Prostate Caner - Genomics & Oncotype DX
by Dr. C.H. Weaver M.D. updated 11/2018
Genomic testing helps individualize treatment. This means that patients with more serious conditions can be identified and offered aggressive and innovative therapies that may prolong their lives, while patients who are diagnosed with a less serious condition may be spared unnecessary treatments.
A new genomic test—the Oncotype DX® Prostate Cancer Test—measures the aggressiveness of prostate cancer and may help scores of men choose between immediate treatment or active surveillance. Each year in the United States, more than 240,000 men are diagnosed with prostate cancer and more than 27,000 die of the disease. Prostate cancer is typically a disease of aging. It may persist undetected for many years without causing symptoms. In fact, most men die with prostate cancer not from prostate cancer. Approximately 20% of men will develop prostate cancer during their lifetime, yet only 3% will actually die of the disease.
The treatment of early-stage prostate cancer is controversial because thus far there is no clear proof that aggressive treatment prolongs survival of all individuals when compared with deferred treatment. Furthermore, treatment can cause lasting side effects, such as impotence and incontinence. Some men opt for a more conservative approach, called active surveillance or watchful waiting—which defers treatment until symptoms appear and/or there is evidence of progression. This approach can help some men avoid unnecessary treatment and potentially long-lasting side effects; however, until now, it wasn’t possible to predict which cancers were aggressive and required treatment and which were slow-growing and could be watched until treatment was necessary.
The Oncotype DX prostate cancer test measures the level of expression of 17 genes across four biological pathways to predict prostate cancer aggressiveness. The test results are reported as a Genomic Prostate Score (GPS) that ranges from 0 to 100 and is combined with other clinical factors to further clarify a man’s risk prior to treatment intervention. Oncotype DX GPS strongly predicted disease aggressiveness, offering information beyond currently available clinical factors, such as PSA and biopsy Gleason Score, to help physicians and their prostate cancer patients confidently choose the most appropriate treatment based on an individualized risk assessment. What’s more, the test has been validated to guide treatment decisions with the prostate needle biopsy sample—meaning low-risk patients could avoid invasive treatments such as surgery or radiation.1
Cancer is the result of genetic abnormalities that affect the function of particular genes. Genes determine the form, function, and growth patterns of cells. Those that accelerate or suppress growth are often involved in cancer. For example, many cancers have an abnormality in a gene that is responsible for stimulating cellular growth and/or the gene that normally prevents cancer is not working properly. Both of these genetic abnormalities can result in uncontrolled and excessive cellular growth, the hallmark trait of cancer. Genomic tests, or assays as they are called by scientists, are a tool for identifying the specific genes in a cancer that are abnormal or are not working properly. In essence, this is like identifying the genetic signature or fingerprint of a particular cancer.
Genomic testing is different from genetic testing. Genetic tests are typically used to determine whether a healthy individual has an inherited trait (gene) that predisposes them to developing cancer. Genomic tests evaluate the genes in a sample of diseased tissue from a patient who has already been diagnosed with cancer. In this way, genes that have mutated, or have developed abnormal functions, are identified in addition to those that may have been inherited.
Genomic testing can help doctors to:
- Determine a patient’s prognosis (potential outcome)
- Determine whether a cancer is aggressive/fast growing or slow growing
- Choose the most effective treatment for each individual cancer
- Monitor patients who are undergoing treatment to determine if the treatment is working
Monitor patients who are in remission to catch a potential disease progression early when it is more treatable
Oncotype DX Influences Breast Cancer Treatment Decisions
The Oncotype DX® breast cancer test may change treatment decisions for more than a third of women with early, estrogen receptor-positive breast cancer. These results were presented at the 2010 San Antonio Breast Cancer Symposium.
The Oncotype DX breast cancer test measures the expression of 21 genes in a sample of tumor tissue. The test generates a Recurrence Score® that provides information about the likelihood of cancer recurrence and the likelihood of chemotherapy benefit in women with early-stage, estrogen receptor-positive breast cancer.
