Hi Shacky73,
Thanks for posting your experience. We all learn from it. In The Paris Reporting System (published in 2015) If cytology says "High grade urothelial carcinoma" it is high grade with 90%+probability, "Suspicious for high grade urothelial carcinoma" 50%+ ," Atypical urothelial cells" 8-35% probability of being high grade. I think different urologists approaches Atypical in cytology, and it seems your urologist has taken an aggressive way to make sure, which is a good thing.
It sounds like you had 6 weeks induction and 3 sets of 3 weeks maintenance treatment, so you have completed the most important part of BCG treatment. I recall Alan had 6 weeks induction and another 6 weeks treatment as maintenance. I was a bit surprised to hear that your urologist stopped the treatment because of the reaction, rather than continuing with reduced dose. I heard Dr. Lerner of Baylor College saying recently that in the SWOG`1602 clinical trial to compare MERCK Tice strain BCG vs Tokyo-172 strain BCG, had seen effective immune response by reducing the dosage to 1/2.1/3, 1/10, 1/30, 1/100 rather than abandoning potential effective therapy. But, your urologist at Moffit likely decided giving a break to the bladder was more appropriate.
Re: Treatment for BCG Unresponsive.
I do not know if your situation is BCG Unresponsive as BCG has been working over a year and the treatment was stopped because of side effects. So, you may be categorized as BCG intolerable. Anyway, as Alan mentioned, there are a few FDA approved treatment for BCG Unresponsive and there are several treatments which are on clinical trials.
There are two FDA approved treatment for BCG Unresponsive non muscle invasive bladder cancer.
Valrubicin- VALSTAR(R) approved in 1998. Approved for BCG Unresponsive CIS. So, this drug may not be applicable for BCG Unresponsive for T1HG. Anyway, this drug was not that effective such that though of 90 patients 19 (21%) had a complete response, including 7 who remained disease-free at the last evaluation, with a median followup of 30 months.
Pembrolizumab - Keytruda (R) approved in 2020. Pembrolizumab is systemic immunotherapy drug. It is administered also via vein for BCG Unresponsive. The treatment is for BCG Unresponsive CIS and BCG Unresponsive HG. This treatment was better than Vlrubicin but not as good as expected, less than 20% complete response at 2 years. So, FDA approved in split decision.
GEM/DOC sequential treatment. This treatment did not require FDA clinical trial as both Gemcitabine and Docetaxel are generic drugs. The treatment was pioneered by University of Iowa team and now have been adopted by many academic hospitals because it is much less expensive than Pembrolizumab immunotherapy drug, better efficacy and less side effects. Gemcitabine is instilled into bladder first and held for 1-2 hours, then voided, then Docetaxel is instilled into bladder and held for 1-2 hours and voided. Someone posted that Docetaxel was like water. Side effects of Gemcitabine and Docetaxel are less that Mitomycin which you had been treated before.
Though BCG relies on immune response to BCG bacteria and BCG infected cells to kill cancer cells, GEM/DOC stops cancer cells to divide and leads to the death of cancer cells.
Drugs on clinical trials for BCG Unresponsive
There are several clinical trials going on for BCG Unresponsive. Below are a couple of treatments which are on Phase III trials with good results with high expectation to receive FDA approval.
IL-15RFc by Immunity Bio. Natural Killer cells (innate immune) are known to kill cancer cells when they are invoked by BCG. But, it has been observed that some of NK cells are invoked but do not attack the cancer cells, and those inactive NK cells are activated by Interleukin 15, which is immune system related stimulator. The result of clinical trial 3 showed 71% complete response rate at 2 years and 48% for HG at 2 years. It turned out that IL-15RFc alone is not as effective as Il-15RFC + BCG.
CG0070 is Oncolytic Adenovirus. Adenovirus is virus which causes common cold but toxin which causes cold had been engineeringly removed. CG0070 selectively enters in to cancer cells and replicate themselves. It also contains drug to stimulate anti-tumor responses. More recently, CG0070 + immunotherapy Pembrolizumab combination improved its efficacy with complete response rate at 12 months to be 89% (n=16/18) at 12 months.
best