Blinded and uniform causes of death verification in cancer screening: a major influence on the outcome of a prostate cancer screening trial?

BACKGROUND: To assess the agreement between the causes of death assigned by a blinded and uniform review panel of the Rotterdam section of the European Randomised Study of Screening for Prostate Cancer and the official vital statistics and to explore the possible effect of the use of either of these two sources on the outcome of the screening trial. METHODS: A total of 670 deaths amongst men with prostate cancer, reviewed by the causes of death committee (CODC) up to 31st December 2006 were included in this study. The kappa statistics with confidence intervals (CI), sensitivity and specificity of the official statistics were determined, with the CODC considered the gold standard. The rate ratio (RR) and 95% confidence intervals (95% CI) for prostate cancer mortality, official statistics relative to CODC, were calculated following the Mantel-Haenszel procedure. RESULTS: The overall concordance and the kappa between official statistics and the CODC were 90.6% and 0.76 (0.71-0.82), remaining comparable when only the CODC category definitely prostate cancer was applied, with the sensitivity of official statistics increasing from 88.3% to 91.3% and specificity hardly changing (91.3% and 90.5%). High specificity and lower sensitivity is observed in the screening arm, whilst the opposite was seen in the control arm in men aged 55-69 and 70-74 years at entry. Considerable lower false positive rate was seen for both age groups in the screening arm (3.9% and 4.7%) compared to the control arm (8.4% and 14.3%). A statistically significant excess of prostate cancer death was observed for the official statistics in the age group 70-74 years, 1.53 (1.07-2.19), whilst it was not significant for men aged 55-69 at entry, 1.06 (0.83-1.36). CONCLUSION: In the Rotterdam ERSPC section, official statistics tended to overreport prostate cancer as an underlying cause of death, particularly in the age group 70-plus in the control arm, which would overestimate the true effect in favour of screening.

Development of a non-invasive strategy to classify bladder outlet obstruction in male patients with LUTS.

To diagnose bladder outlet obstruction in male patients with lower urinary tract symptoms (LUTS), it is necessary to measure the bladder pressure via a transurethral (or suprapubic) catheter. This procedure incurs some risk of urinary tract infection and urethral trauma and is sometimes painful to the patient. We developed an external condom catheter to measure non-invasively the bladder pressure and developed a strategy to classify bladder outlet obstruction (BOO) based on this measurement. Seventy-five patients with a wide range of urological diagnoses underwent a pressure-flow study followed by a non-invasive study. We tested five different strategies to classify the patients using the provisional International Continence Society (ICS) method for definition of obstruction as the gold standard. Leakage of the external catheter occurred in eight (40%) of the first 20 tested patients. In the remaining 55 patients, only five (9%) of the measurements failed because of leakage. Of the 75 patients, 56 were successfully tested non-invasively. According to the ICS nomogram, the PFS showed that 22 of these patients were non-obstructed, 12 patients were equivocal, and 22 patients were obstructed. Ten of these 56 patients strained, and we found that the relatively high abdominal pressures in these patients were not reflected in the externally measured bladder pressure. Of the remaining 46 patients, 12 of 13 non-obstructed patients and 30 of 33 combined equivocal and obstructed patients could be correctly classified. We developed a simple, non-invasive classification strategy to identify BOO in those male patients who did not strain during voiding.