Treatment Developments in Castration-Resistant Metastatic Prostate Cancer


Patients with prostate cancer have to be approached differently depending on the state of their metastases.

When analyzing castration-resistant metastatic prostate cancer, the goal is to provide a framework to allow optimal exposure to lifelong therapies, according to a session at the 2021 American Society of Clinical Oncology Annual Meeting.

Led by Mark T. Fleming, MD, Virginia Oncology Associates, US Oncology Research; Johann S. De Bono, FRCP, MB, MD, PhD, The Institute of Cancer Research and Royal Marsden Hospital; and Ana Aparicio, MD, The University of Texas MD Anderson Cancer Center, the session covered treatment sequences, prostate cancer, and new resistant mutational phenotypes.

Fleming mentioned how research has continued on prior therapies, metastatic sites, symptoms, androgen indifference, germline mutations, AR signaling defects, and somatic mutations, also known as PM SAGAS, on metastatic hormone-sensitive and nonmetastatic castration-resistant prostate cancer in the clinical states model. However, there is no definitive sequence of heterogenous disease based on the current treatments available.

“Only a few studies have evaluated this,” Fleming said. “And patients have to be approached differently depending on their state of metastases.”

De Bono analyzed the new tools used for prostate cancer and how times are changing constantly.

“We have an increasing complexity in treating this disease and more data to consider,” he said. “We also need to be absolutely clear that prostate cancer is not one, but many different diseases”

Further, De Bono mentioned that the key to future optimal care will be better biomarkers to guide treatment, as he feels that oncologists will need multiple kinds of tests on the same biologics in different ways. Although many more novel agents are in development, not all genomic alterations will translate to the same thing, as molecular stratification is a key part of care.

“Men are living longer than ever before with this disease,” he said. “PARP inhibitors work best, but they don’t only work in prostate cancers.”

In her discussion of new resistant mutational phenotypes, Aparicio mentioned how androgen in different biology exists, and how the existence of androgen in different subsets must be taken into account in clinical trials of prostate cancer. In addition, the prevalence of androgen indifferent biology may be increasing as a result of stronger androgen signaling inhibition.

“It’s become clear that androgen in different biology expands beyond histologic variants,” she said. “There is a lot of room for optimism, a lot of clinical trials are building on this subset, building on the chemotherapy backbone, and adding immune checkpoint therapies.”


Aparicio A, De Bono JS, Fleming MT. Beyond the Androgen Receptor: New Avengers in the Treatment of Castrate-Resistant Metastatic Cancer. Presented at: ASCO 2021 Annual Meeting. June 8, 2021. Accessed June 8, 2021.

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