FYI, I saw a post a patient could not tolerate after the initial 6 weeks induction course, then reduced to 1/3 for the maintenance course. The patient was able to complete 21 doses in total. In this case, reducing the dose to 1/3 worked. This is encouraging.
I am like you and many other patients who are trying to learn a little more about our bladder cancers hoping to give the best chance to our own bodies. Like I said if your father is being treated at a reputable hospitable with a urology department and if he is under the care of an experienced and well-versed with the current research on bladder cancer, you had given your dad the best chance already. Also please keep in mind that most of the participants in the forum are like amateur detectives. We are not here to give any medical advice. There will be mistakes and misinformation So, please take it with lots of grains of salt.
First of all, there have been several studies on the efficacy and the side effects of the reduced dose of BCG, which your urologist is considering. I think the trial which is more relevant to the case of your dad was done by European Organisation for Research and Treatment of Cancer - genitourinary cancers group (EORTC-GU) involving over 1300 intermediate- and high-risk Ta, T1 papillary carcinoma of the bladder. I say it is more relevant is because the BCG strain the patients were treated was TICE strain by MERCK, which the patients in the US and Canada are also treated with. Onco-Tice vial comes in 50mg. What I have noticed in other similar studies involved different strains and also the full dose was 80 mg or 90 mg. Some studies reduced to 1/2 dose. A 1/2 dose of 80mg BCG is 40mg which is 80% of 50 mg, which Onco-Tice comes with. But, we have to recognize that other studies gave other insights, which EORT-GU did not address. What is common among various studies is that most BCG Intolerance by side effects happen in the first 6 weeks induction course and the first 3 weeks maintenance course. Incidentally, this coincides with what a urologist I know explaining to other urologists and post-doc residents in the internal lecture series of their urology department.
Anyway, according to the clinical trial by EORTC-GU, the good news is that 1/3 dose and full dose have similar efficacy. The concerning finding is that there are not many differences in the side effects between the 1/3 dose group and the full-dose group. So, there may be a chance that your dad will experience similar side effects at some point even if the dose is reduced to 1/3 given. One difference is that your dad experienced right after the 5th treatment, but the maintenance is 3 doses in 3 weeks, then 3 or 6 months rest. Also, this clinical trial involved only BCG naive ( those who were treated with BCG for the first time) patients, but your dad's case is re-introducing BCG after the initial BCG intolerance. Also, the next treatment is only 3 weeks. So, so many parameters are different. Anyway, I think the urologist will approach the reintroduction of BCG carefully. As there have been suggestions of reducing further the dose so a patient can continue the BCG treatment. Below is what Dr. Lamm, a well-known figure for BCG treatment says about BCG reduction.
In terms of MTB, it will likely require gene sequencing of your dad's tumor. Your hospital may have access to DNA sequencing equipment by the company called Illumina. It used to cost $1M to do the genome sequencing of a human, but I have read that the cost has come down substantially to less than $1,000. I know one bladder cancer patient used the company called FOUNDATION to do the gene analysis. The company's website says the test checks mutations of cancer-causing genes in addition to MTB.
But, please note that the study by Dr. Meeks has a very small cohort and the report says that it needs further study with a much larger cohort to validate the result of his study that MTB is a factor for progression.
Having said that, bladder cancer is known to have high MTB among all types of cancers, the third following melanoma, lung cancer. One idea is that cancer with high MTB produces a high number ( different kinds) of antigens and gives the immune system the opportunity to pick up some of them and deliver them to lymph nodes and activate T-cells, which give our immune system to kill cancer cells. So, immune checkpoint inhibitor immunotherapy is shown to work better for the cancer types with high MTB such as melanoma, lung cancer, and bladder cancer.
Some people expect that genome analysis for diagnosis and selecting the right treatment for bladder cancer will be applied not so far distance in the future. Hope it will come soon.
What's going on in our body is so complex. So, I do not think we can expect any simple factor, even MTB, to lead us to the solution. It is just one of many parameters in order to solve the mystery of our body.
Thank you for your ample knowledge and information which you posses and which helps the community especially for patients with this disease. Your knowledge related to the subject is always appreciable and commendable.
Regarding the TMB its is a very decisive factor especially in case of MIBC wherein high score is good and low score is not considered good news.
I want to know how can I know the TMB in my case ? I have my slides and blocks from HPE and can I use them to get this investigation done?
I am a firm God believer and consider destiny as ultimate decider. But at the same time must consider all medical protocols as well. I am very aggressive related to my father's surveillance and will do whatever it takes. Hopefully I will succeed and he will be out of this.
During this time since my father was diagnosed with BC , I have been doing lots and lots of study and consulted all reputed doctors in my reach. All of them including our Uro saying that TaHG has a good prognosis and can be treated well. What I ask them , can it be cured completely and this is my question to this forum as well. IsTaHG curable or treatable?
Sincerely Thankful to this Forum and especially people like Sara , Alan and Joea73
Thanks for your detailed updates and for sharing what has been going on. Our patients' community can learn much from it.
