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Challenges and Opportunities in Bladder Cancer

Challenges and Opportunities in Bladder Cancer

Harrison, T. R., Muhamad, J., & Malova, E. (2022)


Objective: This paper provides a review of current knowledge and trends in research on firefighters cancer risks and risk reduction efforts and calls for future research focused on European and international firefighters to understand and reduce occupational cancer risk.

Cancer incidence: Firefighters face increased occupational cancer risk.  Firefighting has been linked with multiple types of cancer, including bladder, colorectal, brain and central nervous system, non-Hodgkin’s lymphoma, skin melanoma, and prostate and testicular cancer, with several others types of cancer being found at increased rates.

Cancer risks: Increased occupational cancer risk is, in part, related to carcinogenic exposures at fire events and improper use and cleaning of personal protective equipment (PPE), with role and years in service increasing risk.

Risk Perception: Research on efforts to reduce cancer risk are growing, and include examination of firefighter knowledge, attitudes, norms, and behaviors toward decontamination, screening, and healthy eating. Many firefighters report high perceived susceptibility and severity of cancer risk, and identify fire scene exposures, contaminated gear, diet, sleep disruption, chemical exposure from cleaning products, and barriers to medical care as contributing to increased risk.

Risk Reduction: Firefighters have strong desire to reduce cancer risk and report generally favorable attitudes toward decontamination practices and proper gear use, but face barriers to reducing those risks, including lack of knowledge, occupational needs, organizational culture, policy, and lack of resources. Behavioral interventions to reduce cancer risk through decontamination efforts and dietary change have demonstrated positive results, however there is a dearth of research on these efforts, especially with European and international firefighters.

Future Directions: Future research should focus on understanding European and international firefighters’ knowledge, attitudes, and behaviors toward cancer risk reduction, the impact of the built environment on cancer risk (station layout, clean cabs), improved efforts at tracking exposures, use of new technology and virtual reality in training to reduce cancer risk, and improved understanding of firefighter cancer risk by medical professionals.

Abdsessater, M., Boustany, J., Kanbar, A., Kassis, A., Hachem, C. E., Saad, R., Dabal, C., Boueiri, S., Assaf, S., Khoury, J., Halabi, R., & Khoury, R. E. (2023)


Introduction and objectives: Nicotine is well known to be an addictive compound of tobacco, but it is not primarily carcinogenic. It is metabolized to cotinine, which is considered the best marker of tobacco exposure. Little is known whether recurrence rate of bladder cancer is related to nicotine metabolites eliminated in urine. We aim by this study to evaluate the relation between urinary cotinine level and the recurrence of bladder cancer.

Materials and Methods: Between January 2018 and June 2022, a cross sectional study was conducted. Enrolled patients were smokers already diagnosed with non-muscle invasive bladder cancer, treated by resection only, and presenting for a follow up cystoscopy. Included patients had unchanged smoking habits in the day before the procedure, same ethnicity (Caucasians) and no additional professional exposure. Cotinine level was measured on a sample of voided urine before cystoscopy. Tumor recurrence was considered positive independently from the histological type, and was assessed by direct vision cystoscopy. Patients were considered moderate or heavy smokers depending on the level of cotinine in their urine samples (< or > 550 ng/ml respectively). A Fisher Exact Test was used to assess the relationship between variables.

Results: A total of 135 patients was included. Mean age was 64 years (range 36 to 78). The mean duration of smoking was 30.3 years. Urinary cotinine level was > 550 ng/ml in 80 patients (59.26%) and < 550 ng/ml in 55 patients (40.74%). Recurrence was identified in 70 patients (51.85%) and was absent in the remaining 65 (48.15%). Recurrence was observed in 68.75% of the heavy smokers and in 27.27 % of moderate smokers. Cotinine level higher than 550 ng/mL was linked to an increased risk of bladder cancer, with a relative risk of 4.16 (p-value < 0,025).

