The Role of Opioids and Their Receptors in Urologic Malignancy: A Review

Bladder Cancer
10/06/2020

Lec PM, et al. J Urol 2020.

ABSTRACT

PURPOSE: To review the literature surrounding the role of opioids and their receptors in urologic malignancy. Recent studies have suggested clinically significant effects of agonism or antagonism of opioid receptors on cancer-related outcomes and tumorigenesis. The focus of these efforts has centered on non-urologic malignancies, however a compelling body of evidence is growing in the fields of prostate, bladder and kidney cancer.

MATERIALS AND METHODS: A systematic review of English language articles published through 2020 was conducted with key phrases related to kidney, bladder, or prostate cancer and opioids or narcotics. 837 unique records were identified, of which 49 were selected for full text review and 33 were included in the qualitative analysis. 8 records were identified via citation review and one study recently presented at a national meeting.

RESULTS: Retrospective reviews suggest poorer disease-specific and recurrence-free survival with increased peri-operative opioid administration in patients undergoing prostate or bladder cancer surgery, however data is controversial. Kappa opioid receptors are implicated in both proliferation and inhibition of prostate cancer cell growth across in-vitro studies, with a proposed interaction with the androgen cascade. Similarly, opioid growth factor receptor is highly expressed in prostate cancer cells and repressed by androgens. Prostate cancer tissue stains more intensely for the mu opioid receptor, and patients with higher expression have poorer oncologic outcomes. Opioid agonism in vitro induces urothelial cell carcinoma proliferation, migration, and invasion, with possible additional influence from interactions with the bradykinin b2 receptor. Agonism of the mu, kappa, and delta opioid receptors induces renal cell carcinoma tumorigenesis, possibly via upregulation of survivin. Meanwhile, opioid growth factor receptor agonism has the opposite effect in renal cell carcinoma.

CONCLUSIONS: Evidence surrounding the role of opioids and their receptors in urologic malignancy are provocative and should serve as an impetus for further investigation.