Prospects for Optimized Clinical Management of Bladder Cancer by Application of Phenotypic Markers

Extract

The search for molecular markers that will permit the optimized individual management of patients with urothelial cancer is beginning to pay dividends. The findings reported by Stein et al. (1) in this issue of the Journal demonstrate the prognostic value of p21 expression, confirming the importance of p53- related pathways. However, further refinements will be required before p21 expression as assessed by immunohistochemistry can be exploited clinically. As is true for all markers, the clinical utility of this marker will ultimately depend on how p21 status can contribute to resolving the dilemmas of clinical management.

In our view, the principal therapeutic dilemmas in the management of patients with bladder carcinoma are as follows: 1) predicting whether organ preservation is feasible in selected patients, i.e., predicting which patients will have disease progression following intravesical therapy; 2) assessing the probability of a cure with total extirpation of the bladder, i.e., predicting the presence of occult, disseminated disease; and 3) predicting the sensitivity of a particular patients cancer to available chemotherapy. The first dilemma is complex, requiring both cancerspecific markers and markers reflecting malignant potential; studies in this vein are in progress (2). Most studies reported to date are related to the second dilemma; very few studies have addressed the third. As shown in Table 1, previous studies have established the impact of p53 mutations and altered Rb protein expression on the prognosis of urothelial cancer (3). Whether p53 status and Rb status also predict for sensitivity to chemotherapy remains to be established. The dilemma of whether or not to offer a patient adjuvant chemotherapy is complex, depending on both the risk of relapse and the probability of responding to chemotherapy; these factors may not be independent, and as yet the relationship between them has not been established. At present, one cannot make decisions about adjuvant chemotherapy based solely on the probability of relapse; the very features responsible for relapse may also affect the probability of responding to chemotherapy.