Comparative outcomes of primary, recurrent, and progressive high-risk non-muscle-invasive bladder cancer.

BACKGROUND: The treatment of high-risk non-muscle-invasive bladder cancer (BCa) is problematic given the variable natural history of the disease. Few reports have compared outcomes for primary high-risk tumours with those that develop following previous BCas (relapses). The latter represent a self-selected cohort, having failed previous treatments. OBJECTIVE: To compare outcomes in patients with primary, progressive, and recurrent high-risk non-muscle-invasive BCa. DESIGN, SETTING, AND PARTICIPANTS: We identified all patients with primary and relapsing high-risk BCa tumours at our institution since 1994. Relapses were divided into progressive (previous low- or intermediate-risk disease) and recurrent (previous high-risk disease) cancers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relationships with outcome analysed using multivariable Cox regression and log-rank analysis. RESULTS AND LIMITATIONS: We identified 699 primary, 110 progressive, and 494 recurrent high-risk BCa tumours in 809 patients (average follow-up: 59 mo [interquartile range: 6-190]). Muscle invasion occurred most commonly in recurrent (23%) tumours, when compared to progressive (20%) and primary (14.6%) cohorts (log rank p<0.001). Disease-specific mortality (DSM) occurred more frequently in patients with recurrent (25.5%) and progressive (24.6%) tumours compared to primary disease (19.2%; log rank p=0.006). Other-cause mortality was similar in all groups (log rank p=0.57), and overall mortality was highest in the progressive cohort (62%) compared with the recurrent (58%) and primary groups (54%; log rank p<0.001). In multivariable analysis, progression and DSM were predicted by tumour grouping (hazard ratio [HR]: >1.15; p<0.026), stage (HR: >1.30; p<0.001), and patient age and sex (HR: >1.03; p<0.037). Carcinoma in situ was only predictive of outcome in primary tumors. Limitations include retrospective design and limited details regarding bacillus Camille-Guérin use. CONCLUSIONS: Patients with relapsing, high-risk, BCa tumors have higher progression, DSM, and overall mortality rates than those with primary cancers. The use of bladder-sparing strategies in these patients should approached cautiously. Carcinoma in situ has little predicative role in relapsing, high-risk, BCa tumors.

Disease specific mortality in patients with low risk bladder cancer and the impact of cystoscopic surveillance.

PURPOSE: We determined the risk of disease specific mortality in patients with primary, low risk, noninvasive (G1pTa) bladder cancer and compared it to disease specific mortality in age and gender matched general populations. MATERIALS AND METHODS: We identified all patients with primary low risk cancer at our institution. We excluded those with adverse pathological features and then matched histopathology, pharmacy, hospital episode and Cancer Registry records. We reviewed case notes on patients with subsequent muscle invasion (progression) or disease specific mortality. Patients underwent post-resection surveillance and treatment using standard regimens. National and regional disease specific mortality rates were calculated from appropriate data. RESULTS: A total of 699 patients met study inclusion criteria. Median followup was 61 months (IQR 24-105). Of the patients 17 (2.4%) died of bladder cancer, including 13 of 14 with progression to muscle invasion and 4 of 19 with grade progression to high grade, nonmuscle invasive disease. On Cox regression analyses low grade dysplasia in the initial resection specimen and tumor weight were associated with disease specific mortality (p <0.003). Disease specific mortality in these patients was 5 times the background rate in matched populations. Limitations of this study include its retrospective nature and the low frequency of adverse events. CONCLUSIONS: Patients with low risk bladder cancer rarely progress to muscle invasion but they are at higher risk for disease specific mortality than the general population. Current surveillance regimens appear ineffective for detecting progression in time to alter prognosis.

The long-term outcome of treated high-risk nonmuscle-invasive bladder cancer: time to change treatment paradigm?

