Noninvasive Bladder Cancer: Diagnosis and Management

Immediately following TURBT, it is recommended that patients with low-risk disease undergo single-dose intravesical chemotherapy [66]. When performed within 24 hours (and ideally 6 hours) of resection, intravesical chemotherapy has been shown to decrease the odds of bladder cancer recurrence by up to 40% in low-risk disease [67].The mechanism of action of single-dose intravesical chemotherapy instilled immediately after resection is not definitively known, but it is hypothesized that it destroys any remaining microscopic disease and prevents reimplantation of any freely circulating cells [67]. Single-dose mitomycin C, however, does not decrease the rate of progression in incompletely resected tumors [68]. Administration of intravesical chemotherapeutic agents should be avoided when there is bladder perforation [69].

There is some debate regarding the best approach to treating intermediate-risk bladder cancer. In guidelines released by the International Bladder Cancer Group, a group of experts who evaluated and set forth guidelines based on current recommendations from the NCCN, AUA, European Association of Urology, and the First International Consultation on Bladder Tumors, initiation of BCG therapy with maintenance or intravesical chemotherapy for up to 1 year of adjuvant treatment is recommended following the diagnosis of intermediate-risk bladder cancer [66]. Induction treatments are single intravesical instillations administered weekly for 6 weeks and begun 2 to 4 weeks after resection. Maintenance courses consist of once weekly instillations for 3 weeks undertaken at 3 months, 6 months, and then every 6 months for up to a total of 3 years of treatment [70].

For the management of high-risk disease, most guidelines concur that the optimal treatment is BCG with maintenance, although the recommended length of maintenance varies from 1 to 3 years [66]. The EORTC-GU recently reported the results of a randomized study in which high-risk Ta and T1 lesions were treated with BCG maintenance; they found that a full-dose, 3-year maintenance course of BCG decreased recurrences without increasing toxicity [71].

Although both intravesical chemotherapy and immunotherapy are recommended treatments for NMIBC, there is a preference in the published guidelines toward the use of BCG over intravesical chemotherapy. In multiple meta-analyses, BCG, and especially BCG with maintenance, has been shown to have improved disease-free recurrence when compared with intravesical chemotherapy [72,73]. Malmström et al showed a 32% reduction in the recurrence rate in BCG-treated patients compared with those treated with mitomycin C [74]. Similarly, high-risk patients treated with gemcitabine therapy had a higher recurrence rate and more rapid time to recurrence as compared with those treated with BCG therapy; in intermediate-risk patients, the rate of recurrence was not statistically significant [75].

Cystectomy

In certain high-risk patients, it is also appropriate to offer cystectomy as initial therapy. Though much more invasive than other treatment options, it does offer a chance for cure in a select group of patients with high likelihood of progression of disease. Risk factors associated with progression and consideration for immediate or early cystectomy include large tumor size (> 3 cm), inability to completely resect tumor, difficult resection site, multifocal/ diffuse disease, presence of carcinoma in situ, prostatic urethral involvement, female sex, suspected understaging secondary to lymphovascular invasion, or unfavorable histology [76–81]. While tumor upstaging has been noted in up to one-quarter of high-risk immediate cystectomy patients, it is important to note that multiple retrospective reviews have not found a cancer-specific survival (CSS) benefit to immediate cystectomy versus conservative treatment [82–85]. Hautmann et al examined immediate cystectomy versus deferred cystectomy until after recurrence in high-risk patients and demonstrated a clear 10-year CSS benefit of 79% versus 65% [86]. Because the number of patients who have undergone immediate cystectomy is still relatively small and predictors of aggressive disease are still evolving, immediate cystectomy is still considered a viable treatment option in the appropriately selected patient.