-
Suspicious scope worried about non-BCG options
Had scope last week at Moffitt. Lots of damage from 7 previous TURBT’s + 6 mitomycin and 15 Tokyo BCG. My BCG was stopped after March 2021 due to reactions and impact on bladder.
I had been negative for a year prior to stopping and scopes were clear till last September when there were suspicious areas but nothing definitive. Last September cytology was atypical hence the scheduling of next scope in 3 months instead of 6.
I was pretty anxious this go around as my urgency hasn’t improved at all since 2021 and the thought that I’ve been told I can’t have anymore BCG.
My doctor decided to schedule OR to make sure the not so normal areas are OK as well as place another stent in my right ureter which has been partially blocked and had stent back in 2020.
Waiting for cytology as well.
Trying to stay positive and calm. The waiting periods are the worse. What’s bothering me this time is what are the non-BCG options? Since I’ve been told no more BCG I’m assuming surgery is only option if my T1HG w CIS returns.
T1 Grade 3 with CIS35 Replies-
Sorry to hear another incident of REA. I recall that they thought COVID vaccine and BCG might have screwed up immune responses, but now it seems COVID vaccine is eliminated as a cause. I do not know REA are similar to autoimmune disease in which the immune system attacks the body in various ways. Because BCG works by invoking various immune responses, BCG seems to be the origin of your side effects. It is possible that your doctor – immunologist/urologist may stop BCG for that reason. I would expect they will discuss alternative treatment such as Gemcitabine + Docetaxel i(Gem+Doc) ntravesical chemotherapy. The mechanism of action of killing cancer cells by GEM+DOC is by stopping cell to divide, which leads to programmed cell death (Apoptosis). So, technically, GEM+DOC should not cause REA.
Your situation is classified BCG intolerable if they decide to stop BCG treatment, which is different BCG unresponsive. Since University of Iowa team had published their clinical studies on Gemcitabine + Docetaxel, there have been case studies in different hospitals. A more recent study for longer term follow up with Gem+Doc as rescue therapy for NMIBC by Univ. Iowa team was published in 2022 American Society of Clinical Oncology Journal.
Among 97 patients, there were 35% BCG unresponsive, 38% BCG relapsing, 11% BCG intolerant and 16% unspecified. I do not have access to detail report, so I could not find out the result of BCG intolerant patients. Maybe your doctors have an access to the detail report as reference to determine Gem+DOC is a right choice of the treatment for you. best
https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.6_suppl.573
-
Well it looks like my reactive arthritis is back 2 weeks after 5th BCG re-induction. My left knee is inflamed/swollen. Started feeling a little funny Wednesday and noticed some pain golfing Friday – though we won our flight!
Heading to Rochester NY tomorrow to spend week with family. Will ice and see if I can get in to see my previous orthopedist for possible drain and steroids.
Obviously concerned how this may affect future BCG schedule. In my mind it’s worth it if BCG keeps cancer at bay. Wondering what oncologist will say.
T1 Grade 3 with CIS
As always great info Joe!!!
T1 Grade 3 with CIS
If there were recurrence of high risk NMIBC after min. 5+2 then, then patient is qualified for treatments for BCG Unresponsive which have been approved by FDA or on clinical trials. Of course no recurrence or progression is much preferred. In case of T1HG, if T1HG recurs after the 6 weekly induction course, it is also considered as BCG unresponsive..
Treatment for BCG Unresponsive.
Pembrlizumab (Keytruda) immunotherapy – Intravenous injection. FDA approved in January,2020
Oportuzumab (Vicineum) Phase 3 on pause
Nadofaragene firadenovec (Adstilladrin) – GC0070 Approved in December, 2022
N-803 : IL-15 based Natural Killer cells activating drug Phase 3
GEM+DOC are generic drugs, so it can be used for BCG unresponsive, BCG intolerant and even for BCG naïve.Gemcitabine/Docetaxel and N-803 look most promising for RFS so far.
I heard from a urologist that if patient can complete the induction + 1st maintenance course, the patient would likely be able to complete the entire BCG treatment (27 treatment in total. So the completion of , 5 + 2 or 6 +3 are good start.
