Bladder cancer is a heterogenous neoplasm that ranges from non-life-threatening, low-grade, superficial papillary lesions to high-grade invasive tumors that often metastasizes at the presentation.

It is the most common cancer involving the urinary system and it is the 11th most commonly diagnosed in the world.

Microscopic or gross painless hematuria is the most common presenting complaint.

Principles of Therapy

  • Non-muscle-invasive tumors management is directed at reducing recurrences & preventing progression to a more advanced stage
  • Goals of therapy for muscle-invasive lesions are to determine if the bladder should be removed or preserved without compromising survival, & to determine if the primary lesion can be managed independently, or if patients are at high risk for distant spread requiring systemic approaches to improve the likelihood of cure
    • Therapy for patients w/ metastatic lesions should focus on prolongation & quality of life


Intravesical Chemotherapy

  • In low-risk patients, & those presumed to be at intermediate risk w/ previous low recurrence rate, a single, immediate, post-operative intravesical instillation of chemotherapy has been considered to be the standard & sufficient treatment
    • Shown to act by the destruction of circulating tumor cells resulting from TURB & by an ablative effect (chemoresection) on residual tumor cells at the resection site & on small overlooked tumors
    • Although for other patients, it remains an incomplete treatment because of the considerable likelihood of recurrence &/or progression
    • Should be administered within 24 hours after TURBT
    • Gemcitabine & Mitomycin are the most widely used agents for intravesical chemotherapy
    • Mitomycin C, Epirubicin & Doxorubicin have shown beneficial effects
  • For patients w/ non-muscle-invasive disease, induction or adjuvant intravesical chemotherapy or BCG treatment is a treatment option
    • Most commonly used intravesical chemotherapy are Mitomycin & Gemcitabine
    • Given initially 3-4 weeks after TURBT with or without maintenance
    • During induction weekly installations are given for approximately 6 weeks
    • 2 consecutive cycle inductions is the maximum without complete response
  • Intravesical BCG regimen consists of 6-week induction course followed by maintenance dose w/ 3-weekly installations at 3, 6, 12, 18, 24, 30 & 36 months
    • For patients w/ intermediate risk maintenance is given ideally for 1 year while for those w/ high risk non-muscle invasive disease it is given for 3 years
    • If there is substantial local symptoms experienced during the maintenance therapy dose reduction is encouraged
    • It has been shown in recent data that maintenance BCG therapy results in decreased rate of recurrence of non-muscle invasive disease

Neoadjuvant/Adjuvant Chemotherapy

  • For patients w/ locally advanced or metastatic urothelial bladder cancer who are otherwise physically fit & have adequate renal function, a Cisplatin-based chemotherapy regimen is suggested
  • Neoadjuvant chemotherapy using a Cisplatin combination regimen before radical cystectomy or radical radiotherapy is suggested in patients w/ diagnosed T2-T4a, cN0M0 bladder cancer
  • Adjuvant Cisplatin combination chemotherapy after radical cystectomy is considered for patients w/ a diagnosis of muscle-invasive or lymph-node-positive urothelial bladder cancer for whom neoadjuvant chemotherapy was not suitable
  • For patients w/ muscle-invasive bladder cancer, chemotherapy regimen recommendations include:
    • Preferred neoadjuvant or adjuvant regimen is Gemcitabine & Cisplatin for 4 cycles
      • Alternative is CMV (Cisplatin, Methotrexate & Vinblastine) for 3 cycles
    • DDMVAC (dose-dense Methotrexate, Vinblastine, Doxorubicin & Cisplatin) with growth factor support for 3 or 4 cycles

Systemic Therapy

  • For patients w/ locally advanced or metastatic bladder cancer, first-line chemotherapy regimen include:
    • Preferred regimens for Cisplatin-eligible patients are Gemcitabine w/ Cisplatin or DDMVAC
    • In patients who are ineligible for systemic therapy w/ Cisplatin, the preferred regimens include Gemcitabine & Carboplatin or Atezolizumab or Pembrolizumab
    • Other recommended regimens include Gemcitabine alone or Gemcitabine & Paclitaxel
    • Conditional regimens that may be considered include Ifosfamide, Doxorubucin, & Gemcitabine
  • Checkpoint inhibitors such as Pembrolizumab (preferred), Atezolizumab, Nivolumab, Durvalumab & Avelumab has been recommended as second-line systemic therapy after platinum-based therapy
    • Other recommended regimens include Nab-Paclitaxel, Paclitaxel or Docetaxel, Gemcitabine, & Pemetrexed
    • Conditional regimens that may be considered based on patient’s medical history include Ifosfamide, Methotrexate, Ifosfamide + Doxorubicin + Gemcitabine, Gemcitabine + Paclitaxel, Gemcitabine + Cisplatin, & DDMVAC
  • Recommended systemic therapy for locally advanced or metastatic bladder cancer after checkpoint inhibitor-based therapy
    • Preferred regimens for Cisplatin-eligible patients & without prior chemotherapy: Gemcitabine w/ Cisplatin or DDMVAC
    • Gemcitabine + Cisplatin combination regimen is recommended for patients who are ineligible for systemic therapy & chemotherapy-naive
    • Other recommended regimens include Nab-Paclitaxel, Paclitaxel or Docetaxel, Gemcitabine, & Pemetrexed
    • Conditional regimens that may be considered include Ifosfamide, Methotrexate, Doxorubicin, & Gemcitabine, or Ifosfamide/Doxorubicin/Gemcitabine combination therapy
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