The BCG treatment for bladder cancer has a success rate of about 90%, which is thought to be the best life-saving rate of any treatment.
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How likely is it that bladder cancer will come back following BCG therapy?
The vast majority of bladder cancer casesroughly 70%that are anticipated to be newly diagnosed in the United States in 2019 are non-muscle invasive diseases with cancer confined to the epithelium, the tissue lining the bladder. Transurethral excision of the bladder tumor is the usual first-line therapy, which is followed by immunotherapy, which involves soaking the bladder in intravesical bacillus Calmette-Guerin (BCG), a recombinant tuberculosis bacterium.
“According to medical oncologist Noah Hahn, M.D., it works initially. Max Kates, M.D., a urologist, adds, “While intravesical BCG can induce long-lasting, sustained remissions in up to 35% of patients, up to 60% of patients will experience a cancer recurrence within two years. Final stage muscle-invasive stages and radical cystectomy, or surgical removal of the bladder, are required in 40% of these high-risk patients. One problem with BCG is that many patients do not respond long-term; a second is a fundamental supply issue. Because there is now only one manufacturer, Kates claims that there have been ongoing supply problems and shortages with BCG.
“Clinical outcomes of the GEMDOCE combination were promising, approaching 50 percent recurrence-free survival at two years when used with monthly maintenance.
A better strategy? In the same way that BCG is administered to patients with newly diagnosed bladder cancer, Kates and colleagues have started researching a combination of two chemotherapy medicines, gemcitabine and docetaxel (GEMDOCE). In previously released work at the Brady, Kates and Trinity Bivalacqua, M.D., Ph.D., analyzed patients who were administered GEMDOCE when bladder tumors returned following BCG as part of a multi-institutional research. ” According to Kates, the clinical results of the GEMDOCE combination “approaching 50% recurrence-free survival after two years when taken with monthly maintenance.” Kates has started a Phase 2 clinical trial to test this combination for newly diagnosed patients who have not previously had BCG based on these encouraging results. Additionally, based on the tumor biology of newly diagnosed patients, we will search for a biomarker that can predict GEMDOCE response in order to direct them toward intratumoral chemotherapy or BCG immunotherapy. You may read more about this clinical investigation here.
Molecular characterisation of CIS: At the International Bladder Cancer Network’s Annual Meeting, Hahn recently shared insights on the major regulators of tumor and immune cell biology in patients with a particular kind of non-muscle invasive bladder cancer, known as carcinoma in-situ (CIS). Recent publication in Applied Immunohistochemistry Molecular Morphology of significant research on urothelial CIS and adaptive immune resistance to intravesical BCG in non-muscle invasive bladder cancer. Along with others, the team featured Woonyoung Choi, Trinity Bivalacqua, Max Kates, Kara Lombardo, and Andres Matoso.
The small size of these tumors has made it difficult to understand the specific tumor and immune cell biology of CIS patients, according to Hahn. But he and his colleagues have achieved ground-breaking progress in understanding gene expression in these patients thanks to cutting-edge technologies. The researchers was able to complete thorough gene expression profiling in tissue from 43 out of 50 CIS patients as part of a study with HTG Molecular Diagnostics utilizing that company’s 1,392-gene Precision Immuno-Oncology RNA-based platform.
Even more intriguing: According to Hahn, “We discovered distinct immune gene expression profiles observed solely in patients with CIS. The scientists will then look into whether these new CIS signatures are connected to BCG and other bladder cancer immuno therapies.
How long is the BCG course of treatment?
The likelihood of the illness returning or spreading is decreased by BCG maintenance therapy. 13 years is the maximum duration of maintenance therapy, however therapy sessions become much less frequent (e.g. one dose a month). Ask your doctor for more information as treatment regimens can change.
How long does it take for the bladder to recover following BCG bladder cancer treatments?
Following surgery to treat non-muscle invasive bladder cancer, you could get BCG directly into your bladder. Transurethral resection of a bladder tumor is the name of this kind of procedure (TURBT).
This therapy aids in preventing the bladder lining cancer from returning. Additionally, it lowers the possibility of the cancer spreading to the muscles. If you have high-risk bladder cancer or occasionally if you have intermediate-risk bladder cancer, doctors will typically recommend this treatment.
The time between the cancer removal surgery and the beginning of BCG treatment is typically at least two weeks. This will allow your bladder to recover from the operation.
A BCG treatment typically lasts six weeks, once each week. The induction course is another name for this. More BCG treatments might be recommended to you. Typically, this is referred to as maintenance therapy.
