A Comparative Analysis of the Influence of Gender, Pathway Delays, and Risk Factor Exposures on the Long-term Outcomes of Bladder Cancer

Richard T Bryan; Tim Evans; Janet A Dunn; Gulnaz Iqbal; Sarah Bathers; Stuart I Collins; Nicholas D James; James W F Catto; D Michael A Wallace

doi:10.1016/j.euf.2015.01.001

A Comparative Analysis of the Influence of Gender, Pathway Delays, and Risk Factor Exposures on the Long-term Outcomes of Bladder Cancer

Eur Urol Focus. 2015 Aug;1(1):82-89. doi: 10.1016/j.euf.2015.01.001. Epub 2015 May 19.

Authors

Richard T Bryan¹, Tim Evans², Janet A Dunn³, Gulnaz Iqbal³, Sarah Bathers⁴, Stuart I Collins¹, Nicholas D James⁵, James W F Catto⁶, D Michael A Wallace⁷

Affiliations

¹ School of Cancer Sciences, University of Birmingham, Birmingham, UK.
² Public Health England, Birmingham, UK.
³ Warwick Clinical Trials Unit, University of Warwick, Coventry, UK.
⁴ Primary Care Clinical Research and Trials Unit, University of Birmingham, Birmingham, UK.
⁵ Cancer Research Unit, University of Warwick, Coventry, UK.
⁶ Department of Oncology, University of Sheffield, Sheffield, UK. Electronic address: j.catto@sheffiled.ac.uk.
⁷ School of Surgery, University of Western Australia, Crawley, Australia.

PMID: 28723362
DOI: 10.1016/j.euf.2015.01.001

Abstract

Background: The relationship between pathway delays and bladder cancer-specific survival is complex because of the influence of tumour- and patient-specific factors.

Objective: To investigate the influence of tumour factors, patient factors, carcinogen exposure, and pathway delays on the long-term outcome of urothelial bladder cancer (UBC).

Design, setting, and participants: A cohort of 1537 UBC patients were enrolled between January 1, 1991 and June 30, 1992 and followed up for 17.7 yr. The period from the onset of symptoms to first treatment (transurethral resection of bladder tumour, TURBT) was divided into three components of potential delay.

Outcome measurements and statistical analysis: Associations between patient factors, tumour factors, and delay times were analysed using the Pearson χ² test and the Mann-Whitney U test. Survival was calculated from date of TURBT to date of death or censor date (December 31, 2010). Competing risks of death were assessed with the cumulative incidence function (CIF); CIF comparisons were performed using the Gray test.

Results and limitations: At censor, reliable data were available for 1478 patients, of whom 75% had died. Females presented more commonly with muscle-invasive bladder cancer (MIBC; 30% vs 26%) and less frequently with pT1 disease (18% vs 24%; p=0.06) and had a longer total delay time (median 120 d vs 106 d, p=0.02), and those with MIBC had a significantly higher cumulative incidence of death due to UBC (80% vs 67% at 17 yr; p<0.02). Cox regression identified age, smoking status, and tumour stage, grade, and size as the most significant determinants of poor outcome. We did not capture downstream delays associated with cystectomy or radiotherapy.

Conclusions: Female UBC patients present later than males, and our data suggest that delay in referral may be contributory. The relationship between gender, outcomes, delays, and UBC aetiology is complex.

Patient summary: We followed a large group of bladder cancer patients for more than 17 yr. The relationship between pathway delays and survival is complex. However, female patients present later than male patients, and our data suggest that delay in referral from general practice may be contributory.

Keywords: Delayed diagnosis; Long-term effects; Risk factors; Sex factors; Treatment outcome; Urinary bladder neoplasms.