Management of high-risk non-muscle invasive bladder cancer

Abstract

Risk stratification is of paramount importance for the future treatment and follow-up of patients with transitional cell carcinoma (TCC) of the bladder. Transurethral resection (TUR) is the gold standard for initial diagnosis and treatment of non muscle invasive bladder cancer (NMIBC). Muscle must be present in the pathological specimen in order to correctly stage the tumor. When muscle is not present, the tumor has to be staged as Tx. A second TUR done after two-six weeks of the first resection reduces the rate of tumor left behind and improves staging. Re-TUR in these patients should be considered a must. Since BCG is toxic, an attempt to reduce toxicity was made by reducing the dose. CUETO group showed that 1/3 dose BCG was as effective as full dose in intermediate risk patients but not in high risk. Another study that evaluated the efficacy of low dose BCG is the trial 30962 from EORTC. The results showed a difference of 10% in the five-years recurrence free survival only when 1/3 dose BCG for one year (54.5%) was compared to Full dose BCG for three years (64.2%) suggesting that 1/3 dose or one year full dose are suboptimal treatments. Immediate radical cystectomy should be considered for high grade, multiple T1 tumors, T1 tumors located at a site difficult to resect, residual T1 tumors after resection or high grade tumors with CIS and lymphovascular invasion. Cystoscopy and cytology must be performed at three months. In the case of negative findings, following cystoscopy and cytology assessments have to be repeated every three months for three years, and every six months thereafter until five years, and then annually. For the group of patients with initial BCG induction therapy failure that are unfit or refuse radical cystectomy or have a low or intermediate grade disease an additional course of l BCG is a choice. For patients who failed before completion of maintenance BCG, radical cystectomy has to be considered in presence of a high grade T1 or CIS. BCG maintenance (full dose three years) after Re-TUR is the standard therapy in high-risk TCC of the bladder. Dose reduction to 1/3 dose or one year full dose are suboptimal treatments. Immediate radical cystectomy is indicated in young patients with high-grade T1 tumors who have at least one additional factor associated with a poor prognosis such as: multifocality, associated CIS, prostatic involvement, tumor located at a site difficult to resect, limphovascular invasion. Radical cystectomy is also indicated in patients who recur after three months of therapy as T1 high grade. Device assisted chemotherapy (EMDA, Synergo with MMC) may have a role in BCG failure or BCG resistant patients who cannot receive or refuse cystectomy. Postponing radical cystectomy until progression to muscle invasive disease may have a negative impact on survival.