National Comprehensive Cancer Network, American Association of Clinical Urologists, and Large Urology Group Practice Association Endorse Biomarkers in Prostate Cancer
Robert Finch, MS, CGC
Accurate prediction of the natural history of prostate cancer is necessary to avoid overtreatment, which increases the morbidity rate in men and is costly to the healthcare system. Biomarkers, or molecular testing of the prostate cancer tumor tissue, can more accurately predict the aggressiveness of prostate cancer and help physicians determine who needs definitive treatment and who can safely pursue active surveillance.
Prostate cancer is the most common cancer diagnosed in men, second only to skin cancer.1 However, the gravity of a diagnosis is highly variable and difficult to predict. Some men will have more aggressive disease and should receive definitive treatments, while many others will have indolent disease and may best be followed with active surveillance. Active surveillance, which is the careful observation of patients to make sure the cancer shows no signs of becoming more aggressive, is much less expensive than definitive treatments; however, scientific literature and guidelines to help physicians make this choice don’t always agree. Historically, the decision whether to pursue treatment or active surveillance has relied solely on clinical and pathologic features, such as Gleason score, baseline prostate-specific antigen level, clinical stage, and extent of disease based on core biopsies. Clinical and pathologic features are important, but some of these features have been shown to be highly variable. The combination of these features to create nomograms, such as CAPRA (Cancer of the Prostate Risk Assessment),2 improves upon the use of these features alone, but still leaves many men with inadequate information to make a treatment decision.3
Accurate prediction of the natural history of prostate cancer is necessary to avoid overtreatment, which increases the morbidity rate in men4 and is costly to the healthcare system. Biomarkers, or molecular testing of the prostate cancer tumor tissue, can more accurately predict the aggressiveness of prostate cancer and help physicians determine who needs definitive treatment and who can safely pursue active surveillance.3
Prolaris is a biomarker test that assesses the expression levels of 31 cell cycle progression (CCP) genes, normalized by 15 housekeeper genes. CCP genes are actively expressed during cell replication and division. The higher the expression of these genes, the more quickly tumor cells may be dividing. The expression levels of CCP genes are used to generate a CCP score, which is then combined with the clinical and pathologic features to create a Combined Clinical Risk (CCR) score that refines the risk of prostate cancer mortality. The Prolaris assay was found to be highly prognostic, with the combined score being a better predictor of disease-specific mortality than standard clinical and pathologic features alone.5
Of note, Prolaris is the only biomarker for prostate cancer that has been validated in patients who have not undergone immediate treatment, because they are being conservatively managed. Once validated in this group, CCR scores are evaluated to develop a threshold that can be used to guide patient selection for active surveillance. The chosen threshold was validated in a cohort of 585 conservatively managed men with low-, intermediate-, or high-risk features and a modified cohort of 284 men with high-risk features. There were no observed deaths in men with CCR scores at or below the threshold selected in either cohort.6
With 80% of prostate cancers diagnosed at a clinically localized stage and still treated with definitive surgery before the introduction of biomarkers, Crawford et al examined the clinical utility of Prolaris.7 In a prospective study of 305 patients with newly diagnosed prostate cancer, the authors sought to evaluate the impact of Prolaris on treatment decisions. Overall, 65% of cases showed a change between intended treatment prior to the Prolaris test and treatment recommendations following the test. In 37.2% of cases, men who were planning to have radical prostatectomy changed to active surveillance. Prolaris helps to identify men who can safely pursue active surveillance, reducing the number of patients who pursue definitive treatment options and the healthcare costs associated with overtreatment.
In March of 2018, the National Comprehensive Cancer Network (NCCN) updated its Prostate Cancer Guidelines8 to support the use of biomarkers, including Prolaris, in prostate cancer tumors. The guidelines suggest that tissue-based molecular testing should be considered for low- and favorable intermediate-risk men who have a life expectancy of at least 10 years. The guidelines also suggest that germline testing should be considered for men with localized disease and a strong family history as well as men with high-risk or metastatic disease, irrespective of family history. Research suggests that up to 24.1% of men with prostate cancer may harbor germline mutations that contributed to the development of their disease9 and may have implications for the aggressiveness of the disease.10
Following the support of the NCCN, the American Association of Clinical Urologists (AACU) published a position statement with respect to genomic testing in prostate cancer.11 AACU supports the use of tissue-based molecular testing for prostate cancer to help guide treatment decisions and strongly encourages providers to take a family cancer history and offer germline genetic testing for appropriate patients to help clarify hereditary cancer risk.
Most recently, the Large Urology Group Practice Association (LUGPA) acknowledged and endorsed the AACU position statement12 andthe NCCN Guidelines, providing more direction for LUGPA providers who utilize genomic and genetic testing for men with prostate cancer. Neal D. Shore, MD, FACS, LUGPA president, said in a statement, “LUGPA and AACU are proud to represent more than 6000 American urologists who strive to provide patients with quality, personalized care. Together our organizations are sending a message to policy makers, researchers, payers, and, most importantly, patients and their families, that we are committed to applying the best and most current science to the detection, risk stratification, and appropriate treatment of prostate cancer.”12
The support of the NCCN and 2 prominent urologic professional societies represents the most direct guidance to date for practicing clinicians who treat prostate cancer on these 2 important components of risk stratification. With the utilization of a validated algorithm of clinical, pathologic and genomic variables, as well as a patient’s germline genetic information, healthcare providers are poised to provide the best care to patients with prostate cancer.
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Robert Finch, MS, CGC, is a certified genetic counselor specializing in the genetics and genomics of cancer. He currently serves as a medical science liaison at Myriad Genetic Laboratories, where he provides education and clinical support to healthcare providers treating men with prostate cancer.