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The challenging reality of bladder cancer

In 2020, Martin was among the ~204,000 people in Europe diagnosed with bladder cancer.[1] Specifically, Martin was diagnosed with metastatic urothelial carcinoma (mUC), which means that as well as the devastating physical burden of his disease,[2] he faces a 5-year survival rate of ~6.4%.[3]

The patient described is fictional and has been used for illustrative purposes only.

The bladder is a hollow organ in the lower pelvis[4]
The bladder has flexible, muscular walls that can stretch to hold urine and squeeze to send it out of the body.[4] Bladder cancer starts when cells that make up the urinary bladder start to grow out of control.[4]

There are various types of bladder cancer:[5]

Urothelial carcinoma (UC)

which begins in the urothelial cells of the urinary tract and accounts for ~90% of bladder cancers

Squamous cell carcinoma

which begins in squamous cells in the bladder lining and accounts for ~4% of bladder cancers

Adenocarcinoma

which develops from glandular cells and accounts for ~2% of bladder cancers

UC is the most common type of bladder cancer[5]

UC, which is also known as transitional cell carcinoma (TCC), can be located in the lower urinary tract (bladder and urethra) or the upper urinary tract (pyelocaliceal cavities and ureter).[4][6]

Bladder tumours account for 90–95% of UCs and are the most common urinary tract malignancy[6]

Upper urinary tract
Upper urinary tract

Renal pelvis Ureter

Lower urinary tract
Lower urinary tract

Bladder Urethra

Adapted from Fairview, 2021; Rouprêt et al. 2018; American Cancer Society, 2021.[4][6][7]

Smoking is the main risk factor for bladder cancer,[8] other risk factors include:[8][9][10]

Exposure to aromatic amines
Radiotherapy
Chemotherapy with cyclophosphamide
Arsenic exposure in drinking water
Schistosomiasis (a disease caused by parasitic worms)
Genetic factors
Bladder cancer is the fifth most common cancer in Europe[1]

In Europe in 2020, there were ~204,000 new cases of bladder cancer,[1] and ~67,000 deaths.[11]

Europe has amongst the highest incidence rate, and by far the highest mortality rate for bladder cancer worldwide.[8] This is expected to increase by 2030, in part due to the aging European population.[12]

Number of deaths from bladder cancer in Europe in 2020[13]

Numper of deaths from bladder cancer in Europe in 2020

Adapted from International Agency for Research on Cancer/World Health Organization, 2020.[13]

3 times

In Western Europe, bladder cancer is approximately three times more common in men than in women and three times more men die from it.[14]

At Janssen Oncology, we are working tirelessly so that the words “you have bladder cancer”, will be less terrifying for patients to hear and less distressing for healthcare professionals to say

To achieve this, we put our focus where we can make the most difference to patients, partners, and the entire oncology community. Because anything average is unacceptable.

Haematuria, or blood in the urine, is often the first sign of bladder cancer. Other symptoms include:[2][15]

Pain or burning during urination
Frequent urination
Trouble urinating or having a weak urine stream
Urgency to urinate

Symptoms experienced by those suffering from advanced bladder cancer include:[2][15]

Inability to urinate
Lower back pain on one side
Feeling tired or weak
Swelling in the feet
Loss of appetite and weight loss
Bone pain

Several techniques are used to diagnose bladder cancer[2][16]

Urinary tract imaging
  • Using x-rays, magnetic fields, ultrasound waves, or radioactive substances
Cystoscopy
  • Inserting a long, thin, flexible tube with a light and lens/small video camera into the bladder
Transurethral resection of the bladder tumour (TURBT) histology
  • Pathological examination of specimens obtained by TURBT histology (removal of the tumour and some of the surrounding bladder muscle to look for cancer, also used as a treatment)[15]
bladder cancers harbour potentially actionable genetic alterations

61% of bladder cancers harbour potentially actionable genetic alterations[17]

The molecular biomarkers and pathways involved in bladder cancer are key to understanding its biological heterogeneity and identifying specific subtypes that can be used to predict clinical outcomes.[18][19]

The molecular understanding of muscle invasive bladder cancer has led to a consensus classification of tumour classes with distinct oncogenic mechanisms[18]

