Practical Applications of Intravesical Chemotherapy and Immunotherapy in High-risk Patients with Superficial Bladder Cancer

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Initial steps: adequate resection and perioperative cytotoxic chemotherapy

Chemotherapy and immunotherapy have the capacity to ablate small (<1.5 cm) residual tumors; however, recurrence rates are never as good as when therapy is applied in the prophylactic (no visible disease remaining) setting [2]. It is mandatory that as complete a resection as possible be performed before starting intravesical therapy. In some cases, this may mean additional sessions to remove tumor completely and achieve adequate staging information. With bulky or multifocal high-risk tumors,

Choosing a post–transurethral resection regimen for previously untreated patients

Although one-dose perioperative chemotherapy is a vital first step in decreasing tumor recurrence, fully two thirds of patients with multifocal tumors will still relapse. A sequential regimen of repetitive intravesical therapy can provide additional benefit. The choice of whether this should be a chemotherapy- or immunotherapy-based program is determined not only by personal preference but also by a careful assessment of the risk-benefit ratio for the agent in a particular patient. Chemotherapy

Maintenance chemotherapy

The use of additional treatments of intravesical chemotherapy after completion of the induction cycle at a time when the patient is already in complete clinical remission is known as “maintenance” therapy. The rationale for maintenance therapy is to prevent the emergence of new cancers from a diseased premalignant urothelium or to eradicate small clinically undetectable nests of residual cancer. The most common regimen involves monthly therapy, usually for at least a year, but variations of

Intravesical immunotherapy

Based on an absolute superiority in activity coupled with an increased familiarity and acceptance of its side effects, BCG has become the most popular choice for intravesical therapy in North America by an almost 2:1 majority. Interestingly, Europeans do not share this enthusiasm for BCG and use it only about one-third of the time. For low-to-intermediate risk cases of superficial bladder cancer, primary chemotherapy and BCG remain appropriate options; however, for high-risk cases, there is

Optimized administration of bacillus Calmette-Guérin

As is true for intravesical chemotherapy, many details of BCG administration have not been subjected to scientific rigor; rather, they have been derived from empiric observations. At least 7 to 14 days should elapse after the TUR before beginning BCG. Earlier administration has been associated with BCG sepsis. Many clinicians choose to wait 3 to 4 weeks or longer until all postoperative bleeding is over. A full induction cycle usually consists of six weekly treatments, but 8- and 12-week

What to do when treatment fails

Despite the strides made with intravesical chemotherapy and immunotherapy, most patients will eventually have a recurrence of disease. For intermediate-and high-risk patients treated with chemotherapy, the answer is simple—try BCG next. For BCG failures, the problem is more complicated, because salvage chemotherapy with traditional agents rarely achieves a greater than 20% 3-year disease-free rate [52]. Because a second course of BCG still provides between a 30% to 50% response, it is probably

Role of interferon, alone and combined with bacillus Calmette-Guérin

Interferons are natural glycoproteins that mediate host immune responses such as the stimulation of phagocytes, cytokine release, enhanced natural killer cell activity, and activation of T and B lymphocytes. Of all the interferons, IFN-α has been the best studied as an intravesical treatment agent [58]. When used by itself, IFN-α is well tolerated, causing minimal cystitis and only occasional low-grade fevers or flulike symptoms [59]. Its efficacy is clearly dose dependent, with minimal

Emerging technologies

Although not yet readily available to urologic practitioners in North America, two device technologies developed in Europe that facilitate drug delivery are showing great promise for primary and salvage therapy. Local hyperthermia using a specially designed microwave antennae Foley catheter in conjunction with concomitant MMC therapy (chemothermotherapy) has demonstrated encouraging results in ablating large tumor burdens as well as preventing recurrence after TUR of bladder tumor [78], [79].

Summary

The following steps are practical in the treatment of intermediate-to-high risk patients with superficial bladder cancer:

  • Resect all visible tumor at the time of first TUR of bladder tumor. Strongly consider re-resection, especially for high-risk, large, multifocal, stage T1 tumors.

  • Apply one dose of cytotoxic chemotherapy perioperatively within 6 hours of TUR (ideally immediately).

  • Once histopathology is available, consider intravesical induction chemotherapy for intermediate-risk patients and

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