Molecular Biomarkers in Localized Prostate Cancer

Publication Date: December 12, 2019

Introduction

Prostate cancer is the most commonly diagnosed cancer in men in the United States (~174,650 in 2019), nearly 20% of all new cancers, and the second leading cause of cancer-related death (~31,620 in 2019).

At diagnosis, there is a diverse spectrum of clinical course ranging from indolent features with a negligible likelihood of morbidity or mortality to characteristics reflecting near certitude of eventual metastases and cancer-specific death.

Predicting future clinical behavior is imperfect but constitutes the foundation of physician counseling and patient management decisions.
A variety of molecular biomarkers have been developed, evaluated, and commercialized with an overarching aim to further personalize risk stratification, more comprehensively inform management decisions, and consequently improve quality of care.

Diagnosis

Commercially available molecular biomarkers (i.e., Oncotype Dx Prostate, Prolaris, Decipher, ProMark) may be offered in situations where the assay result, when considered in toto with routine clinical factors, is likely to impact management. Routine ordering of molecular biomarkers is not recommended. ( EB , I , M )
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Any additional molecular biomarkers evaluated do not have sufficient data to be clinically actionable or are not commercially available, thus should not be offered. ( EB , Ins , M )
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The Expert Panel recommends consideration of a commercially available molecular biomarker (e.g., Decipher Genomic Classifier) in situations where the assay result, when considered in toto with routine clinical factors, is likely to impact management. In the absence of prospective clinical trial data, routine use of genomic biomarkers in the post-prostatectomy setting to determine adjuvant versus salvage radiation or to initiate systemic therapies should not be offered. ( EB , I , M )
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In men with newly diagnosed prostate cancer eligible for active surveillance, both MRI and genomics intend to identify clinically significant cancers. The Expert Panel endorses their use only in situations where the result, when considered with routine clinical factors, is likely to impact management. This may include, for instance, in the initial management of men potentially eligible for active surveillance, where each of these approaches may provide clinically relevant and actionable information. These tests may provide information independent of routine clinical parameters and independent of one another. ( IC , L , W )
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Recommendation Grading

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Molecular Biomarkers in Localized Prostate Cancer

Authoring Organization

Publication Month/Year

December 12, 2019

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

To provide recommendations for use of molecular biomarkers in management of localized prostate cancer

Target Patient Population

Men with localized prostate cancer

Target Provider Population

Medical oncologists, radiation oncologists, urologists, other health care practitioners, patients, and caregivers

Inclusion Criteria

Male, Adult, Older adult

Health Care Settings

Ambulatory, Laboratory services

Intended Users

Genetics, nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening

Keywords

prostate cancer, biomarkers, prostate carcinoma, molecular testing

Source Citation

DOI: 10.1200/JCO.19.02768 Journal of Clinical Oncology - published online before print December 12, 2019

