Muscle-Invasive Bladder Cancer (MIBC) is defined as the tumor has spread through the bladder lining and into the bladder muscle. Optimal treatment strategies for MIBC requires the involvement of a specialist multidisciplinary team (MDT), with collaboration between surgeons, medical oncologists, radiation oncologists, pathologists and other specialists.
Bladder preservation is an alternative to cystectomy for patients deemed unfit for surgery. The MDT board should develop a treatment strategy tailored to meet the needs of patients seeking bladder preservation. The management of locally advanced operable bladder cancer and the role of pre and postoperative systemic treatments have become increasingly intricate. Neoadjuvant cisplatin-based chemotherapy has been the standard of care for some years. Adjuvant immunotherapy has now emerged as a new standard of care for postoperative patients with high risks. Nonetheless, there remain gaps that need to be addressed for practicing oncologists to gain an in-depth understanding of individualized treatment strategies for MIBC.
Let's watch the recorded video on 'Frequently Asked Questions (FAQs) for MIBC' to gain comprehensive insights from leading experts – Dr. Francisco X. Real from National Cancer Research Center of Spain, Dr. Félix Guerrero Ramos from Hospital Universitario 12 de Octubre in Madrid, Dr. Natalia Carballo and Dr. Enrique Grande from MD Anderson Cancer Center Madrid.
Again, from a pathologist perspective, it's morphological evidence that the tumor has invaded the muscularis propria. So this is a classification of non-muscle versus muscle-invasive bladder cancer that is strictly defined by the involvement, the invasion or the lack of invasion of the muscularis propria by the tumor. So it's very strictly a pathological definition. As I mentioned, the definition of non-muscle-invasive bladder 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. We all know since years ago that neoadjuvant chemotherapy gives the patients an overall survival benefit of 5 to 8% at five years. So neoadjuvant chemotherapy should be offered to all the patients who are undergoing a radical cystectomy due to a muscle-invasive bladder cancer. There are, however, some patients who are not candidates for neoadjuvant chemotherapy, especially if they are not cisplatin-fit patients who have some cardiac problems or patients with impaired renal function or neurological or cardiac function. So if a patient is a candidate for neoadjuvant chemotherapy, these options should be offered as a part of the therapy, which will be subsequently followed by a radical cystectomy. We have learned from previous studies that if you are not giving any therapy to the patient prior to radical cystectomy, this surgery shouldn't be delayed more than 90 days after performing the TURBT. And if there is a neoadjuvant therapy which should be offered to every patient who is fit for it before radical cystectomy. The timing will be given by the neoadjuvant chemotherapy, it's usually 3 to 4 cycles of chemotherapy with a disease assessment after the chemotherapy and prior to the radical cystectomy. So our oncologist will be in contact with us, with our patient being treated with systemic therapy to calculate according to the last cycle of the treatment when we have to perform the radical cystectomy, but we shouldn't delay the radical cystectomy many weeks once the chemotherapy has been completed. The standard of care for muscle-invasive bladder cancer is radical cystectomy with neoadjuvant chemo plus adjuvant chemo or immunotherapy. But certain selected patients or some of them refusing radical cystectomy are candidates for a bladder preservation strategy with trimodal therapy. This trimodal therapy includes both chemo and radiotherapy and a radical TURBT. The technique of this radical TURBT is very important, it is of paramount importance in these patients, and it will impact the prognosis. So for these patients we should do a TURBT of the exophytic tumor in several parts. First, we have to take the part, the most exophytic part of the tumor and send it to the pathology department. Apart from it, we have to take the endophytic part of the tumor. Then we have to take a third part which would be the tumor bed biopsy. And then with a cold cup forceps, we have to take a biopsy of the perivesical fat to rule out a cT3A tumor invading the perivesical fat. Also in these patients, random biopsies with cold cup biopsies should be needed to rule out extensive CIS, which should be a contraindication for trimodal therapy and prostatic urethral biopsy, which again could be a contraindication for trimodal therapy. Adjuvant treatment