Liquid Biopsy Shows Promise for Guiding Prostate Cancer Treatment

Microscopic image of stained cells, six blue and one red.
Summary

Liquid biopsy, which analyzes a patient’s blood sample for tumor cells or tumor DNA, is a noninvasive alternative to conventional biopsy. A new version of this test examines the appearance and genetic makeup of tumor cells and could guide treatment decisions for certain prostate cancer patients.

Highlights
  • Liquid biopsy analyzes a blood sample for tumor cell DNA.
  • A new type of liquid biopsy quickly scans a tumor cell’s appearance and genetic makeup.
  • Information from this test could guide prostate cancer treatment decisions for some prostate cancer patients.

Liquid biopsy, a new alternative to tissue biopsy, analyzes a patient’s blood for tumor cells or tumor DNA. It holds the tantalizing promise of a less invasive, more comprehensive way to deliver more-targeted therapy and to monitor response. 

In December, Memorial Sloan Kettering researchers reported that liquid biopsy can reveal essential information about how breast cancers respond to therapies.

Now a new study shows that liquid biopsy could help guide decisions on the most appropriate treatments for patients with prostate cancer.

Medical oncologist Howard Scher, Chief of MSK’s Genitourinary Oncology Service, presented these initial results today at the American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco.

We spoke with Dr. Scher about the potential of this novel approach and the prostate cancer study.

What were you trying to find in the study using this type of liquid biopsy?

Horizontal image of stained cells similar in appearance, most blue but three red.

We wanted to learn how many different types of cancer are in the individual prostate cancer patient. We analyzed circulating tumor cells (CTCs), malignant cells shed into the bloodstream by solid tumors. In patients with advanced disease, CTCs are released both from the site of the original tumor as well as from areas where the cancer has spread, or metastasized. Because of this, CTCs are good indicators of tumor heterogeneity — the diversity of the cancer cells both within the primary tumor and within different metastatic sites.

Earlier research told us that individual patients can have a range of different types of CTCs. We looked at multiple individual CTCs in a patient to find out how many different variations existed. The new liquid biopsy test uses cutting-edge technology to scan the entire landscape of CTCs that are spread out on a glass slide and analyze both their appearance and, separately, their genetic makeup. This gives us a sense of how heterogeneous, or diverse, the cell populations are.

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Why is the level of cancer cell heterogeneity important?

Horizontal image of stained cells, with many round blue cells and three elongated red cells.

Tumor cell heterogeneity can make cancers more difficult to treat. Newer therapies such as abiraterone or enzalutamide, which target androgen receptor signaling and the androgen receptor itself, can effectively shrink and control the additional spread of prostate cancer in many men. They work by blocking the effects of the hormone testosterone — an androgen — which stimulates the growth of prostate cancer cells. But not all men respond equally well to these drugs, and some don’t respond at all. In addition, the drugs often stop working as the cancer evolves and develops resistance.

Using a liquid biopsy can give you cells that are representative of multiple metastatic sites, so you have a better chance of understanding why a treatment may not be working, This contrasts with a single site biopsy, which may or may not be representative of the disease as a whole. In addition, being able to measure heterogeneity might help predict how well a patient will respond to a particular therapy.

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What was the main finding of the study?

We looked at 221 blood specimens that had been drawn from 179 patients with metastatic prostate cancer who were about to begin treatment with either abiraterone or enzalutamide or a type of chemotherapy drug called a taxane.

Knowing the level of heterogeneity of a patient's prostate cancer could be used to help select the [best] treatment.
Howard I. Scher
Howard I. Scher medical oncologist

This study found that patients with more diverse — or heterogeneous — cell populations did not respond as well or live as long after treatment with a hormone drug relative to patients whose CTCs were more homogenous.

This makes sense because the hormonal agents are more targeted, and a diverse population of cells may contain many cancer cells lacking that target. In contrast, the level of heterogeneity did not appear to affect response to chemotherapy.

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How does the blood test determine the level of heterogeneity?

