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Type of bladder tumor determines treatment

By Dr. V. Upender Rao
Published January 8, 2007

Cancers of the urinary bladder are either superficial or muscle-invading. Superficial cancers are papillary (finger-like projections) arising from the lining of the bladder. These tumors are generally restricted to the lining only and seldom spread deep into the muscle.

Muscle invasion has serious implications because the tumor seedlings acquire access to lymphatic and blood channels in the muscle, through which they can spread to distant sites, precluding any curative treatment.

Muscle-invading bladder cancers that have not yet spread are treated by radical surgery, which includes removal of the bladder and surrounding lymph nodes and creation of an external bag into which urine flows. Attempts at construction of a "neo bladder" are usually not very satisfactory.

Some of these muscle-invasive bladder cancers can be treated with chemotherapy before surgery (neo adjuvant) or after surgery. Such treatment can prevent or delay distant spread in a minority of cases. The vast majority of muscle-invasive cancers, however, eventually recur.

The present standard of diagnosis, prognosis and treatment assignment is based on pathologic examination. While pathologic examination has served us well for many years, it is somewhat subjective and subject to inter-observer variation.

More importantly, such examination cannot reliably predict behavior of the tumor or its prognosis. In other words, it cannot accurately tell us whether the tumor is aggressive, has the capacity to spread or will acquire drug resistance; it also can't assess the tumor's potential to kill the patient.

In the Dec. 10 issue of the Journal of Clinical Oncology, researchers from the University of Southern California Keck School of Medicine published a comprehensive monograph on the molecular markers and pathways of both superficial and muscle-invasive bladder cancers. According to them, the molecular footprints and pathways for the superficial and invasive cancers are distinct.

They describe abnormalities in the FGFR (fibroblast growth factor receptor) gene and constitutive activation of the H-ras oncogene pathways in superficial, noninvasive papillary cancers, and mutations in the all-important tumor suppressor genes Tp53 and RB (retinoblastoma) in the muscle-invasive cancers.

The implication of the molecular diagnosis is that it can predict biology and behavior, which simple pathologic diagnosis cannot.

For instance, a superficial papillary cancer diagnosed by pathologic exam showing a deleterious Tp53 mutation indicates the possibility of an aggressive phenotype that needs aggressive treatment, without which the tumor can metastasize and kill the patient.

Likewise, a muscle-invasive cancer diagnosed by microscopy that lacks deleterious p53 or RB mutations may indicate an indolent tumor that could potentially be spared the standard radical and mutilating surgery and its lasting consequences.

Of course, these assertions are based on promising but preliminary information that need validation by further clinical trials.

The journal article also described other aspects that aid tumor growth and spread, including angiogenesis and epigenetic silencing of tumor suppressor genes by way of methylation. They also cite several promising treatment strategies of gene transfer, anti angiogenesis, monoclonal antibodies, antisense and demethylating agents currently in phase I and phase II clinical trials.

The authors of this article also point out that the study of the molecular pathways not only aids in prognosis and treatment assignment, but also identifies targets along these pathways against which new drugs can be developed.

V. Upender Rao, MD, FACP, practices at the Cancer and Blood Disease Center in Lecanto.

[Last modified January 7, 2007, 20:43:21]