Thank you for sharing very detailed events and side effects your dad has gone through. It is good to know that you had Mitomycin right after the first TURBT. That is the first thing I would check if the treatment is following the guidelines. For several reasons, I ended up with a urologist in a local click and I did not receive the intravesical chemo treatment after the first TURBT. I am not happy about it as it could have reduced the chance of recurrence. I was a bit disappointed to hear the urologist saying that the one-time Mitomycin was used before and found not effective just before I was wheeled into the OR. I could not just jump off the bed and went to find a second opinion. Had I known what I know now, I would have asked the question even before cystoscopy. But, like many other patients who were initially diagnosed with bladder cancer. I had been in panic mode from the first time I saw red urine without pain, rushing to ER when the toilet of the basin in a public washroom became covered with the blood in my urine, trying to expertise the appointments with a urologist till getting the TURBT done, waiting for the pathology report, which I could not understand what it said. It took a while to understand what the pathology report said. Then I realized that the pathologist used the older grading system G1, G2, and G3 instead of PUNLMP, Low Grade, and High Grade. Mine was G2. Also, the sample did not include muscle tissue. Much later, I asked the urologist why muscle tissue was not sampled. He said something like the tumor had not invaded to some layer. I estimate my urologist has dealt with over 5,000 new bladder cancer patients over his career. He is known to be a skilled surgeon. So, I try to think that because he has done over 10,000 TURBTs, he can tell if a tumor has reached the connective tissue or not, and he will not go and get the muscle specimen for those. Anyway, I would recommend any new bladder patient to try to go to a larger cancer center or university-affiliated hospitals, so we do not need to question if the treatment is correct or not.
In terms of your father's reaction to the BCG treatment, has the urologist mentioned what caused the side effects more severe than other patients with BCG treatment?
Several patients in the discussion forum say that the side effects from BCG are cumulative and get worse as the treatment continues. But some patients go through 3 years of BCG treatment with little problem. I do not think the medical community has found out who is susceptible to the side effects from intravesical BCG treatment. Because everyone gets the same MERCK TICE strain BCG, so the severity of the side effects must be more dependent on the host ( patient). I know a patient who has an autoimmune disease - Rheumatoid arthritis and the patient was on immune suppression drug during BCG treatment. After the 5th dose of the 6 weeks initial induction, the patient experienced severe side effects and the patient's doctor stopped the subsequent BCG. The patient's urologist put the patient on observation. The patient has been NED for 9 months, I do not know they are going to try BCG again. It is noted that the patient was diagnosed with T1HG. This patient's side effects were not urgency or the pain in the bladder or peeing. The patient has still some of the side effects even 9 months later. In this case, it is plausible that BCG stimulates immune activities has affected the patient's autoimmune disease conditions.
But the symptoms your father has experienced, i.e. urgency, frequency, and pain are different, and similar to what interstitial cystitis patients experience. I know a patient who was diagnosed with interstitial cystitis, later developed bladder cancer, told her a similar experience before she removed the bladder. One of the causes of interstitial cystitis is UTI / bacteria infection. According to Dr.Shehab of St. Joseph Hospital in California (youtube), bacteria break the lining of the bladder, which protects urine to penetrate into the epithelial cell, the outer tissues like the connective tissue. most UTI patients recover with anti-biotics regrow the lining but some patients never grow back the lining or the lining is too thin and when there is any insult makes patients feel like UTI but actually, it is irritation or inflammation. Could it be possible that your dad had experienced bacteria infection and the lining of the bladder was not fully regenerated as other patients and made it worse when subsequent BCG was administered?
BCG is live bacteria. Though tuberculosis-causing toxicity has been eliminated to the minimum level in the manufacturing process, BCG is still alive bacteria. It infects all surfaces of the bladder and breaks the umbrella layer of the bladder. Actually, that is what we want. We want our immune system to be activated by BCG bacteria and BCG infected cancer cells so our immune system kills the cancer cells. Unfortunately, BCG bacteria would not know normal cells from cancer cells, so normal cells will be infected by BCG bacteria, so cystitis can happen not only where the tumor was eliminated by TURBT but all over the bladder surface. I cannot find any study if cystitis happens more in the area where the tumor was scraped out by TURBT. Usually, the first dose of BCG is given 4-8 weeks after TURBT. I do not know if a urologist usually checks the lining of the bladder before the BCG treatment starts.
There is an interesting article by Dr. Beachy - a developmental cell biologist of Standford University who has studied the mechanism of repairing bladder infection damage, which I think applies to cystitis caused by BCG. The bladder's inner lining is made up of a tightly connected layer of umbrella cells that protect the underlying cells from toxins and waste in the urine. He says "Most of the time, the cells in this tissue undergo little or no cell divisions (I have learned that the lining layer cells of a bladder of a mouse are replaced about every 40 days), but injury with chemical or bacteria infection causes rapid proliferation" to repair and replace damaged cells. In fact, Beachy and his colleagues found in this study that it normally takes about 10 months to replace about half of the cells in the inner lining in the bladders of female laboratory mice. In contrast, in the presence of harmful bacteria, the cells of the bladder begin dividing dramatically and most turn over within 24 hours. So, this explains that many patients with BCG can tolerate at least the 6 weeks induction course and a few maintenance treatments because one week of rest between the BCG treatment will replace the protective lining of the bladder. But, some patients' bodies cannot regenerate the lining that soon as Dr. Shehab said. So, it is possible that your dad's bladder fits into the latter category.