The test, which was developed by Epic Sciences, involves placing a blood specimen onto a glass slide and staining it to distinguish normal blood cells from CTCs. A machine then scans the slide to analyze various features of the CTCs, including size and shape. It works like facial recognition software used at airport security. The software can quickly identify a CTC by examining these features.

Researchers can then select individual cells of interest, pick them up from the slide, and check for genetic abnormalities. By looking at variation in CTC appearance and an individual’s genetic makeup, we can assign a heterogeneity score to that patient.

The study showed that a high heterogeneity score correlated with poorer response to the hormone therapy.

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How could this technology change the treatment of prostate cancer?

Knowing the level of heterogeneity of a patient’s prostate cancer could be used to help select the treatment to which a patient is more likely to respond. For example, if a patient has a high level of heterogeneity in their CTCs, the clinician would choose chemotherapy rather than hormonal therapies — sparing the patient side effects or problems that may result from a treatment likely to be ineffective. This would provide a clear clinical benefit.

Also, unlike a tissue biopsy, blood samples are noninvasive and easily obtained at any time, so treatment adjustments could be made sooner.

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This is really groundbreaking technology. CTCs are very small in number compared with other cells in the bloodstream — approximately one cell in a billion — so being able to isolate them reliably and analyze them quickly is an important advance.

Before we can make this particular liquid biopsy part of routine practice, we first need to validate it in a clinical trial, which we are now designing to conduct through the Prostate Cancer Clinical Trials Consortium. This will give us definitive answers about how well it predicts patient outcomes. But this type of test was not even conceivable just a few years ago — the technology is evolving so quickly it’s incredible.

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This study received funding from the Prostate Cancer Foundation, MSK SPORE, and MSK Core Grant.

Comments

Information on prostate cancer for my husband..

Would like to know if a liquid prostate biopsy would be suitable for me. I have a 1.83 psa with a nodule found during dre . Thank you,

Richard Grilli

Richard, thank you for reaching out. While this technology is still new, our doctors are working in the areas of liquid biopsy or blood-based molecular diagnostics with different tests at different points in the illness. In addition, one of or physicians is working on an interesting urine test that may be relevant.

If you would like to make an appointment with a Memorial Sloan Kettering physician for a consultation, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment.

You also can read more about prostate cancer and its treatment at Memorial Sloan Kettering here:

https://www.mskcc.org/cancer-care/types/prostate

My father has CRPC. The PC has gone to his bones and possibly his lung. Drs are currently evaluating whether a lung biopsy would be safe for him. He is 74 years old and feels great. We are trying to figure out which treatment would be best for him to live a long, quality filled life. Would he be a candidate for this liquid biopsy? Or any other suggestions? Thank you so much.

Thank you for reaching out. We suggest your father consult with his medical team on his best treatment options. The liquid biopsy technology is still new and being investigated.

If you would like to make an appointment with a Memorial Sloan Kettering physician for a consultation, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment.

You also can read more about prostate cancer and its treatment at Memorial Sloan Kettering here:

https://www.mskcc.org/cancer-care/types/prostate

You mention in a Jan 15 reply that "one of or physicians is working on an interesting urine test that may be relevant." I also read in a Hopkins research pub that they are working on urine based technology to detect PCa. And, I have taken the Michigan MiPS test which correlated well with results from a biopsy. Are these three urine tests programs similar? At some point will these tests reduce or even eliminate the need for needle biopsy? Have there been any studies to quantify the the risk of needle biopsies - does puncturing tumors so they bleed into the body have any risk of metastasis?
PS I'm already a satisfied patient at MSKCC

Douglas, thank you for reaching out. We consulted with MSK physician James Eastham, who responds:

The PCA3 urine test is approved in the setting of a man with a persistently elevated PSA blood test but a previously negative prostate biopsy. It is used to help determine if the man should or should not undergo another biopsy. There are several other urine tests being investigated but none will likely replace a prostate biopsy, at least in the foreseeable future. We have no evidence that a biopsy promotes growth or spread of cancer cells.

