Wednesday, August 27, 2014

BCG Alternatives for Non-Muscle Invasive Bladder Cancer

Bacillus Calmette-Guerin (BCG) immunotherapy is the standard, most commonly used intravesical treatment for patients with NMIUBC (non-muscle invasive urothelial bladder cancer).  [Please see our prior blog entries on BCG treatment below]  However, upwards of 40% of patients will "fail" intravesical treatment and have a recurrence or progression of their bladder cancer. Due to the aggressive nature of MIUBC (muscle-invasive urothelial bladder cancer), early radical cystectomy is advocated by many urologists who care for patients with progressive disease.  However, radical cystectomy is a morbid and life-changing operation and many patients seek alternative treatments to BCG before submitting to radical surgery.  In addition, some patients cannot tolerate BCG treatment due to side effects.  Finally, in times of shortage (we are currently undergoing a BCG shortage in the US), alternative treatments can be used in lieu of premature radical surgery.

A prior blog entry reviewed Immunotherapy Alternatives to BCG.  Many of these medications are in the experimental phase of investigation and have not been proven to be useful in humans.  In this blog, we review intravesical chemotherapy, device-assisted chemotherapy and thermochemotherapy alternatives to intravesical BCG and the data with each modality.


Mitomycin C (MMC) has long been used for low-grade, non-invasive urothelial cancer of the bladder.  However, MMC has limited efficacy after BCG failure with only 4 of 21 patients responding in a small, Scandinavian study.[1]

Gemcitabine is the standard systemic therapy given to patients with MIUCB.  Two early (Phase I-II) studies demonstrate the potential efficacy of gemcitabine given intravesically.  In one study of 18 patients, 7 demonstrated a complete response (negative biopsy and cytology for cancer) and 4 patients demonstrates a partial response (negative biopsy, positive cytology).[2]  Twenty-two of 39 (56%) patients with intermediate- and high-risk of recurrence after BCG therapy were recurrence free after 6 weeks of treatment.  In addition, none of the non-responders had progression of disease while receiving gemcitabine therapy.[3]

Docetaxel is another systemic chemotherapeutic agent used in advanced cancers. Researchers at Columbia University in New York demonstrated a 59% complete response rate in 32 of 54 patients after 6 weekly cycles (18 patients received maintenance therapy).  This translated into recurrence-free survival rates of 40% and 25% at 1- and 3-years respectively; 25% underwent radical cystectomy; and 5-year cancer-specific survival was 85%.[4]

In preliminary research, the combination of Gemcitabine/Docetaxel demonstrates promising results with lower side effect profiles than other intravesical chemotherapies and with excellent short-term response rates. We are currently using this regimen at Johns Hopkins in patients with BCG failures, refractory disease and in those patients who cannot receive BCG with promising results.


Photodynamic therapy (PDT) involves treating the bladder with a photosensitizing medication that selectively binds to tumors and using a strong intravesical light source to destroy tumors.  Five-aminolevulinic acid (5-ALA) was given orally to 24 BCG-failure patients and, after two years, 16 were tumor free.[5]

From Wild P J et al. Mol Cancer Ther 2005;4:516-528
MMC and EMDA (electromotive drug administration) has been demonstrated to enhance the delivery of the medication to the urothelial cells lining the bladder.  Using a pulsed electrode inserted into the bladder via a urinary catheter, 108 BCG-failure patients were randomized to MMC, MMC with EMDA or BCG.  MMC with EMDA demostrated a better response rate (58%) at 6 months than MMC alone (31%), however this was not improved compared to BCG (64%) alone.[6]


Heating the bladder to 42 degrees Celsius (107 degrees F) while administering MMC has been demonstrated to have some effect in patients with BCG failure.  Using a special microwave and catheter, the recurrence rates have been observed between 14% at 1-year and 24% at 2-years if no prior BCG exposure; and in patients who previously failed BCG treatment, 1- and 2-year recurrence rates were 23% and 41% respectively.[7]  In a study of 15 European centers, the complete response rate was 92% at 1-year but fell precipitously to 50% at 2-years.[8] A recent meta-analysis of 22 studies demostrated a 59% relative reduction in risk of recurrence for all patients with NMIUBC treated with heated MMC compared to MMC alone.[9] 

Thermochemotherapeutic system demonstrated from Lammers etal [9].


May patients do not continue with intravesical BCG treatments due to "failure" (recurrence or progression of disease), intolerance of the medication or inavailability of the drug.  Reasonable intravesical chemotherapeutic agents include: mitomycin c, gemcitabine, docetaxel and combinations of these medications.  Device-assisted therapeutics and thermochemotherapy remain alternatives.

Availability of BCG alternatives will vary by center and urologist.  Any patient who fails BCG is at high-risk for disease progression and death from urothelial cancer.  A thorough discussion of the alternatives and risk of disease progression should be undertaken prior to embarking on any alternative treatment.