24%

8%

15%

15%

35%

3%

Luminal papilary

Luminal non-specified

Luminal unstable

Stoma-rich

Basal/squamous

Neuroendocrine-like

Differentiation

Urotheilal/Lumina




Basal

Neuroendocrine

Oncogenic mechanisms

FGFR3+PPARG+CDKN2A-


PPARG+
PPAR+GE2F3+,ERG82+Genomic Instability cellcycle+
EGFR+
TP53-, RB1-,
Cell cycle+
Mutations
FGFR3 (40%)
KDM6A (38%)
ELF3 (35%)
TP53 (76%)
ERCC2 (22%) TTMB+APOBEC+
TP53 (61%)
RB1 (25%)
TP53 (61%)
RB1 (25%)
Stromal inflitrate
Fibroblasts
Smooth muscle
Fibroblasts
Myofibroblast
Fibroblasts
Myofibroblast
Immune infiltrate
B cells
CD8 T cells
NK cells
Histology
Papillary
morphology (59%)
Micropapillary variants (36%)
Squamous
differentiation
(42%)
Neuroendocrine
differentiation
(72%)
Clinical
T2 stage +
Older patients+(80%)
Woman +T3/T4 stage +
Median overall survival (years)

4

1.8

2.9

3.8

2.1

1

APOBEC=apolipoprotein B mRNA editing catalytic polypeptide-like; CD8 T cells=cytotoxic T lymphocytes; CDKN2A=cyclin-dependent kinase inhibitor 2A; E2F3=gene encoding E2F transcription factor 3; EGFR=epidermal growth factor receptor; ELF3=gene encoding E74 like ETS transcription factor 3; ERBB2=gene encoding receptor tyrosine-protein kinase erbB-2; ERCC2=gene encoding XPD protein; FGFR=fibroblast growth factor receptor; KDM6A=gene encoding lysine-specific demethylase 6A; NK cells=natural killer cells; PPARG=peroxisome proliferator-activated receptor gamma; RB1=gene encoding pRB tumour suppressor; STAG2=gene encoding cohesin subunit SA-2; T2=tumour growth into muscle; T3=tumour growth into fat layer; T4=tumour growth outside of the bladder; TMB=tumour mutational burden; TP53=gene encodes p53.
Adapted from Kamoun A et al. 2020.[18]

Alterations in the FGFR family of genes are present in 31.7% of UCs.*[20][21] What’s more, FGFR3 alterations are identified in all grades and stages of UC.[22]

* Based on a study of sequencing data from 4,853 cancers of various types, of which urothelial carcinomas (cancers of the renal pelvis [21 cases], ureter [6], bladder [90], and not otherwise specified [9]) comprised 126 cancers.[21]

Altered FGFR signalling is common in a wide variety of cancers and represents an important potential tumour driver.[20]

bladder_asset

Bladder cancer is staged according to the tumour-node-metastasis (TNM) system[2]

In this system, T describes the extent of local invasion (Tis–T4);[23] N describes whether the tumour has spread to local lymph nodes (N0–N3);[24] and M describes distant metastatic spread (M0-M1b).[2]

Following radical cystectomy for clinically localised disease, up to 50% of patients later develop metastases.[25] Metastasis often occurs in the lymph nodes, bone, lung, liver, and peritoneum.[26]

5-year relative survival rates in bladder cancer vary depending on staging[3]

graph_pre-login_Bladder_cancer

Adapted from National Cancer Institute. 2021.[3]

The time that bladder cancer leaves patients with is often affected by the physical and emotional burden of their illness[27][28][29]

Various factors contribute to the quality of life declines experienced by patients with bladder cancer[27][28][29]
Pain
Impairment of daily living and work activities
General health problems
Chemotherapy-induced toxicity
Impaired mental health
Emotional problems
Reduced energy and fatigue
Impairment of social activities

Bladder cancer patients face harsh physical and emotional challenges.[27] Patients, their families, and the entire oncology community deserve meaningful change.

At Janssen Oncology, our purpose is to make cancer a manageable and, ultimately, curable condition. We’re in pursuit of better outcomes for patients, their families, and the entire oncology community.

