Bladder Cancer Fast Facts

  • Begins in the urothelial cells lining the inside of the bladder
  • Urothelial bladder carcinoma type (UBC) accounts for the majority of bladder cancer (~90%)1
  • It is the 6th most common cancer in the U.S.; approximately 2.3% of men and women will be diagnosed in their lifetime2
  • There is a strong male predominance, with male to female ratio of 4:1
  • Cigarette smoking and environmental exposure account for >50% of cases3
  • There is no standard or routine screening tests for UBC in asymptomatic individuals
  • Work up for UBC is initiated with evidence of microscopic hematuria (≥ 3 RBC/HPF*)4 or gross hematuria
  • Most common presenting symptoms include: painless hematuria (80% of patients), irritative symptoms and flank pain5

Bladder Cancer Risk Factors

  • Smoking (> 50% attributed to exposure)
  • Age (90% of diagnosis older 55yo)
  • Sex (4:1 male to female ratio)
  • Chronic infections and irritation
  • Family history (two-fold increase)6
  • Environmental exposure to arsenic, hair dye and industrial chemicals (account for 6.5% UBC diagnosis) 7

Bladder Cancer Testing

  • Urinalysis (looks for blood in the urine)
  • CT or MR Urogram
    • Evaluates upper urinary tract for lesions (kidneys and ureters)
    • Use of iodinated contrast acceptable with GFR*≥ 458
  • Cystoscopy
    • In-office evaluation to look for bladder abnormalities
  • Urine Cytology
    • Looks for abnormal or cancer appearing cells
    • Not used as a primary method for diagnosis; limited sensitivity
  • Routine blood work: Complete Blood Count, and Metabolic Profile
    • Obtain prior to imaging with iodinated contrast
  • Transurethral resection or biopsy of suspicious lesion
    • If tumor is suspected on imaging or seen on cystoscopy, additional biopsy in the operating room is necessary

Bladder Cancer Prognosis

While the overall 5-year survival among all bladder cancer patients is around 76%, this number varies however, based on tumor stage, histopathology, grade and response to treatment.9

Bladder Cancer Tumor Histology

Bladder cancer histology can be classified as urothelial or non-urothelial. While majority of bladder cancer is considered urothelial (~90%),  non urothelial variants do exist including:

  • Squamous Cell Carcinoma (2.7%)10
    • Adenocarcinoma (1.4%)10
    • Neuroendocrine differentiation (i.e. Small Cell Carcinoma; 1%)10


Bladder cancer staging is based depth of invasion, starting with superficial inner lining, and progressing through lamina propria(T1) and muscle layers of the bladder (T2). Increasing involvement of the fat surrounding the bladder (T3) and nearby structures (T4), or lymph nodes (N+) designates advanced bladder cancer.

Chalasani V, Chin JL, Izawa JI. Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer. Can Urol Assoc J. Dec 2009;3(6 Suppl 4):S193-8.
Chalasani V, Chin JL, Izawa JI. Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer. Can Urol Assoc J. Dec 2009;3(6 Suppl 4):S193-8.


Grade is a categorization of a continuously increasing nuclear atypia, mitotic activity, and pattern of urothelial cancer cells.11 Tumor grade is an essential risk factor for progression and disease management in non-muscle invasive bladder cancer (NMIBC).

  • Cells considered low grade show minimal deviation from the morphology of the normal urothelium
  • Cells considered high grade display high nuclear atypia, lack of cohesion, and cell disorder

Bladder Cancer Survival Rates

Survival is based on grade, stage of disease, and tumor histology. The reported 5-year OS* in patients diagnosed with bladder cancer12:

Incidence, survival and mortality rates of stage-specific bladder cancer in United States: a trend analysis. Cancer Epidemiol. Jun 2013;37(3):219-25.
Incidence, survival and mortality rates of stage-specific bladder cancer in United States: a trend analysis. Cancer Epidemiol. Jun 2013;37(3):219-25.

