Bladder cancer.Advances in laboratory innovations and clinical management, with emphasis on innovations allowing bladder-sparing approaches for patients with invasive tumors

Abstract

In the present decade important progress has been made in the understanding of the biology and management of bladder cancer. Experimental laboratory models and new investigative tools have revealed potentially important prognostic markers and have led to an improved understanding of the histogenesis of the disease. Advances in the management of superficial bladder cancer (intravesical chemotherapy or immunotherapy, improved urinary cytology, laser technology, flexible fiberoptic cystoscopy, and photodynamic therapy) have, in some subgroups, improved tumor control while decreasing patient complications. For invasive bladder cancer (invasive of bladder muscle or beyond) improved techniques of cystectomy and radiotherapy have reduced the complications of treatment and may have contributed small but important improvements in cure. A major improvement in the last decade has occurred in objective remission rates with chemotherapy for patients with metastatic bladder cancer. From 20% to 40% of patients achieve a complete remission, and 10% to 20% may survive for more than 3 years. Randomized Phase III trials are currently in progress and must be completed to define the true role of multidrug chemotherapy in patients with metastatic disease and to validate data from the regimens of cyclophosphamide, methotrexate, and vincristine (CMV) and methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) before any of these approaches to treatment can be considered of proven benefit. Preliminary data from the Massachusetts General Hospital are presented of a potentially effective approach to select patients with invasive tumor for successful bladder preservation. In this approach transurethral debulking surgery is combined with upfront CMV chemotherapy plus cisplatin and 4000 cGy. If tumor is found on cystoscopic reevaluation with biopsy and cytology immediately following cisplatin and 4000 cGy, cystectomy is performed; if not, consolidation by a radiation boost to 6480 cGy plus cisplatin is given. The approach is fairly well tolerated, allows cystectomy without undue complications, has yielded a 88% complete response rate in patients selected for bladder preservation, and resulted in 90% of patients free of distant metastases with follow-up ranging from 6 to 30 months. A randomized Phase III trial with and without neoadjuvant MCV chemotherapy for selective bladder preservation is now under way and accruing well.