ERBB2, Erb-B2 receptor tyrosine kinase 2; BRAF, B-Raf. CCND1, cyclin D1. CTLA-4, cytotoxic T-lymphocyte-associated protein 4. FGFR, fibroblast growth factor receptor. ICI, immune checkpoint inhibitor. MDM2, mouse double minute 2. mUC, metastatic urothelial carcinoma. PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha. PTEN, phosphatase and tensin homolog. TCC, transitional cell carcinoma. TNM, tumour-node-metastasis. TSC1, TSC complex subunit 1. TURBT, transurethral resection of the bladder tumour. UC, urothelial carcinoma.

Date of preparation: June 2021 | CP-230391


References

International Agency for Research on Cancer/World Health Organization. Estimated number of new cases in 2020, Europe, both sexes, all ages. Available at: https://bit.ly/3n5DB4l. Accessed May 2021.
American Cancer Society. Bladder Cancer Early Detection, Diagnosis, and Staging. Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8559.00.pdf. Accessed May 2021.
National Institutes of Health, Surveillance, Epidemiology, and End Results Programme. Cancer Stat Facts: Bladder Cancer. Available at: https://seer.cancer.gov/statfacts/html/urinb.html. Accessed May 2021.
American Cancer Society. About Bladder Cancer. Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8557.00.pdf. Accessed May 2021.
Cancer. Bladder Cancer Introduction. Available at: https://www.cancer.net/cancer-types/bladder-cancer/introduction. Accessed May 2021.
Rouprêt M et al. Eur Urol 2018; 73(1): 111–122.
Fairview. Anatomy of the Pediatric Urinary Tract. Available at: https://www.fairview.org/patient-education/40091. Accessed May 2021.
Antoni S et al. Eur Urol 2017; 71(1): 96–108.
Lopez-Beltran A et al. Semin Diagn Pathol 2018; 35(4): 218–227.
European Association of Urology. Muscle-invasive and Metastatic Bladder Cancer Full Text Guidelines, 3. Epidemiology, aetiology and pathology. Available at: https://uroweb.org/guideline/bladder-cancer-muscle-invasive-and-metastatic/#3. Accessed May 2021.
International Agency for Research on Cancer/World Health Organization. Estimated number of deaths in 2020, Europe, both sexes, all ages. Available at: https://bit.ly/3v2RenO. Accessed May 2021.
Leal J et al. Eur Urol 2016; 69(3): 438–447.
International Agency for Research on Cancer/World Health Organization. Estimated age-standardized mortality rates (World) in 2020, bladder, both sexes, all ages. Available at: https://bit.ly/3ekqbO7. Accessed May 2021.
International Agency for Research on Cancer/World Health Organization. Bladder fact sheet. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/30-Bladder-fact-sheet.pdf. Accessed May 2021.
Bellmunt J et al. Ann Oncol 2014; 25 Suppl 3:iii40–48.
Medscape. Bladder Cancer Guidelines, Diagnosis. Available at: https://emedicine.medscape.com/article/438262-guidelines#g4. Accessed May 2021.
Iyer G et al. J Clin Oncol 2013; 31: 3133–3140.
Kamoun A et al. Eur Urol 2020; 77: 420–433.
Inamura K. Cancers (Basel) 2018; 10(4): 100.
Helsten T et al. Clin Cancer Res 2016; 22(1): 259–267.
Helsten T et al. Clin Cancer Res 2016; 22(1): Supp Info.
Di Martino E et al. Adv Urol 2012; 42913.
Knowles MA et al. Nat Rev Cancer 2015; 15(1): 25–41.
Rena O et al. J Thorac Dis. 2016; 8(11): 3049–3052.
Svatek RS et al. Can Urol Assoc J 2009; 3(6 Suppl 4): S228–S231.
Kobayashi T et al. Asian J Urol. 2016 Oct; 3(4): 211–222.
Smith AB et al. BJU Int 2018; 121(4): 549–557.
Lehmann J et al. Crit Rev Oncol Hematol 2003; 47(2):171–179.
Winters BR et al. J Urol 2018; 199(3): 669–675.