Background: Luteinizing hormone-releasing hormone (LHRH) agonists are the most frequently used drugs for the delivery of androgen deprivation therapy (ADT) in prostate cancer (PCa). In PCa therapy, achieving and maintaining effective testosterone (T) suppression to the levels attained with surgical castration is the cornerstone of ADT for advanced PCa. Increasing evidence suggests achieving and sustaining very low T levels at <20 ng/dL with ADT is desirable and correlates with improved disease-specific survival in patients with advanced PCa. However, T levels may rise above castrate level (<50 ng/dL) between injections, especially if a subsequent dose is delayed. If prostate-specific antigen (PSA) levels rise, it may be unclear whether this is a result of late dosing of ADT, inadequate T suppression, or disease progression to castrate-resistant PCa.
Objectives: To determine the scope and impact of late dosing of ADT in PCa patients, this study evaluated the timeliness of LHRH agonist dosing, subsequent rate of T breakthroughs above 20 ng/dL, and frequency of T and PSA tests prior to dosing.
Methods: A retrospective review of electronic medical records and associated claims data (1/1/07-6/30/16) of LHRH agonist injections (n = 85,030) evaluated the frequency of late dosing (defined as occurring after days 32, 97, 128, and 194 for 1-, 3-, 4-, and 6-month formulations, respectively), T tests >20 ng/dL, and frequency of T/PSA tests prior to dosing.
Results: Of all LHRH agonist injections, 26.9% were late: 14.4% were ≤1 week late (prior to days 40, 105, 136, and 202 for 1-, 3-, 4-, and 6-month formulations, respectively); 3.1% were between 1 and 2 weeks late; and 9.4% were >2 weeks late (on or after days 47, 112, 143, and 209 for 1-, 3-, 4-, and 6-month formulations, respectively). For late injections, 43% of T values exceeded 20 ng/dL, while only 21% exceeded this level for early/on-time injections. Of LHRH injections, 83% had a PSA value drawn prior to dosing; however, only 13% had a similarly timed T assessment.
Conclusions: Across LHRH agonists, greater than a quarter of injections were late. When LHRH agonist dosing was late, the proportion of T tests with T >20 ng/dL increased, while early/on-time dosing decreased the chance of T breakthrough. Late injections correlated with ineffective castration over 40% of the time, yet T values were not routinely assessed in many patients. Considering the clinical benefits of maintaining effective T suppression throughout the course of ADT, nurses should ensure that treatments are within approved dosing instructions, T levels are routinely monitored, and patients are prescribed treatments with proven efficacy through the dosing interval to maintain T at castrate levels. Additionally, nurses can educate patients on the importance of adherence to dosing interval and T testing.