Did your oncologists either at MSK or Moffit suggest prescribing Ofloxacin – fluoroquinolone antibiotics to reduce side effects you are experiencing? Ofloxacin is the only antibiotics which was clinically tested (2006) antibiotic to reduce side effects of BCG treatment. Dr. Ashish Kamat of MD Andersons seems to prescribe Ofloxacin to every BCG treatment. Ofloxacin is orally taken at 6 hours and at 12 hours after BCG instillation. The rationale is that all necessary immune responses are obtained after 6 hours of BCG instillation, so it is okay to kill BCG bacteria which are still in the bladder, also there were no difference in efficacy between Ofloxacin group and placebo group. Below is the link to the article on Ofloxacin.
I see 5of 6 induction and 2 of 3 maintenance requirements in the qualifications for CG 0070.
so is that considered a successful course of BCG?
and yes took Tylenol. I can’t take NSAIDs.
T1 Grade 3 with CIS
Glad to know it is subsiding. Did you take any medicine such as tylenol or motrin to ease the pain and spasm?
Positive outcomes I see are that BCG this time has not caused reactive arthritis, and you have completed the induction part of so called adequate BCG is 5 or 6 weekly induction + 2 or 3 weekly 1st maintenance treatment . I guess you and your urologist will decide if you take 2 weeks break or 1 week before the 6 BCG.
Extreme pain from what feels like prostate/bladder entrance. More toward the end of urinating. The small amounts of urine after procedure were killer. Bladder spasms with it.
getting better now after about 18 hours.
I was getting pain day before procedure which i attributed to not being hydrated enough.
T1 Grade 3 with CIS
Sorry to hear that. What’s happening?
I had #5 today. Ouch!!!!
I can’t see myself getting #6.
T1 Grade 3 with CIS
Thank you for all the information!!!
T1 Grade 3 with CIS
I was a bit concerned about repeating BCG after you had experienced with reactive arthritis (REA) as autoimmune immune disease such as rheumatoid arthritis (RA) is contraindication of BCG treatment as RA are often are being treated with immunosuppression. But, apparently REA and RA are different in such that REA is triggered by a bacterial infection, particularly of the genitourinary (2-4%) or gastrointestinal (GI) tract, (0-15%) and rare cases by Intravesical BCG. A study on REA by Intravesical BCG (iBCG) was published in 2022 by University of Kochi Rheumatolog team in japan. The study shows about 2%, 5.6%, 0.5% of Intravesical BCG patients are diagnose with REA in Japan, Europe and North America respectively. With regard to the immunopathogenesis of REA after iBCG therapy, it has been shown that iBCG therapy can provoke a systemic hypersensitivity reaction (both CD4+ (helper) and CD8+ (Killer) T cells) in addition to the previously discussed local immunity. Therefore, activated and memory immune cells may translocate to joints, resulting in the development of arthritis. The paper says the first treatment action should be the discontinuation of iBCG therapy until the complete resolution of symptoms, and a benefit-risk assessment must be conducted before resuming iBCG treatment. I am hoping that the REA you experienced was one time thing.
Fig. Hypothetical mechanism of action of iBCG causing REA. Note that our immune system responds to fragments of BCG bacteria or full bacteria equally as pathogens. a) Immune cells such as Macrophage engulf BCG bacteria and reaches to joints and/or b) bits of BCG bacteria reaches to joints and immune system responds to bits of BCG as pathogen, and/or primed T cells for BCG bacteria attack cells in joints.
Gem/doc chemo has shown to be effective. The treatment was developed by University of Iowa team with Dr. Michael O’Donnell who is considered as a GURU for treatment for NMIBC along with Dr. Lamm of University of Arizona.
Repeat BCG induction remains an option for select non-muscle invasive bladder cancer (NMIBC) patients who fail initial therapy. Alternative salvage intravesical regimens such as Gemcitabine and Docetaxel (Gem/Doce) have been investigated. the adjusted 1- and 2-year RFS was 61% and 53% after BCG/IFN versus 68% and 46% after Gem/Doc. Note that MERCK dropped Interferon (IFN) business, so BCG/IFN is no longer available. Instead, there are several treatment for BCG Unresponsive now., including CG0070.
