. Cumulative incidence of VTE increased during 24 months after diagnosis and first treatment date. VTE were less common in patients with previous cardiovascular disease. CONCLUSIONS: VTE was commonly observed after 30 days from diagnosis and from first treatment date in patients with T2-T4 UBC, particularly after chemotherapy. The findings suggest that long-term intervention studies of benefit and possible harms of VTE prophylaxis after UBC should be undertaken. Show more

Keywords: Bladder cancer, population-based, venous thromboembolism, chemotherapy, cystectomy, prophylaxis

DOI: 10.3233/BLC-200409

Citation: Bladder Cancer, vol. 7, no. 2, pp. 161-171, 2021

Authors: Schuettfort, Victor M. | Pradere, Benjamin | Mostafaei, Hadi | Laukhtina, Ekaterina | Mori, Keiichiro | Quhal, Fahad | Motlagh, Reza Sari | Rink, Michael | Karakiewicz, Pierre I. | Deuker, Marina | Moschini, Marco | Stolzenbach, Lara Franziska | Trinh, Quoc-Dien | Briganti, Alberto | D’Andrea, David | Shariat, Shahrokh F.

Article Type: Research Article

Abstract: BACKGROUND: Radical cystectomy (RC) is the standard treatment for muscle invasive bladder cancer, but approximately half of all patients will ultimately succumb to disease progression despite apparent cure with extirpative surgery. Elderly patients are at especially high risk of advanced disease and may benefit from perioperative systemic therapy. OBJECTIVE: To assess the real-world benefit of adjuvant chemotherapy (AC) in patients ≥75 years old. METHODS: We retrospectively reviewed patients who underwent RC for non-metastatic urothelial carcinoma of the bladder (UCB) from 12 participating international medical institutions. Kaplan-Meier survival curves and Cox regression models were used to assess …the association between age groups, administration of AC and oncological outcome parameters such as recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: 4,335 patients were included in the analyses, of which 820 (18.9%) were ≥75 years old. These elderly patients had a higher rate of adverse pathologic features. In an univariable subgroup analysis in patients ≥75 years with lymph node metastasis, 5-year OS was significantly higher in patients who had received AC (41% vs. 30.9%, p = 0.02). In a multivariable Cox model that was adjusted for several established outcome predictors, there was a significant favorable association between the administration of AC in elderly patients and OS, but no RFS or CSS. CONCLUSIONS: In this large observational study, the administration of AC was associated with improved OS, but not RFS or CSS, in elderly patients treated with RC for UCB. This is of clinical importance, as elderly patients are more likely to have adverse pathologic features and experience worse survival outcomes. Treatment of UCB should include both a multidisciplinary approach and a geriatric evaluation to identify patients who are most likely to tolerate and benefit from AC. Show more

Keywords: MIBC, NMIBC, bladder cancer, elderly, adjuvant chemotherapy, systemic therapy, transitional cell carcinoma

DOI: 10.3233/BLC-200391

Citation: Bladder Cancer, vol. 7, no. 2, pp. 173-185, 2021

Authors: Modai, Jonathan | Kovalyonok, Alexey | Scherz, Avigdor | Preise, Dina | Avda, Yuval | Shpunt, Igal | Sasson, Keren | Jaber, Morad | Peretz, Yamit | Croock, Roy | Shilo, Yaniv | Ikher, Sergey | Lindner, Uri | Leibovici, Dan