Prior Blog Entries on BCG Therapy:
Success Rates for Intravesical BCG Treatments for Bladder Cancer (2/24/14)
BCG Complications for Bladder Cancer: Who, What, When and How to Treat? (3/12/14)
BCG For Bladder Cancer: Why it Works, How it Works (4/25/14)
BCG Immunotherapy Alternatives (7/16/14)
[1] Malmstrom PU, Wijkstrom H, Lundholm C, et al. 5-year followup of a randomized prospective study comparing mitomycin C and bacillus Calmette-Guerin in patients with superficial bladder carcinoma. J Urol. 1999;161:1124–7.
[2] Dalbagni G, Russo P, Sheinfeld J, et al. Phase I trial of intravesical gemcitabine in bacillus Calmette-Guerin-refractory transitional-cell carcinoma of the bladder. J Clin Oncol. 2002;20:3193–8.
[3] Gontero P, Casetta G, Maso G, et al. Phase II study to investigate the ablative efficacy of intravesical administration of gemcitabine in intermediate-risk superficial bladder cancer (SBC) Eur Urol. 2004;46:339–43.
[4] Barlow L, McKiernan JM, Benson MC.  Long-term survival outcomes with intravesical docetaxel for recurrent nonmuscle invasive bladder cancer after previous bacillus Calmette-Guérin therapy.  J Urol. 2013 Mar;189(3):834-9. doi: 10.1016/j.juro.2012.10.068. Epub 2012 Oct 30.
[5] Waidelich H, Stepp R, Baumgartner E, et al. Clinical experience with 5-aminolevulinic acid and photodynamic therapy for refractory superficial bladder cancer. J Urol. 2001;165:1904–7.
[6] Di Stasi SM, Giannantoni A, Stephen RL, et al. Intravesical electromotive mitomycin C versus passive transport mitomycin C for high risk superficial bladder cancer: a prospective randomized study. J Urol. 2003;170:777–82.
[7] Van Der Heijden AG, Kiemeney LA, Gofrit ON, et al. Preliminary European results of local microwave hyperthermia and chemotherapy treatment in intermediate or high risk superficial transitional cell carcinoma of the bladder. Eur Urol. 2004;46:65–72.
[8] Alfred Witjes J, Hendricksen K, Gofrit O, Risi O, Nativ O.  Intravesical hyperthermia and mitomycin-C for carcinoma in situ of the urinary bladder: experience of the European Synergo working party.World J Urol. 2009 Jun;27(3):319-24. doi: 10.1007/s00345-009-0384-2. Epub 2009 Feb 22.
[9] Lammers RJ, Witjes JA, Inman BA, Leibovitch I, Laufer M, Nativ O, Colombo R. The role of a combined regimen with intravesical chemotherapy and hyperthermia in the management of non-muscle-invasive bladder cancer: a systematic review.  Eur Urol. 2011 Jul;60(1):81-93. doi: 10.1016/j.eururo.2011.04.023. Epub 2011 Apr 20. Review.


  1. Do you loved ones are suffering form cancer…. That requires A highly costly treatment …No worry , we have a solution and help for you to have massive compensation in treatment cost.For more information fill out application form

  2. Generic Bendamustine (Ribomustin) is a cancer medication that is used to treat chronic lymphocytic leukemia.

  3. Nice Blog and explained very well about therapy for cancer. BCG proved to be the only truly successful therapy for bladder cancer and i also read that DCA could prevent cancers from growing as it's a possible new treatment

  4. Dr for sythe is also practising alternative cancer treatments in his cancer care center for long. You can get some very helpful advice from him as well.

  5. Good article. I absolutely appreciate this website. Continue the good work!
    surgical weight loss

  6. This exert a mild anti-bacterial effect and in most circumstances will not destroy biological filtration bacteria,

  7. My name is Gary David,i just want to share my testimony with the world on how Doctor Trust Help me to enlarge my pines. Please read my good news carefully and i am sure it will affect your life positively on how you will also enlarge your pines,because i know some many people out there also need his help!

    I came across so many comments about Dr Trust Penis Enlargement Medicine some weeks ago, though I had really wanted my penis to be large, long and thick,because i was not able to have sex with my wife..It was really affecting our marriage and my wife was about to divorce me. I had about 8.128cm – 3.2 inches before. Am really amazed on the fast results archived within 3 days of using Dr. Trust Penis Enlargement Medicine. It work and now I have got 22.87cm – 10.5 inches now. And my wife love it more now, i began to feel the enlargement of my penis, This went on for a little period of about 5 days and to my surprise my wife keeps screaming that she love my big dick now. And my penis is now 10.5 inches long on erection and off course very large round. I am very happy for this Penis Enlargement experience. He can help with all kinds of cure you may need as flows:

    Pines Enlargement
    Low sperm count
    Weak Erection
    Love spell
    Herpes spell
    HIV spell
    Pregnancy spell
    Marriage for spell
    watering sperm
    womb fertilization
    penis erection
    witch craft attack
    s t d diseases
    internal heat
    low sperm count
    long time sickness
    with doctor,Dr. Trust you are in safe hands your healing is assured or
    Web site
    Call +2348156885231