Is liquid biopsy by epic of value in patients with newly diagnosed prostate cancer with Gleason > 6?

Cynthia, thank you for reaching out. This technology is still new, but our doctors are working in the areas of liquid biopsy or blood-based molecular diagnostics with different tests at different points in the illness.

Epic Sciences has posted information about potentially commercializing their test by 2017:

http://www.epicsciences.com/news-events/press-releases/genomic-health-a…

If you would like to make an appointment with a Memorial Sloan Kettering physician for a consultation, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment.

You also can read more about prostate cancer and its treatment at Memorial Sloan Kettering here:

https://www.mskcc.org/cancer-care/types/prostate

My husband was diagnosed with Prostate Ca in Nov. 2014 by rising PSA and 12 needle biopsy (all 12 biopsies were +). He then had DaVinci robot surgical removal of prostate gland. His margins were clear and lymph nodes negative in post-op reports. In the past years his PSA has been slowly rising and he was referred to our our local regional cancer center for further investigation and treatment with his PSA at 0.25. He had multiple scans, CT and MRI; all were negative for metastasis. They recommended 8 wks of radiation to the pelvic area, with side effects to bladder and bowel. Our concern is radiation to a vulnerable area that is assumed clear according to recent scans. What are the benefits of radiation to prostate area when no prostate is present? Are there statistics that show benefits of this targeted radiation when prostate has been removed that outweigh the risks?

Dear Margaret, unfortunately we are not able to answer individual medical questions on our blog. This is something you and your husband should discuss with his healthcare team. If he is interested in making an appointment at MSK to speak to one of our experts, the number to call is 800-525-2225. You can go to https://www.mskcc.org/experience/become-patient/appointment for more information. Thank you for your comment.

I am 76 and have had a history of prostate tumor which was treated by IRE in Germany. Post Op at six months revealed clear prostate but small tumor in the pelvic lymph gland. Also, my blood analysis has shown a significant increase in my tumor cell count. My PSA has also steadily risen from 4.0 post surgery to about 14 at present. A whole body scan and abdomen scan (MRI) done in past six months has been clear except for the pelvic node. I have also had immunotherapy with vaccine from my blood, but it hasn't curtailed my rising cell count. I would prefer to have my care in the US and wonder what you think the next step should be and which of your facilities would be best for me to be seen. I have not yet had a c-11 Pet scan. Would an appointment on line be possible? Thank you. Gary Cole

Dear Gary, we're sorry to hear you're going through this. If you would like to come to MSK from outside the US, we recommend that you contact our International Center. You can learn more about this program at https://www.mskcc.org/experience/become-patient/international-patients. The experts there will be able to speak with about what is involved in coming here from outside the US, and will also be able to talk to you about arranging a records review with one of our doctors. Thank you for your comment, and best wishes to you.

Does this liquid biopsy have any efficacy in genomic sequencing of one diagnosed with Stage IV cancer post IMRT to prostate and lymph nodes that may drive treatments if for example BRACA1/BRACA2in the use of for example PARP inhibitors or or their DNA mutations ?

Dear Edward, we sent your comment to Dr. Michael Berger, an expert in genomic testing of tumors, who responded: "We are actively working on this. Our MSK-IMPACT test isn’t yet validated or approved for clinical use on liquid biopsies, but we are doing a lot of R&D and are hoping to offer a comprehensive liquid biopsy clinical sequencing test in the near future. Currently the Molecular Diagnostics Service in the Department of Pathology does offer liquid biopsy clinical testing for certain important mutations (for instance the EGFR T790M mutation that causes drug resistance in lung cancer)." Thank you for your comment.

I am clinical geneticist in Turkey. Some oncologist are requesting some mutation, deletion , insertion and dublication such as (cancer panel) from FFPE samples
Some oncologist are requesting liquid biopsy from their patient.
If you are wiling to accept patient from Turkey. I will be very happy to froward patients from Turkey to you.

Could you send me more information about your cancer panel and price of the test
Could you send me an example of these test results?

Best Regards

Dr. Mustafa ULASLI

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