How many BCG treatments for bladder cancer are permitted?
A catheter is used to insert a liquid solution containing BCG into the bladder. The individual then waits two hours before peeing after holding the solution in the bladder. Usually beginning two to three weeks following the last TURBT, the treatment is administered once a week for six weeks.
What occurs if BCG treatments are unsuccessful?
A contentious management problem for both patients with non-muscle-invasive bladder cancer (NMIBC) and their doctors is the decision of an acceptable course of action after the failure of intravesical bacillus Calmette-Guerin (BCG) treatment. Since between 30 and 40 percent of patients don’t benefit from this treatment, it poses a regular problem. Patients with low-grade disease who do not respond to treatment should be given different treatment choices than those with high-grade disease and/or progress who do not respond, the latter of which is linked to a bad prognosis. NMIBC consists of two biologically distinct disorders, although being categorized under the same name. Although they extremely seldom advance, most low-grade NMIBC are likely to reoccur. In these patients, failure following intravesical BCG is typically mild and superficial. On the other hand, as these tumors frequently advance to muscle invasion, failure to respond to BCG in high-risk T1 bladder cancer and/or carcinoma in situ (CIS or TIS) is more troublesome. 3
The European Association of Urology (EAU) guidelines on bladder cancer prescribe BCG as the first line of treatment for high-risk individuals and intermediate-risk patients who have not responded to intravesical chemotherapy.
3 However, because to an improved toxicity profile, the EAU recommendations advise intravesical chemotherapy in low-risk individuals.
Many urologists in North America and Canada use BCG as a first line of defense in low-grade illness.
4 Failure of BCG typically carries a risk of advancement, but seldom a danger of recurrence. Intravesical chemotherapy is a viable treatment option for low-grade failure. 1 Contrast this situation with the failure of BCG intravesical therapy in high-risk T1 disease and/or CIS, where a 50% chance of advancement occasionally exists. The best course of action for high-risk superficial bladder cancer is in dispute1,2 (stage T1, grade G3 or the new classification of high grade). 2,3 When compared to conservative care, immediate cystectomy offers the best probability of survival but may be accompanied by decreased quality of life (QOL). BCG administration is a different choice. Responders to BCG keep their bladders and avoid cystectomies and their related problems, preserving their quality of life. When BCG fails, there may be a natural tendency to put off definitive local therapy, putting patients at an increased risk of developing invasive and possibly metastatic disease. This is true even as new drugs and therapeutic modalities are researched and experience with a second BCG regimen and combination immunotherapy grows. 5 The worry is that a doctor would postpone recommending cystectomy for too long. Recent data indicate that the 5-year postoperative survival rate is lower than reported in recent studies when cystectomy is carried out after conservative measures in cases of high-risk NMIBC, particularly when cystectomy is carried out on a patient whose disease has advanced to T2 NMIBC as opposed to patients with T1 NMIBC. 5
Using a decision-analytic Markov model6, Kulkarni and associates recently assessed the following two treatment plans for high-risk T1G3 bladder cancer: In patients with resistant or progressing illness, (1) immediate cystectomy with neobladder development versus (2) conservative care with intravesical BCG and delayed cystectomy The authors showed that early cystectomy increased life expectancy and quality of life in younger individuals with high-risk T1G3 bladder. 6 Discussions that take the patient’s age, comorbidities, and preferences into account may determine whether to seek an urgent cystectomy or conservative therapy. A more cautious initial therapeutic approach may be beneficial for patients over the age of 70 or those who place a high importance on bladder preservation.
In contrast, advancement was seen in 30% of cases in a large cohort of primary high-grade T1 patients from Toronto and Rotterdam (n = 136) that were handled conservatively and followed for more than 5 years (median 6.5 years), whereas the other 70% of cases did not progress.
7 These observations draw attention to some of the difficulties in managing high-risk NMIBC and BCG failure.
Is chemo superior to BCG?
With more than 430,000 new cases each year worldwide, bladder cancer is the fourth most prevalent among men and women, respectively (1). Non-muscle invasive bladder cancer (NMIBC) accounts for approximately 75% of newly diagnosed bladder cancer cases, of which Ta accounts for 60%, T1 for 30%, and Tis for 10%. (26). Although the outlook for individuals with NMIBC has significantly improved, the malignancy’s therapy still faces significant challenges because to recurrence and progression (7). Of individuals with NMIBC, 60 to 70 percent will experience recurrence, whereas 20 to 30 percent may advance to more advanced stages (6). Therefore, extensive monitoring and treatment place a heavy financial strain on both nations and people.