Article Type: Research Article

Abstract: BACKGROUND: Urologic guidelines recommend perioperative instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) to decrease tumor recurrence, yet implementation of this recommendation is partial due to associated morbidity. Hypertonic saline destroys cells by osmotic dehydration and might present a safer alternative. OBJECTIVE: To evaluate the safety of 3% hypertonic saline (Hypersal) intravesical instillation following TURBT in rats and in humans. METHODS: In 8 rats whose bladders were electrically injured, intravesical blue-dyed Hypersal was administered. We measured serum sodium levels before and after instillation and pathologically evaluated their pelvic cavity for signs of inflammation or …blue discoloration. Twenty-four patients were recruited to the human trial (NIH-NCT04147182), 15 comprised the interventional and 10 the control group (one patient crossed over). Hypersal was given postoperatively. Serum sodium was measured before, 1 hour and 12–24 hours after instillation. Adverse effects were documented and compared between the groups. RESULTS: In rats, average sodium levels were 140.0 mEq/L and 140.3 mEq/L before and following instillation, respectively. Necropsy revealed no signs of inflammation or blue discoloration. In humans the average plasma sodium levels were 138.6 mEq∖L, 138.8 mEq∖L and 137.7 mEq∖L before, 1 hour and 12–24 hours after instillation, respectively. During the postoperative follow-up there was one case of fever. A month after the surgery, dysuria was reported by 5 patients while urgency and hematuria were reported by one patient each. The most severe adverse events were grade 2 on the Clavien-Dindo scale. Adverse events were similar in the control group. CONCLUSIONS: Hypersal instillation is safe and tolerable immediately after TURBT. Show more

Keywords: Bladder tumor, intravesical instillation, hypertonic saline solution, clinical trial, phase 1, animal research

DOI: 10.3233/BLC-200328

Citation: Bladder Cancer, vol. 7, no. 2, pp. 187-192, 2021

Authors: van Hoogstraten, Lisa M.C. | Witjes, J. Alfred | Ripping, Theodora M. | Nooter, Ronald I. | Kiemeney, Lambertus A. | Aben, Katja K.H.

Article Type: Research Article

Abstract: BACKGROUND: EAU guidelines recommend a single instillation (SI) of intravesical chemotherapy (e.g. Mitomycin C) within 24 hours after transurethral resection of a bladder tumour (TURBT) in patients with low- to intermediate risk non-muscle invasive bladder cancer without (suspected) bladder perforation or bleeding requiring bladder irrigation. However, remarkable variation exists in the use of SI. The risk of severe complications is likely to contribute to this variation, but evidence is limited. OBJECTIVE: To investigate the absolute severe complication and mortality risk after SI in low- and intermediate risk bladder cancer. METHODS: In this observational, historic cohort study, …data on 25,567 patients diagnosed with TaG1G2 urothelial bladder carcinoma (UBC) between 2009 and 2018 who underwent TURBT were collected from the Netherlands Cancer Registry. Data were supplemented with information on cause of death and severe complications after cancer treatment by re-examining the electronic health records and the 14-day complication risk and the 30-day mortality risk were evaluated. RESULTS: On average, 55% of patients had a SI after TURBT, varying from 0–>80% between hospitals. The 30-day mortality risk was 0.02% and the 14-day risk of severe complications was 1.6%. CONCLUSIONS: As the absolute risk of mortality and severe complications is very low, SI after TURBT can be considered a safe treatment in patients with low- to intermediate UBC without contraindications for SI. These results imply that a part of eligible patients is denied effective treatment. Show more

Keywords: Non-muscle invasive bladder cancer, NMIBC, urothelial carcinoma, intravesical instillation, complications, treatment guidelines, variation in healthcare

DOI: 10.3233/BLC-201515

Citation: Bladder Cancer, vol. 7, no. 2, pp. 193-203, 2021

Authors: Kimura, Takahiro | Onuma, Hajime | Sato, Shun | Inaba, Hiroyuki | Fukuokaya, Wataru | Urabe, Fumihiko | Kimura, Shoji | Tashiro, Kojiro | Tsuzuki, Shunsuke | Miki, Jun | Furuta, Akira | Takahashi, Hiroyuki | Egawa, Shin

