Non-muscle invasive bladder cancer (NIMBC) is the most common type of bladder cancer, with 80% of patients presenting with Ta (papillary non-invasive disease) in 70%, T1 disease (invasion into the submucosa of the bladder) in another 25%, and carcinoma in situ (high-grade, non-invasive) in 5%.
Bladder tumors are particularly heterogeneous, making outcomes difficult to predict, with up to 80% of patients experiencing recurrence after transurethral resection alone.
The primary treatment goal for NIMBC is to prevent recurrence and progression, and based on grading and staging, treatment options include perioperative intravesical chemotherapy and resection. When surgery is required, it is usually not a one-time procedure and re-excision within 4 weeks is particularly important for higher grade tumors, especially when there is no muscle sent in the high-grade T1 tumor specimen.
Single-dose perioperative intravesical chemotherapy for low-grade Ta disease is important. Intravesical BCG therapy is also a treatment option for patients with carcinoma in situ, and BCG maintenance therapy should be considered for all patients receiving BCG induction therapy.
Indications for intravesical therapy including BCG immunotherapy or chemotherapy include multiple tumors (more than 3), tumors larger than 3 cm, tumor recurrence on first follow-up cystoscopy, high-grade Ta tumors, positive urothelial cytology after complete resection, presence of carcinoma in situ or lymphovascular invasion.
The gold standard of treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy, and bilateral pelvic lymph node dissection. Indications for radical cystectomy include recurrent or refractory disease with transurethral resection within 6 months, presence of T1 disease or re-excision (approximately 80% at risk of progression), extensive multicentric high-grade disease, T1 disease with lymphovascular invasion, poor prognosis or mixed histology (e.g., micropapillary disease).
Dr. Clark said there is now so-called Level I evidence to support preoperative treatment of MIBC with cisplatin-containing neoadjuvant chemotherapy in combination with cystectomy. However, the evidence for adjuvant chemotherapy in this setting is not solid enough because of the lack of high-quality studies supporting a survival benefit. Even so, the evidence suggests that chemotherapy may be used more frequently in the adjuvant setting than in the neoadjuvant setting.
Cisplatin-containing multidrug adjuvant chemotherapy is an acceptable option for disease with high risk factors, such as T3 and above or lymph node-positive disease, in those who have not received neoadjuvant chemotherapy preoperatively.
From a practical point of view, bladder preservation is desirable, but some patients may have poor outcomes with bladder preservation, including those who require pretreatment of hydronephrosis, incomplete transurethral resection, and patients with carcinoma in situ. In other patients, careful coordination of the three treatment modalities may preserve the bladder.
Typical bladder preservation therapy should include maximal transurethral resection and chemoradiotherapy, the latter typically 40 Gy of external irradiation combined with cisplatin-containing chemotherapy, possibly in combination with 5-FU, paclitaxel, and gemcitabine.
Bladder preservation is feasible, and if this is desired a triple therapy needs to be used, and the treatment should include oncologists, urologists, and ensure a multidisciplinary approach to such cases, which are actually very complex.
Dr. Judith Leary of New Jersey asked Dr. Clark if there is a shortage of BCG, whether there is a reasonable alternative treatment for maintenance therapy to manage patients without in situ cancer.
According to Dr. Clark, the priority treatment for BCG shortage is to do so. For patients with high-grade stage Ta, use intravesical mitomycin therapy instead of BCG as first-line maintenance therapy, or consider cystectomy instead of immunotherapy and chemotherapy for patients with recurrence.
Leary told MedscapeMedicalNews that she had two patients who needed to initiate intravesical therapy and that she had to treat the patients with mitomycin due to a lack of BCG.
Dr. Muhammad Hamdan of Michigan told MedscapeMedicalNews that he does not agree with the guidelines’ recommendation for perioperative chemotherapy based on surgical staging. Such staging relies entirely on the surgeon’s decision about T-staging, and surgeons make mistakes in 30 percent of cases, and the other 70 percent are not guaranteed to be error-free. Therefore, intravesical chemotherapy should be delayed in patients just a few hours after surgery, as this treatment is not without side effects. His personal preference is to watch carefully before chemotherapy.