Conclusion: High urinary cotinine levels (>550 ng/ml) conveys a 4 folds’ risk for the recurrence of bladder cancer in smokers. Additional prospective studies are needed to better understand the relation between urinary cotinine levels and bladder cancer, and its usefulness in bladder cancer surveillance.

Van Ginkel, N., Meijer, D., Boormans, J. L., Mertens, L. S., Van Beek, S., & Vis, A. N. (2023)


Introduction Radical cystectomy improves survival of patients with muscle invasive and high-risk non-muscle invasive bladder cancer, but is a challenging surgical procedure as patients may experience major complications after surgery.

Objectives To assess the incidence of Clavien-Dindo ≥3 complications in patients who underwent radical cystectomy and to assess the association of these complications with pre-operative and peroperative parameters. The secondary aim was to study the association of complications with long-term oncological outcome.

Methods A nationwide registry was set up in 19 Dutch hospitals that studied patients with muscle invasive bladder cancer and high-risk non-muscle invasive bladder cancer treated by radical cystectomy. Major complications were classified as complications that were related to uretero-ileal anastomosis, intra-abdominal (e.g. urinoma, bowel leakage) infectious and cardiovascular complications. Multivariable logistic regression analyses were performed to assess the correlation between these groups and perioperative, clinical and pathological factors. Kaplan-Meier survival curves were constructed to analyze the correlation between complications and overall survival.

Results The study population consisted of 1,464 patients, of whom 420 (29%) developed severe complications. The most common complications were intra-abdominal (n=328, 60%) and uretero-ileal anastomosis related (n=92, 17%). Male gender (odds ratio 1.6, p=0.007), American Society of Anaesthesiologists score ≥3 (odds ratio 1.6, p=0.003), Charlson Comorbidity Index score ≥5 (odds ratio 2.1, p=0.002) and blood loss >700ml (odds ratio 1.4, p=0.044) were associated with severe complications. In addition, open radical cystectomy was associated with multiple complications (odds ratio 2.6, p=0.001). Furthermore, the overall survival of patients with major complications was worse than those who had no major complications. The median overall survival was 3.8 years versus 6.2 years for patients with and without severe complications (p<0.001).

Conclusions In a real-world setting, 29% of patients undergoing radical cystectomy developed severe complications. The risk of severe complications was higher in men, patients with impaired pre-operative condition, and in those who underwent open surgery. Severe complications had a negative impact on overall survival.

Gergelis, K. R., Breen, W., & Choo, R. (2022)


Muscle-invasive bladder cancer (MIBC) typically affects older adults, with a median age at diagnosis of 73.   Due to its aggressive disease course, definitive treatment is required.  With curative-intent treatment, patients with muscle-invasive bladder cancer have an overall survival ranging from 48-57% with a cancer-specific survival ranging from 52-71% at 5 years.

Radical cystectomy (RC) +/- neoadjuvant chemotherapy (CHT) has been considered a standard of care for MIBC. However, RC carries a high incidence of perioperative complications, including a mortality rate of 1.5-3%.  In addition, many elderly patients with bladder cancer suffer from additional comorbidities, prohibiting RC.  These patients are often not offered other curative treatment options.  Untreated patients with MIBC are at a very high risk of mortality, with five-year overall survival and cancer-specific survival of approximately 5% and 14%, respectively.  Tri-modality therapy (TMT), incorporating maximal transurethral bladder tumor resection, radiotherapy, and CHT, is efficacious with a relatively low incidence of major toxicity for MIBC. As a result, TMT has been acknowledged as a viable alternative to RC, and an attractive option for elderly patients who often have major medical comorbidities and/or prefer bladder-preservation.

The object of this review is to discuss the utility, rationale, and efficacy of TMT in elderly patients, which can offer a curative treatment for life-threatening MIBC but also safeguard the quality of life with organ-preservation.

