The natural history of secondary muscle-invasive bladder cancer

BACKGROUND: The management of patients with high-grade non muscle invasive bladder cancer (NMIBC) brings diagnostic and therapeutic challenges. In the current study, we sought to study the natural history of progression to "secondary" muscle-invasive bladder cancer (MIBC)-cancer that developed during follow up of patients presenting with non-muscle invasive bladder cancer (NMIBC). METHODS: Between 1998 and 2008, 760 patients were treated for bladder cancer. Primary MIBC (>=T2) tumors (present upon presentation) were diagnosed in 114 patients. All patients with high-grade NMIBC were treated with intravesical BCG. Mean follow-up was 44 months. RESULTS: Forty patients (6.1%) developed secondary MIBC after a mean period of 21 months from initial diagnosis of bladder cancer. The 2- and 5-year disease-specific survival rates were better for patients with secondary MIBC (90% and 56% compared to 69% and 42% for patients with primary disease, p=0.03). The Kaplan-Meier curves of the two groups were parallel but displaced by approximately 2 years. CONCLUSION: In the current series, MIBC progression occurred among initially presenting patients with NMIBC in 6.1%. In most patients, the initial diagnosis of NMIBC is correct and muscle invasion occurs after a mean period of about 2 years. This supports a non-radical approach in patients with high-grade T1, Ta or Tis. Meticulous follow-up with liberal biopsy of any suspicious lesion may provide early diagnosis of invasive disease

Is radical cystectomy mandatory in every patient with variant histology of bladder cancer

Urothelial carcinomas have an established propensity for divergent differentiation. Most of these variant tumors are muscle invasive but not all. The response of non muscle invasive variant tumors to intravesical immunotherapy with BCG is not established in the literature, and is reported here. Between June 1995 and December 2007, 760 patients (mean age of 67.5 years) underwent transurethral resection of first time bladder tumors in our institution. Histologically variant tumors were found in 79 patients (10.4%). Of these 57 patients (72%) of them had muscle-invasive disease or extensive non-muscle invasive tumors and remaining 22 patients (28%) were treated with BCG immunotherapy. These included 7 patients with squamous differentiation, 4 with glandular, 6 with nested, 4 with micropapillary and 1 patient with sarcomatoid variant. The response of these patients to immunotherapy was compared with that of 144 patients having high-grade conventional urothelial carcinomas. Median follow-up was 46 months. The 2 and 5-year progression (muscle-invasion) free survival rates were 92% and 84.24% for patients with conventional carcinoma compared to 81.06% and 63.16% for patients with variant disease (P=0.02). The 2 and 5-year disease specific survival rates were 97% and 91.43% for patients with conventional carcinoma compared to 94.74 % and 82% for patients with variant disease (P=0.33). 5 patients (22.7%) of variant group and 13 patients (9.03%) of conventional group underwent cystectomy during follow-up (P=0.068)

Clinical Significance of Urine Heparanase in Bladder Cancer Progression1

Heparanase is an endo-β-glucuronidase capable of cleaving heparan sulfate (HS), an activity implicated in tumor metastasis. Heparanase expression is upregulated in primary human tumors, correlating with reduced post operative survival and elevated microvessel density. An ELISA method was used to quantify heparanase in urine from 282 individuals. Urine was collected from healthy volunteers (n = 41), patients diagnosed with noncancerous pathologic disorders (n = 90), and bladder cancer patients (n = 92). Fifty-nine bladder carcinoma patients after transurethral resection (TUR) with no evidence of disease (NED) were also included. Heparanase levels were significantly elevated in urine from bladder cancer patients compared with healthy controls (P < .001) and with noncancerous urinary disorders (P < .05). Heparanase elevation strongly correlated with tumor grade (P < .001) and stage (P = .027). An optimal cutoff value of 154 pg/ml was determined. Of 199 individuals enrolled (59 patients after TUR and 24 patients with recurring disease were excluded), 65 had heparanase levels above 154 pg/ml. Only 3 of 65 (4.6%) were healthy individuals. In contrast, 52.3% (34 of 65) of individuals with heparanase levels above 154 pg/ml were bladder cancer patients. The results indicate that urine heparanase levels are elevated during bladder cancer progression, suggesting that the ELISA method may be applied for bladder cancer diagnosis