Second transurethral resection and prognosis of high-grade non-muscle invasive bladder cancer in patients not receiving bacillus Calmette-Guérin.

OBJECTIVE: To define the natural history of T1G3 bladder tumor not receiving intravesical Bacillus Calmette-Guerin (BCG) and assess the diagnostic and therapeutic value of a second transurethral resection (Re-TUR) in these patients. PATIENTS AND METHODS: Retrospective study on the natural history of 210 patients treated at two institutions for T1G3 bladder carcinoma without associated CIS. In no case was BCG administered; 79 (37.6%) received TUR alone, and 131 (62.4%) Re-TUR 4 to 6 weeks later; 23 (12.4%) underwent cystectomy for tumor progression. RESULTS: Median follow-up was 55 (78 IQR) months, male/female ratio 8/1, and mean age 70.6+11.8 (range 37-93). 19.5% were free of recurrence at 10 years, and 61.9% free of progression. Independent prognostic factors for progression were solid pattern (HR: 2.71; P=.0004), multiplicity (HR: 2.26; P=.003), and recurrence at 3 months (HR: 3.4; P=.003). Cancer-specific survival was 81.5% at 5 and 69% at 10 years. Independent predictors of survival were: progression during the first year (HR: 17.9; P<.0001), solid pattern (HR: 2.13; P=.02), multiplicity (HR: 2.05; P=.03), and age>65 years (HR: 2.9; P=.03). Re-TUR avoided under-staging (7.4%), detected T1G3 residual disease (10.7%), reduced recurrence rate at 3 months (11.4 to 4.6%; P=.06), and rate of progression on the 1st year (13.9 to 3.8%; P=.0075). However, in these patients the risk remains and no differences were detected in the long term in terms of recurrence (log-rank, P=.14), progression (P=.91), or cancer death (P=.21) in patients treated with Re-TUR. CONCLUSION: The recurrence in the first 3 months of a T1G3 tumor not receiving BCG is the main risk factor for progression, and progression of this type of tumors within the first year is the main factor of cancer death. The Re-TUR improves both variables but it does not change the long-term prognosis.

[Detection and molecular staging of bladder cancer using real-time RT-PCR for gelatinases (MMP-2, MMP-9) and TIMP-2 in peripheral blood]. / Detección y estadificación molecular del cáncer vesical mediante RT-PCR a tiempo real para gelatinasas (MMP-2, MMP-9) y TIMP-2 en sangre periférica.

INTRODUCTION: Molecular staging of bladder cancer based on the detection of mRNA of urothelial specific genes in circulating cancer cells has been inconclusive. We analyze whether real-time RT-PCR evaluation of gelatinases (MMP-9, MMP-2) and TIMP-2 in peripheral blood to diagnose and characterize patients with bladder neoplasm. MATERIAL AND METHOD: Total RNA is extracted from circulating blood cells in 42 individuals (11 healthy controls, 31 patients with bladder cancer of different stages) and real-time RT-PCR performed using specific primers for MMP-9, MMP-2, TIMP-2 and ribosomal 18S. The quantification values of mRNA are described as relative to 18S mRNA (ΔΔCt method) and the results are blindly compared with data obtained from histological diagnosis and clinical staging. RESULTS: Normalized levels of MMP-9 and MMP-2 mRNA are higher in patients with cancer than controls (1.82±0.6-fold and 2.7±0.6-fold, respectively; P<.05). Patients with metastatic disease also have increased MMP-9, MMP-2 and TIMP-2 mRNA levels (9.6±0,20-fold, 5.22±0.26-fold and 1,97±0,22-fold, respectively; P<.05). MMP-9 and MMP-2 are also associated with advanced clinical stage and grade (P<.05). A ratio between variables that increases the ability to segregate patients with Ta, T1, T2-4M0 and T2-4M1 tumours is proposed. CONCLUSIONS: Both non-invasive bladder tumor recognition and molecular staging of the disease is possible using real-time RT-PCR-based detection of gelatinases and TIMP-2 in peripheral blood. The ability to distinguish metastatic disease is higher for MMP-9 but MMP-2 discriminates better levels of tumour invasion. Further investigation in this field could yield promising results regarding molecular evaluation of bladder neoplasia.