Gao, L., Ni, J., Shi, X., Gao, S., Zuo, L., & Zhang, L. (2023)


Background: The significance of interleukin-10(IL-10) on the susceptibility of malignant tumor is one of the hot spots of current research. 1082A > G (rs1800896) and -819C > T (rs1800871) are two genetic variants of IL-10, and their effects on malignancy need to be further explored. Therefore, in order to further explore the relationship between IL-10 polymorphisms and cancer susceptibility and the role of IL-10 in the occurrence and development of malignant tumors, in this paper, we use of odds ratios (ORs), corresponding 95% confidence intervals (CIs), and in silico tools. analysis to study the relationship between the two. Furthermore, GSEA was used to analyze the expression of IL-10 in renal cell carcinoma, bladder cancer and prostate cancer. We conducted a systematic analysis of 50 controlled trials involving 15,418 cancer patients and 18,597 controls. The analysis showed that the -1082A>G (rs1800896) and -819C>T (rs1800871) polymorphism were associated with the risk of bladder cancer. GSEA showed that IL-10 was highly expressed through the Cytokine-Cytokine-receptor-interaction pathway, JSK-STAT-signaling pathway, Natural killer cell mediated cytotoxicity pathway and Leukocyte transendothelial migration pathway.

Martellini, M., Leung, K. N., Gherardi, G., & Falzone, L. (2023)


Alpha-particle emitting radioisotope Actinium225 (225Ac) is of great interest for use in Targeted Alpha Therapy (TAT) treatments of e.g., brain tumors, bladder cancer, neuroendocrine tumors and leukemia. A suitable 225 Ac radioligand is also potentially resolutive for the treatment of advanced and metastatic Castration-Resistant Prostate Cancers (mCRPCs). The mCRPC has a mean survival rate of 9-36 months and encompasses a heterogeneous ample range of molecular cancer behavior with a high risk of progression.

Global demand for the 225 Ac has spurred several production efforts including extraction from 233U, high energy protons or photon irradiation of 226Ra or spallation of 232Th by, at least, 100 MeV protons. Instead of using accelerators systems such as cyclotrons or LINACs, a Compact Neutron Generator (CNG) system has been developed. A 400kV-10 mA DC (D_7Li) CNG potentially able to produce substantial amount of 225Ac with low 227Ac impurities is here presented. Exploiting the high flux of 10 and 13 MeV energy neutrons generated by the (D_7Li) reactions to bombard a thin target layer of 226Ra, 225Ra/225Ac is produced via the 226Ra(n,2n)225Ra nuclear reaction. By irradiating a 5 mm thick 226Ra layer for 100 hours, about 11-13 mCi of 225Ac can be produced – corresponding to the TAT treatment of about 65 oncological patients – with an estimated 227Ac contamination of about one percent, which is below the acceptable limit for clinical use. This 225Ac production scheme by a suitable CNG should allow to adopt a local/regional approach avoiding the shipment costs of 225Ac.

The aim of this paper is to inform the production chain of radioisotopes to be used in medical field and the medical community involved in the application of radiopharmaceuticals for the cure of cancer, that a new technology based on Compact Neutron Generators (CNG) is in a R&D phase and will allow to produce the necessary quantity of radioisotopes for clinical and research purpose. This will be essential in treatment advanced metastatic cancer as for instance the metastatic Castration – Resistant Prostate Cancer.

Jana, B., Rischall, A., & Gibson, D. C. (2023)


Urothelial carcinoma therapy is a rapidly evolving and expanding field. Traditional cytotoxic chemotherapy regimens have not produced optimal long-term outcomes, and many urothelial cancer patients have comorbidities that disqualify them as chemotherapy candidates. In recent years, a plethora of novel therapeutic agents that target diverse molecular pathways has emerged as alternative treatment modalities for not only metastatic urothelial carcinoma, but also for muscle-invasive bladder cancer and non-muscle invasive bladder cancer in adjuvant and definitive settings. This review paper aims to discuss the various categories of therapeutic agents for these different types of urothelial cancer, discussing immunotherapy, antibody-drug conjugates, kinase inhibitors, CAR-T cell therapy, peptide vaccination, and other drugs targeting pathways such as angiogenesis, DNA synthesis, mTOR/PI3K/AKT, and EGFR/HER-2.