Mechanisms of recurrence of Ta/T1 bladder cancer

Abstract

Introduction: Bladder cancer recurrence occurs via four mechanisms - incomplete resection, tumour cell re-implantation, growth of microscopic tumours, and new tumour formation. The first two mechanisms are influenced by clinicians before and immediately after resection; the remaining mechanisms have the potential to be influenced by chemopreventive agents. However, the relative importance and timing of these mechanisms is currently unknown. Our objective was to postulate the incidence and timing of these mechanisms by investigating the location of bladder cancer recurrences over time.

Patients and methods: The topographical locations of tumours and their recurrences were analysed retrospectively for 169 patients newly-diagnosed with Ta/T1 bladder cancer, with median follow-up of 33.8 months. Tumours were assigned to one or more of six bladder sectors, and time to recurrence and location of recurrences were recorded.

Results: Median time to first tumour recurrence was 40 months. Median times between subsequent recurrences were 6.6, 7.9, 8.0 and 6.6 months for recurrences 1 to 2, 2 to 3, 3 to 4, and 4 to 5, respectively. The risk of first tumour recurrence in any given bladder sector increased by nearly 4-fold if the primary tumour was resected from that sector (P < 0.001); this association was not significant for subsequent recurrences. The proportion of tumour recurrences in multiple bladder sectors increased from 13% for the first recurrence to 100% for recurrence seven onwards.

Conclusions: First tumour recurrence appears different to subsequent recurrences; incomplete resection and tumour cell reimplantation may dominate at this time-point. Only later does genuine new tumour formation appear to increase in importance. This has important implications for clinical trials, especially those involving chemopreventive agents.

Figure 1

Topographical definition of the six bladder sectors.

Figure 2

Recurrence-free survival following diagnosis of primary, following recurrences one to four inclusive. In this figure, n is the number of patients in the analysis, and ethe number of patients experiencing a recurrence. Small sample size prevents display of recurrences beyond number 5.

Figure 3

Time to first recurrence in a sector for all bladder sectors combined, by whether the location of the primary was in that sector. n is the number of patients in the analysis, and e the number of patients experiencing a recurrence.

Figure 4

Time from first to second recurrence in a sector for all bladder sectors combined by whether the location of the primary was in that sector. n is the number of patients in the analysis, and e the number of patients experiencing a recurrence.