Tag: prostate cancer treatment

Using Radiation, Radioimmunotherapy and Radioactive Isotopes such as Lutetium 177 to Treat Prostate Cancer

Radiation is a mainstay in the treatment of prostate cancer. In men with localized prostate cancer (confined to the prostate gland), using radiation can help cure the cancer. In men with advanced disease, radiation can improve survival and help to manage pain.

Radiation can be delivered a variety of different ways. For example, there are external beams that can be used to deliver radiation from an external machine into the prostate, radioactive “seeds” that can be implanted, or ways to inject special radioactive isotopes directly into the bloodstream.

In the United States (U.S.), there are older FDA-approved treatments utilizing radioactive isotopes for men with prostate cancer that has spread to the bones to decrease pain, called samarium-153 (brand name Quadramet) and strontium-89 (Metastron). More recently, a bone-targeted alpha particle called radium-223 (brand name Xofigo®) was approved because it leads to longer overall survival in men with symptomatic metastatic castration-resistant bone metastases. These bone-targeted radioisotopes have been useful because prostate cancer commonly spreads to bone. However, those drugs cannot treat other sites of tumors such as in the prostate, lymph nodes, or lung.

We are also able to use parts of the immune system as a way to deliver radioactive particles or other targeted cancer treatments to the prostate cancer. We have engineered very specific monoclonal antibodies and molecules that will bind only to PSMA, leading to the opportunity for “molecularly targeted” radiotherapy for prostate cancer. When we combine immunotherapy with monoclonal antibodies with radioactive isotopes, we call the treatment approach radioimmunotherapy. Radioimmunotherapy involves attaching a radioactive isotope (such as Lutetium 177) to a cancer-targeting antibody or small molecule that binds only to a specific cancer-related molecule on a tumor cell. This is similar to a “lock and key” scenario, where the antibody or molecule serves as a key that will only recognize a very specific lock (the cancer-related molecule). In prostate cancer, nearly all cells have a specific “lock” that lives on the surface of each cell called prostate-specific membrane antigen (PSMA).

j591_psmaFor nearly 15 years, we have been utilizing a monoclonal antibody known as J591, which is a version of a specific key that will only recognize and enter cells with the specific lock PSMA. We successfully utilized this antibody tagged with small radioactive particles to either visualize or treat prostate cancer tumors within the prostate, bone, lymph nodes, and other sites in the body. Our initial studies demonstrated safety and signaled anti-tumor efficacy. In addition, we showed that the antibody went to virtually all sites of tumors (sometimes discovering new ones) and did not target other normal organs (with the exception of the liver which helps clear the drug from the body). Subsequently, our larger studies have shown responses in larger numbers of patients. In Europe, physicians picked up on our results and Lutetium 177 (also known as Lu-177, 177-Lu or 177 Lutetium) has become a very popular radioactive particle that can be directed to prostate cancer via PSMA. It has been used to kill prostate cancer cells and treat hundreds of prostate cancer patients. This commonly-used approach uses a small molecule which recognizes PSMA to deliver Lu-177 to prostate cancer cells (termed radioligand therapy or radioimmunotherapy therapy).

Lutetium-177 PSMA therapy is associated with a good prostate cancer response and many men travel from all over the world to Europe in order to access this treatment. In the U.S. it is only available via clinical trials, and for more than 10 years, Weill Cornell Medicine and NewYork-Presbyterian have been one of the few centers in the U.S. to offer Lutetium 177 and other targeted treatments using radioactive particles.

Learn more about how this treatment works in this video:

Diagnosis Decisions: Is Active Surveillance the Right Prostate Cancer Treatment Choice for You?

jch9011We’re launching a new blog series to help provide some direction to the decision making process that typically follows a cancer diagnosis.

To kick off the series, we sat down with Dr. Jim Hu, one of our internationally-renowned urologists, to determine some of the factors that should go into the decision to pursue active surveillance as a prostate cancer treatment approach.  

A cancer diagnosis typically involves much more than just detecting the presence of cancer in the body. Additional information about the nature of the cancer and where it started and may have spread helps physicians recommend the best course of treatment, especially since depending on cancer type (very low, low, intermediate or high risk), there can be a wide ranging degree of aggressiveness.

For most types of cancers, there are different standards used to “grade” or assess this aggressiveness on a common scale. Usually this information is then used in conjunction with information about whether the cancer has already spread or metastasized to other parts of the body. It can also be used alongside other genetic and molecular information about the cancer that tells us whether this specific cancer is likely to respond to a certain treatment and the rate at which the cancer is likely to spread.

For a long time, prostate cancer has been known as an “indolent” or slow-growing cancer relative to other cancers such as pancreatic or lung cancers. The aggressiveness or rate at which it is likely to grow is measured by studying the appearance of the cancer cells under a microscope to determine the grade. For prostate cancers, we refer to this as the Gleason score. The lowest prostate cancer grade is currently Gleason 3+3=6. Grade 6 prostate cancer is thought to be non-aggressive and unlikely to spread to other places in the body.

