About This Study
INTRODUCTION
INCIDENCE OF PROSTATE CANCER
According to the National Cancer Institute (NCI), approximately 191,930 men in the United States will be diagnosed with prostate cancer in 2020. This accounts for over 20% of all new cancer cases in men and makes it the most common cancer to affect men. It is estimated that approximately 1 in 9 men will be diagnosed with prostate cancer at some point during their lifetime.
Importantly, prostate cancer is actually much higher than these rates reflect. Studies of men who passed away from other causes suggest that cancers are commonly found at very high rates. A man aged 60-70 has as high as a 60% chance of having prostate cancer in the prostate; most are quite small and slow-growing. Men in their 80’s may have a 70-80% chance of having similar cancer. By contrast, about 2-3% of men in the U.S. die from prostate cancer, demonstrating that a small fraction of cancers will cause harm.
SURVIVAL RATES WITH EARLY DIAGNOSIS
With early diagnosis of prostate cancer, the 5-year survival rate exceeds 99%. Unfortunately, without screening, as prostate cancer rarely has any symptoms to indicate its presence, the first symptoms to develop are usually after spread of the disease has occurred. When such spread occurs, most commonly to bones, the five-year survival drops to 30%. It is for this reason that many experts agree on the importance of early diagnosis of the disease.
ASSESSING THE LONG-TERM CANCER RISK
Because the majority of prostate cancer cases progress slowly, many prostate cancers don’t need immediate treatment. To help doctors assess how aggressively to treat your newly diagnosed prostate cancer, they need to assess the risk. They do this by categorizing the tumors into three general risk groups based on the amount of cancer present, prostate-specific antigen (PSA) blood test results, and prostate biopsy findings. Tumors are often categorized as “low-risk”, “intermediate-risk” or “high-risk”.
TREATING LOCALIZED PROSTATE CANCER
Although localized prostate cancer has a very high chance of being cured with treatment, traditional treatments have risks of complications or side effects. Because of the range of risk of different types of cancer, treatment recommendations are tailored to the cancer risk and to the medical condition and priorities of the patient. There are three traditional approaches to treating localized prostate cancer: active surveillance, surgery and radiation therapy.
TRADITIONAL TREATMENTS
ACTIVE SURVEILLANCE
As many prostate cancers found at prostate biopsy are small and appear under the pathologist’s microscope to have features to suggest that they are slow-growing, some patients have a low risk of ever requiring treatment. Additionally, in older men or in men with medical conditions that could be adversely affected by treatment or which may limit life expectancy, prostate cancer risk during their lifetime may be small. For such tumors in which the risk of cancer complications or death is expected to be low during a man’s lifetime, active surveillance is a commonly-recommended approach. Active surveillance refers to monitoring the tumor on a regular basis (often, every 6 to 12 months or so) with digital rectal examination, PSA blood test, an Axumin® (fluciclovine F 18) PET/CT scan and/or a periodic prostate cancer biopsy — potentially in combination with a Magnetic Resonance Scan (MRI) of the prostate.
RADICAL PROSTATECTOMY
Radical prostatectomy is an operation in which the entire prostate, along with the seminal vesicle glands (which are attached to the prostate), is removed. The operation often includes removal of adjacent lymph nodes. After the prostate is removed, the bladder is reconnected to the urinary channel (urethra). In men whose tumors appear to have not spread locally, the surgeon may preserve the two sets of erectile nerves that are present along the sides of the prostate; this maneuver increases the likelihood that erections will be present after surgery. If the prostate cancer is completely confined to the prostate, the cure rate is high. For some men with larger prostate cancer, radical prostatectomy may be followed by radiation therapy. During surgery, there is a risk of bleeding, organ injury, or postoperative infection. During the period after surgery, there is a risk of impotence (problems with erections), urinary leakage (incontinence), development of narrowing in the urinary channel (stricture), or recurrence of cancer. Long-term follow-up generally requires only PSA testing as (1) PSA should be zero after all cancer is removed and (2) a detectable PSA after radical prostatectomy generally indicates cancer recurrence.
