clinical topic updates

Standards of Medical Care for Patients With Advanced Prostate Cancer

by Daniel J. George, MD

Overview

The standards of care in advanced prostate cancer reflect the importance of optimizing cancer treatments in view of their efficacy and the complications associated with these therapies. The timing, type, sequencing, and layering of treatments are central to this optimization.

Expert Commentary

Daniel J. George, MD

Professor of Medicine and Surgery
Divisions of Medical Oncology and Urology
Director, Genitourinary Oncology
Duke Cancer Institute
Duke University Medical Center
Durham, NC

“Advanced prostate cancer encompasses a wide range of disease, and we consider not only which therapies are appropriate at each stage but also the best timing for introducing these treatments for each individual patient.

Daniel J. George, MD

Our standards of care reflect the importance of optimizing cancer treatments while taking both their efficacy and their associated complications into consideration. Advanced prostate cancer encompasses a wide range of disease, and we consider not only which therapies are appropriate at each stage but also the best timing for introducing these treatments for each individual patient.

We have level 1 evidence demonstrating that, for patients with metastatic hormone-sensitive prostate cancer, intensified treatment produces longer overall survival in clinical trials. Intensified treatment includes either docetaxel or novel androgen receptor (AR)–targeted agents (ie, abiraterone acetate, enzalutamide, or apalutamide) in addition to standard androgen deprivation therapy. Yet, real-world data suggest that there may be a relative underutilization of those combinations. In the analysis we presented at the recent 2021 American Society of Clinical Oncology Annual Meeting, data spanned from 2014 to 2019, but even in 2019 (ie, 1 year after the US Food and Drug Administration approval of abiraterone in this space and 3 years after the benefits of docetaxel emerged), more than half of patients with metastatic hormone-sensitive disease did not receive intensified treatment; those who did receive intensified treatment appeared to have shorter durations of treatment than were used in the respective registration trials.

Standards of care have also been evolving in the castration-resistant disease space. Among men with metastatic castration-resistant prostate cancer who were previously treated with docetaxel in the CARD trial, improved outcomes were reported with cabazitaxel after failure of a single AR-targeted therapy, as opposed to an alternative AR-targeted therapy. Yet, this is not always standard practice today. Safety and quality-of-life data also contribute to these standards. For instance, in patients with castration-resistant disease, antiresorptive agents can decrease the risk of symptomatic skeletal-related events in the setting of AR-targeted agents, chemotherapy, and even radionuclide agents such as radium-223. Thus, bone health is an important part of our standards.

A relatively new standard of care is the genetic profiling of patients with advanced prostate cancer. We now have 2 poly (ADP-ribose) polymerase inhibitors, rucaparib and olaparib, that are approved for select patients with metastatic castration-resistant prostate cancer (ie, those who have BRCA2 or other homologous DNA repair deficits, whether germline or somatic).

Finally, although there is no optimal one-size-fits-all treatment sequence for patients with advanced disease, it is my belief that we should try to treat patients with the available therapeutic modalities while they still have a good performance status. That means stopping a therapy that is not producing a clinical benefit and switching to another therapy. It also means being proactive in explaining to patients why it may be in their best interest to try therapies that do have side effects even while they are feeling pretty good.

References

Body A, Pranavan G, Tan TH, Slobodian P. Medical management of metastatic prostate cancer. Aust Prescr. 2018;41(5):154-159. doi:10.18773/austprescr.2018.046

de Wit R, de Bono J, Sternberg CN, et al; CARD Investigators. Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer. N Engl J Med. 2019;381(26):2506-2518. doi:10.1056/NEJMoa1911206

George DJ, Agarwal N, Rider JR, et al. Real-world treatment patterns among patients diagnosed with metastatic castration-sensitive prostate cancer (mCSPC) in community oncology settings. J Clin Oncol. 2021;39(suppl 15):5074. doi:10.1200/JCO.2021.39.15_suppl.5074

Mukherji D, Youssef B, Dagher C, et al. Management of patients with high-risk and advanced prostate cancer in the Middle East: resource-stratified consensus recommendations. World J Urol. 2020;38(3):681-693. doi:10.1007/s00345-019-02872-x

Parker CC, James ND, Brawley CD, et al; Systemic Therapy for Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) Investigators. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392(10162):2353-2366. doi:10.1016/S0140-6736(18)32486-3

Sweeney CJ, Chen Y-H, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373(8):737-746. doi:10.1056/NEJMoa1503747

Teo MY, Rathkopf DE, Kantoff P. Treatment of advanced prostate cancer. Annu Rev Med. 2019;70:479-499. doi:10.1146/annurev-med-051517-011947

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. 2021;39(11):1274-1305. doi:10.1200/JCO.20.03256

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