Dr Scher on the Importance of Molecular Testing in Prostate Cancer

Howard I. Scher, MD, head, Biomarker Development Program, D. Wayne Calloway Chair in Urologic Oncology, Memorial Sloan Kettering Cancer Center, discusses the evolution of molecular testing mechanisms in patients with prostate cancer and highlights the importance of making patient-centered decisions based on test results.

When oncologists test for biomarkers in patients with prostate cancer, they should understand what the presence of these biomarkers means for the patients’ prognosis and treatment options, Scher says. When the first biomarker test for prostate cancer using prostate-specific antigen (PSA) was introduced in the field, patients felt uneasy about receiving their PSA results, because these tests revealed instances of prostate cancer recurrence in some patients who had undergone surgery and were asymptomatic, Scher explains. To help patients understand the reason for their disease recurrence and guide them toward optimal treatments, oncologists need to know why patients’ PSA levels rise, Scher notes. This involved determining the rate of PSA level increases, which correlate with rapid cancer growth, according to Scher. Conversely, many patients with prostate cancer experience slow rates of PSA level increases, meaning they can live several years with their disease, Scher says.

When clinical trial investigators evaluate novel drugs, they need to ensure these agents are only tested and used in patients who need them, as cancer therapies are often associated with adverse effects that are unreasonable for patients to experience unnecessarily, Scher explains. Carefully selecting populations of patients who are eligible to receive certain therapies decreases the risk of patients experiencing therapy-related toxicities while achieving minimal clinical benefit from these treatments, Scher notes.

The treatment steps that oncologists take upon receiving biomarker test results for their patients are crucial, and these decisions should always be in the patients’ best interests, according to Scher. Now that the array of biomarker tests for patients with prostate cancer has expanded beyond PSA, oncologists should choose tests that will lead to optimal treatment options for patients, Scher concludes.

Editor's Note: Clinicians referring a patient to MSK can do so by visiting msk.org/refer, emailing referapatient@mskcc.org, or by calling 833-315-2722.

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Howard I. Scher, MD, discusses the evolution of molecular testing mechanisms in patients with prostate cancer and highlights the importance of making patient-centered decisions based on test results.

Howard I. Scher, MD, chief, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the potential that liquid biopsies will have in the treatment landscape of prostate cancer.

In prostate cancer, the numbers of mutations that clearly predict for sensitivity are fewer, Scher explains. Additionally, it is more difficult to identify the types of changes that are predictive using circulating tumor cell DNA, although there have been many technological advancements.  

Research has shown that liquid biopsies can detect overexpression or amplification of the androgen receptor, which is turning out to be a predictor of nonresponse. Now, the assays have to get to the point of establishing analytical validity, he adds. The whole concept of companion diagnostics is where the field is headed, and it is imperative to monitor the change in a tumor over time. 

Dr. Scher on Promise of Liquid Biopsies in Prostate Cancer

Howard I. Scher, MD, chief, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, discusses the genetics of patients with metastatic castration-resistant prostate cancer (mCRPC).

If researchers examine the genetics of the metastatic lesions and primary sites of prostate cancer versus a localized disease, Scher explains, the frequency and types of changes are very different from one another. If there is a focus on treating mCRPC, he says, it is imperative to study the cancer at the time and make a decision to choose an optimal treatment. This is often done via a biopsy of a metastatic lesion, he says.

The most common site of metastases in prostate cancer is the bone, where the ability to do consistent molecular profiling is quite low. The community's experience in using directed biopsies is only about 50%, and it is also an invasive procedure that can be expensive. This is a more difficult situation if patients have 10 individual metastatic lesions, as they are not biologically similar to one another.

Howard I. Scher, MD, chief, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, discusses understanding the genetics of patients with metastatic castration-resistant prostate cancer.

Dr. Scher on Predicting Sensitivity to Treatment for mCRPC

Howard I. Scher, MD, Chief of the Genitourinary Oncology Service at the Sidney Kimmel Center for Prostate and Urologic Cancers at Memorial Sloan-Kettering Cancer Center, discusses an updated analysis of the COU-AA-302 trial, which examined treatment with abiraterone acetate plus prednisone in men with metastatic castration-resistant prostate cancer (mCRPC) prior to the administration of chemotherapy.

This trial reported several important findings, Scher believes. First, he states, the trial established that a hormonal agent is capable of delaying time to progression and potentially could improve survival in men with mCRPC. Additionally, the trial established an important new endpoint for clinical trials in mCRPC through the validation of radiographic progression-free survival (rPFS).

This endpoint was established through the application of predefined assays that standardized the interpretation of bone scans. In the trial, a correlation between rPFS and overall survival was observed in a reproducible and consistent fashion. This endpoint will serve as a useful tool in future trials, Scher notes, especially for comparing agents and in trials seeking regulatory approval.

Howard I. Scher, MD, from the Memorial Sloan-Kettering Cancer Center, discusses an updated analysis of the COU-AA-302 trial, which examined treatment with abiraterone in men with mCRPC prior to the administration of chemotherapy.

Dr. Scher on Key Findings From the COU-AA-302 Trial

Howard I. Scher, MD, Chief of the Genitourinary Oncology Service at the Sidney Kimmel Center for Prostate and Urologic Cancers at Memorial Sloan-Kettering Cancer Center, discusses the impact of corticosteroids on outcomes for men with metastatic castration-resistant prostate cancer (mCRPC) receiving treatment with enzalutamide.

