Androgen deprivation therapy prevents bladder cancer recurrence

Abstract

Although accumulating preclinical evidence indicates the involvement of androgen receptor signals in bladder cancer (BC) development, its clinical relevance remains unclear. We aimed to evaluate the predictive role of androgen deprivation therapy (ADT) in BC recurrence in prostate cancer (PC) patients.We retrospectively reviewed 20,328 patients with PC diagnosed during 1991–2013 and identified 239 (1.2%) men having primary BC. After excluding ineligible patients, 162 patients made up a final cohort.With a median follow-up of 62 months, 38 (50%) of 76 control patients without ADT experienced BC recurrence, while 19 (22%) of 86 did in ADT group. Thus, patients having received ADT for their PC showed a significantly lower risk of BC recurrence (5-year actuarial recurrence-free survival: 76% v 40%; P < 0.001) and also had a significantly smaller number of recurrence episodes (5-year cumulative recurrence: 0.44 v 1.54; P < 0.001), compared to the control patients. A multivariable analysis revealed ADT as an independent prognosticator (hazard ratio, 0.29; 95% confidence interval, 0.17–0.49) for BC recurrence.This is the first clinical study showing that ADT significantly reduces the risk of BC recurrence.

The emerging role of the androgen receptor in bladder cancer

“…Much of the presented data suggests that androgen signaling promotes the formation of both male and female bladder tumors. These data are consistent with two possible hypotheses regarding male vs female bladder cancer incidence; i) Males have higher AR expression or ii) higher levels of circulating androgens predispose to bladder cancer (Izumi et al 2014).…”

“…One hypothesis that resolves these discrepancies is that androgen signaling, rather than AR levels, is primarily responsible for the discrepancy between male and female incidence of bladder cancer (Izumi et al 2014). Although the AR can be variably expressed and seems to play a role in the disease, males have higher circulating androgen than do females.…”

“…Efficacy of androgen deprivation therapy (ADT) in attenuating bladder cancer recurrence comes from a study of prostate cancer patients who also had primary bladder cancer of varying grades and stages ranging from Ta to beyond T1 (Izumi et al 2014). Retrospective analysis of patients who did and did not receive ADT for prostate cancer revealed that men given ADT had longer 5 year recurrence free survival rates and had fewer subsequent recurrences (Izumi et al 2014).…”

“…Retrospective analysis of patients who did and did not receive ADT for prostate cancer revealed that men given ADT had longer 5 year recurrence free survival rates and had fewer subsequent recurrences (Izumi et al 2014). This analysis also found ADT was an independent prognosticator of bladder cancer recurrence and that the effect of ADT on recurrence is time dependent indicating longer treatment periods provide more patient benefit (Izumi et al 2014). Based on the work presented here, ADT could become a novel way to treat and better prevent recurrence of bladder tumors.…”

Expression of steroid hormone receptors and its prognostic significance in urothelial carcinoma of the upper urinary tract

“…Recent retrospective clinical studies have also implied that androgen deprivation therapy for prostate cancer prevents bladder cancer development and recurrence. 36,37 These findings further suggest potential application of currently available therapeutic options used for other pathological conditions to the treatment of urothelial tumors.…”