Learning Objective

At the conclusion of the activity, participants will be able to:

• Discuss the 2020 AUA/ASTRO/SUO Guideline for the management of advanced prostate cancer.

Prostate cancer remains the most commonly diagnosed solid organ malignancy in men in the U.S. and stands as the second leading cause of cancer deaths in this population. Nearly 250,000 new diagnoses of prostate cancer and over 34,000 deaths are estimated in the U.S. for 2021.¹ As the diagnostic and therapeutic options available to advanced prostate cancer patients continue to rapidly evolve, clinicians are challenged to remain current with respect to the array of options available for disease prognosis and management. The increasing complexity of advanced prostate cancer treatment highlights the need for the current clinical practice guideline, developed to provide a logical basis for treatment of patients with advanced disease based on a systematic review of the highest quality published data available. The 2020 AUA Advanced Prostate Cancer Guideline expands on the Castration-Resistant Prostate Cancer (CRPC) Guideline, originally published in 2013, and now includes a number of advanced disease states, including nonmetastatic biochemically recurrent prostate cancer, metastatic hormone-sensitive prostate cancer, and nonmetastatic and metastatic CRPC. Following additional U.S. Food and Drug Administration (FDA) approvals since the 2020 publication of the guideline, the document was updated in 2021 to reflect new availabilities in the areas of androgen deprivation therapy and advanced imaging.

The Advanced Prostate Cancer Guideline explores the currently available prognostic and treatment modalities available for each disease state while acknowledging ongoing research in the field and current unmet needs. Treatments evaluated in the guideline include conventional androgen deprivation therapy alone and in combination with first and second line antiandrogens, chemotherapy, radiation therapy, surgery, radiopharmaceuticals, immunotherapy, and surveillance strategies. Outcomes of interest include overall survival, prostate cancer mortality, progression-free survival, prostate specific antigen progression-free survival, failure-free survival, metastases-free survival, time to metastases, time to progression, skeletal events, and adverse events.

Multidisciplinary Approach to Patient Care

Central to this guideline is the understanding that multimodality approaches and integration of care are critical to improving the care for men with advanced prostate cancer. Multidisciplinary clinics and the resulting multimodality treatment approaches can optimize treatment selection, maximize results, and minimize overtreatment and side effects. As the therapeutic landscape evolves to include further combinations of systemic therapies with or without local therapies, advances in imaging, and genetic testing, treatment of advanced prostate cancer increasingly requires that clinicians embrace such management approaches. Team members should include urologists, medical oncologists, and radiation oncologists at a minimum when supporting treatment decisions for advanced disease. While focusing on disease treatment, patient care must also address issues related to patient quality of life and symptom management; as such, additional specialists may also include genitourinary pathology, genetic counseling, palliative care, and holistic specialists in addition to primary care. Further, clinicians should inform patients about suitable clinical trials and encourage patients to consider participation in such trials based on eligibility and access. In appropriate patients, clinical trial options should be considered, and trial options should be discussed with patients as part of the shared decision making process.

Guideline Updates

Advanced Imaging

It is important for the practicing clinician to note that the studies underpinning this guideline’s recommendations were largely predicated upon the use of conventional imaging including computerized tomography, magnetic resonance imaging, and bone scan. As the medical evidence evolves to more consistently incorporate next generation imaging, the definition of “nonmetastatic” and “metastatic” will evolve owing to the significant differences in sensitivity to detect metastatic disease between conventional and advanced imaging modalities. The guideline further explores appropriate use of such modalities to direct the conversation on disease prognosis.

The prostate cancer community has witnessed considerable developments in the detection of disease with next generation prostate cancer imaging. Positron emission tomography (PET)-computerized tomography has emerged as a sensitive and specific imaging test to detect prostate cancer metastases, particularly among men with biochemical recurrence after primary therapy.^2,3 Multiple PET tracers have demonstrated promise in the evaluation of extent of prostate cancer including ¹⁸F-fluciclovine, ¹⁸F-sodium fluoride, ¹¹C-choline, and various tagged prostate-specific membrane antigen (PSMA) isoforms. Since the initial publication of this guideline, the FDA has approved 2 new PET agents for the management of advanced prostate cancer, ⁶⁸Ga-PSMA-11 and ¹⁸F-DCFPyl.^4,5 Both are indicated for patients with suspected prostate cancer metastasis considering surgery or radiation therapy and also indicated for patients with suspected prostate cancer recurrence based on elevated serum prostate specific antigen levels. Additional PSMA agents are currently under investigation. While there remains uncertainty about how image-directed therapies will impact oncologic outcomes, there is an emerging literature detailing the use of next generation imaging to guide management decisions in recurrent prostate cancer.^6,7

Androgen Deprivation Therapy

The use of primary androgen deprivation therapy for the management of certain advanced prostate cancer disease states has been the standard of care since its discovery in the 1940s.⁸ At the time of initial publication of this guideline, the methods for achieving castrate levels of testosterone (<50 ng/dL) were either surgical or injectable. In 2020, the FDA approved relugolix as the first oral gonadotropin-releasing hormone receptor antagonist for adult patients with advanced prostate cancer.⁹ Additional non-oral options include luteinizing hormone-releasing hormone analogues, other gonadotropin-releasing hormone antagonists, or orchiectomy. These treatments have been considered equivalent in cancer control, although they weren’t compared in large randomized controlled trials.

Unmet Needs

While dramatic recent advances have been made, many unmet needs remain in prostate cancer management. Personalized care with predictive markers for treatment selection based on tumor and host biology has not yet been achieved. There has been movement toward identification of prognostic markers and identification of molecular markers based on immunohistochemistry and use of genomic signatures, but these have yet to yield predictive results. As we move forward as a field, we need to focus on the biological make-up of tumors and how these can be better leveraged to identify treatment options for patients. Further, advanced imaging technologies using novel tracers have emerged as sensitive and specific tools to detect metastatic disease at an earlier point in the progression timeline.

Several key areas of future research need emphasis to improve clinical care and provide a path to better patient outcomes with advanced prostate cancer. Historically, the median survival for men with metastatic CRPC was less than 2 years,¹⁰ but due to several factors including standardized definitions, the impact of new therapies, and the sequencing of therapies, the median survival has now more than doubled. It is against this backdrop that the Panel provides evidence-based guidance for the management of advanced prostate cancer and looks to the future with cautious optimism.