AUA 2020: Management of Superficial Bladder Cancer

( Nurse practitioner, Anne Calvaresi, reviewed the current state of bladder cancer (BCa). She began the lecture with these facts: BCa is the 6th most commonly diagnosed malignancy in the U.S. 81,000 new cases/year in U.S., >17,000 deaths/year with an overall survival of 77%.  More men (4th most common cancer in men) than women are diagnosed with BCa and average age is 73 yrs.  At presentation, 50% of tumors are found to be superficial, 50% invasive, and approximately 4% are metastatic; 51% of tumors are “carcinoma in-situ (CIS)”, 1 out of 3 are localized and only a small percentage are in advanced stages.  Ms. Calvaresi reviewed the histology of BCa as seen in this Figure (Chap 25, Bladder Cancer, SUNA Core Curriculum for Urology Nurses):

  • Ta: low risk, low grade (often papillary), superficial, noninvasive Non‐Muscle Invasive Bladder Cancer (NMIBC)
  • Ta/T1:  occurs within the superficial or lamina propria layers, high risk NMIBC 
  • T2/T3: Muscle‐Invasive Bladder Cancer (MIBC), through the superficial and lamina propria layers and into the bladder muscle 

The diagnosis of BCa is usually made by cystoscopy with pathology confirming urothelial cancer.  If tumor is found or suspected, transurethral resection is performed.  This presentation described the two types of cystoscopy, white light, which is the traditional method and blue light which is used concurrently with white light.  Blue light has been shown to enhance the diagnosis of BCa.  It identifies neoplastic tissue as red fluorescence.  But the use of blue light involves some planning as hexaminolevulinate hydrochloride is instilled in the bladder pre-operatively.   Ms. Calvaresi also mentioned “narrow band imaging (NBI)” which does not require pre-cysto bladder instillation but filters white light into specific light wavelengths that “are absorbed by hemoglobin, providing enhanced visualization of capillary networks and mucosal morphology”. Cystoscopy pictures differentiating bladder mucosal with blue and white light were shown and as well as those detected by NBI. 

Management of NMIBC depends on pathology. Single-dose peri-operative intravesical instillation of mitomycin should be considered.  If low grade urothelial CA is suspected (cTa, cT1), management includes office cystoscopy, cytology with CT or MRI of abdomen and pelvic followed by TURBT (transurethral resection of bladder tumor).  Surveillance in these patients includes cystoscopy at 3 months, then at increasing intervals.  If the cancer is recurring, consider TURBT with or without intravesical treatment.   There are several options for recurrent high-grade urothelial cancer after intravesical treatment and cystectomy maybe considered.  If there are there are 2 or more recurrences of high risk NMI urothelial cancer after intravesical treatment, cystectomy is strongly recommended.  Nurse practitioner Anne Calvaresi noted the resource from the AUA and SUNA collaboration on standard procedure for intravesical treatments for BCa and interstitial cystitis.  A nice review of intravesical treatments was presented and are listed here:

  • Perioperative chemotherapy of mitomycin
    • Instilled in post‐anesthesia care unit
    • 40 mg mixed in 20‐30 mL of  Dextrose 5% in water
    • Bladder dwell time is 45‐60 minute 
    • Post‐operative intravesical therapy ‐ Induction
    • BCG (Bacillus Calmette-Guerin [TheraCys, TICE]) in combination with TURBT, is the most effective treatment for high-risk NMIBC
    • Interferon, can be utilized with BCG
    • Chemotherapy (mitomycin, valrubicin, gemcitabine, docetaxel). Speaker finds gemcitabine may be better tolerated mitomycin and valrubicin.
    • Mitomycin, used for recurrent Ta, can be irritative, avoid skin contact
    • Valrubicin, Doxorubicin (Adriamycin) analogue, 800 mg x 6 wks, used for BCG refractory, irritative voiding symptoms are common side effects.
    • Gemcitabine, better tolerated, can be used in combination with mitomycin and docetaxel
    • Docetaxel, cytotoxic agent, used in combination with other agents

A review of BCG was provided, noting that there is a shortage and all urology offices are finding administration in recommended doses to be a challenge.  BCG may be combined with interferons with weekly treatments for 6 weeks, then maintenance dose of 1 treatment for 3 weeks.  The patient is asked to hold the BCG in the bladder for 15 mins, and after voiding, needs to place bleach in toilet for 15 mins.  The most common side effects are irritative symptoms (urgency, frequency, dysuria), mild flu‐like symptoms and many will decrease dose by 50% if patient finds it intolerable at full dose.

Merck & Co is the only maker and supplier of BCG to the U. S. and they are experiencing a global shortage of BCG, due the growing use and need for this product around the world.  In this lecture, Ms Calvaresi noted the BCG shortage and detailed the recommedations that the AUA and others have made including:

    • Do not give to low risk patients as intermediate risk and recurrent low grade should receive intravesical chemotherapy
    • If patient is experiencing BCG refractory/relapsing/failure, consider alternative agent
    • Prioritize high‐risk NMIBC to BCG full dose, them may consider decreasing to 1/2 or 1/3 dose
    • Those patients who are on maintenance, decrease to 1/3 BCG dose for one year
    • If BCG is not available, consider other agent
    • Patients with high risk MIBC, consider radical cystectomy

Clinicians are paring 1/2 and 1/3 doses with patients on same day appointments so BCG bottle can be split (not wasted).  Ms. Calvaresi detailed APP roles in superficial BCa including screening, prescribing diagnostic tests, administering intravesical treatment.

Presented by: Anne E. Calvaresi, DNP, CRNP, RNFA, Thomas Jefferson University, Sidney Kimmel Cancer Center

Written by: Diane Newman, DNP, ANP-BC, Adjunct Professor of Urology in Surgery, Perelman School of Medicine, University of Pennsylvania and Co-Director of the Penn Center for Continence and Pelvic Health