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

    1. I was cured of HIV with the used of natural herbs. My name is cellina jolly
      and am from US. I love herbs so much. Most times, injection and drugs are
      just a waste of time. I was cured 8months ago, i suffered from HIV for
      13yrs but with the help of Dr. voodoo herbal medicine, i was cured within
      few weeks of drinking the herbs he sent to me through courier delivery
      service. This same doctor also cured my Aunty from herpes, as soon as i
      heard she had herpes, i quickly refer her to Dr. voodoo and she was cured
      too after drinking his herbs.I have referred more than 15 persons to Dr.
      voodoo and they were all cured from their various illness. Have you taken
      herbs before?. You have spent so much money on drugs,injections,surgeries
      etc and yet you have no good result to show for it. Contact Dr. voodoo now,
      he is a herbalist doctor, i assured you of a cure if you drink his natural
      herbs. Dr. voodoo have herbs that cures HIV, Herpes, diabetics, asthma,
      hepatitis, HBP, STD, cancer, chronic, etc. Contact Dr voodoo through his
      Email address on: or WHATSAP/CALL
      him on +2348140120719 Please share the good news to other people once you are cured

    2. I’m recommending Dr Godday to everyone who have herpes virus to get the cure from him. I was diagnose of genital herpes in 2015 and i have been searching and asking questions to see if i could get something to cure the disease because i did not believe what the doctors say that no cure is found yet. I came across a comment on Youtube and the person testify how she was cured from herpes and hpv after using Dr Godday herbal medicine. I quickly contact Dr email and explain my problem to him and he prepare the herbs and send it to me through courier and gave me instructions on how to use it and tell me to go for checkup after usage which i did after two weeks of taken the herbal medicine and my result was NEGATIVE. I waited another month and retested the result was still NEGATIVE and my doctor told me that am completely free from herpes. Am so happy and grateful to Dr Godday for what he has done for me and i will continue to share this for people out there to know that there is cure for herpes. You can contact Dr Godday on email and WhatsApp to get the cure from him. Or Call/What’s-app +1{919}4956404

  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

  8. I had my first outbreaks and I was tested back in 2010 for both HSV-1 and
    HSV-2. Both my husband and I tested positive for HSV-1. Last year I found
    out my husband was cheating, so I decided to do a retest on all STDs
    including HSV-1 and HSV-2, only difference is that this time I went to a
    different clinic. Anyway I tested positive for HSV-1 which I knew I had but
    surprisingly HSV-2 as well, I was so upset and got divorced with my
    husband. 3 months ago a friend of mine recommended me to an African Herbal
    doctor DR.Alfred. I explained everything that I have been passing through
    all these years to him and he encouraged me that I will be cured
    completely!. I ordered for his herbal exploit/medicine and used it
    accordingly to his direction and within short period of using the herbal
    medicine I was cured completely from my HSV-1 and HSV-2. I'm so relieved to
    say that I've not had even one outbreak ever since again and I was also
    tested Negative by my doctor. I'm feeling so great! from within and I truly
    endorse this product, it really works. His herbal medicine is very active
    and effective.and he can cast spell to restore broken marriages,and other
    can of cure for #HERPES, #DIABETES, #CANCER, #HEPATITIS, #HPV..... You can
    contactl doctor alfred on and
    you can call/whatsapp him with +2348119017866 for your own cure too..

  9. Its a miracle that I am alive today. I encounter HERPES SIMPLEX VIRUS (HSV1/2) for good four (4) years, six (6) months and twelve (12) day with my calculations, before I meet the great Dr. ovia I am jerry edmonds from Albany newyork, united state of America and I was affected with herpes virus.Herpes is a viral infection cause by the Herpes simplex virus, marked by painful, watery blister in the skin or mucous membrane or on the genitals. This was what I suffered for good four years. I have visited CVS Pharmacy in Fresno for treatment but no improvement. I meet Dr.ovia online while I was searching for herpes cure I read a testimony about his work. I give a try that now becomes a testimony in my life. I contacted Dr.ovia on Email: or WhatsApp: +2348117923986  

  10. Finally a Natural Product to cure Herpes and Cold Sores is Available at HealthyLife Herbal Centre. earning that you have HERPES  can be one of the most difficult experiences you go through in life. You may feel scared, sad or even angry – this is OK, and a completely natural part of coping with something that can be life changing.
    It will probably take a while for the news to sink in.

    My name is Bella faith gilmore and i am from the United States.

    I remember spending so much money buying drugs from hospitals hoping that i will be cured from HERPES INFECTION, but all to no avail. I contacted so many  doctors and they prescribe medicine for me which they indeed tried their best but was unable to provide for me a possible cure, luckily i saw a comment about a great work of (Healthylife herbal centre) online.

    I then contacted him (herbalist roman) through email After much chat and enquiry with the doctor, i decide to take a leap of faith because i have nothing to loose.
    To my greatest surprise, healthylife herbal centre prepare a medicine and  send me a Herbal Medicine through FEDEX courier Service, and he gave me guidelines on how am to take it. I followed all procedures as instructed, and after 2 weeks of taking it i was cure from HERPES  his medicine is legit and it is real.

    I just want to encourage all individuals out there living with HERPES ,  ITCHY SHINGLES , Genital Herpes, HSV1&2, HIV/AIDS/ HPV, COPD, CANCER, Hepatitis b, Lupus, PCOS, Kindney failure, Lung cancer and alot more. That there is still a huge chance that you can get cure only with the help of  healthylife herbal centre. kindly contact him via email: or whatsapp +2348074216045

  11. I have been suffering from (HERPES) disease for the last four years and had constant pain, especially in my knees. During the first year, I had faith in God that I would be healed someday.This disease started to circulate all over my body and I have been taking treatment from my doctor, a few weeks ago I came on search on the internet if I could get any information concerning the prevention of this disease, on my search I saw a testimony of someone who has been healed from (Hepatitis B and Cancer) by this Man Dr. Silver and she also gave the email address of this man and advise we should contact him for any sickness that he would be of help, so I wrote to Dr. Silver telling him about my (HERPES Virus) he told me not to worry that I was going to be cured!! hmm i never believed it,, well after all the procedures and remedy given to me by this man few weeks later I started experiencing changes all over me as the Dr. assured me that I have cured, after some time i went to my doctor to confirmed if I have been finally healed behold it was TRUE, So friends my advice is if you have such sickness or any other at all you can email Dr. Silver ( sir I am indeed grateful for the help I will forever recommend you to my friends!!! with your lovely Email Address ( or whatsapp him on +2347032474849

  12. Dr Sanjeev gupta is one of the best Urologist in Ludhiana and has provided a lot of patients. call us and know more about urology treatment.


  13. I was diagnosed as HEPATITIS B carrier in 2013 with fibrosis of the
    liver already present. I started on antiviral medications which
    reduced the viral load initially. After a couple of years the virus
    became resistant. I started on HEPATITIS B Herbal treatment from
    ULTIMATE LIFE CLINIC ( in March, 2020. Their
    treatment totally reversed the virus. I did another blood test after
    the 6 months long treatment and tested negative to the virus. Amazing
    treatment! This treatment is a breakthrough for all HBV carriers.

  14. Great article about Bladder Cancer. If anyone want to interested to know about top 5 Gall Bladder Surgeon in Ludhiana , check my blog.