Transurethral resection of bladder tumor (TURBT) is the mainstay of treatment for NMIBC, which is then followed by adjuvant intravesical therapies, primarily bacille Calmette-Gurin (BCG) immunotherapy (6). Due to significant adverse effects, BCG could not be administered to all NMIBC patients even though it has been shown to be beneficial in reducing tumor recurrence and development (2, 8, 9). There is an urgent need for alternate therapies because a significant fraction of NMIBC patients tolerate BCG inadequately. Intravesical chemotherapy could reduce the incidence of recurrence, however with a less effective method than BCG (10). To maximize the benefits of BCG and lessen its negative effects, a treatment combining intrathecal BCG with chemotherapy has been devised. Patients are more likely to take the intravesical BCG plus chemotherapy combination with a lower BCG dose, minimizing side effects. Meanwhile, the anti-tumor mechanism of chemotherapy will be used to trigger the immune response of BCG, potentially amplifying its effects, leading to the eventual achievement of an optimum treatment regimen (7). Unfortunately, these combinations do not always result in significantly slower progression or recurrence in trials (7). The combination had no advantage over BCG alone among NMIBC patients, according to a 2013 meta-analysis (11). Furthermore, nothing is known about the effectiveness of combining intravesical BCG with chemotherapy in the treatment of NMIBC, and there is still a dearth of clinical data with this strategy. Combination therapy has been the subject of numerous trials, which has increased interest in its effectiveness. The purpose of this meta-analysis is to examine if BCG combination therapy is more effective than BCG monotherapy and has fewer negative effects.
Can the bladder be harmed by BCG treatment?
Because of its shown efficacy and favorable safety profile, intravenous Bacillus Calmette-Gurin (BCG) is a crucial medication for the management of non-muscle invasive bladder cancer. The majority of BCG treatment-related problems are mild in nature. They consist of frequent urination, cystitis, fever, and hematuria. Although severe consequences are uncommon, people with disseminated mycobacterial infection might experience severe, life-threatening sepsis. We evaluate the literature on the potential side effects of this therapy technique and report a rare instance of periurethral diverticulum formation following intravesical BCG.
What long-term impacts might the BCG therapy have?
Urine tract infections, detrusor hyperreflexia of the bladder, fever, hematuria, urinary frequency, urinary urgency, vomiting, chills, and malaise are among the side effects of bcg that are frequently observed. Arthralgia is among the other negative effects. For a complete list of side effects, see below.
What qualifies as a BCG failure?
The fifth most frequent malignancy in the country to receive a diagnosis is bladder cancer (BC). In the United States in 2009, it is anticipated that 70 980 men and women would receive a diagnosis of BC, and 14 330 people will pass away from the condition. Around 51 1790 people in the US had bladder cancer as of January 1, 2004.
The most potent surgical procedure for bladder cancer that has advanced locally is a radical cystectomy (RC). Perioperative mortality in sites with high patient volumes ranges from 0.7 to 5.6 percent. There is a desire to adopt a bladder-preserving strategy and stay away from RC as a result of this diagnosis. Intravesical Bacillus Calmette-Gurin (BCG) therapy is one of the treatments for HG Ta/T1 and carcinoma in situ (CIS).
Intravesical BCG has been used extensively in the treatment of high-grade, non-muscle-invasive bladder cancer since it was first introduced by Morales in 1976. (NMIBC). Its effectiveness in lowering tumor recurrence after transurethral excision of bladder cancers has been supported by numerous research (TURBT). The rates of progression and recurrence after endoscopic resection for HG Ta tumors are, respectively, 25% and 47%. Recurrence and advancement rates are 42 and 23 percent, respectively, for HG T1 bladder cancer (tumor invasion of lamina propria), with a 14 percent delayed cystectomy rate. The 5- and 10-year recurrence-free rates for CIS (flat, high-grade, non-invasive cancer) are 63 and 54 percent, respectively. The progression-free rates at 5 and 10 years are 79 and 77%, respectively, while after 5 and 10 years, disease-specific survival is 90 and 86 percent.
Patients with high-grade NMIBC are increasingly offered a second transurethral resection to remove any remaining tumors and determine the stage and grade of the tumor after their initial transurethral resection. Within four weeks of the first diagnosis, this is done. Up to 33% of patients have residual cancer that is discovered. Understaging of NMIBC at an early diagnosis, particularly when there is little muscle in the specimen, is a significant issue. Clinical T1 tumor patients showed under staging in 78% of cases, while only 34% of these patients had muscularis propria. According to a recent study, the disease-free survival rate for muscle-invasive bladder cancer was dramatically decreased when radical cystectomy was performed more than 12 weeks after transurethral resection.