BACKGROUND: The treatment of high-risk nonmuscle-invasive bladder cancer (NMIBC) is difficult given its unpredictable natural history and patient comorbidities. Because current case series are mostly limited in size, the authors report the outcomes from a large, single-center series. METHODS: The authors reviewed all patients with primary, high-risk NMIBC at their institution from 1994 to 2010. Outcomes were matched with clinicopathologic data. Patients who had muscle invasion within 6 months or had insufficient follow-up (<6 months) were excluded. Correlations were analyzed using multivariable Cox regression and log-rank analysis (2-sided; P < .05). RESULTS: In total, 712 patients (median age, 73.7 years) were included. Progression to muscle invasion occurred in 110 patients (15.8%; 95% confidence interval [CI], 13%-18.3%) at a median of 17.2 months (interquartile range, 8.9-35.8 months), including 26.5% (95% CI, 22.2%-31.3%) of the 366 patients who had >5 years follow-up. Progression was associated with age (hazard ratio [HR], 1.04; P = .007), dysplastic urothelium (HR, 1.6; P = .003), urothelial cell carcinoma variants (HR, 3.2; P = .001), and recurrence (HR, 18.3; P < .001). Disease-specific mortality occurred in 134 patients (18.8%; 95% CI, 16.1%-21.9%) at a median of 28 months (interquartile range, 15-45 months), including 28.7% (95% CI, 24.5%-33.3%) of those who had 5 years of follow-up. Disease-specific mortality was associated with age (HR, 1.1; P < .001), stage (HR, 1.7; P = .003), dysplasia (HR, 1.3; P = .05), and progression (HR, 5.2; P < .001). Neither progression nor disease-specific mortality were associated with the receipt of bacillus Calmette-Guerin (P > .6). CONCLUSIONS: Within a program of conservative treatment, progression of high-risk NMIBC was associated with a poor prognosis. Surveillance and bacillus Calmette-Guerin were ineffective in altering the natural history of this disease. The authors concluded that the time has come to rethink the paradigm of management of this disease.

Cardiac tamponade secondary to haemopericardium in a patient on warfarin.

Excessive anticoagulation with warfarin may contribute to certain complications, including bleeding into body cavities. Haemopericardiac tamponade secondary to warfarin is rare outside cardiac surgery. The present report describes an unusual presentation of spontaneous cardiac tamponade in a patient on warfarin and recently treated for chest infection with erythromycin. The patient was referred to the surgeons with acute abdominal pain and hypotension. Blood tests revealed an international normalised ratio (INR) of 16.9. An emergency abdominal computed tomography (CT) scan revealed pericardial effusion. Intravenous vitamin K and prothrombin complex concentrate were administered and urgent referral to a cardiologist was made for pericardiocentesis. Monitoring INR in patients on warfarin is paramount in avoiding the potential detrimental complications of excessive anticoagulation. Clinicians should be aware of drug interactions of warfarin and risk factors associated with its prolonged half-life. Internal bleeding, including haemorrhagic cardiac tamponade, should be ruled out in patients with unexplained hypotension and excessive anticoagulation.

Should sildenafil be available over the counter?

INTRODUCTION: This article considers the process of re-classification of prescription drugs from prescription-only medications to over-the-counter (OTC) prescription drugs. SOURCES OF DATA: The recent change in classification for emergency contraception and simvastatin is explored in detail with similarities and differences being considered for a similar argument to be made for sildenafil. AREAS OF AGREEMENT: The benefits for patients, physicians and other healthcare professionals are considered in detail. AREAS OF CONTROVERSY: We raise concerns about recently developed and existing patient group directions that, although extensive in their assessment, may omit to identify significant contributory factors which would necessitate appropriate medical intervention. GROWING POINTS: While the decision for re-classification to OTC would depend on a number of factors, we argue that, with the proviso of proper assessments being made, sildenafil should be made available as an OTC medication. AREAS TIMELY FOR DEVELOPING RESEARCH: The safety and use of OTC medications for erectile dysfunction at a time when many first line prescription agents are reaching generic status.