However, there are cases when more aggressive cancer may have been hidden and then subsequently discovered. The challenge is that in 75% of cases, prostate cancer is multi-focal, meaning that it grows within several areas of the prostate. This makes it difficult to accurately stage the tumor entirely, as only one section of the cancer is being analyzed to determine its aggressiveness. As a result, the decision to pursue active surveillance or careful monitoring and watching in patients with low-grade tumors on the Gleason scale depends on several factors. These factors include a man’s overall health, life expectancy, the age of diagnosis, and personality type.

The rationale for this approach is that low-risk prostate cancer grows very slowly and some question whether it ever spreads. Therefore the majority of these cancers may not be life threatening within a 10 year time frame, so men can avoid prostate cancer therapies that may affect quality of life. For this group, active surveillance is an alternative to the over-treatment of prostate cancer and potential side effects that can come along with it For example, in men who have numerous medical conditions and a shorter life expectancy, active surveillance is a reasonable treatment option, even with Gleason 3+4=7 prostate cancer, or intermediate risk disease.

With active surveillance, it is important to be monitored regularly by a urologist who will test your PSA levels and perform digital rectal examinations of the prostate. Imaging with Magnetic Resonance Imaging (MRI) and targeted biopsy of suspicious areas should also be part of the routine to accurately assess prostate cancer severity.

Targeted biopsies use ultrasound fused to the MRI to guide the procedure, greatly increasing the accuracy and likelihood that the tissue sample is of the most suspicious section of the prostate. A guided biopsy takes approximately 10 minutes and carries a small risk of infection or bleeding (like a standard biopsy). Many academic medical centers, including Weill Cornell Medicine/NewYork-Presbyterian Hospital offer targeted biopsies, but many community practices do not. Additionally, there is a learning curve to the procedure, so the experience of the urologist is critical.

There are also biomarkers that have recently been developed to evaluate the need for a prostate biopsy. These include the 4K test and Prostate Health Index (PHI), which are blood tests that assess the likelihood that prostate cancer may be contributing to a rise in PSA level.

Additionally, for men diagnosed with low risk prostate cancer, there are new tests that assess the genetics of the tissue to determine whether more aggressive disease may have been missed on the biopsy, and present in other parts of the prostate. These assays are called Oncotype Dx, Decipher and Polaris.

We offer all of these tests at Weill Cornell and NewYork-Presbyterian, and together they paint a much more complete picture of the prostate cancer and whether it is progressing. This comprehensive, big picture is what we use to make recommendations for your overall course of prostate cancer treatment, including whether it would be a good idea to pursue active surveillance.

Weill Cornell Researchers Create Device to Collect Living Prostate Tumor Cells; Potential to Inform Development of New Drugs

Cancer metastases (spreading from the initial cancer tumor to other parts of the body) account for the majority of cancer-related deaths because of poor responses to anti-cancer therapies.

Researchers at Weill Cornell Medical College, in collaboration with engineers from Cornell University in Ithaca, NY, have created a new device that searches the blood for living, circulating tumor cells. The device allows researchers to capture and molecularly characterize circulating tumor cells (CTCs) isolated from castrate-resistant prostate cancer patients (CRPC) receiving taxane chemotherapy. This new device will allow physicians to monitor drug response at the cellular level, which will potentially allow physicians to tailor prostate cancer treatments to an individual patient. The device is the first functional assay of a microtubule-targeting agent on living circulating tumor cells microfluidically extracted from patient blood.

The researchers  include Dr. Brian Kirby at Cornell University and  Dr. Paraskevi Giannakakou, Dr. Neil Bender, Dr. Scott Tagawa and Dr. David Nanus at Weill Cornell Medical College.

Background

Circulating tumor cells are prostate cancer cells which have escaped from prostate tumors (from the prostate, bone, or other areas) and are circulating in blood.  The FDA has cleared a specific type of test to enumerate (or count) the number of these cells in a tube of blood, called the CellSearch test.  The advantage of this test is that it has been well studied at many centers and has been validated to yield prognostic information.  However, this test is not very sensitive; men with metastatic prostate cancer may have no detectable cells.  In addition, this test is not specific to prostate cancer – the same test also picks up different cells (it is also cleared for breast and colon cancer).

The New Device

The collaborating researchers at Weill Cornell and Cornell University developed a new test called the “Geometrically Enhanced Differential Immunocapture” device. The device has been optimized based upon flow and size characteristics of prostate cancer cells.  Importantly, the device uses additional technology developed at Weill Cornell, a monoclonal antibody against Prostate Specific Membrane Antigen (PSMA).  The anti-PSMA antibody called J591, developed by Dr. Neil Bander in the Weill Cornell Department of Urology,  specifically recognizes the PSMA protein which is present on the surface of virtually all prostate cancer cells.  The combined technology has allowed Weill Cornell researchers to collect and analyze more prostate cancer cells than the standard device.

In addition to prognostic information, it is hoped that the capture and analysis of CTCs may serve as a type of “liquid biopsy” to allow researchers to gain information about a patient’s tumor.  Initial work has led to promising results in the ability to predict future responses to chemotherapy based upon a blood test prior to the drug or after only 1 dose.

The authors write, “these measurements constitute the first functional assays of drug-target engagement in living circulating tumor cells and therefore have the potential to enable longitudinal monitoring of target response and inform the development of new anticancer agents.”

Click here to read the published research paper.