Comparing an Imaging-guided Pathway with the Standard Pathway for Staging Muscle-invasive Bladder Cancer: Preliminary Data from the BladderPath Study.

Transurethral resection of bladder tumour (TURBT) is central to the diagnosis of muscle-invasive bladder cancer (MIBC). With the oncological safety of TURBT unknown, staging inaccuracies commonplace, and correct treatment of MIBC potentially delayed, multiparametric magnetic resonance imaging (mpMRI) may offer rapid, accurate, and noninvasive diagnosis of MIBC. BladderPath is a randomised trial comparing risk-stratified (5-point Likert scale) image-directed care with TURBT for patients with newly diagnosed BC. To date, we have screened 279 patients and randomised 113. Here we report on the first 100 participants to complete staging: 48 in pathway 1 (TURBT) and 52 in pathway 2 (mpMRI for possible MIBC, Likert 3-5). Fifty of 52 participants designated Likert 1-2 (probable NMIBC) from both pathways were confirmed as having NMIBC (96%). Ten of 11 cases diagnosed as NMIBC by mpMRI have been pathologically confirmed as NMIBC, and 10/15 cases diagnosed as MIBC by mpMRI have been treated as MIBC (5 participants underwent TURBT). The specificity of mpMRI for identification of MIBC remains a limitation. These initial experiences indicate that it is feasible to direct possible MIBC patients to mpMRI for staging instead of TURBT. Furthermore, a 5-point Likert scale accurately identifies patients with low risk of MIBC (Likert 1-2), and flexible cystoscopy biopsies appear sufficient for diagnosing BC. PATIENT SUMMARY: We are conducting a clinical trial to assess whether some bladder tumour surgery can be replaced by magnetic resonance imaging scans to determine the stage of the cancer in patients whose tumours appear to be invasive. Our early data suggest that this approach is feasible. The data also show that using a visual score ('Likert scale') can help to identify bladder tumours that are very unlikely to be invasive, and that taking a biopsy in the outpatient clinic when first inspecting the bladder via a camera (diagnostic flexible cystoscopy) is useful for confirming bladder cancer.

Warfarin thromboprophylaxis in cancer patients with central venous catheters (WARP): an open-label randomised trial.

BACKGROUND: The role and dose of anticoagulants in thromboprophylaxis for patients with cancer receiving chemotherapy through central venous catheters (CVCs) is controversial. We therefore assessed whether warfarin reduces catheter-related thrombosis compared with no warfarin and whether the dose of warfarin determines the thromboprophylactic effect. METHODS: In 68 clinical centres in the UK, we randomly assigned 1590 patients aged at least 16 years with cancer who were receiving chemotherapy through CVCs to no warfarin, fixed-dose warfarin 1 mg per day, or dose-adjusted warfarin per day to maintain an international normalised ratio between 1.5 and 2.0. Clinicians who were certain of the benefit of warfarin randomly assigned patients to fixed-dose or dose-adjusted warfarin groups. The primary outcome was the rate of radiologically proven, symptomatic catheter-related thrombosis. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN 50312145. FINDINGS: Compared with no warfarin (n=404), warfarin (n=408; 324 [79%] on fixed-dose and 84 [21%] on dose-adjusted) did not reduce the rate of catheter-related thromboses (24 [6%] vs 24 [6%]; relative risk 0.99, 95% CI 0.57-1.72, p=0.98). However, compared with fixed-dose warfarin (n=471), dose-adjusted warfarin (n=473) was superior in the prevention of catheter-related thromboses (13 [3%] vs 34 [7%]; 0.38, 0.20-0.71, p=0.002). Major bleeding events were rare; an excess was noted with warfarin compared with no warfarin (7 vs 1, p=0.07) and with dose-adjusted warfarin compared with fixed-dose warfarin (16 vs 7, p=0.09). A combined endpoint of thromboses and major bleeding showed no difference between comparisons. We did not note a survival benefit in either comparison. INTERPRETATION: The findings show that prophylactic warfarin compared with no warfarin is not associated with a reduction in symptomatic catheter-related or other thromboses in patients with cancer and therefore we should consider newer treatments. FUNDING: Medical Research Council and Cancer Research UK.