Available Predictive Tools

  • EORTC model (European Organization for Research and Treatment of Cancer) allows providers to calculate the probability of recurrence and progression over 1-5 years based on patient’s clinical and tumor characteristics. This predictive model can only be utilized for Stage 0/I disease (NMIBC)13.
  • IBCNC model (International Bladder Cancer Nomogram Consortium) predicts the risk of recurrence at 5 year following radical cystectomy and pelvic lymph node dissection. Nomogram accuracy (75%) exceeds AJCC TNM staging alone (68%)14.
  • MSKCC model (Memorial Sloan-Kettering Cancer Center) postoperative nomogram predicting risk of recurrence after radical cystectomy. Similar to IBCNC model, it outperforms AJCC TNM staging in accuracy15.  Both IBCNC and MSKCC models are used in muscle invasive bladder cancer (pT2 and higher).

Bladder Cancer Management

Management of UBC is dependent on stage of disease at presentation, as well as consideration of patient goals and side effects of treatment. Many times, the best option may include more than one type of treatment or combination of different treatments (chemotherapy, radiation, and surgery).

Treatment of Non-Muscle Invasive Bladder Cancer

  • Bladder preservation is key
    • Optimal removal of all visible lesions with transurethral resection followed by installation of intravesical chemotherapy or immunotherapy BCG (Bacillus Calmette-Guerin)
    • Treatment duration and frequency vary based risk stratification16

Treatment of Muscle Invasive Bladder Cancer

  • Upfront neoadjuvant chemotherapy followed by radical cystectomy remains the gold standard care for locally invasive Stage II-IV non metastatic UBC
    • Receipt of neoadjuvant chemotherapy (NAC) prior to surgery improves 5-year OS and disease free survival by 5-10%17
    • Bladder preservation therapy is a reasonable option for patients medically unfit for surgery or seeking an alternative. It is comprised of: Aggressive resection of all visible tumorChemotherapyRadiation

Treatment of Metastatic Bladder Cancer

  • Cisplatin containing combination chemotherapy is standard in advanced or metastatic UBC
    • Patients not eligible for cisplatin-based chemotherapy, are eligible for immunotherapy such as Atezolizumab18 or Pembrolizumab19

Considerations of Specific Treatment Modalities

  • Surgery
    • Radical cystectomy (RC)with bilateral pelvic lymph node dissection (PLND) is the standard of care in MIBC. Surgery is also an option for patients with persistent high-grade cancer after several courses of intravesical therapy
    • Upon removal of the bladder, urinary continuity may be reconstructed as a continent diversion: neobladder vs catheterisable pouch (i.e., Indiana pouch), or incontinent diversion: ileal conduit
    • Continent urinary diversion such as neobladder and catheterisable pouch experience 32% and 38% higher risk of complications compared to ileal conduit, respectively
    • Patient selection is key to optimize right patient for the right surgery20
  • Radiation
    • There is no evidence demonstrating advantage of adjuvant radiation after RC/PLND
    • Bladder preservation therapy for MIBC via trimodal therapy (TMT) (transurethral resection, radiation, and chemotherapy) is reserved for patients who are:
      • Medically unfit for surgery
      • Seeking alternative to RC
    • To be considered eligible for TMT, patients must have tumor that can undergo visible resection, no evidence of hydronephrosis (blockage of urine from kidneys), no invasion into prostate or diffuse carcinoma in situ
    • 5-year OS with trimodal therapy range 36-72%21
    • 1:5 patients will require removal of bladder due to recurrence after TMT22
  • Systemic Therapies
    • Cisplatin-gemcitabine (GC) or accelerated methotrexate, vinblastine, adriamycin and cisplatin (ddMVAC) are most widely given NAC regimens
    • 3-year progression free survival was 65% in the ddMVAC group vs 56% in gemcitabine/cisplatin group. Despite improvement in PFS, there were more serious grade ≥ 3 complication in ddMVAC group23
    • Patients who did not receive NAC prior to surgery may be eligible for adjuvant therapy with GC or ddMVAC. Patients who were eligible to receive adjuvant chemotherapy experience a 23% decreased risk of mortality at 5 years, and 36% decreased risk of recurrence24. Again, selection is key, as not many patients after surgery can undergo adjuvant chemotherapy

Bladder Cancer Surveillance Following Therapy

Surveillance following treatment in bladder cancer is dependent on stage of disease and treatment modality:

