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:

Best of ASCO 2016: Prostate Cancer Treatment Updates

Beltran_HeadshotLast weekend, Dr. Himisha Beltran traveled to Washington, D.C. to speak at the “Best of ASCO” meeting. She hosted the session on prostate cancer and summarized some of the most important studies presented at the 2016 American Society of Clinical Oncology (ASCO) meeting in Chicago.

She also represented Weill Cornell Medicine and NewYork-Presbyterian on a panel of the nation’s leading experts. The panel answered questions regarding some of the most challenging cases in genitourinary (GU) cancer care.

What’s new in research and treatment?

For men with advanced (metastatic) prostate cancer, the class of chemotherapy that has consistently proven to improve survival is called “taxanes.”

There are two taxanes that have been FDA-approved to treat prostate cancer, docetaxel (brand name: Taxotere) and cabazitazel (brand name: Jevtana). While these drugs are similar, men whose tumors have grown despite taking one drug often respond to the other.

Much of the important research at this year’s ASCO meeting focused on some key questions related to these two treatment options:

1. What treatment dose is best to maximize response, but minimize side effects?
2. Does the order in which patients receive these treatments matter?
3. When should oncologists switch between treatments if one is not working?
4. What is the impact on quality of life?

Another hot topic was the value and cost of treatments, and the link between treatment cost and access to care, since there can be financial barriers associated with certain treatments.

Below, we’ve outlined some of the key studies and clinical takeaways for prostate cancer treatment that Dr. Beltran discussed at the Best of ASCO meeting:

Chemotherapy Updates
  • For patients with untreated metastatic prostate cancer, large studies have recently demonstrated the improved survival impact of using a combined treatment of both chemotherapy and hormonal therapy as opposed to only hormonal therapy for men with metastatic prostate cancer. A new research study examined the CHAARTED study data and evaluated the quality of life (QOL) of patients treated on the study. This research found that while the QOL was initially worse (at 3 months), there was no long-term negative impact, and QOL was better at 12 months for chemo patients relative to those who only received hormonal therapy. This has important implications for counseling patients, as some are worried about side effects. It is comforting to know that while side effects may occur, they are temporary and the longer-term benefit of cancer control leads to improved QOL in the longer term.
Radiation Updates
  • A randomized trial examined radiation therapy for treating localized prostate cancer that had not spread beyond the prostate gland in men with intermediate risk disease. This study compared the standard eight-week course of treatment with a shorter course of four weeks, called hypofractionation. The shorter course of treatment did not see any reduction in treatment response and did not increase toxicity. The results from this study in combination with two other similar studies (RTOG 0415 and ChIPP) support using hypofractionation as a new standard for men with intermediate risk prostate cancer, as it is more convenient since it requires fewer visits to complete and is potentially less costly for patients.
Genomic Updates
  • In a large multi-institutional study of nearly 700 patients (including Weill Cornell), over 11% of patients with metastatic prostate cancer had inherited mutations in DNA repair genes (such as BRCA2 or ATM). This has important family risk and treatment implications since these genes can be passed down through the family tree and are not only linked with prostate cancer, but other cancer risk, as well. This is practice changing and supports genetic counseling and testing for all men with metastatic prostate cancer. In addition, research is ongoing to utilize drugs that may work especially well in this situation.

Stereotactic Body Radiation for Prostate Cancer

JOSEPHINE KANG, MD, PhD

Linear Accelerator Stereotactic Body Radiation
One of the linear accelerators used to deliver stereotactic body radiation therapy (SBRT) for prostate cancer at Weill Cornell Medicine/NewYork-Presbyterian Hospital

Advances in radiation therapy have enabled physicians to deliver high doses of radiation treatment with extreme precision, shortening treatment duration and reducing exposure to normal organs. For men with localized prostate cancer that hasn’t spread outside the prostate gland, this has led to radiation treatments that can be completed within just five treatments.

Initially this approach was developed on the Cyberknife Radiosurgery Platform. Cyberknife radiosurgery doesn’t actually refer to a knife or traditional “surgery,” but rather a specific type of machine that delivers radiation. Now, this five-treatment radiation for prostate cancer can be delivered using many different types of radiation machines, and as a result has undergone a bit of a name change. We now refer to this treatment as “stereotactic body radiation” or SBRT for short.

There are multiple reasons to select SBRT as treatment for prostate cancer. First, it only requires a total of five treatments over the span of one to two weeks, in contrast to standard external beam radiotherapy, which requires nine weeks of daily treatments. Additionally, prostate cancer success rates from SBRT appear comparable to other treatment modalities based on monitoring for up to nine years post-treatment. These outcomes were recently reported at the 2016 American Society of Clinical Oncology (ASCO) Genitourinary meeting.

This retrospective study reflects the longest follow up monitoring to date and demonstrates local control of the cancer, with nine-year freedom from PSA failure (rise of 0.2 ng/ml above nadir) of 95% for low-risk patients, 89% for intermediate-risk patients, and 66% for high-risk patients (determined based on National Comprehensive Cancer Network risk criteria). In the study, toxicity from radiation was low, and the dose utilized was 7.0 – 7.25 Gy per fraction. In prostate SBRT, appropriate treatment dosing is critical as higher doses have been linked with unacceptably high rates of toxicity. At the level used in the study, patients reported some bowel and urinary side effects that lasted less than one year. Overall, this study suggests that increased radiation doses and additional hormonal therapy did not improve outcomes; however, prospective studies are ongoing.

There is now enough data regarding using SBRT for prostate cancer treatment that it is an accepted treatment regimen by the American Society of Radiation Oncology (ASTRO), and the National Comprehensive Cancer Network (NCCN) guidelines. However, these guidelines explicitly state that prostate SBRT should, when elected, be performed at a center with high-volume and expertise. The physicians at Weill Cornell Medicine and NewYork-Presbyterian are very experienced in delivering SBRT for localized prostate cancer and have published many articles on this approach and when it should be used.

We will soon be opening a randomized study looking at prostate SBRT in conjunction with rectal spacer versus endorectal balloon in an ongoing effort to refine our treatments. The rectal spacer is a gel, placed between the prostate and rectum. By displacing the rectum from the prostate, it reduces exposure of the rectal wall to radiation. The spacer degrades over a period of three months and has been shown to reduce toxicity in patients undergoing standard external beam radiation therapy. We hypothesize that there will be similar toxicity reduction after SBRT. An endorectal balloon is another way to reduce overall rectal wall dose, by pushing the posterior rectal wall away from the prostate during radiation treatment.

As data for prostate SBRT continues to mature, more individuals with low- and intermediate-risk prostate cancer will likely opt for this convenient and efficacious form of radiation over more protracted courses.

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