The administration of corticosteroids is common and appropriate in the management of symptoms for patients with prostate cancer, Scher notes. However, the impact of progression on corticosteroid efficacy has not been examined. To address this issue, a retrospective, initially unplanned, analysis of the AFFIRM trial was designed to explore the on-study impact of corticosteroid administration on outcomes.

In the phase III AFFIRM trial, 1199 men with mCRPC who had progressed on treatment with docetaxel were randomized 2:1 to receive enzalutamide or placebo. Results from the trial showed a significant improvement in median overall survival, which led to the FDA approval of the agent.

In general, patients receiving corticosteroids had more advanced disease and were generally sicker, Scher explains. To compensate for this, a multivariate analysis was performed to correct for several factors associated with worse outcomes. Following this analysis, the study found that corticosteroid administration remained a factor that correlated with worse outcomes. However, despite this, enzalutamide still provided benefit for these patients in the trial.

Scher notes that the key to this information is context. The administration of a corticosteroid by itself does not seem to have any negative effects. However, patients who are progressing on steroids seem to demonstrate a negative effect. Preliminary, Scher explains, there is evidence suggesting that in some settings corticosteroids may actually contribute to tumor growth.

View coverage from the 2013 GU Cancers Symposium

Howard I. Scher, MD, from Memorial Sloan-Kettering Cancer Center, discusses the impact of corticosteroids on outcomes for men with metastatic castration-resistant prostate cancer receiving treatment with enzalutamide.

Dr. Scher on Corticosteroids and Enzalutamide in mCRPC

Howard I. Scher, MD, chief of the Genitourinary Oncology Service at the Sidney Kimmel Center for Urologic and Prostate Cancers at Memorial Sloan-Kettering, lead author of the COU-AA-301 trial that investigated circulating tumor cells (CTC), describes using the CTC test; a blood test designed to assess the prognosis of patients with metastatic cancer.

Dr. Scher says one of the reasons they were able to use the test in the trial was because samples could be processed up to 72 hours after the blood is drawn. They got all samples from North America sent to Memorial Sloan-Kettering, but there are also several reference laboratories that can perform the test. Some hospitals that don't see a lot of patients may not want to invest in the technology on their own, but it can be sent to reference laboratories and be performed, and have the results be available.

Dr. Howard Scher from MSKCC on Using the Circulating Tumor Cells Test

Dr. Scher on Using the Circulating Tumor Cells Test

Howard I. Scher, MD, chief of the Genitourinary Oncology Service at the Sidney Kimmel Center for Urologic and Prostate Cancers at Memorial Sloan-Kettering, lead author of the COU-AA-301 trial that investigated circulating tumor cells (CTC), elaborates on the future of the CTC blood test.

Dr. Scher says the CTC blood test has a clearance as an aid to monitoring patients with breast cancer, colorectal cancer, and prostate cancer. Dr. Scher and colleagues wanted to take the test one step further and see if they could develop a biomarker panel that could be used in clinical trials in order to predict early that a drug will prolong life. That requires a test that is analytically validated and also requires a series of clinical trials no different than what's done with drugs of an exploratory phase, phase I, phase II, and phase III. In this case, it requires multiple phase III trials which will show consistent results that the biomarker that is developed is predictive of survival. When that goal is accomplished, they can then apply to the FDA for a formal qualification, which will allow that endpoint to be used in trials in place of survival.

Dr. Howard Scher from Memorial Sloan-Kettering on the Future of the Circulating Tumor Cell Test

Dr. Scher on the Future of the Circulating Tumor Cell Test

Howard I. Scher, MD, chief of the Genitourinary Oncology Service at Memorial-Sloan Kettering Cancer Center in New York, lead author of the COU-AA-301 that examined abiraterone acetate for metastatic prostate cancer and prospectively investigated circulating tumor cell (CTC) enumeration as an efficacy response biomarker of overall survival (OS).

Scher says in his practice he checks the CTC levels as an indicator of response. CTC levels can be used as a tool for monitoring a patient's response to therapy. Scher recommends using CTC levels rather than PSA testing, which can be misleading in some cases. Additionally, interpreting bone scans can be difficult, whereas measuring CTC seems to be a more accurate indicator of response.

Dr. Howard Scher from Memorial Sloan-Kettering on Circulating Tumor Cells in Prostate Cancer

Dr. Scher on Circulating Tumor Cells in Prostate Cancer

Howard I. Scher, MD, chief of the Genitourinary Oncology Service at the Sidney Kimmel Center for Urologic and Prostate Cancers at Memorial Sloan-Kettering, lead author of the COU-AA-301 trial that investigated circulating tumor cells (CTC), discusses the CTC blood test that is used to assess prognosis of patients with metastatic cancer.

Dr. Scher says that with any test a physician orders, they should first ask themselves why they are ordering the test. From patients with breast cancer, colorectal cancer and prostate cancer, Dr. Scher and colleagues have learned that if there is a large number of circulating tumor cells in the blood, the prognosis of that patient is worse than if the cells are not present or low. The CTC blood test can immediately inform a physician of a patient's prognosis. Clinical trial data shows that if CTC numbers are decreased with treatment, the patient will have a better prognosis than those whose counts do not decrease.

Dr. Howard Scher form Memorial Sloan-Kettering Cancer Center Discusses Circulating Tumor Cells

Howard I. Scher, MD

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