  • Surveillance NMIBC
    • Dependent on the risk stratification of recurrence and progression determined by pathology and work up, patients are monitored every 3 to 6 months for the first 2 years with longer follow up thereafter
    • Surveillance is performed via urine cytology, cystoscopy and imaging (CT or MR Urogram)
  • Surveillance Following Surgery
    • No single follow-up plan is appropriate for all patients, the recommendations provided maybe modified based on individual patient, and reassessment of disease activity should be performed in patients with new or worsening symptoms
    • Patients with MIBC post-surgery require CTU or MRU with CT chest every 3-6 months first 2 years, with CBC, CMP, and LFT25
NCCN Guidelines Insights: Bladder Cancer, Version 5.2018. J Natl Compr Canc Netw. 09 2018;16(9):1041-1053.
NCCN Guidelines Insights: Bladder Cancer, Version 5.2018. J Natl Compr Canc Netw. 09 2018;16(9):1041-1053.
  • Surveillance During Chemo/Immunotherapy
    • CTU or MRU imaging every 3-6 months or any clinical change or symptoms
    • CT chest every 3-6 months
    • Blood work including CBC, CMP and LFT every 1-3 months with additional bloodwork per therapy and side-effect profile25

*RBC/HPF; Red Blood Cells per High Power Field
GFR: Glomerular Filtration Rate
OS: Overall Survival