EXTERNAL BEAM RADIATION THERAPY
External beam radiation therapy is a well-established method to treat prostate cancer. Using imaging studies such as a CT scan, computer programs allow the Radiation Oncology physician to plan a series of treatments with ionizing radiation from a machine that are delivered through a large number of beams, focusing on treating just the prostate. With current technology, often using Intensity Modulated Radiation Therapy (IMRT), very high doses are delivered to the prostate with minimal dose to adjacent organs. In general, external beam radiation therapy is felt to be as effective as surgery in curing localized prostate cancer. For men who have a risk of cancer spread to the local lymph nodes, radiation can be given to the lymph nodes as well. Traditional radiation therapy requires treatments every day, Monday through Friday (with weekends off), for about eight weeks. It is also possible to give higher daily amounts of radiation to reduce the number of treatments (hypofractionated radiation therapy). Side effects can include impotence (problems with erections), urinary symptoms (difficulty emptying, burning with urination, urinary leakage), rectal or bladder irritation or bleeding, and there has been reported a small potentially increased risk of cancer of the bladder or rectum. For higher-risk prostate cancer, radiation is generally combined with medications that lower testosterone levels to improve cancer cure rates. Hormone therapy may be used for periods of 6-36 months, depending on the aggressiveness of the tumor. Side effects of hormone therapy include hot flashes, impotence, loss of sex drive, weight gain, fatigue, anemia, osteoporosis (weakening of the bone), loss of muscle mass, and other, less-common side effects.
BRACHYTHERAPY ('RADIATION SEEDS')
Brachytherapy is an alternative approach to delivery of radiation therapy that uses small radioactive pellets or “seeds” that are placed inside the prostate allowing the cancer to receive radiation “internally”. The pellets are typically placed inside the prostate using small needles and the pellets remain in the prostate permanently but become inert over time. After treatment, patients are advised to stay away from pregnant women and small children for a period of time. Side effects of brachytherapy are similar to those of external beam radiation. Unlike external beam radiation which is given without sedation or anesthesia, brachytherapy is a surgical procedure that requires anesthesia or sedation.
NANOPARTICLE THERAPY
INTRODUCTION
For patients with a “low-risk” and “intermediate-risk” localized prostate cancer, there is active research into developing new methods of treatment that may be simpler and may have reduced risk of long-term side effects compared to standard treatments. Many of these treatments are examining the possibility of ‘tumor ablation’ in which, instead of treating the entire gland for a tumor that may occupy only a small fraction of the prostate, treatment is delivered to eliminate only the cancer, preserving the prostate gland. MagForce USA is developing a new approach to treating localized prostate cancer using its nanotechnology-based thermal ablation system. This system consists primarily of two components — the NanoTherm™ Liquid and the NanoActivator® Device. Both components are investigational, meaning they have not been reviewed by the FDA for safety or effectiveness, and are undergoing clinical testing (The MagForce® Prostate Cancer Study) to evaluate these outcomes.
THE NANOTHERM™ LIQUID
The centerpiece of the MagForce thermal ablative therapy is the NanoTherm™ Liquid. It contains billions of tiny particles (nanoparticles) of iron oxide that are 500 times smaller than a red blood cell. A key property of the nanoparticles is that they act like tiny bar magnets when they are exposed to an external magnetic field. If the nanoparticles are exposed to a magnetic field that is rapidly changing, they flip back-and-forth intensely, and heat is generated. Another key property of the nanoparticles is the special silica coating that helps the nanoparticles clump together and remain inside the prostate cancer lesion after being injected. It is this property of the NanoTherm™ particles, to clump together after injection and, with magnetic activation, to heat up and potentially kill cancer cells, that is being testing in this clinical trial.
THE NANOACTIVATOR® DEVICE
After the NanoTherm™ nanoparticles are injected into a prostate cancer lesion, they need to be “activated” in order to generate the heat that is intended to kill the cancer cells. This is done using a specially designed machine built by MagForce called the NanoActivator® device. The NanoActivator® device generates a rapidly changing (or oscillating) magnetic field that causes the iron oxide nanoparticles to intensely vibrate and create heat in the tissues surrounding it. This device is similar to an MRI machine, in that it uses magnetic fields, but instead of imaging the cancer, it is designed to kill the cancer by heating the cancer cells to a level where they die. When not in an activation device, the magnetic particles remain inert within the prostate.
THE NANOTHERM™ THERAPY
The first step in the process is to examine the prostate cancer using a special type of MRI called a multi-parameteric MRI — or mpMRI for short. The imaging data from the mpMRI is downloaded into a targeting software system that shows the prostate cancer on ultrasound imaging. This then allows targeting of the cancer and instillation of the NanoTherm™ liquid. Once it is confirmed by CT scan that the NanoTherm™ Liquid has been instilled into the proper location, the patient then lies in the NanoActivator® device. The magnetic field strength is slowly increased over a period of 15 minutes and, once temperature inside the target area reaches 55 degrees Celsius, the treatment session is begun. After 60 minutes of activation, the magnetic field is turned off and the temperatures within the prostate return to normal and the treatment is complete.
