Topic: Metastatic Prostate Cancer

PSA Screening in 2023

Gerald L. Andriole, Jr., reviews evidence supporting a more comprehensive family history and biomarkers in screening and treating prostate cancer. Andriole underscores the power of a well-taken family history. He suggests doctors counsel patients on their hereditary risk of prostate cancer, emphasizing the importance of one diagnosed high risk family member, to reduce the rate of mortality.

Describing the Germline Mutations in Metastatic PCa, Andriole recommends all patients with prostate cancer who have certain characteristics be encouraged to speak to their physicians about whether they may need genetic testing for an inherited mutation. When looking in detail at polygenic risk scores (GRS,) knowledge of high GRS decreased mortality rate.

Andriole highlights the Prompt Test, the direct to consumer, poly-genomic test in the US. In comparison, the UK Biobank data compares prevalence and hazard ratio to show the frequency is higher, some predict cancer aggressiveness. He expects to hear a lot about the prompt test in future.

Dr. Andriole recommends identifying patients with clinically significant PCa earlier through a lower PSA cutpoint. He suggests using image guided Micro US or MRI, or a transperineal biopsy to show potentially indicative biomarkers.

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Standard Treatments and Global Perspective

Marc B. Garnick, MD, the Gorman Brothers Professor of Medicine at Harvard Medical School and the Beth Israel Deaconess Medical Center, summarizes recent developments in nomenclature, disease states, and standard treatments for advanced prostate cancer. Using material from a chapter he wrote for ASCO-SEP with David J. Einstein, MD, Assistant Professor of Medicine at Harvard Medical School, Dr. Garnick begins by considering the new language used to describe different states of advanced prostate cancer, including non-metastatic castrate-sensitive prostate cancer (nmCSPC), non-metastatic castrate-resistant prostate cancer (nmCRPC), metastatic castrate-sensitive prostate cancer (mCSPC), and oligometastatic prostate cancer. He then discusses new standards of care for these different states, highlighting recent research indicating the benefits of using darolutamide, enzalutamide, and apalutamide in the nmCRPC setting, and explaining how to appropriately layer and sequence therapies across disease states. He briefly looks at the role of next-generation sequencing in informing the potential benefit of PARP or PD-L1 inhibitors and touches on bone considerations in mCRPC. Dr. Garnick concludes with some comments on the global inequities of prostate cancer treatment, citing data on the significant disparity in mortality-to-incidence rate of prostate cancer in high-income countries compared to low- to middle-income countries.

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Clinical Case Discussion: Metastatic Prostate Cancer and Evidence for More Precision Therapy

A. Edward Yen, MD, Assistant Professor of Medicine in the Hematology and Oncology Section at Baylor College of Medicine, introduces a metastatic prostate cancer case, and through it explores and reviews treatment options. He discusses homologous recombination and the role that it plays in DNA repair pathways, noting that 25% of patients with advanced prostate cancer have deleterious mutations in DNA damage repair genes which lead to an increased risk of prostate cancer and chance of having nodal and/or distant metastases. Dr. Yen then reviews the TRITON2 study on rucaparib in mCRPC patients with homologous recombination deficiency and the PROfound study on olaparib in mCRPC patients with homologous recombination repair alterations, both of which found a far greater response to treatment in the cohorts with the target mutations. Next, Dr. Yen discusses PARP inhibitors and their side effects, such as fatigue, nausea, pulmonary embolism, anemia, and others. Through his exploration of treatment options, Dr. Yen concludes that next-line chemotherapy is the best option for the patient given the visceral progression of their disease.

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TITAN Study Leads to FDA Approval of Apalutamide for Patients with Metastatic Castration-Sensitive Prostate Cancer

Kim N. Chi, MD, and E. David Crawford, MD, discuss the findings of the TITAN study regarding the use of apalutamide in patients with castration-sensitive prostate cancer (mCSPC) who are also undergoing androgen deprivation therapy (ADT). These findings led to the FDA approval of apalutamide for these patients. The results showed a significant reduction in radiographic progression or death and a reduction in overall risk of death, and therefore support the addition of apalutamide to ADT for a broad range of patients with mCSPC. Apalutamide was initially approved in 2018 for patients with non-metastatic castration-resistant prostate cancer.

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Sequencing of Adjuvant Therapies

Daniel P. Petrylak, MD, provides his perspective on optimal drug sequencing for castration resistant prostate cancer (CRPC) and metastatic CRPC (mCRPC). He reviews the literature regarding available and emerging immunotherapeutic, hormonal, cytotoxic, and DNA damaging treatment options and when to time each drug.

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Incorporating New PET Imaging and Theranostic Approaches into Prostate Cancer Practice | Interesting Cases

Robert R. Flavell, MD, offers an introductory overview of theranostics and advances in nuclear imaging and therapies, especially prostate-specific membrane antigen (PSMA) agents. Subsequently, he leads a panel with Susan F. Slovin, MD, PhD, E. David Crawford, MD, and Phillip J. Koo, MD in reviewing four distinct prostate cancer cases, sharing their thoughts and recommendations with regard to use of recently developed imaging agents and therapies.

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Immunotherapy 101 for the Urologist

Raoul S. Concepcion, MD, summarizes the mechanism of action behind the immune response to cancer. He also provides an update on the current and emerging immunotherapies for cancer treatment, including vaccines, checkpoint inhibitors, CAR T-cell therapies, viral vectors, and adoptive cell therapy.

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