Two-year follow-up of the phase II marker lesion study of intravesical apaziquone for patients with non-muscle invasive bladder cancer.

OBJECTIVES: To study the time-to-recurrence and duration of response in non-muscle invasive bladder cancer (NMIBC) patients, with a complete ablative response after intravesical apaziquone instillations. METHODS: Transurethral resection of bladder tumour(s) (TURBT) was performed in patients with multiple pTa-T1 G1-2 urothelial cell carcinoma (UCC) of the bladder, with the exception of one marker lesion of 0.5-1.0 cm. Intravesical apaziquone was administered at weekly intervals for six consecutive weeks, without maintenance instillations. A histological confirmed response was obtained 2-4 weeks after the last instillation. Routine follow-up (FU) was carried out at 6, 9, 12, 18 and 24 months from the first apaziquone instillation. RESULTS: At 3 months FU 31 of 46 patients (67.4%) had a complete response (CR) to ablative treatment. Side-effects on the long-term were only mild. Two CR patients dropped out during FU. On intention-to-treat (ITT) analysis 49.5% of the CR patients were recurrence-free at 24 months FU, with a median duration of response of 18 months. Of 15 no response (NR) patients, only two received additional prophylactic instillations after TURBT. On ITT-analysis 26.7% of the NR patients were recurrence-free (log rank test, P = 0.155). The overall recurrence-free survival was 39% (18 of 46 patients) at 24 months FU. CONCLUSIONS: The CR of the marker lesion in 67% of patients was followed by a recurrence-free rate of 56.5% at 1-year FU, and 49.5% at 2-year FU. These long-term results are good in comparison with the results of other ablative studies.

Discrepancy between clinical staging through bimanual palpation and pathological staging after cystectomy.

OBJECTIVES: In muscle invasive bladder cancer (MIBC), careful clinical staging is essential for patient counseling and decision-making. Bimanual palpation (BP) is an integral part and guideline advice of clinical staging. Until now, however, the value of BP has never been studied. With this study, we aim to determine the accuracy of clinical staging through BP. METHODS: Detailed clinical data were collected from a population-based series of 1,409 patients with MIBC, diagnosed between 1989 and 2005, in the region of the Comprehensive Cancer Centre East in The Netherlands. Selected were all patients who underwent BP (n = 738). Preoperative tumor-stage (cT-stage) determined through BP was compared with post-cystectomy pT-stage. Contingency tables were made to determine the correlation between cT-stage and pT-stage. RESULTS: In 18 of 142 patients in whom BP showed an organ-confined tumor, the tumor was unresectable (pT4) at the time of surgery. Four out of 9 patients who had a suspected T4 tumor on BP but who underwent cystectomy anyway appeared to have operable tumors at cystectomy. In 87 patients (57.6%), accurate staging through BP was observed. In 17 patients (11.3%), clinical overstaging was found, and in 47 patients, (31.1%) clinical understaging. CONCLUSIONS: Frequently, pT-stage after cystectomy does not correlate with preoperative cT-stage based on BP. Discrepancy was observed in 42% of the patients: in 11%, clinical overstaging and in 31%, clinical understaging. Based on these data, some caution is suggested when interpreting the outcome of BP. Prospective data is needed for a more formal evaluation of the staging accuracy of BP.

Prognostic factors for survival in patients with recurrence of muscle invasive bladder cancer after treatment with curative intent.

UNLABELLED: Prognostic factors for survival after recurrent MIBC are unknown and were evaluated using a population-based series of 1409 MIBC patients. 330 Patients who underwent RC or RT with curative intent and who suffered from recurrence were selected. Multivariable survival analyses were performed. Clinicopathological factors that predict survival after recurrence are recurrence location, treatment for recurrence and age at recurrence diagnosis. PURPOSE: We conducted this study to evaluate the prognostic factors for survival among patients with recurrent muscle-invasive bladder cancer (MIBC) after initial treatment with curative intent. PATIENTS AND METHODS: Clinical data were collected from a population-based series of 1409 patients with MIBC. We selected 330 patients who underwent radical cystectomy (RC) or radiotherapy (RT) for urothelial carcinoma with curative intent and who experienced recurrence. Multivariate survival analyses were performed with death from MIBC as the endpoint. Covariates were gender, time to recurrence, age at diagnosis of recurrence, recurrence multiplicity, localization, and treatment for recurrence. Analyses were performed separately for patients initially treated with RC (i-RC) or external beam radiotherapy (i-EBRT). RESULTS: Patients with recurrence after i-RC showed a 1- and 3-year survival of 17% and 6%, respectively. Localization and treatment for recurrence were significantly associated with survival. Patients with recurrence after i-EBRT showed a 1- and 3-year survival of 31% and 12%, respectively. Age at diagnosis of recurrence, localization, and treatment for recurrence were significantly associated with survival. CONCLUSION: This study confirms the extremely poor prognosis after recurrence of MIBC in patients initially treated with surgery or RT. Clinicopathologic factors that predict survival after disease recurrence are location of recurrence, treatment for recurrence, and age at diagnosis of recurrence. Improved diagnosis of primary MIBC to detect extravesical disease and more effective therapeutic approaches to target recurrent MIBC are needed.

Phase II marker lesion study with intravesical instillation of apaziquone for superficial bladder cancer: toxicity and marker response.

PURPOSE: We studied the ablative activity of intravesical apaziquone (EOquin) on a papillary marker tumor and determined the incidence of side effects. MATERIALS AND METHODS: A total of 46 patients with multiple pTa or pT1 bladder tumors underwent visible lesion resection except for 1 marker tumor. Patients were then treated with 6 instillations of apaziquone at weekly intervals. The response was determined 2 to 4 weeks after the last instillation. RESULTS: One patient withdrew informed consent and refused the last treatment due to side effects. A histologically proven complete response was seen in 30 patients. Progression to invasive stage was not observed. Local side effects in this study were comparable to those due to other chemotherapy instillations, such as mitomycin C and epirubicin, but less severe and less frequent compared to those of bacillus Calmette-Guerin instillations. CONCLUSIONS: The histological complete response rate after 6 consecutive instillations of apaziquone in patients with superficial bladder cancer was 67% (95% CI 51 to 80). Local side effects were comparable to side effects due to other chemotherapy instillations.