New Guideline Issued for Managing Advanced Prostate Cancer

Three major medical organizations have released a new clinical guideline to help physicians manage advanced prostate cancer (PCa).¹

The guideline, a joint effort of the American Urological Association (AUA), American Society for Radiation Oncology (ASTRO), and Society of Urologic Oncology (SUO), provides recommendations for early evaluation and counseling as well as diagnostic workups and treatments.

The guideline, which was developed by a panel of experts, provides recommendations for men with biochemical recurrence without metastatic disease after exhaustion of local treatment options; metastatic hormone-sensitive prostate cancer (mHSPC); nonmetastatic castration-resistant prostate cancer (nmCRPC); metastatic castration-resistant prostate cancer (mCRPC); and bone health.

In an AUA news release, William Lowrance, MD, MPH, who chaired the guideline panel, noted that PCa care has been evolving rapidly in the past several years because of changes in PSA screening standards and the approval of new classes of treatment options for use in various prostate cancer disease states.² The new guideline comprises clinical recommendations based on this new evidence “and aims to further support the medical community and patients as they navigate through the various stages of this disease,” Dr Lowrance said.

The guideline panel strongly recommends that continued androgen deprivation therapy (ADT) in combination with either androgen pathway directed therapy or docetaxel chemotherapy be offered to patients with mHSPC. Androgen pathway directed therapy includes abiraterone plus prednisone, apalutamide, and enzalutamide. The panel also strongly recommends that these patients not be offered first-generation antiandrogens (such as bicalutamide or flutamide) in combination with luteinizing hormone releasing hormone (LHRH) agonists, except to block testosterone flare. Both of these recommendations are based on what the guideline panel considers grade A evidence, defined as coming from well-conducted and highly-generalizable randomized controlled trials (RCTs) or exceptionally strong observational studies with consistent findings.

To establish prognoses for men with mHSPC, the panel makes a moderate recommendation, based on grade B evidence (defined as data from RCTs with some weaknesses of procedure or generalizability or moderately strong observational studies with consistent findings), that clinicians should assess if patients with newly diagnosed mHSPC “is experiencing symptoms from metastatic disease at the time of presentation to guide discussions of prognosis and further disease management.” As clinical principles, according to the panel, clinicians should assess the extent of metastatic disease using conventional imaging in men with newly diagnosed mHSPC and obtain a baseline PSA measurement and serial PSA measurements at 3- to 6-month intervals after starting ADT and consider periodic conventional imaging. The panel defined a clinical principle “as a statement about a component of clinical care widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature.”

In addition, the panel recommends, based on expert opinion, that men with mHSPC be offered genetic counseling and germline testing, regardless of age and family history.

For men with nmCRPC, clinicians should obtain serial PSA measurements every 3 to 6 months and calculate a PSA doubling time (PSADT) starting from onset of castration resistance, a recommendation based on clinical principle. Clinicians also should assess patients for development of metastatic disease using conventional imaging at intervals of 6 to 12 months, a recommendation based on expert opinion.

Regarding treatment, the guideline panel strongly recommends, based on grade A evidence, that clinicians offer patients apalutamide, darolutamide, or enzalutamide with continued ADT to those at high risk of progressing to metastatic disease, defined as patients with a PSADT of 10 months or less.

Clinicians should assess men with mCRPC for extent of metastatic disease using conventional imaging at least annually or at intervals determined by lack of response to therapy. They should also offer patients germline testing and somatic tumor genetic testing “to identify DNA repair deficiency mutations and microsatellite instability status that may inform prognosis and counseling regarding family risk as well as potential targeted therapies.” Both of these recommendations are based on expert opinion.

The guideline strongly recommends that patients with newly diagnosed mCRPC be offered continued ADT with abiraterone plus prednisone or enzalutamide (grade A evidence) or docetaxel (grade B evidence).

The panel strongly recommends, based on grade B evidence, that clinicians offer radium-223 treatment to patients who have symptomatic bony metastases from mCRPC and without known visceral metastases.

Noting that optimal sequencing of agents in mCRPC remains an understudied area of research, the guideline panel gives a moderate recommendation, based on grade B evidence, to “consider prior treatment and consider recommending therapy with an alternative mechanism of action.”

The panel strongly recommends, based on grade B evidence, that men with mCRPC who received prior docetaxel chemotherapy and abiraterone plus prednisone or enzalutamide be offered cabazitaxel instead of an alternative androgen pathway directed therapy.

Bone Health

The also offered clinical principles with respect to bone health in men with advanced PCa. Clinicians should discuss the risk of osteoporosis associated with ADT and assess the risk of fragility fracture. They also should recommend preventative treatment for fractures and skeletal-related events (SREs), including supplemental calcium, vitamin D, smoking cessation, and weight-bearing exercise. For patients with a high fracture risk due to bone loss, clinicians should recommend preventative treatments with bisphosphates or denosumab.

In a moderate recommendation based on grade B evidence, the guideline advises clinicians to prescribe a bone-protective agent such as denosumab or zoledronic acid for men with bony metastases to prevent SREs.

“The treatment landscape of advanced prostate cancer has expanded rapidly over the past decade driven by our better understanding of the molecular underpinning of prostate cancer,” said Keyan Salari, MD, PhD, a urologic oncologist and surgeon at Massachusetts General Hospital in Boston. “The new guideline provides an important, unified resource for the medical community to help navigate this complex landscape.”

Notably, Dr Salari told Renal & Urology News, the guideline recommends germline genetic testing for all patients with metastatic hormone-sensitive or castration-resistant PCa as well as somatic tumor genetic testing in patients with mCRPC to identify DNA repair deficiency mutations and microsatellite instability status. “This new guideline reflects our growing appreciation of how the genetic makeup of a patient’s tumor can inform prognosis and treatment decisions and ultimately help us realize the potential of precision cancer medicine,” he said.

References

1. Lowrance W, Breau R, Chou R, et al. Advanced prostate cancer: AUA/ASTRO/SUO guideline.
2. American Urological Association. Leading organizations release new clinical guideline on advanced prostate cancer. American Urological Association [June 25, 2020 press release].