Incidentally, GEM/DOC showed very high efficacy for BCG naïve patients according to recent retrospective study by University of Iowa team. 92% at 6 months, 85% at 12 months, and 81% at 24 months which were better than BCG group with 76% )at 6 months, 71% at 12 months, and 69% at 24 months.
It is good that you are being treated academic hospital like Moffitt as GEM/DOC are not usually not offered in community hospitals as it is too much work for them. Also, I am pretty sure GEM/DOC will not cause REA because GEM/DOC stop cancer cells from dividing (growing) by inhibiting uncoiling of DNA and disrupting of formation of microtubules before cell division, which leads to cell death. GEM/DOC does not depend on our immune system to kill cancer cells whereas BCG treatment depends, and this immune response caused REA.
CG0070
CG Oncology Inc. who developed CG0070 announced Phase 2 clinical trial (18 patients) of the combination of CG0070 + immunotherpay – pembrolizumag (Keytruda) by Merck with better efficacy than CG0070 alone. 89% achieved complete response rate at 3 months. Of those achieved CR at 3 months , 85%,78%, 75% maintained CR at 6 months, 9 months, 12 months respectively. So, perhaps better to join the clinical trial of CG0700 + Keytruda than getting CG0700 alone if you consider to have CG0070 treatment in future, which I hope unnecessary to you. Below are the links to related studies
Incidentally I go to a local community hospital. The first priority of nurses at recovery room is to get patients asap to secure beds for next patients. One time, after TURBT, I could not walk straight because I chose spinal anesthesia, still the nurse wanted to be released, so I had to act like falling down to get another 2 hours of stay in the hospital. 2 hours bed for BCG sounds very envious.
GEM/DOC for BCG Unresponsive
https://pubmed.ncbi.nlm.nih.gov/34092482/GEM/DOC for BCG Naïve
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2801788Interim results of Phase 2 CG0070 + Keytruda for BCG unresponsive
https://www.cgoncology.com/news/press-releases/041322/
Had number 4 of 6 BCG Thursday. I did a little better. My wife came so she could drive the 1 hour 45 min drive home.
I hydrated better. Took an extra Mybetriq for the spasms. Overall better than week 3.
2 more to go!
T1 Grade 3 with CIS
The joint issue I had was reactive arthritis. Much different from BCG getting into joints which I hear happens but rarely.
two things pointed to reactive arthritis diagnosis:
First it got better after steroids. If it had been bacterial it would have gotten worse – this from my Orthopedist.
Second the timing of COVID/BCG likely overloaded my immune system – this from Immunologist at MSK.
This happened during COVID and I used orthopedist in Rochester NY.
I was priority for COVID vaccine via MSK. I actually tried to move the COVID vaccine appointment but the vaccine people urged me to keep it as rescheduling would be iffy.
In hindsight I should not have had the vaccine so close to BCG.
T1 Grade 3 with CIS
So gland to hear that joints were healed. I was concerned that you could not do BCG anymore. Hope it will be smoother journey this time. Moffitt sounds like a fantastic place to be treated.
My joints were fine after they were drained and steroids kicked in. No long term issues.
Had my first of six BCG at Moffitt yesterday. I was anticipating the guttural pain on urinating and bladder spasm for first 6 hours.
I was delightfully surprised that it was nowhere near discomfort from 2 years ago. I imagine it may get a little worse as I go through 6 week re-induction but I’m starting at a very tolerable level.
Moffitt staff was great! Private treatment room with bath. And I stayed laying in bed ( turning now and then. I think this may have prevented the BCG from collecting at entrance to bladder. In NY I had to leave as soon as BCG was in bladder. So walking around the driving car to hotel probably caused more localized irritation and pain.
Moffitt nurses are excellent. I didn’t even have to ask for them to pinch off end to keep lidocaine in for a minute or two. My prostate really appreciated that!!!
T1 Grade 3 with CISSign In to reply.
