AUA 2021: Practical Clinical Applications for AR Inhibitor Therapy

( To close the plenary session entitled “Advances in Prostate Cancer: Androgen Deprivation Therapy Across the Disease Continuum” held in conjunction with the American Urologic Association Annual Meeting this evening, Dr. Dan Lin hosted a discussion of pertinent clinical questions along with Dr. Alicia Morgans and Dr. David Penson. In this session, Dr. Lin had laid out the landscape of nmCRPC and mCSPC while Drs. Penson and Morgans highlighted novel treatment approaches for each of these disease states, respectively.

Based on audience feedback and questions, Dr. Lin first posed the question of how we should consider and manage bone health, in particular considering the patient who has low bone mineral density but we feel needs androgen deprivation. In responding, Dr. Penson first commented that we must be aware and attuned to this issue. To understand the patient’s risk, we must perform bone densitometry (DEXA scan) and consider algorithms (such as the FRAX calculator) to quantify their risk of fracture. Beginning then with more general approaches, Dr. Penson emphasized the importance of supplemental vitamin D and calcium, along with weight-bearing exercise and smoking cessation. In addition to the bone health benefits of exercise, he also highlighted the beneficial effects on quality of life and mental health.

For those who require further therapy, denosumab and zoledronic acid are used. Dr. Penson emphasized that denosumab is relatively easily administered in a urologist’s office while zoledronic acid requires an infusion. Additionally, he pointed out that oral bisphosphonates could be considered. Further, for patients starting ADT, he stressed the importance of DEXA imaging at 1 year following the initiation of therapy to identify adverse changes.

Dr. Lin then asked how we may manage treatment intensification for patients who have significant diabetes or hypertension. Dr. Morgans highlighted the importance of collaborative care for these patients, including primary care, endocrine, cardiology, and cardio-oncology. Further, she emphasized that, based on the pivotal trials leading to the approval of these agents, there is a one to four-month ADT lead-in prior to initiating the combination therapy. Thus, this represents a window for medical optimization before introducing these oral agents.

While the presence of severe or brittle diabetes, may necessitate avoiding abiraterone and prednisone, she emphasized that this is rare and it is often possible to manage diabetic patients on prednisone 5mg once daily without significant adverse effects on their blood sugar levels.

In the context of hypertension, Dr. Morgans highlighted the opportunity of the ADT lead-in period for collaboration with primary care or cardiology to optimize blood pressure control. Further, she noted that in her experience, most patients are motivated by knowing that a life-prolonging treatment is available but requires blood pressure management prior to its safe initiation.

Dr. Lin then asked about the role of GnRH antagonists in combination therapy. While the pivotal trials in both nmCRPC and mCSPC have included a GnRH agonist backbone in both the control and intervention arms, both Dr. Morgans and Dr. Penson suggested that continuing on GnRH antagonists if patients are stable and tolerating these well is reasonable. This is particularly relevant if the antagonist had been chosen for a potential cardiovascular benefit.

Finally, Dr. Lin considered the question of imaging. As highlighted in Dr. Penson’s talk in this session, nmCRPC is a disease state defined based on the insensitivity of conventional imaging. Thus, the use of next-generation imaging is likely to render most of these patient metastatic. How then, Dr. Lin asked, should we treat the. Dr. Morgans emphasized data demonstrating that nearly all patients meeting criteria for the SPARTAN trial have evidence of metastasis on PSMA PET-CT. This, in her mind, supports routine treatment intensification in this patient population. In the castration-sensitive biochemically recurrent disease space, Dr. Penson highlighted that we have little evidence to guide us. However, based on his gestalt, he felt that clinical instincts will lead to treatment intensification on the basis of these next-generation imaging results. As a result, these patients are likely to receive therapies as if they were metastatic.

Presented by: Dan Lin, MD, Chief of Urologic Oncology at the University of Washington's Department of Urology David Penson, Vanderbilt University Medical Center 

Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2021 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 – Mon, Sep 13, 2021.