Article Type: Research Article

Abstract: BACKGROUND: The impact of incidental prostate cancer (IPC) on oncological outcomes after radical cystoprostatectomy (RCP) specimens from patients with bladder cancer (BC) remains controversial. This relationship has not been well elucidated in Asian countries, where the incidence of prostate cancer has recently shown dramatic increases. OBJECTIVES: This study retrospectively compared pathological features and oncological outcomes between BC patients with and without IPC in the RCP specimens. METHODS: This study included 142 men who underwent RCP for BC. Men who were previously diagnosed with prostate cancer were excluded. Each prostate gland and seminal vesicle was processed as …whole mounts and 4-mm close-step sectioning was performed. A single genitourinary pathologist diagnosed IPC. The pathological features and oncological outcomes such as overall survival (OS), bladder cancer-specific survival (BCSS), and progression-free survival (PFS) were compared between patients with IPC (IPC+group, n  = 45) and without IPC (IPC- group, n  = 97). P values less than 0.05 considered to indicate statistical significance for patients’ characteristics. Because of multi-primary endpoint, P values less than 0.0167 was considered statistical significance for oncological outcomes. RESULTS: We detected IPC in 45 RCP specimens (31.6%). Patients in the IPC- group were significantly younger at surgery than those in the IPC+group (P  < 0.001). The pathological features of the RCP specimens did not differ significantly. In multivariable analyses, presence of IPC was significantly associated with worse OS (P  = 0.005), but not with either BCSS or PFS (P  = 0.038 and 0.326, respectively). In Kaplan–Meier analyses, OS tended to be longer in the IPC- group than that in the IPC+group (NR vs 65 months, P  = 0.0017). CONCLUSIONS: Our results suggested significantly better OS in patients without IPC than that in those with IPC. Show more

Keywords: Bladder cancer, incidental cancer, prostate cancer, pathology, Japanese

DOI: 10.3233/BLC-200396

Citation: Bladder Cancer, vol. 7, no. 2, pp. 205-211, 2021

Authors: Patschan, Oliver | Spiess, Philippe E. | Thalmann, George N. | Redorta, Joan Palou | Gakis, Georgios

Article Type: Systematic Review

Abstract: BACKGROUND: In patients with non-invasive urothelial carcinoma of the prostatic urethra (PUC), treatment with Bacillus Calmette-Guérin (BCG) could be beneficial. OBJECTIVE: To assess the response rates to BCG in the different tumor stages, to describe the clinical impact of transurethral resection of the prostate (TURP) before BCG treatment, and to review the side effects of BCG treatment for PUC. METHODS: A systematic search was conducted using the PubMed database to identify original studies between 1977 and 2019 reporting on PUC and BCG. RESULTS: Of a total of 865 studies, ten were considered for evidence …synthesis. An indication for BCG treatment was found in non-stromal invasive stages (Tis pu, Tis pd) and in stromal infiltrating cases (T1) of primary and secondary PUC when transitional cell carcinoma was the histology of origin. Studies including patients treated with TURP before BCG showed a better local response in the prostatic urethra with a higher disease free survival (DFS) (80–100% vs. 63–89%) and progression free survival (PFS) (90–100% vs. 75–94%) than patients in studies in which no TURP was performed. However, this difference in recurrence and progression in the prostate neither affected the total PFS (57–75% vs. 58–93%), nor the disease specific survival (70–100% vs. 66–100%). CONCLUSIONS: The use of resection loop biopsies of the prostatic urethra in appropriate cases during the primary work-up for suspected PUC, as well as the use of the current TNM classification for PUC, need to be improved. BCG therapy for non-stromal invasive stages of PUC show a good local response. Local response is further improved by a TURP before BCG therapy, although the overall prognosis does not seem to be affected. Further evidence for BCG treatment in the rare cases of stromal invasive PUC is needed. Specific side effects of BCG treatment for PUC are not reported. Show more

Keywords: BCG, transitional carcinoma, prostatic urethra

DOI: 10.3233/BLC-201516

Citation: Bladder Cancer, vol. 7, no. 2, pp. 213-220, 2021