Intravesical Therapy of Superficial Bladder Cancer

Abstract

Transurethral resection (TUR) of the superficial transitional cell carcinoma (TCC) of the bladder is known to be insufficient in controlling the disease because of the unacceptable rates of recurrence, progression and ultimate cystectomy. Adjuvant intravesical chemo-and/or immunotherapy is administered in an effort to enhance the efficacy of surgery alone. The initial tumor stage and grade, the multifocality of this cancer and the history of previous recurrences remain the determinant factors in survival. It is important to decide exactly which patients are at risk, and, therefore, do need treatment. Knowledge of the natural history of the disease will facilitate this decision making, although the natural history of TCC is largely unpredictable owing to tumor heterogeneity. Several cytotoxic and immune modifying agents have been used intravesically in different treatment schedules. However, despite their effectiveness, no consensus exists about the optimal antineoplastic regimen. The selection of the latter is a subject of continuous investigation. Intravesical treatment with cytotoxic drugs has been demonstrated to achieve an acceptable reduction in short- and intermediate-term recurrence rates, but has no proven ability in preventing disease progression to muscle-invasive cancer or prolonging survival. On the other hand, bacillus Calmette-Guerin (BCG) currently appears to be the most effective agent for intravesical use, especially in patients with high grade and stage neoplasms but the optimum strain, dosage and duration schedule have not been determined. Clinical trials have shown that BCG provides long-term protection from tumor recurrence, while there is evidence that it may favorably alter the progression rate of the disease with prolongation of survival. Toxicity of intravesical chemo- and immunotherapy still remains a major problem and attempts at reducing the dosage, and, thus, toxicity without affecting efficacy are underway. This review endeavors to present updated information on intravesical chemotherapy in treating superficial bladder cancer, the expanding role of intravesical immunotherapy, the recent work comparing various immunotherapeutic regimens with chemotherapeutic intravesical therapies, and the progress made towards achieving optimal treatment regimens.

Thermochemotherapy for Non-Muscle-Invasive Bladder Cancer: Is There a Chance to Avoid Early Cystectomy?

“…Several other studies showed that net benefit after 1 year of follow-up is 12% for patients treated with mitomycin C (MMC) compared to patients without adjuvant treatment [4,5]. However, intravesical chemotherapy had no impact on progression to MIBC.…”

“…PDT showed some encouraging results [9] as well as those obtained by De Stasi et al [10] with sequential BCG and EMDA/MMC and both increase recurrence-free time; anyway, like chemotherapy, they have no effect on progression. It has been reported that the combination of heat treatment and chemotherapy instillation offers anticancer advantages over chemotherapy instillation alone in preventing or delaying tumor recurrence or progression [4,5]. A clear synergistic effect of MMC and hyperthermia was demonstrated in four human bladder cancer cell lines [6]: the uptake of the drug by the malignant cells and the intracellular distribution are improved by an increased cellular permeability; furthermore, drug metabolism and reaction with DNA is increased and DNA repair is inhibited [7].…”

In vivo Evaluation of Mucoadhesive Nanoparticulate Docetaxel for Intravesical Treatment of Non–Muscle-Invasive Bladder Cancer

“…Approximately 70% to 80% of patients with bladder cancer initially present with superficial disease that does not invade the muscularis propria (3). Transurethral resection (TUR) is the primary treatment method for nonmuscle-invasive or "superficial" carcinoma, which consists of the surgical removal of tumor nodules from the bladder wall (4,5). However, there is a high rate of tumor recurrence and high chance of disease progression after TUR alone (6).…”

Adjuvant Intravesical Mitoxantrone versus Recombinant Interferon-α after Transurethral Resection of Superficial Bladder Cancer: A Randomized Prospective Study

“…Although transurethral resection (TUR) of superficial bladder cancer initially controls the disease, 65% of superficial tumors will recur at 5 years (90% at 15 years) and 10-20% will progress to muscle invasion at 5 years [2]. In order to prevent the post-TUR recurrence and progression of superficial bladder cancer, adjuvant intravesical chemoimmunotherapy has been introduced into clinical practice the last two decades [3].…”

“…Several cytotoxic and immune modifying regimens have been tested, but current treatment schemes are usually empirical and insufficient [3]. Therefore, numerous prospective clinical trials concerning adjuvant intravesical therapy are in progress.…”