You mentioned puss lasted 2.5 months after stopping the BCG treatment. My understanding is that puss is dead white blood cells, which include various immune cells such as antibodies (B-cells) and T-cells. So, I think your dad's immune system had continued to respond to the BCG bacteria-infected cells of the bladder. This may be good news for your dad. BCG is known to have long-term efficacy. A case in point is that once Dr. Ashish Kamat of MD Andersons explained the longevity of BCG efficacy by stating that the complete response rate of BCG for Carcinoma In-situ is 55% after the 6 weeks induction. But the complete response rate increases to 69% even without a maintenance course. So during the time, puss was being found in urine, the immune system was active to BCG bacteria and bacteria-infected cells. Note. I do not know how long BCG bacteria survive once infected the bladder cells.
In terms of future treatment, given the tumor was TaHG and less than 3 cm, which is considered as intermediate risk by AUA, and its recommended treatment is either BCG or Intravesical Chemotherapy of 6 weeks induction and one-year maintenance. II know you have chosen to treat as high risk. I agree that wait till the condition of your dad recovers and try with a reduced dose is likely the approach since your dad has done BCG already. Another option is just surveillance assuming that the BCG treatment received so far killed all cancer cells. The other option is to switch to intravesical chemotherapy as it has lesser side effects than BCG, or perhaps keep it as a treatment option in case of recurrence from BCG treatment. This is the point we need to trust the urologist's clinical experience and knowledge of your dad and other patients.
Again, pat yourself on the back. The caregiver/attendant is always a huge part of one's recovery on medical concerns. From an outside view, you and your doc team are doing everything with compassion and normal guidelines. You are hopefully past the worst part and everything is downhill from now on.
DX 5/6/2008 TAG3 papillary tumor .5 CM in size. 2 TURBS followed by 6 instillations of BCG weekly with a second round of 6 after a 6 week wait.
Thanks for the reply and response. Appreciate as always. I am lucky that I am member of this forum which such beautiful people to support.
Regarding the BC risk category , I have done so much research and study that I am second to a Medical expert and your link also cleared some doubts. But even though my case will fall in Intermediate risk , I will consider it as High risk only because to be proactive and take all necessary precautions and be under aggressive surveillance.
Types of Side effects:
Till dose 3rd my father was kind of OK and frequency lasted for 3 to 4 days with slight ( tidiness, weakness and slight fever). Side effects were normal till 4 or 5 day. But since the 4 dose was given , urination was very high and he had to urinate within 20 to 3 min during day and night. His frequency increased day by day and nights were also sleepless. the total number of urination during 24hrs were 20 to 24 in number. This along with the burning sensation during and after urination was same for 4 to 5 weeks.
He also was passing protein in Urine which was 100mg/ml which made him very weak. When it was time for the 5th BCG doctor said he cannot tolerate to keep it within the bladder for the required time when seeing his condition. Urine examination during these months were 50-80 puss cells, 5-6 RBCs, Clumps in Urine, but no blood. This continued for 2.5 months.
So Uro suggested to stop the BCG and let him recover. He will adjust remaining BCG in maintenance course. Things are becoming normal now as he is able to hold urine for 2 to 3 hrs and his protein disappeared and no RBC and clamps in Urine. Only thing remaining is the weak and dehydration which he had from frequent Urination. This was the most worst period of the treatment.
Mytomycin C 80mg :
Yes regarding the Chemo within the 24 hrs of TURBT ,he was given Mytomycin C 80mg within 24hrs of TURBT.
DG Stent Removal and First Cystoscopy on 06 Nov 2020:
During TURBT Uro put a DG stent in his left ureter for avoiding urine blockage. It was removed after 6 weeks & along with the removal he did cystoscopy as well which was clear for any recurrence. Uro wrote bladder looked healthy with no recurrence.
We have Cystoscopy next week with biopsy of areas where Uro think was HG. Followed by 3 BCG with dose reduction. Biopsy is for upstaging which Uro mentioned has a 25% chance. I HOPE & PRAY THIS MUST BE CLEAR AS WELL, GOD WILLING.
Frankly speaking I consider myself lucky that I am part of this ultimate forum and group of people who are always supporting and advising. I will keep posting and updating you all for our progress.
Special thanks for Sara, Alan, Joea73 for support and advises. Respect and God Bless.
The risk stratification for non-muscle-invasive bladder cancer has been defined by Americal Urological Association. The recommended treatment is based upon the risk stratification. As Allan mentioned, If HG is found, it is considered high risk with the exception that if the tumor has not progressed to the connective tissue layer (Lamina propria), it is TaLG and the guideline considers intermediate risk. See table 4 for the AUG guideline. Because the pathology report says lamina propria and deep muscle invasion not seen, it is considered intermediate risk. Other factors which affect the risk stratification in the case of your dad are the size of the tumor and if there were multiple tumors or a single tumor. The report does not indicate multiple sites so, I assume it was a single site tumor. In terms of the tumor size, URO wrote down 3-4 cm. The pathologist wrote down 2.2x2x0.5cm. Maybe, the largest sample in one piece that the URO could take out was 2.2x2x0.5cm unless URO used the En-Block resection method and was able to remove it in one piece. Anyway, the tumor was on the borderline of being Intermediate risk TaLG or high-risk TaLG. The recommended treatment for intermediate-risk is either 6 weeks of BCG or 6 weeks of intravesical chemotherapy. The recommended treatment for high risk is the 6 weeks BCG induction course + maintenance courses. This is what the guideline recommends but it is up to the URO's clinical experience and knowledge to decide which treatment protocol is suitable for your dad. Can you share what kind of side effects your dad had experienced that were severe enough that he needed to stop after the 4th treatment?
What I did not see in the history of the treatment is that if your dad had received one-time intravesical chemotherapy after the first TURBT on 2020-09-14, which they say can reduce the recurrence rate by 5-10 %.