Previous studies have indicated that use of the Oncotype DX breast cancer test can influence breast cancer treatment decisions. Test results may, for example, change the treatment recommendation from chemotherapy plus hormonal therapy to hormonal therapy alone (or vice versa).
To provide additional information about the impact of Oncotype DX on breast cancer treatment decisions, researchers combined information from seven studies that enrolled a total of 912 patients.
- Physicians who used Oncotype DX changed their treatment decisions for over one-third of patients.
- Overall, there was a 28% reduction in use of chemotherapy as a result of the test.
- 4% of women had chemotherapy added to hormonal therapy as a result of the test. These women were initially considered low risk but were reclassified as high risk based on their Recurrence Score.
These results provide additional evidence that Oncotype DX can play an important role in treatment decisions for early breast cancer.
In another study presented at the San Antonio Breast Cancer Symposium, researchers evaluated a combination of the Oncotype DX Recurrence Score and factors such as tumor size and tumor grade. The combined score did not predict chemotherapy benefit as well as the Recurrence Score alone.
Large Independent Validation Study Validates Oncotype DX Prostate Cancer Test.
Genomic Health, Inc. announced positive preliminary results from an additional independent clinical validation study conducted by the Center for Prostate Disease Research (CPDR) demonstrating that the Oncotype DX® Genomic Prostate Score (GPS) predicts multiple clinical endpoints related to disease aggressiveness in men with low- and intermediate-risk prostate cancer. This study validated the Oncotype DX prostate cancer test as a predictor of biochemical recurrence, a rise in prostate-specific antigen (PSA) following surgery, which is a measure of longer-term outcomes for aggressive disease. It also reconfirmed the test’s ability to predict adverse pathology from the biopsy, as previously demonstrated in a published validation study performed by the University of California, San Francisco (UCSF).
Additional, important endpoints of this landmark prostate cancer study include the development of metastatic disease and outcomes in African-American patients. Genomic Health and CPDR have submitted the results from this study for medical meeting presentation later this year.
“Given the need for more accurate risk stratification of men with newly diagnosed prostate cancer, our prospectively designed and rigorously conducted study provides further validation of the earlier studies at Cleveland Clinic and UCSF showing that the Oncotype DX test is an independent predictor of clinical outcomes in patients with low- and intermediate-risk disease,” said Shiv Srivastava, Ph.D., co-director of CPDR who led the evaluation of the Oncotype DX test and its utility as an independent predictor of clinical outcomes under a Cooperative Research and Development Agreement with the Uniformed Services University’s (USU) CPDR.
The CPDR is a multi-disciplinary prostate cancer research program of the Department of Surgery, USU, the Department of Defense’s federal health sciences university, and it is a collaboration with The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., a private, not-for-profit organization authorized by Congress to support medical research and education at the Uniformed Services University of the Health Sciences.
“In the past year, the growing number of physicians and patients using the Oncotype DX prostate cancer test demonstrates the value it provides to help make the most appropriate choice between immediate treatment or active surveillance,” said Phil Febbo, M.D., chief medical officer, Genomic Health. “Once presented, we believe these new results will further increase physician and patient confidence in the Oncotype DX prostate cancer test and allow more men with recently diagnosed prostate cancer to make a better informed treatment decision based upon the biology of their individual cancer.”
More than fifty percent of men diagnosed with prostate cancer have low-risk disease with less than a three percent chance of developing advanced, life-threatening disease. However, the large majority currently receive immediate invasive treatment because conventional clinical and pathological evaluations of their needle biopsies do not adequately predict whether aggressive cancer is present in the prostate at time of diagnosis.
Developed and validated in collaboration with Cleveland Clinic and UCSF, the Oncotype DX prostate cancer test addresses the unique challenges in making treatment decisions for men with clinically localized prostate cancer, by identifying patients who can consider active surveillance with greater confidence and thus avoid unnecessary treatment, as well as those men who have more aggressive disease and should consider immediate treatment.
