Androgen receptor expression tied to poor urothelial carcinoma outcomes

In patients with metastatic urothelial carcinoma (mUC), a positive expression of androgen receptor (AR) appears to worsen survival outcomes, according to a recent study.

“In recent years, there has been a significant progress in the treatment landscape of mUC with the advent of immune checkpoint inhibitors and antibody–drug conjugates,” the researchers said, adding that targeted therapies options for these patients have remained sparse.

“In this retrospective study, we showed that AR expression is a predictor of poor outcome in patients with mUC receiving first-line platinum-containing chemotherapy,” they added, suggesting that AR could be a potential therapeutic target for mUC.

The study included 90 tissues sample retrieved from the phase III trial LaMB, which enrolled patients with HER 1/2-positive mUC of the bladder who had received first-line platinum-based treatment. A single blinded pathologist assessed AR expression using immunohistochemistry. Outcomes included overall (OS) and progression-free (PFS) survival.

Fifty-six samples (62 percent) were found to be AR negative, while the remaining 34 samples (38 percent) had clear AR expression at varying levels. The rate of AR expression did not differ between male and female mUC patients (38 percent vs 37 percent). Similarly, neither tumour stage (r, –0.10) and grade (r, 0.05) at diagnosis nor subsequent lapatinib treatment (r, –0.04) correlated with AR expression. [Front Urol 2022;doi:10.3389/fruro.2022.863784]

In terms of survival, the overall cohort showed a median PFS and OS of 5 and 13 months, respectively, from the end of chemotherapy.

AR expression appeared to significantly influence survival. For instance, AR-negative patients had a slightly longer median PFS of 6 months, as opposed to the 5-month outcome in AR-positive comparators. Multivariate analysis confirmed that such impact on disease progression or death from disease was statistically significant (hazard ratio [HR], 0.54, 95 percent confidence interval [CI], 0.31–0.92; p=0.02). These findings were robust to subgroup analyses regarding the intensity of tissue staining.

Similarly, OS was much more favourable in those with AR-negative disease (16 vs 11 months), an effect confirmed to be statistically significant by multivariate analysis (HR, 0.55, 95 percent CI, 0.31–0.98; p=0.04).

Important study limitations included the use of retrospective data and the relatively small sample size, particularly when looking at those with AR-positive disease. Moreover, data were retrieved after the completion of chemotherapy and during the maintenance targeted therapy phase, which was not part of the standard of care.

“The effects from a more orthodox frontline perspective are unknown,” the researchers said. “A large, prospective randomized study may be justified to validate these findings and potentially repurpose AR-modulating agents in this context.”