Highlighting Clinical Trials NonMuscle Invasive Bladder Cancer Part II

so doctors mazak talked to a little bit about the layers of the bladder and the staging and it's important to note as you can see on this slide that the stages of the bladder cancer really depends on the depth of invasion and when we talk about recurrence and progression the most important factors are the depth of invasion and the grade of the cancer and bladder cancers are either low grade or high grade so one of the most difficult aspects of bladder cancer is its high propensity for occurrence and progression and we talked about recurrence we mean the same cancer comes back at the same stage in grade so if you had a non-invasive high grade cancer the cancer can recur as a non-invasive high grade and that would be termed of recurrence a progression though means the cancer got worse so it either went from low grade to high grade ore from a non-invasive to an invasive tumor low-grade tumors are mostly considered a nuisance tumors in the census mostly they recur which is a good thing they very rarely turn into high grade cancers and they very rarely progress to invasive disease once you get to high grade cancers though the risk of invasion increases significantly and a non-invasive tumor might become invasive into the lamina propria as high as forty percent of the time and invade the wall of the bladder as much as twenty five percent of the time if it's already invading the lamina propria in which case the t1 tumor about a quarter of patients have that diagnosis at that stage a diagnosis but these tumors are much more likely to recur and progress in a relatively short time frame carcinomatous a2 is also a high-grade non-invasive tumor it's usually a flat tumor and it most often happens with other tumors in the bladder and it's also associated with a very high rate of recurrence and progression the there are different ways for us as clinicians to identify risk factors for patients and predict the likelihood of recurrence and that's based on primarily the number of tumors that somebody has the size of the tumor whether or not they've had many tumors in the past or whether or not this is the first tumor and then the stage of whether or not they have invasion the lamina propria carcinoma in situ and then finally the grade this is an older grading system one two three but really one is low grade and then three is high grade and to fall in between this is a figure and what this really shows is that if you take the different risk factors and you add them up and you can get a recurrence score and what it basically shows is that obviously those with the highest numbers highest score are at a very high risk of recurrence you can see at two years as many as eighty percent and the very top curve but even the patients who are very low risk the solid dark line have a risk of recurrence at as high as twenty to thirty percent over the first five years so there is no group of patients with what i would consider safe bladder cancer the good news is at progression to muscle invasion is very rare at least in the very low risk group which is we see if nearly flat line down there by the zero risk the year percent unfortunately the risk rises pretty quickly and as you have more risk factors the risk of progression Rises fairly dramatically and there are some patients who are quite high risk for progression which is concerning as was mentioned earlier we use treatments in the bladder to try to reduce the chance for recurrence and progression and we try to we wait for the bladder to heal from the initial resection about two to six weeks and then we give treatments primarily the patients at higher risk for recurrence and those patients with carcinoma type 2 and rarely those patients we cannot completely respect their tumor mostly this means intermediate and high risk patients those patients with solitary low-grade tumors are such a low risk for progression that we usually spare them the side effects of the treatments in the bladder the main treatments that we give our BCG which is a live and attenuated form of tuberculosis and we don't know exactly how it works we've been using as though for over 40 years and the main way we think it works is by stimulating the immune response to fight bladder cancer the alternative to that is chemotherapy which works to kill cells and keep them from dividing interestingly and enough though there are many studies that have shown the BCG superior to chemotherapy largely because the chemotherapy does not get absorbed by the bladder wall and so even though it's quite effective at killing cells if they can't reach them because they are deep to the lining then it's just then it can't work well and so BCG works in about sixty sixty-five percent of patients initially in the chemotherapy about thirty to forty percent of the time so we're talking about clinical trials and these treatments these interval therapies are an important area where clinical trials have been very beneficial to us and certainly we've been very appreciative that patients have been willing to participate in these trials as I mentioned when people start using BCG about 40 years ago with and even today we don't know exactly how it works but we wanted to find out whether or not it's more effective than chemotherapy or not and so there have been many studies comparing BCG to giving different types of chemotherapy and whether or not you should use maintenance therapies and the bottom line is that through these clinical trials we've been able to find out that not only does BCG work better than the chemotherapy but it's important to do maintenance treatments in fact for high-risk patients is important to do not only maintenance but three years of maintenance that a full dose compared to reduce doses which we use sometimes in patients with lower risk disease or patients we're having a lot of side effects and we also know that based on trials BCG is a first-line therapy for person on the side too because it works twice as good as chemotherapy in the blood why do we still need to do trials well the problem is a BCG doesn't work in everybody you can see here in this graph that the blue columns rougher what happens after one price so after the first cycle of BCG in other words patients who have never gotten BCG before it worked in about seventy-seven percent of patients and only seven percent of patients developed invasive disease or metastasis but in people would previously gotten BCG who record and now you give them another cycle of BCG you see the response rate goes down and the risk of invasive and disease and metastasis goes up finally you see that in if you failed after two cycles of BCG or or i should say the BCG failed you you'll find that it only works twenty percent of the time by the time you give a third cycle and that's in odds and metastasis ghost up to fifty percent so after two cycles of BCG we don't think that giving more BCG is a good idea if you if the cancers didn't respond because the high likelihood that it won't work and that metastases will occur so the guidelines for patients who have a recurrence after BCG basically say that if you need to resect all of it and if you have lamina propria invasion you might need to be reset to make sure you don't have additional tumor but this is the point where we have a problem is that we should consider removing the bladder because of the fact that our alternative treatments are not very good and giving more BCG is not very good but there are options obviously to give other intravesical therapies and this is where clinical trials right now play an important role because we're trying to find out if we have other treatments that are effective so that we can avoid having to take out the bladder this is a somewhat complex figure but what it shows you is that these are sort of national guidelines for patients who don't have a complete response to BCG and what you can see again is suspected me or bladder removal is one of the top options changing agents is an option in some patients but it's important to note that the guidelines recommend clinical trials as an important consideration for patients because we know that what we're doing right now is not good enough for many patients and we still prefer to avoid removing the bladder if we and to spare some patients the decrease in quality of life so just to you know just to let you know sort of when of why we want to avoid a suspect to me is because they're obviously side effects on the other hand removing the bladder when the cancer is still confined to the bladder is the best chance of cure it's definitive treatment you don't have to worry about recurrences and progression as much but we worry about quality of life implications the benefits of intravesical therapy is that you preserve the bladder on the other hand there's a chance that the cancer will progress or spread oh while while you're trying to keep your bladder and trying other treatments and then and you might end up dying a bladder cancer which could have been preventable you