NCCN Guidelines for Treatment of Localized Prostate Cancer
Kelvin A. Moses, MD, PhD, FACS, discusses updates to the National Comprehensive Cancer Network (NCCN) guidelines for localized prostate cancer treatment.
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Topic: Non-Metastatic Castration-Resistant Prostate Cancer
PCa Commentary | Volume 171 – November 2022
This Commentary explores treatment regimens combining enzalutamide, apalutamide, or darolutamide with androgen deprivation for nmCRPC.
Read MoreStandard 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.
Read MoreNon-Metastatic CRPC: Finding Advanced Disease with Next Gen Imaging Matters
Gerald L. Andriole, Jr., MD, the Robert K. Royce Distinguished Professor and Chief of Urologic Surgery at Barnes-Jewish Hospital, the Siteman Cancer Center, and Washington University School of Medicine in St. Louis, Missouri, defines non-metastatic castration-resistant prostate cancer (nmCRPC) as having rising PSA measurements on three consecutive measurements with a PSA of greater than two. He also defines next-generation imaging as PET scans. He discusses FACBC scans and PSMA-based PET scans, as well as the history and treatment of nmCRPC. Dr. Andriole reviews the SABR-COMET study, the STOMP trial, and the ORIOLE study. He concludes that next-generation imaging is necessary for patients with nmCRPC, that metastasis-directed therapy shows benefits, and that larger and longer trials are warranted.
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New Prescribing Information on Survival Benefit for Nubeqa® (Darolutamide) Approved
E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology and Professor of Urology at the University of California, San Diego, interviews Neal D. Shore, MD, Medical Director for the Carolina Urologic Research Center in Myrtle Beach, about the recent FDA amendment to the package insert for NUBEQA®, or darolutamide. The amendment includes new information for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) from the ARAMIS trial on overall survival and other endpoint data, including time to pain progression and time to the requirement for cytotoxic chemotherapy. Drs. Crawford and Shore discuss how the recent data demonstrating darolutamide’s overall survival benefit validates the previous use of metastasis-free survival as a surrogate for value. They also talk about the value of darolutamide for patients with nmCRPC who may not see much benefit to taking another medication. Drs. Crawford and Shore conclude by considering darolutamide’s future, mentioning the ARASENS trial looking at darolutamide’s benefits for patients with metastatic hormone-sensitive prostate cancer and discussing potential new research into darolutamide in the mCRPC space.
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Challenging Cases in Advanced Prostate Cancer: nmCRPC
R. Jonathan Henderson, MD, a urologist with Regional Urology, LLC, discusses an unusual case of non-metastatic castration-resistant prostate cancer (nmCRPC) with a panel featuring Laurence Klotz, MD, FRCSC, Daisaku Hirano, MD, and Michael S. Cookson, MD. The case in question involves an asymptomatic patient in his 70s who was successfully treated for localized prostate cancer and then, ten years later, was treated with cryotherapy for recurrent cancer, after which point cancer stopped appearing in imaging, but the patient’s PSA rapidly rose even as he was treated with abiraterone. Drs. Klotz, Hirano, and Cookson discuss whether it is appropriate to give such treatments to a persistently asymptomatic patient and note that his high PSA could be a response to abiraterone. They also consider the possibility that advanced imaging techniques like PSMA-PET would reveal that the man does have metastases and ponder which of the approved treatments for nmCRPC might suit this patient best.
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PROfound Trial Shows Increased rPFS in mCRPC Patients with BRCA1, BRCA2, and ATM Mutations
Maha H. Hussain, MD, FACP, FASCO, and Celestia S. Higano, MD, discuss the PROfound Trial, which demonstrated increased radiographic progression-free survival (rPFS) with the use of olaparib for mCRPC patients displaying the genetic mutations BRCA1, BRCA2, and ATM. Dr. Hussain outlines previous research of genetic mutations in mCRPC that led to this study, the study design and rationale of using two cohorts with specific mutations (BRCA1, BRCA2, and ATM) and non-specific mutations (other genetic alterations), and results that demonstrate promise for gene-targeted therapies in the future.
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Response to Apalutamide Among Patients With Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC) From SPARTAN by DECIPHER Genomic Classifier Score
Fred Saad, MD, FRCS, presents findings from an exploratory analysis he led and presented at the American Urological Association’s 2019 Annual Meeting. The study evaluated the association between DECIPHER genomic classifier (GC) score and metastasis-free survival following apalutamide treatment in nonmetastatic castrate-resistant prostate cancer (nmCRPC) patients included in the SPARTAN study.
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Navigating the M0 Space
E. David Crawford, MD, reviews the historical developments in androgen deprivation therapy (ADT) for prostate cancer and the emergence of the non-metastatic castration-resistant, or M0, prostate cancer. He then describes future directions for treatment options for these patients with a focus on androgen pathway inhibitors.
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Navigating the M0 Space- Results of RADAR III
Neal D. Shore, MD, reviews the recently-published guidelines focused on next generation imaging for early detection of disease progression in M0 prostate cancer in the Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence III (RADAR III). He also reviews the goals and conclusions from RADAR I and II.
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Immunotherapy for Castration Resistant Prostate Cancer
Daniel P. Petrylak, MD, provides a brief update on data regarding sipuleucel-T for castration resistant prostate cancer (CRPC), as well as pembrolizumab for microsatellite instability (MSI) -high metastatic prostate cancer patients.
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The Role of Targeting DNA Repair Mutations in Advanced Prostate Cancer with PARP Inhibitors
Daniel P. Petrylak, MD, provides a brief update on clinical trials evaluating therapies that target DNA repair mutations in castration resistant prostate cancer (CRPC) patients, including poly (ADP-ribose) polymerase (PARP) inhibitors, agents that exploit hypoxia-inducing BRCAness, and next generation anti-androgens.
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