About 70% to 80% of bladder cancers present as non-muscle-invasive bladder cancer (NMIBC). The management of NMIBC includes transurethral resection of bladder tumor (TURBT), followed by single-dose intravesical immunotherapy with bacille Calmette-Guérin (BCG) or intravesical chemotherapy (mitomycin C, epirubicin, or doxorubicin). The decision to instill BCG and/or chemotherapy is based on the risk of cancer progression or recurrence.
For practicing oncologists, it is crucial to address Frequently Asked Questions (FAQs) regarding NMIBC such as how to define individual risk groups and treatment recommendations for each group, how to identify BCG refractoriness and relapse in clinical practice, and how to manage patients who are BCG refractory.
Let's watch the recorded video on 'Frequently Asked Questions (FAQs) for NMIBC' to gain comprehensive insights from leading experts – Dr. Francisco X. Real from National Cancer Research Center of Spain and Dr. Félix Guerrero Ramos from Hospital Universitario 12 de Octubre in Madrid, Spain.
As you mentioned, the definition of non-muscle-invasive cancer is strictly pathological. So it is based on the histological analysis of the tumor. And the definition stands for the fact that the tumor does not invade the muscularis propria or beyond the muscularis propria. Therefore, it only goes through the lamina propria. Individual risk groups in non-muscle-invasive bladder cancer can be defined according to several scoring systems or classifications. There are three predictive models based on individual patient data, which are EORTC, CUETO and EAU 2021 classifications. And there are another six ways of classifying these patients according to the risk of recurrence and progression, which are expert panels based on consensus of experts, which are AUA, NCCN, and those EAU classifications previous to 2020. In general, patients are classified into low, intermediate and high-risk groups according to the risk of recurrence, but also the risk of progression. And some of the classifications also include a very high-risk group where due to the high rate of progression, they would recommend radical cystectomy as an upfront therapy. All these classifications have several limitations, some of them do not include patients treated with BCG, some of them do not include patients treated with TURBT, and some of them overestimate the rates of recurrence and progression. So probably in the future, we will need more accurate systems for these purposes. Every patient should undergo TURBT once diagnosed with bladder cancer. Those patients with low and intermediate risk, with a rate of recurrence of less than one tumor per year, should also receive a post-operative instillation of chemotherapy in 6 to 24 hours after the surgery, after the TURBT. And those lo- risk patients could be managed only with follow-up, to check if there is any recurrence. For those intermediate-risk patients, either intravesical chemotherapy, especially with mitomycin C, or BCG for one year are recommended. Patients in the intermediate-risk group could be sub-stratified into intermediate low and intermediate high, and use BCG for those intermediate high, that is, those who are recurrent or have previously received mitomycin, and treat with chemo those with intermediate low risk. Then for the high-risk patients, BCG is the standard of care therapy and these BCG should be administered as an induction plus maintenance schedule. If we do not administer maintenance to a patient, the results won't be better than with the use of chemotherapy. The duration of the treatment should be at least one year, but up to three years. And then for the very high-risk group, the EAU guidelines, for example, recommend discussing with the patients about upfront radical cystectomy, and BCG for those patients who refuse or who are not candidates for radical cystectomy. It's important to identify the response to BCG, because this defines also the prognosis of the patients and the need of more or less aggressive therapies after BCG, depending on the response. There is the BCG unresponsive scenario where patients are either refractory or early relapsing. To sum up, BCG unresponsive patients are those who have a high-grade relapse after six months of finishing their BCG, if they have a papillary tumor, or in the first year after finishing their BCG. Those refractory, which is the worst group in the BCG unresponsive are those with high-grade relapse, during the treatment with BCG, no matter their original tumor was papillary or CIS. Then if patients have a relapse more than one year after having finished BCG, that is called late relapsing. These patients have a worse prognosis than a BCG naive patient. However, rechallenging with BCG may be an option. For BCG unresponsive patients, remember, it includes BCG refractory plus early relapsing, BCG is not an option because response rates are residual, and these patients should be advised on other alternatives. BCG refractory patients are individuals who are not going to respond to further BCG instillations. The response rate to intravesical chemotherapy is also quite low. There are some data on retrospective data with device-assisted intravesical chemotherapy, where response rates look promising. But this is based on retrospective data and the most oncologically safest option is radical cystectomy, and this is the first alternative that is recommended in the guidelines. Radical cystectomy should be the treatment offered to these patients. But the level of evidence we have for radical cystectomy is three. Then the second option would be the inclusion of the patients on one of the numerous clinical trials that are currently running with all the new drugs and the new formulations of well known drugs for this scenario. And as a third option, as I said, we can try with chemo either normothermic, or if you have device-assisted, choose this option over cold chemo, and BCG since patients are probably not responding to BCG.