There are many definitions of “BCG failure” in the literature, according to a thorough literature search. BCG failure was divided into 4 categories by the First International Consultation on Bladder Tumors (FICBT). When BCG is administered initially and maintenance or re-treatment is administered after 3 months due to chronic or quickly recurrent disease, the patient is said to be BCG refractory. 3 months following the first BCG cycle, it also includes any change in stage or grade (i.e., non-improving or worsening disease, despite BCG). As a result, BCG is considered ineffective if, for instance, a patient with HG Ta TCC received 6 weeks of BCG and the 3-month follow-up endoscopy revealed the tumor had advanced to T1. When the disease returns or persists three months following the induction cycle, it is considered BCG resistant. At six months following BCG re-treatment with or without TUR, it is of a decreased degree, stage, or grade and has disappeared (i.e., disease improves and then resolves with further BCG). A tumor after six months of BCG is considered a BCG recurrence. Recurrences are further classified as early (within 12 months), intermediate (12 to 24 months), and late (>24 months) relapses. BCG intolerance denotes tumor recurrence following a therapeutic regimen that wasn’t sufficiently effective because of a side effect of the BCG. The terms “BCG refractory” and “BCG resistant” are unclear in our opinion. Refractory is described in the dictionary as “Resistant to treatment or cure.
According to the National Cancer Institute (NCI) guidelines on bladder cancer for stage 0 (Ta N0 M0 and CIS N0 M0)/stage (T1 N0 M0), patients who have a T1 tumor at the 3-month evaluation following a 6-week course of BCG, as well as patients whose CIS persists after a second 6-week course of BCG, have a high likelihood of developing muscle-invasive disease, and should therefore be given the option of cystectomy. In support of its recommendation for RC if a T1 tumor is present at the initial 3-month evaluation, the NCI cited three papers. A second BCG course was recommended by two reports. Only one BCG course was attempted in the third report.
Treatment with BCG is deemed to have failed in the following circumstances according to the European Association of Urology (EAU) guidelines on NMIBC: Whenever a muscle-invasive tumor is found during follow-up, whenever a high-grade, non-muscle-invasive tumor is present at both 3 and 6 months, and whenever there is evidence of a worsening of the disease while receiving BCG treatment, such as an increase in recurrences, a rise in T-stage or grade, or the emergence of CIS despite an initial response. If HG NMIBC (Ta/T1) is present at the initial 3-month review, the EAU guidelines, in contrast to the NCI guidelines, recommend a second treatment of BCG. With a second course of BCG, the EAU responds to two reports showing a 50% full response.
There wasn’t much information about BCG failure in the American Urological Association’s non-NMIBC guidelines. An index patient (index patient 4) with HG NMIBC (HG Ta/T1 and/or CIS) was described under the AUA guidelines. It is advisable to start with a 6-week BCG course and then maintain it. Early radical cystectomy is a treatment option for high-risk disease in the same patient, such as large tumor size, high-grade tumor location in a site difficult to remove completely, diffuse disease, the presence of CIS, infiltration of lymphatic or vascular spaces, and involvement of the prostatic urethra. After receiving first BCG therapy, if the same patient (index patient 5) developed recurrent T1 disease, it is indicated to undergo either an emergency radical cystectomy or another course of 6 weeks of BCG. The report by Herr and Sogani served as the foundation for the AUA guidelines’ advice to proceed with a radical cystectomy. After BCG failed in this report, 90 individuals underwent radical cystectomies. For muscle-invasive bladder cancer, 55 patients underwent RC, while 35 patients underwent RC to control recurrent NMIBC (MIBC). Patients who had RC before or after 2 years from the initiation of BCG therapy in the NMIBC group had survival rates of 92 and 56%, respectively. Patients who had RC before or after 2 years from the initiation of BCG therapy in the MIBC group had a survival rate of 41 and 18%. The median time to a radical cystectomy, in both the early and late groups, was 11 months, while the average number of recurrences in the NMIBC group prior to cystectomy was 3.7. Given the median time to RC and the average number of recurrences, it is unclear from the study how many courses of BCG were tried, but one would infer that a significant portion of these patients tried at least 2 courses of BCG.
BCG failure definitions in the National Comprehensive Cancer Network (NCCN) recommendations are quite similar to FICBT.