You say that your father can hold it for 2-3 hours even if he is fully hydrated definitely is I think is a sign of healing inside the bladder also I trust that his quality of life has improved significantly. I remember that when they found my bladder cancer, they also found enlarged prostate pushing the bladder, which happened to be the main cause of frequent urination in less quantity. So, when I had TURBT done, I pretty much lost control. I wet my pants a few times while I was dring at the intersection because I could not hold even one minute till the traffic signal changed. So, it is good to know your father has regained the quality of life in that aspect.
It seems that the prediction of recurrence and progression is challenging. I understand researchers have been trying to find biomarkers to detect and predict the recurrence and the progression. What I don't understand much is why some high-grade patients respond well to the treatment like BCG and some have recurrence and progress to muscle-invasive in spite of the same treatment. These days, researchers are looking for genomic biomarkers. In 2016, Dr. Joshua Meeks (he is a urologist and well known as a genomic researcher for bladder cancer) and his team at Northwestern University analyzed genomics ( gene mutations) of 25 high-risk non-muscle-invasive bladder cancer patients who had BCG treatment and 11 metastatic patients. Then divided 25 non-metastatic patients into two groups, the ones who had progressed and those who did not. Then checked if there are differences in gene mutations in each group. 25 patients consisted of 18 T1HG, 4 T1HG+CIS, 1 TaHG +CIS, 2 TaHG.
The result: 10 T1HG had progressed to muscle-invasive within 3 months to 44 months. 8 T1HG, 4 T1HG+CIS, TaHG+CIS, and 2 TaHG did not progress with follow-up of 23 to 81 months. In the case of two TaHG, one follow-up was 72 months and the other one was 81 months, Though the cohort was small (25 patients), 2 patients with TaHG have shown a very good prognosis. I sincerely hope that your dad's TaHG will behave similarly to those two TaHG patients who had a good prognosis in the study
Dr. Meeks' group did not find major differences in the type of gene mutations between the non-progression group and progression groups, but one finding from the study is that the group which had not progressed showed a high Tumor Mutation Burden compared to the group which had progressed and the metastatic group. The tumor mutation burden (TMB) indicates the frequency of gene mutations found in the tumor. TMB of the nonprogression group was 15 at the time of initial diagnosis. TMB of the progression group was 12, and TMB of the metastatic group was 5. It is counter-intuitive to find those who had less frequency of gene mutation had a worse prognosis than those who had high TMB. But it also means that high TMB responded better to BCG treatment than those with lower TMB. We need to wait and see if the TMB will be used as a biomarker for predicting the prognosis of high-risk urothelial carcinoma.
Thanks for a detailed and informative response and certainly I feel blessed and gifted with such a supportive people who advises and helps people in the journey of treatment. Really appreciated your information and advises which you share for me.
Since we stopped BCG for 5th dose I monitored father with regular checkups and tests other than cystoscopy.
Every 4 weeks I was doing
1. CBC Count test
2. Vit D test
3. KFT, LFT
and most importantly the 3D USG as these checks were not that aggressive as Cystoscopy.
USG was revealing Bladder Cystitis of 6mm in one of the areas of bladder. I guess and think it is the area where father has developed HG.
Uro while doing cystoscopy in Nov 2020 also suggested that there was an area of swelling which could be due to BCG side effect in the bladder and has not took a sample for biopsy as he thinks it was not tumor.
I also saw that you mentioned that bladder epithelial in some patients is not regrown after the week's wait of BCG and my dad is one such candidate. I agree with you that this might be the case as it was evident that he could not hold his urine for more 40 to 50 min.
Regarding the bladder injury with TURBT , Uro suggested us to start BCG after 6 weeks after full healing of bladder. He advised that bladder should be properly healed from TURBT before BCG is instilled. According to the aritcle which you have shared and based on my research human Bladder is MASTER of self regeneration, meaning no internal organ is healing itself as Bladder does, which is also a good news for healing the wounds after TURBT which could have caused serious issues.
But the situation right now is much much improved as I see him go to bathroom after 2 to 3 hrs which is very normal when he is taking lots of water during the day. One important thing which I noticed that when he takes fluid during the day , his Urine analysis is absolutely fine with no puss cell and all OK and Urine is clear in appearance. Only the morning urine is yellowish and urine analysis shows 10-12 puss cells which according to Uro is normal.
Also Uro mentioned that puss cells are good sign ( as mentioned by you as well) as it signifies that immune systems has worked as expected and puss cells are WBC which could have been there because of fighting with Cancer cells. Over all I am seeing and hearing good feedback from the side effects which my father had gone through.
The only think and am scared of is the recurrence and progression which according to Uro has 15-25% chances in our case as we had HG.
We have cystoscopy and reTURBT tomorrow which was scheduled 4 weeks before but could not went through becoz of the situation of not ready for the procedure physically( weakness and all).
Future Plan: BCG maintenance with reduced dosage
I PRAY, PRAY AND HOPE WE HAVE THIS CYSTOSCOPY CLEAR AND BIOPSY WITHOUT Ca.
I thank you Joea73 for you thorough explanation and valuable information.
Thanks to Alan and Sara and rest of members as well.