A recent ASCO guideline update, prompted by data from several phase III randomized controlled trials, summarizes the evidence supporting the best initial treatment options for the management of noncastrate advanced, recurrent, or metastatic prostate cancer. The hope is that the guideline will help build consensus across all available treatment options and reduce variability in practice patterns.
The guideline—“Initial Management of Noncastrate Advanced, Recurrent or Metastatic Prostate Cancer: ASCO Guideline Update”—was published online ahead of print in the Journal of Clinical Oncology on January 26, 2021.1
“As you might imagine, it took quite some time to gather and review 13 years of literature for each of the study questions from the original 2007 guideline,” said Katherine S. Virgo, PhD, MBA, FASCO, oncology researcher with Emory University and Co-Chair of the guideline’s expert panel. “In the interim, a sufficient number of [randomized controlled trials] reached completion to also inform recommendations regarding the use of newer therapies—such as docetaxel, abiraterone, enzalutamide, and apalutamide—in combination with androgen-deprivation therapy as initial therapy for men with metastatic disease. This guideline thereby also updates another existing ASCO guideline from Morris et al in 2018,2 which previously only provided guidance on the use of docetaxel and abiraterone for men with metastatic disease.”
Katherine S. Virgo, PhD, MBA, FASCO
New Directions in Metastatic Noncastrate Prostate Cancer
The guideline update gives new directions about the use of docetaxel, abiraterone, enzalutamide, and apalutamide—each, when administered with androgen-deprivation therapy, representing four separate standards of care for metastatic noncastrate prostate cancer. “The use of any of these agents in any particular combination or in any particular series cannot yet be recommended,” Dr. Virgo said. “However, we were able to make a recommendation for each agent individually.”
Specifically, the expert panel recommended that men with metastatic noncastrate prostate cancer and high-volume disease who are candidates for chemotherapy should be offered docetaxel as an adjunct to androgen-deprivation therapy. For men with high-risk, de novo metastatic noncastrate prostate cancer, the panel recommended abiraterone in addition to androgen-deprivation therapy. For men with low-risk disease, the panel noted the relatively lower strength of evidence compared with the evidence for men with high-risk disease.
Lastly, regarding enzalutamide and apalutamide, the guideline states that men with metastatic noncastrate prostate cancer—including both men with de novo metastatic disease and those who have received prior therapies (eg, radical prostatectomy)—should be offered either of these medications along with androgen-deprivation therapy.
Additional Research Needed
In some instances, a lack of robust evidence meant the expert panel was unable to make a recommendation either against or in support of a given therapy. For instance, the guideline was unable to comment on the use of enzalutamide plus leuprolide for men with high-risk, nonmetastatic prostate cancer progressing after radical prostatectomy, or radiotherapy, or both; it is currently unclear whether this combined treatment improves metastasis-free survival compared with enzalutamide monotherapy or placebo.
The expert panel was also unable to make a recommendation regarding the benefit of early vs delayed androgen-deprivation therapy for patients with prostate-specific antigen relapse after local treatment. Although existing studies suggest a potential overall survival benefit, additional research is needed, given that currently available studies are underpowered. However, the panel did recommend intermittent androgen-deprivation therapy for men with high-risk, biochemically recurrent, nonmetastatic prostate cancer after radical prostatectomy and/or radiotherapy, based on the noninferiority of overall survival for intermittent vs continuous androgen-deprivation therapy.
Implications for Clinicans and Patients
Dr. Virgo noted that practice patterns of most clinicians based at large university medical centers likely already approximate the guidance provided in the update, at least with respect to the treatment of men with de novo metastatic high-risk or high-volume disease. “But some oncologists may be surprised by the current lack of evidence for the use of docetaxel among patients with de novo metastatic low-volume disease,” she added. “Also, the new guideline should be particularly useful for community-based clinicians who are not actively involved in clinical trial enrollment.”
Furthermore, the guideline could benefit patients directly by helping them better understand the various treatment options available to them, depending on the extent of their disease and any previous treatment they may have already received. These recommendations also highlight treatment options that should not be offered to patients with certain characteristics and hopefully assist patients with adjusting their expectations about treatment outcomes and side effects.
The guideline update includes a cost table designed to give patients and their families more specific information about the variability in price across types of treatment as well as indicates when a less costly generic equivalent is available.
Finally, the expert panel suggested oncologists counsel patients about the potential side effects associated with androgen-deprivation therapy, such as depression, dementia, stroke, myocardial infarction, deep venous thrombosis, hot flush, fatigue, and nausea, as they may significantly impact patient functioning and quality of life.
“Side effects vary by type of [androgen-deprivation therapy] as well as by age and patient comorbidities,” Dr. Virgo said. “Knowing upfront that such side effects are possible can assist patients in having more informed conversations with their physician when treatment discussions are underway.”
1. Virgo KS, Rumble RB, de Wit R, et al: Initial management of noncastrate advanced, recurrent or metastatic prostate Cancer: ASCO guideline update. J Clin Oncol. January 26, 2021 (early release online).
2. Morris MJ, Rumble RB, Basch E, et al: Optimizing anticancer therapy in metastatic non-castrate prostate cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 36:1521-1539, 2018.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, January 27, 2021. All rights reserved.