is very important in those patients that after surgery have worse prognostic factors, as we can define as pT3 with lymphovascular invasion, pT4 patients or those patients who have lymph node positive after lymphadenectomy or those with margins positive after surgery. So for those patients, we have demonstrated in several studies that adjuvant treatment is important because with one of those factors, the local relapse goes up to 30-33% of cases. When we compare radiation therapy alone with chemoradiation therapy, the results are much better in the combination of chemoradiation therapy. So we must consider adjuvant treatment for those patients with more adverse risk factors after surgery. Bladder preservation is a strategy for those patients that obviously want to preserve the bladder, but we must consider those patients that fit for that type of preservation protocol. So first of all, we need to look at patients with very good health. We also need to look at the renal function because those patients are going to receive cisplatin-based chemotherapy. Also we need to look at the hydronephrosis because if they do have it before starting the chemoradiation therapy treatment, we need to solve it. And also when we look at the tumor, it is not mandatory but probably we need to think about not including those big bulky diseases on the bladder and also those patients with multifocal disease. So for those candidates, this strategy with chemo and radiation therapy is optimal. We may propose to those patients two types of treatments. One will be with chemoradiation therapy, but in a more conventional fashion that is 6 or 7 weeks of treatment because we are giving 2 Gray per day fraction of radiation therapy. So the whole treatment will last for a total of seven weeks with cisplatin based chemotherapy. And a second schedule could be with a shorter radiation therapy. Because we are giving 2.75 Gray per day, we reduce from seven weeks to four weeks. And on these cases, the protocols were combining this radiation therapy hypofractionated radiation therapy, with 5FU and mitomycin C. So in both cases, the most important issue was the Grade 3/4 late toxicity that when we look at these five years, long-term Grade 3/4 toxicity for those cases, those scenarios. Toxicity was on terms of gastrointestinal less than 2% and on the genitourinary less than 5%. Because right now we are giving radiation therapy with more sophisticated techniques like IMRT and VMAT that preserve toxicity and increase outcome results. Yes, there is a potential combination for radiation therapy and immuno-checkpoint inhibitors, because we have learned from other diseases that the mechanisms of radiotherapy when we deliver radiation therapy to a tumor is multifactorial. For example, we increase the PD-L1 expression with radiation therapy. We also increase and release to the bloodstream some proteins, pro-inflammatory stress proteins, we also increase the antigen expression and also immune cells inflammation and infiltration. So for all these reasons, radiation therapy is a treatment that may enhance the potential role of immunotherapy on those patients. For the treatment of our patients with muscle-invasive bladder cancer that are candidates to receive neoadjuvant or adjuvant, we are following the Galsky's criteria. Because the standard backbones for this perioperative treatment are based on cisplatin. No matter if you will use dose-dense MVAC or cisplatin/gemcitabine, you need to follow these criteria. The thing is, all of these patients are fit enough to receive dose-dense MVAC, how much growth supportive factor like G-CSF (granulocyte colony stimulating factor) are needed before the use of this neoadjuvant approach? Well, that's the question that we address in the clinic. In the adjuvant treatment, the use of cisplatin and gemcitabine as an adjuvant treatment is something that is well established if the patients did not receive neoadjuvant approach and they were operated through a cystectomy upfront. This is not the ideal scenario, but we have robust evidence and meta-analysis showing an overall improvement in the survival in the range of 6% of the overall survival of our patients. Ideally, patients should be treated with neoadjuvant approach based on cisplatin before the surgery. By doing that, the meta-analysis is suggesting an improvement in the overall survival of these patients of 8%. Consistently, all the main guidelines, European Association of Urology guidelines, ESMO guidelines and NCCN guidelines are consistently recommending the use of cisplatin as a neoadjuvant approach ahead of the use of adjuvant treatment after upfront cystectomy to the patients.