CancerConnect News: Genomic Health, Inc.
today announced results from two studies of the Oncotype DX® prostate cancer test demonstrating its value in low- and intermediate-risk prostate cancer to enable physicians and patients to avoid over- and under-treatment of the disease. Both studies were presented, December 3, at the Society of Urologic Oncology (SUO) Annual Meeting, in Bethesda, Md.
Results from the latest clinical validation study, published in European Urology this month online*,* show that the Oncotype DX test predicts near- and longer-term outcomes in a racially diverse group of men with clinically localized prostate cancer. The analyses, conducted in collaboration with the Uniformed Services University of the Health Sciences’ Center for Prostate Disease Research (CPDR), reconfirmed the biopsy-based Oncotype DX prostate cancer test as a predictor of whether adverse pathology would be found if the prostate were removed by surgery. Additionally, for the first time, the Oncotype DX prostate cancer test was validated as a strong independent predictor of biochemical recurrence, which is a rise in PSA following surgery. Furthermore, the study, in which 20 percent of patients were African-American men, demonstrated that Oncotype DX is similarly predictive of outcomes in both Caucasian and African-American men.
“Our recently conducted survey of African-American men showed that more than 70 percent think prostate cancer is best treated immediately and that their loved ones would want them to do so,” said Thomas A. Farrington, founder and president of the Prostate Health Education Network (PHEN). “These statistics highlight a significant potential for prostate cancer over-treatment and underscore the need for more knowledge about genomic tests like Oncotype DX, which provides a scientifically precise assessment of each patient’s prostate cancer aggressiveness, and can help relieve the anxiety experienced by men and their families in making the proper treatment decision.”
“Each year, 240,000 men are diagnosed with prostate cancer in the Unites States alone. Importantly, more than half of these men have low-risk disease and can be candidates for active surveillance,” said Phil Febbo, M.D., chief medical officer, Genomic Health. “With eleven prostate cancer studies in more than 1,500 patients, Genomic Health has developed and validated the only genomic test that has met the most actionable endpoint of adverse pathology, giving physicians the confidence to put many low- to intermediate-risk patients on active surveillance, while identifying those patients who might be missed by conventional measures and could benefit from more aggressive treatment.”
Separately, the results of the first Oncotype DX prostate cancer test decision impact study showed that the use of the test significantly changed treatment recommendations. Conducted in collaboration with academic and community practices at Columbia University, Delaware Valley Urology and Orange County Urology, this prospective study in a contemporary population of men with low- or intermediate-risk disease showed that the use of the test substantially increased the number of men who would be eligible for active surveillance. Additionally, use of the test increased physician confidence in their treatment recommendations.
“Prostate cancer comes in many different forms and having confidence in your treatment recommendation and decision is crucial,” said Ketan K. Badani, M.D., lead investigator of the study and vice chairman of Urology and Robotic Operations at Mount Sinai Health System, New York. “Nearly half of prostate cancer is not aggressive and now we have more advanced tools like genomic profiling with the Oncotype DX test to determine a man’s individual risk.”
The complete results of this first Oncotype DX clinical utility study in prostate cancer have been accepted for publication in Urology Practice, an official journal of the American Urological Association.
 Hornberger J, Chien R. Meta-analysis of the decision impact of the 21-gene breast cancer Recurrence Score in clinical practice. Presented at the 33rd annual San Antonio Breast Cancer Symposium, December 8-12, 2010. Abstract P2-09-06.
 Tang G, Costantino JP, Crager M, Shak S, Wolmark N. Comparing the prediction of chemotherapy benefit in patients with node-negative, ER-positive breast cancer using the Recurrence Score and a new measure that integrates clinical and pathologic factors with the Recurrence Score. Presented at the 33rdannual San Antonio Breast Cancer Symposium, December 8-12, 2010. Abstract S4-9.
1 Cooperberg M, Simko J, Falzarano S, et al. Development and validation of the biopsy-based genomic prostate score (GPS) as a predictor of high grade or extracapsular prostate cancer to improve patient selection for active surveillance. Presented at the 2013 annual meeting of the American Urological Association. May 4-8, 2010. San Diego, CA. Abstract 2131.