Prediction models for progression of non‐muscle‐invasive bladder cancer: A review

An accurate prediction of progression is critically important in the management of non‐muscle‐invasive bladder cancer. At present, three risk models are widely known for prediction of the risk of tumor recurrence and progression of non‐muscle‐invasive bladder cancer: the European Organization for Research and Treatment of Cancer, Club Urológico Español de Tratamiento Oncológico, and new European Organization for Research and Treatment of Cancer models. Bladder neck involvement has been shown to be one of the significant predictors for progression in non‐muscle‐invasive bladder cancer, and a new scoring model (Tokyo Medical and Dental University model) consisting of bladder neck involvement, tumor grade, and stage has been developed and externally validated. However, the predictive abilities of these models are still unsatisfactory, and more precise models are necessary for accurate individual prediction of prognosis. Until now, time‐fixed analysis has been used for most studies predicting the prognosis and outcome of non‐muscle‐invasive bladder cancer patients. In order to predict progression more precisely, time‐dependent models should be developed using multiple‐event analytical techniques, as non‐muscle‐invasive bladder cancer often progresses to muscle‐invasive bladder cancer after multiple recurrences and changes in tumor characteristics over a long natural history. Integration of molecular markers is also a promising approach. A validated model that accurately predicts the risk of progression would help urologists and patients decide whether and when to choose radical cystectomy on an individual basis.     

Bacillus Calmette–Guérin treatment of non‐muscle invasive bladder cancer

Bacillus Calmette–Guérin (BCG) has been used in the intravesical treatment of non‐muscle invasive bladder cancer (NMIBC) for nearly 35 years; however, its use is still subject to controversy. The objective of this paper is to review the role of BCG in the treatment of patients with NMIBC. Clinical trials, meta‐analyses and guidelines related to the administration, safety and efficacy of intravesical BCG were reviewed. Intravesical BCG is more effective than intravesical chemotherapy in decreasing the risk of recurrence and progression to muscle invasive disease; however, it is associated with more local and systemic side‐effects. It is the gold standard in patients at high risk of progression. Maintenance BCG is required in order to achieve the best therapeutic results; however, the optimal dose, induction and maintenance schedules, and duration of treatment are unknown and might be different for each patient. Patients failing BCG treatment have a poor prognosis, and cystectomy is then the recommended treatment. Patients at low risk of recurrence and progression should not receive BCG, because of its side effects. Intermediate‐risk patients might be treated with either intravesical chemotherapy or BCG; however, for patients at high risk of progression, BCG is recognized as the treatment of choice. Further research is urgently needed to identify markers associated with BCG failure and to develop effective alternatives to cystectomy in patients failing BCG.     

A chemosensitivity test to individualize intravesical treatment for non‐muscle‐invasive bladder cancer

OBJECTIVE

To describe the design of a new chemosensitivity assay based on the expression of genes involved in the resistance to standard intravesical regimens, to allow individualization of therapy for high‐risk non‐muscle‐invasive bladder cancer.

PATIENTS AND METHODS

To date, 35 patients with high‐risk no‐nmuscle‐invasive bladder cancer have been enrolled, all candidates for transurethral resection of the bladder (TURB) followed by intravesical treatment. The intravesical regimen was chosen according to the risk profile of each patient. All patients were evaluated by cystoscopy 3 and 6 months after TURB. According to the molecular characterization of each tumour, our team of molecular oncologists determined for each patient a molecular profile of chemosensitivity to BCG, mitomycin c, anthracyclines and gemcitabine. This profile was then correlated to the response to intravesical therapy 6 months after TURB.

RESULTS

This chemosensitivity test was able to predict response to treatment in 96% of patients. The assay is easy to perform, inexpensive and quick.

CONCLUSION

Our results, although preliminary, are encouraging for the future of an individualized therapeutic approach, with the aim to provide a higher treatment success rate while sparing patients unnecessary toxicity from drugs that are not suited for their tumours.     

Clinical significance of immediate urine cytology after transurethral resection of bladder tumor in patients with non‐muscle invasive bladder cancer

Objectives: To assess the clinical significance of immediate urine cytology (IUC) after transurethral resection of bladder tumor (TURBT) for non‐muscle invasive bladder cancer (NMIBC). Methods: We reviewed the records of 174 patients who underwent IUC after TURBT for NMIBC. IUC was obtained just before Foley catheter removal after TURBT. The relationship between IUC and tumor stage, grade, size and multiplicity, as well as preoperative urine cytology and immediate intravesical epirubicin therapy, were assessed. The relationship between a positive IUC and cancer recurrence was also assessed. Multivariate Cox proportional hazards regression analysis was carried out, including IUC, tumor stage, tumor grade, tumor size, tumor multiplicity, preoperative urine cytology and immediate intravesical epirubicin therapy. Results: IUC was positive in 76 patients (43.7%) and negative in 98 patients (56.3%). In the positive IUC group, tumor stage and grade were higher (P = 0.001, <0.001), tumor size was larger (P = 0.001), tumor multiplicity was higher (P = 0.002) and positive preoperative cytology was more likely (P = 0.006) than in the negative IUC group. In the positive IUC group, the cancer recurrence rate was 72.3% and that of the negative IUC group was 30.6% (P < 0.001). In a multivariate Cox proportional hazards regression analysis, positive IUC (HR 1.83, P = 0.019), tumor size (HR 1.72, P = 0.045), tumor multiplicity (HR 3.63, P = 0.015), preoperative urine cytology (HR 1.23, P = 0.043) and immediate intravesical epirubicin therapy (HR 0.171, P = 0.001) were independent prognostic factors for cancer recurrence. Conclusion: These data suggest that IUC after TURBT for NMIBC can be an independent prognostic factor to predict cancer recurrence.