In men, prostate cancer has the highest incidence of any neoplasm and is the second-leading cause of cancer-related mortality. A plethora of tissue-based biomarkers are available to inform the diagnosis and prognosis for men with newly diagnosed, clinically localized prostate cancer. However, to date, no biomarker in this setting has demonstrated clinical utility, and thus evidence-based guidance has been lacking.
ASCO, in partnership with members of the European Association of Urology, American Urological Association, and College of American Pathologists, recently published a set of recommendations in the Journal of Clinical Oncology1 to address this issue and to provide medical oncologists, radiation oncologists, urologists, other health-care practitioners, patients, and caregivers with a framework for prostate cancer management decisions.
Parsing the Evidence
Scott E. Eggener, MD
These recommendations comprise the first formal organizational guideline for molecular biomarkers in prostate cancer. “A number of commercially available, tissue-based prostate cancer genomic biomarkers have become available,” said Scott E. Eggener, MD, of the University of Chicago Medicine, who co-chaired the guideline committee. “Because there are a spectrum of indications, potential impacts, and remaining uncertainties, a systematic review of the literature and resultant guideline were warranted. The committee admirably compiled the available data and provided guideline statements.”
The guideline committee found that many molecular biomarkers have been developed to improve risk stratification and disease management, but few have undergone extensive validation. Although these tissue-based tests were shown to improve risk stratification when added to standard clinical parameters, the guideline recommends considering their use when the assay result (considered along with routine clinical factors) is likely to affect management. Examples include select men with high-volume, low-risk, or favorable, intermediate-risk prostate cancer considering active surveillance or men with high-risk features considered for treatment intensification.
“In reviewing all the biomarkers, we identified a few that have been tested in large cohorts, albeit in retrospective analyses but also independently validated. The ones we highlighted in the guideline may provide additional information beyond the standard clinical model for prognostication and patient selection for therapy,” said Himisha Beltran, MD, of Dana-Farber Cancer Institute, who also co-chaired the committee. “But these tests aren’t for everyone, so it’s important to understand their advantages and limitations, how to use them, and how to incorporate these data into patient discussions.”
Himisha Beltran, MD
Although testing may influence treatment selection, there is no high-level evidence that available biomarkers improve quality of life or cancer-specific outcomes. Additional biomarkers have been evaluated, but, at this time, there are not sufficient data showing them to be clinically actionable, or they are not commercially available. Thus, the guideline recommends continued investigation of tissue-based molecular biomarkers in the context of clinical trials.
More Informed Disease Management
The guideline is intended to help oncologists better target individuals who should be recommended for active surveillance, helping patients avoid unnecessary exposure to interventions, adverse effects of local or systemic therapies, and high treatment costs. Dr. Eggener noted that the committee’s findings make it clear that reflexive ordering of genomic biomarkers for all men with newly diagnosed prostate cancer is strongly discouraged.
“There are two primary clinical situations [in which] genomic biomarkers can be useful,” he explained. “First, when a patient is deciding between active surveillance or treatment—typically surgery or radiation—a genomic biomarker can be integrated with the totality of clinical and genomic information guiding that decision. Second, when a patient undergoes prostatectomy for adverse pathologic features and has an undetectable postoperative PSA [prostate-specific antigen level], a genomic biomarker can be integrated with other relevant information to inform the decision of observation vs early adjuvant radiation therapy.”
Because these genomic biomarkers are first-generation tests and because the study methodologies reviewed by the committee typically used retrospective archival tissue linked with prospectively collected outcomes, the committee members anticipate more investigation of tissue-based molecular biomarkers in the context of clinical trials. Although the prognostic and diagnostic biomarkers that are available do provide useful information to allow better patient selection for active surveillance and more intense treatment for high-risk patients, there is a strong need to identify biomarkers that are more useful for guiding management decisions.
This field is changing rapidly, and additional biomarkers in prostate cancer are being investigated and brought to market. This means that oncologists will continue to have many tools from which to choose, underscoring the importance of provider education.
“Guidelines improve clinician confidence, and there are many considerations to balance when deciding how to use the biomarkers or not use them. This guideline will help with implementation in that it will improve education and clinician and patient understanding of the nuances of the data,” Dr. Beltran said. “We also hope it will encourage patients to participate in clinical research studies, as this will give us more precise risk stratification such that patients can go on to get the most appropriate therapy.”
DISCLOSURE: For full disclosures of all study authors, visit ascopubs.org.
1. Eggener SE, Rumble RB, Armstrong AJ, et al: Molecular biomarkers in localized prostate cancer: ASCO guideline. J Clin Oncol. December 12, 2019 (early release online).
Originally published in ASCO Daily News. ©American Society of Clinical Oncology. ASCO Daily News, December 18, 2019. All rights reserved.