Original articleCharacterizing intermediate-risk non–muscle-invasive bladder cancer: Implications for the definition of intermediate risk and treatment strategy
Introduction
Stratification of low-, intermediate-, and high-risk non–muscle-invasive bladder cancer (NMIBC) has been widely employed to predict prognosis and to guide relevant adjuvant treatment. Initial and solitary pathological low-grade Ta tumors are generally defined as low-risk, and tumors of high-grade, stage pT1, or with concomitant carcinoma in situ are regarded as high risk [1], [2]. Although low- and high-risk disease have been pathologically well defined using this system, the intermediate-risk category has traditionally been defined as any patient not fitting into either of the earlier 2 categories. Therefore, intermediate-risk disease comprises a very heterogeneous population, ranging from those with a solitary, but recurrent, low-grade Ta tumor, to those with multiple low-grade Ta tumors that recurs after bacillus Calmette-Guérin (BCG) therapy. Furthermore, no guideline has clearly stated whether all patients who initially had a high-risk tumor should be treated as high risk throughout their entire lives even if they have a subsequent low-grade tumor recurrence. These cases might be reassigned to the intermediate-risk.
Thus, the recommended treatment strategies for patients with intermediate-risk disease are diverse among the current clinical practice guidelines, and do not agree with each other in some respects [3], [4], [5]. Options for intermediate-risk disease after transurethral resection of bladder tumor (TURBT) ranging from only observation without any intravesical instillations to adjuvant intravesical chemotherapy or BCG. It has also remained uncertain whether induction alone, or induction plus maintenance of intravesical chemotherapy or BCG therapy should be used for patients with intermediate-risk disease.
In the present study, we reviewed 326 patients with intermediate-risk tumors who were treated with conservative therapy and analyzed subsequent tumor recurrence and stage progression. We then classified these intermediate-risk tumors into 3 groups by clinical courses. This classification may provide a better understanding of this heterogeneous risk group, and allow practical recommendations for the management of intermediate-risk disease.
Section snippets
Patients and methods
Our risk stratification of NMIBC was based on the international bladder cancer group statements [1], [2]. We defined the intermediate-risk category as including those who did not fulfill the requirements of either the low-risk (solitary, primary low-grade, and Ta tumor) or high-risk (any high grade, stage T1, or carcinoma in situ tumors) categories. We did not include tumor size to classify the risk stratification of our patients with NMIBC. Some guidelines assigned large low-grade solitary
Patients׳ characteristics
The clinical characteristics of Groups A, B, and C are summarized in the Table. The proportion of those with a previous history of intravesical BCG adjuvant therapy just before diagnosis of the intermediate-risk tumor was 49% in Group C, which was significantly higher when compared with Group B (17%, P<0.01), and no administration of adjuvant therapy was more frequent in Group B (77%) when compared with Group C (37%, P<0.01). The interval between the prior tumor and the recurrent
Discussion
This is the first study, to the best of our knowledge, focusing on the intermediate-risk category of NMIBC. We demonstrated that this category consists of a very heterogeneous population; thus, we propose a new subclassification system of intermediate-risk NMIBCs. First, cases with a past history of high-risk NMIBC (Group C) should be discriminated from the other intermediate-risk cases (Groups A and B), because their recurrence rate was shown to be significantly higher when compared with the
Conclusions
Our subclassification analysis suggested that intermediate-risk tumors that recurred after a high-risk tumor should be treated with adjuvant BCG therapy, owing to the high probability of subsequent recurrence. In addition, the definition of intermediate risk may include some BCG refractory cases. Such BCG refractory cases had a significantly higher rate of stage progression in the present study, and we conclude that such BCG refractory tumors need to be managed as a separate category.
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