Background Multiple recurrences develop in individuals with high-risk non-muscle-invasive bladder malignancy. 2 694 (59.6%) had multiple recurrences within 2 years of diagnosis. Compared with individuals who only experienced 1 recurrence those with ��4 recurrences were less likely to undergo radical cystectomy (risk percentage [HR] = 0.73 95 CI: 0.58-0.92) yet more likely to undergo radiotherapy (HR = 1.51 95 CI: 1.23-1.85) and systemic chemotherapy (HR = 1.58 95 CI: 1.15-2.18). For individuals with ��4 recurrences only 25% were treated with curative intention. The 10-yr cancer-specific mortality rates were 6.9% 9.7% 13.7% and 15.7% for those with 1 2 3 and ��4 recurrences respectively. Conclusions Only 25% of individuals with high-risk non-muscle-invasive bladder malignancy who experienced recurrences at least 4 VU 0357121 instances underwent radical cystectomy or radiotherapy. Despite portending worse results increasing recurrences do not necessarily translate into higher treatment rates. = 4 521 Table 2 Cohort characteristics stratified by recurrences Decreased incidence of radical cystectomy was observed with advancing age (��70 y) male sex non-married status comorbid conditions (Charlson 1) and people experiencing 4 or more recurrences within 2 years of analysis (Table 3). Conversely improved incidence of radical cystectomy was associated with female sex married status median household income (>$55 0 unfamiliar institution type and tumor phases Tis and T1. Decreased incidence of radiotherapy was only observed with yr of analysis (for each yr after 1992); improved incidence of radiotherapy was observed with unknown institution type undifferentiated tumor grade tumor stage T1 and people experiencing 2 or more recurrences. Treatment with systemic chemotherapy was more frequent with black race median household income ($35 0 0 and people experiencing 4 or VU 0357121 more recurrences within 2 years of diagnosis. Table 3 Multivariate competing-risks regression analysis of incidence of subsequent treatment The cumulative incidence of undergoing aggressive treatment at 2 5 and 10 years from your competing-risks regression analyses was derived for the group as a whole (Fig. 1). The incidence of radical cystectomy at 10 years was 10% 9 9 and 7% in individuals with 1 2 3 and ��4 recurrences respectively. Correspondingly The incidence of radiotherapy at 10 years was 13% 16 17 and 18%. The incidence of systemic chemotherapy at 10 years was 4% 4 4 and 7% respectively. Therefore the incidence of treatment for curative intention (radical cystectomy and radiotherapy) at 10 years was 23% 25 26 and 25% after 1 2 3 and ��4 recurrences respectively. Rabbit Polyclonal to MGST1. Fig. 1 Cumulative incidence of treatment stratified by the number of recurrences overall. (Color version of figure is available online.) As the decision to pursue aggressive medical treatment must consider many factors we restricted our analysis to treatment methods in an environment conducive to aggressive treatment (Fig. 2). Among this group of individuals most amenable to aggressive intervention at 10 years 38 37 35 and 30% underwent radical cystectomy after 1 2 3 and ��4 recurrences respectively. Correspondingly the incidence of radiotherapy at 10 years was 9% 11 12 and 13% VU 0357121 and the incidence of systemic chemotherapy at 10 years was 8% 7 8 and 13%. With this ideal cohort of individuals the incidence of treatment for curative intention at 10 years was 47% 48 47 and 43% after 1 2 3 and ��4 recurrences respectively. Fig. 2 Cumulative incidence VU 0357121 of treatment stratified by the number of recurrences in an ideal environment. (Color version of figure is available on-line.) VU 0357121 After 5 years when compared with individuals who experienced 1 recurrence (4.3%) those with 2 (6.1% = 0.03) 3 (8.6% < 0.01) and at least 4 recurrences (9.9% < 0.01) were more likely to die of bladder malignancy (Table 4). After 10 years the mortality rates were 6.9% (referent) 9.7% (= 0.03) 13.7% (< 0.01) and 15.7% (< 0.01) for individuals with 1 2 3 and ��4 recurrences respectively. Table 4 Propensity-score modified competing-risk regression analysis quantifying the association of quantity recurrences with cancer-specific.