  1. Hansel DE, Amin MB, Comperat E, et al. A contemporary update on pathology standards for bladder cancer: transurethral resection and radical cystectomy specimens. Eur Urol. Feb 2013;63(2):321-32. doi:10.1016/j.eururo.2012.10.008
  2. Richters A, Aben KKH, Kiemeney LALM. The global burden of urinary bladder cancer: an update. World J Urol. Aug 2020;38(8):1895-1904. doi:10.1007/s00345-019-02984-4
  3. Cumberbatch MGK, Jubber I, Black PC, et al. Epidemiology of Bladder Cancer: A Systematic Review and Contemporary Update of Risk Factors in 2018. Eur Urol. 12 2018;74(6):784-795. doi:10.1016/j.eururo.2018.09.001
  4. Barocas DA, Boorjian SA, Alvarez RD, et al. Microhematuria: AUA/SUFU Guideline. J Urol. 10 2020;204(4):778-786. doi:10.1097/JU.0000000000001297
  5. Powles T, Bellmunt J, Comperat E, et al. Bladder cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 03 2022;33(3):244-258. doi:10.1016/j.annonc.2021.11.012
  6. Kiemeney LA. Hereditary bladder cancer. Scand J Urol Nephrol Suppl. Sep 2008;(218):110-5. doi:10.1080/03008880802283755
  7. MG C, M R, JW C, C LV. The Role of Tobacco Smoke in Bladder and Kidney Carcinogenesis: A Comparison of Exposures and Meta-analysis of Incidence and Mortality Risks. European urology. 2016-9 2016;70(3):458-66.
  8. Goldfarb S, McCullough PA, McDermott J, Gay SB. Contrast-induced acute kidney injury: specialty-specific protocols for interventional radiology, diagnostic computed tomography radiology, and interventional cardiology. Mayo Clin Proc. Feb 2009;84(2):170-9. doi:10.1016/S0025-6196(11)60825-2
  9. Wang P, Zang S, Li G, et al. The role of surgery on the primary tumor site in bladder cancer with distant metastasis: significance of histology type and metastatic pattern. Cancer Med. 12 2020;9(24):9293-9302. doi:10.1002/cam4.3560
  10. Chalasani V, Chin JL, Izawa JI. Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer. Can Urol Assoc J. Dec 2009;3(6 Suppl 4):S193-8. doi:10.5489/cuaj.1195
  11. van der Kwast T, Liedberg F, Black PC, et al. International Society of Urological Pathology Expert Opinion on Grading of Urothelial Carcinoma. Eur Urol Focus. 03 2022;8(2):438-446. doi:10.1016/j.euf.2021.03.017
  12. Abdollah F, Gandaglia G, Thuret R, et al. Incidence, survival and mortality rates of stage-specific bladder cancer in United States: a trend analysis. Cancer Epidemiol. Jun 2013;37(3):219-25. doi:10.1016/j.canep.2013.02.002
  13. Shariat SF, Margulis V, Lotan Y, Montorsi F, Karakiewicz PI. Nomograms for bladder cancer. Eur Urol. Jul 2008;54(1):41-53. doi:10.1016/j.eururo.2008.01.004
  14. MC M, M M, H Z, et al. Nomogram Predicting Bladder Cancer-specific Mortality After Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-invasive Bladder Cancer: Results of an International Consortium. European urology focus. 2021-11 2021;7(6):1347-1354.
  15. Vickers AJ, Cronin AM, Kattan MW, et al. Clinical benefits of a multivariate prediction model for bladder cancer: a decision analytic approach. Cancer. Dec 01 2009;115(23):5460-9. doi:10.1002/cncr.24615
  16. Chang SS, Boorjian SA, Chou R, et al. Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline. J Urol. Oct 2016;196(4):1021-9. doi:10.1016/j.juro.2016.06.049
  17. Vale CL. Neoadjuvant Chemotherapy in Invasive Bladder Cancer: Update of a Systematic Review and Meta-Analysis of Individual Patient Data: Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. European Urology. 2005/08/01/ 2005;48(2):202-206. doi:
  18. Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 01 07 2017;389(10064):67-76. doi:10.1016/S0140-6736(16)32455-2
  19. Powles T, Csőszi T, Özgüroğlu M, et al. Pembrolizumab alone or combined with chemotherapy versus chemotherapy as first-line therapy for advanced urothelial carcinoma (KEYNOTE-361): a randomised, open-label, phase 3 trial. Lancet Oncol. 07 2021;22(7):931-945. doi:10.1016/S1470-2045(21)00152-2
  20. Monn MF, Kaimakliotis HZ, Cary KC, et al. Short-term morbidity and mortality of Indiana pouch, ileal conduit, and neobladder urinary diversion following radical cystectomy. Urol Oncol. Nov 2014;32(8):1151-7. doi:10.1016/j.urolonc.2014.04.009
  21. Ploussard G, Daneshmand S, Efstathiou JA, et al. Critical analysis of bladder sparing with trimodal therapy in muscle-invasive bladder cancer: a systematic review. Eur Urol. Jul 2014;66(1):120-37. doi:10.1016/j.eururo.2014.02.038
  22. Schuettfort VM, Pradere B, Quhal F, et al. Incidence and outcome of salvage cystectomy after bladder sparing therapy for muscle invasive bladder cancer: a systematic review and meta-analysis. World J Urol. Jun 2021;39(6):1757-1768. doi:10.1007/s00345-020-03436-0
  23. Pfister C, Gravis G, Fléchon A, et al. Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients With Nonmetastatic Muscle-Invasive Bladder Cancer: Results of the GETUG-AFU V05 VESPER Trial. J Clin Oncol. Jun 20 2022;40(18):2013-2022. doi:10.1200/JCO.21.02051
  24. Leow JJ, Martin-Doyle W, Rajagopal PS, et al. Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials. Eur Urol. Jul 2014;66(1):42-54. doi:10.1016/j.eururo.2013.08.033
  25. Flaig TW, Spiess PE, Agarwal N, et al. NCCN Guidelines Insights: Bladder Cancer, Version 5.2018. J Natl Compr Canc Netw. 09 2018;16(9):1041-1053. doi:10.6004/jnccn.2018.0072

Author Bio

Dr. Laura Bukavina is a urologic oncology fellow at Fox Chase Cancer Center, with focus in bladder and kidney cancer. She is an incoming urologic oncology faculty at University Hospitals Cleveland Medical Center/Case Western Reserve University. Dr. Bukavina’s career commitment is to advance the understanding and treatment of bladder cancer through integration of science and surgery. She continues her work with support from American Urologic Association and Bladder Cancer Advocacy Network grants focusing on microbiome modulation, tumor microenvironment and treatment response. The goal of her research is to understand responses to therapy based on unique patient immune environment and interaction with host bacteria. More information about her research can be seen here:

Twitter: @LauraBukavinaMD