Supplemental Methodology Resources

Data Supplement

Methodology

Number of Source Documents
169
Literature Search Start Date
January 1, 2013
Literature Search End Date
January 31, 2019
Description of External Review Process
ASCO has a rigorous review process for guidelines. After the draft has been approved by the Expert Panel, the guideline is independently reviewed and approved by the Clinical Practice Guideline Oversight Committee (CPGC). Select members of the CPGC are asked to critically review the guideline prior to the next scheduled CPGC meeting. The CPGC members then present the results of their reviews to the full committee, discuss the review with the full committee, and the CPGC votes on whether to approve the guideline (with recusals from members who have relationships with affected companies). Approved ASCO Guidelines are then submitted to the Society’s journal for consideration of publication.
Description of Public Comment Process
ASCO Guidelines are available for open comment for a 2 to 3‐week period. Guideline recommendations available for open comment are posted on asco.org/open‐comment‐guidelines. Prospective reviewers must contact ASCO to request to review the draft guideline recommendations and are required to sign a non‐disclosure and confidentiality agreement before receiving the draft guideline recommendations. Reviewers must identify themselves by name and affiliation; anonymous comments will not be accepted. Guidelines staff review and summarize comments and bring relevant comments to the Expert Panel Co‐ chairs, and to the entire panel if necessary. Any changes made from the open comment process will be reviewed by the entire panel prior to CPGC approval. Comments are advisory only and ASCO is not bound to make any changes based on feedback from open comment. ASCO does not respond to reviewers or post responses to comments; however, major edits to the draft will be reflected in the open comment discussion.
Specialties Involved
Oncology, Urology, Medical Oncology, Radiation Oncology, Oncology, Oncology
Description of Systematic Review
The Protocol specifies the purpose of the guideline product, target patient population, clinical outcomes of interest, key features of the systematic literature review, and a proposed timeline for completion. ASCO staff, the Expert Panel Co‐Chairs, and possibly other panel members selected by the Co‐Chairs (the Expert Panel Steering Committee), will typically draft the protocol for full panel review. A standard protocol worksheet is used for consistency. Once the Co‐Chairs have approved a first draft of the Protocol, the Protocol will be shared with the full Expert Panel. At the discretion of the Guidelines Director, the CPGC leadership and/or the CPGC Methodology Subcommittee may review the Protocol to make suggestions for revision intended to clarify aspects of the plan for developing the guideline. These suggestions are sent to the Expert Panel Co‐Chairs. Work on the systematic literature review can proceed upon the sign‐off of the Protocol by the Expert Panel.
List of Questions
See full text
Description of Study Criteria
See supplement.
Description of Search Strategy
Upon approval of the Protocol, a systematic review of the medical literature is conducted. ASCO staff use the information entered into the Protocol, including the clinical questions, inclusion/exclusion criteria for qualified studies, search terms/phrases, and range of study dates, to perform the systematic review. Literature searches of selected databases, including The Cochrane Library and Medline (via PubMed) are performed. Working with the Expert Panel, ASCO staff complete screening of the abstracts and full text articles to determine eligibility for inclusion in the systematic review of the evidence. Unpublished data from meeting abstracts are not generally used as part of normal ASCO guideline development (“Meeting Data”). However, abstract data from reputable scientific meetings and congresses may be included on a case‐by‐case basis after review by the CPGC leadership. Expert Panels should present a rationale to support integration of abstract data into a guideline. The CPGC leadership will consider the following inclusion criteria for the unpublished scientific meeting data: 1) whether the data were independently peer reviewed in connection with a reputable scientific meeting or congress; 2) the potential clinical impact of the unpublished data; 3) the methodological quality and validity of the associated study; 3) the potential harms of not including the data; and 4) the availability of other published data to inform the guideline recommendations.
Description of Study Selection
Literature search results were reviewed and deemed appropriate for full text review by two ASCO staff reviewers in consultation with the Expert Panel Co-Chairs. Data were extracted by two staff reviewers and subsequently checked for accuracy through an audit of the data by another ASCO staff member. Disagreements were resolved through discussion and consultation with the Co-Chairs if necessary. Evidence tables are provided in the manuscript and/or in Data Supplement.
Description of Evidence Analysis Methods
ASCO guideline recommendations are crafted, in part, using the GuideLines Into DEcision Support (GLIDES) methodology. ASCO adopted a five‐step approach to carry out quality appraisal, strength of evidence ratings and strength of recommendations ratings. The ASCO approach was primarily adapted from those developed by the AHRQ,, USPSTF, and GRADE, however with the validation of the GRADE methodology, the sole use of GRADE is being evaluated by the Clinical Practice Guidelines Committee.
Description of Evidence Grading
High: High confidence that the available evidence reflects the true magnitude and direction of the net effect (i.e., balance of benefits v harms) and that further research is very unlikely to change either the magnitude or direction of this net effect. Intermediate: Moderate confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research is unlikely to alter the direction of the net effect; however, it might alter the magnitude of the net effect. Low: Low confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research may change either the magnitude and/or direction this net effect. Insufficient: Evidence is insufficient to discern the true magnitude and direction of the net effect. Further research may better inform the topic. The use of the consensus opinion of experts is reasonable to inform outcomes related to the topic.
Description of Recommendation Grading
ASCO uses a formal consensus methodology based on the modified Delphi technique in clinically important areas where there is limited evidence or a lack of high‐quality evidence to inform clinical guidance recommendations. Evidence Based: There was sufficient evidence from published studies to inform a recommendation to guide clinical practice. Formal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. Therefore, the Expert Panel used a formal consensus process to reach this recommendation, which is considered the best current guidance for practice. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). The results of the formal consensus process are summarized in the guideline and reported in the Data Supplement (see the Supporting Documents" field). Informal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. The recommendation is considered the best current guidance for practice, based on informal consensus of the Expert Panel. The Panel agreed that a formal consensus process was not necessary for reasons described in the literature review and discussion. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). No recommendation: There is insufficient evidence, confidence, or agreement to provide a recommendation to guide clinical practice at this time. The Panel deemed the available evidence as insufficient and concluded it was unlikely that a formal consensus process would achieve the level of agreement needed for a recommendation.
Description of Funding Source
ASCO provides funding for Guideline Development.
Company/Author Disclosures
ASCO Conflict of Interest Policy complies with the CMSS Code for Interactions with Companies. ASCO requires disclosure by individuals involved in drafting, reviewing, and approving guideline recommendations.
Percentage of Authors Reporting COI
100