CAB – Combined Androgen Blockade

Since my therapy has entered a new phase, incorporating 'Combined Androgen Blockade' (CAB) and Radiation Therapy, I thought a review of Hormone Therapy (HT) was necessary. In what follows you will see how HT and Anti-Androgen Therapy combine to become CAB. In a further post, we will look at the combination of CAB and IMRT with 'gold seed markers'.

The male sex hormone testosterone feeds the growth of prostate cells and prostate cancer. Male hormones are called androgens. Prostate cancer hormone therapy works by ablating or depriving testosterone in the body. With no hormone to fuel their growth, the cells stop growing. Hormone therapy does not provide a cure; the prostate cancer does not “starve” to death, but for a time the spread of the disease can be slowed or even halted.

Hormone therapy is most versatile of the postate cancer treatments. the ablation and deprivation of testosterone can be used as adjuvant therapy, neoadjuvant therapy, or monotherapy for either primary or salavage treatment. Adjuvant and neoadjuvant hormone therapy is more common for primary treatment. Androgen ablation and deprivation monotherapy is more common during salvage treatment.

During primary therapy, hormone therapy is given to shrink the volume of the prostate gland and tumor. Eventually, the prostate cells become resistant to the androgen deprivation therapy and begin to grow again. When prostate cells become resistant, the next steps are either to stop hormone therapy to see if the reintroduction of testosterone can slow the growth, or chemotherapy.

The testicles produce 90 percent to 95 percent of the body’s testosterone. The adrenal glands produce the remaining 5 percent to 10 percent. The two types of hormone therapies used to combat prostate cancer are castration or anti – androgens. There are two types of castration: surgical castration, also called orchiectomy or orchidectomy, and chemical castration, caused by LHRH agonists and LHRH antagonists.

LHRH agonists and antagonists are usually taken through injections or analogs which continuously release the therapy over a period of time. Castration affects production of testosterone in the testicles, while LHRH antagonists and agonists interrupt the communication in the brain when the brain is ordering the production of more testosterone.

Anti – androgens affect the hormones that are produced in the adrenal glands. They are designed to block receptors in the prostate cells and prevent androgens from feeding cancer cell growth. Anti-androgens are taken orally as a pill or tablet. The female sex hormone, estrogen is also sometimes used for hormone therapy.

When several hormone therapies are used together, it is called Combined Androgen Blockade or CAB, but may also be called total androgen blockade, combined hormonal therapy, or complete hormonal blockade. Combined androgen blockade usually consists of castration and anti – androgens. All men who undergo hormone therapy will experience side effects, however, men who undergo CAB tend to experience more side effects due to the elimination of 100 percent of the body’s testosterone.

Gold Markers Improve Radiation Treatment For Prostate Cancer Patients At Community CancerCare

Marking a prostate cancer tumor with “gold markers” has improved the efficacy of the latest radiation therapy for prostate cancer patients at the Community CancerCare Radiation Therapy centers located in the John DeQuattro Community Cancer Center in Manchester and the Phoenix Community Cancer Center in Enfield.

“By placing three gold markers into the prostate,” says Tim Boyd, a Community CancerCare and Hartford Hospital radiation oncologist, “we can see precisely where the prostate tumor is each day immediately before the patient is treated, which allows us to be as accurate as possible in developing the radiation treatment.”

Accuracy is always important in radiation treatment. Physicians must protect healthy tissue and organs from radiation that kills all cells, not just cancerous ones. An especially high degree of accuracy in radiation therapy has become even more important as radiation technology has improved. IMRT, intensity modulated radiation therapy, for example, is among the most advanced and accurate now used at the Community CancerCare centers.

With standard radiation therapy, according to Community CancerCare’s radiation oncologist Kenneth Leopold, MD, radiation fields of equal intensity converge from all directions on the tumor. With IMRT, the intensity of each field changes to follow more precisely the shape of the tumor. If the contents of a patient’s bladder or rectum moves the tumor between treatments, or if the patient, and so the tumor, moves even slightly during treatment, the dose to the tumor may be compromised and surrounding healthy tissue in the prostate, bladder and rectum may be damaged.

With the addition of gold seed markers to the therapy, computer software can use the radiation beam itself for alignment and hit the tumor, which is a non-uniform, three-dimensional target, precisely each time.

Three gold markers, each about the size of a grain of rice, are placed into the tumor in the prostate during a 10-minute procedure in the urologist’s office.

Radiation treatment’s side effects have been reduced because of IMRT’s high degree of accuracy, Dr. Leopold says, and in some cases IMRT has allowed increases in radiation dose without increasing side effects. The goal of any cancer treatment is to kill the cancer with the least healthy tissue damage and fewest side effects. Using gold markers may allow physicians to strike this balance even better.

“Prostate cancer patients who undergo gold marker implantation may experience fewer treatment side effects, including bladder and bowel problems,” Dr. Boyd says, “Because the gold markers allow us to be more precise and adjust for any change in position of the prostate internally in the pelvis, we’re treating less normal tissue, like the rectum and the bladder, which may result in reduced side effects.”

The American Cancer Society estimates that 2,900 Connecticut men will be diagnosed with prostate cancer in 2007, and 390 of them will die from the disease, but the good news, according to the National Cancer Institute, is that progress in cancer treatment (like the use of gold seed markers), along with progress in prevention and early detection, continues to reduce American’s risk of dying from cancer.

Intensity Modulated Radiation Therapy (IMRT)

More on the latest Radiation technology which I will be undergoing - Intensity Modulated Radiation Therapy (IMRT). But firstly, let's take a look at its most immediate predecessor.


(3D-CRT)

3-dimensional conformal radiotherapy (3D-CRT) combines multiple radiation treatment fields to deliver precise doses of radiation to the affected area. Tailoring each of the radiation beams to accurately focus on the patient's tumor allows coverage of the cancer while at the same time keeping radiation away from nearby healthy tissue.


(IMRT)

Intensity modulated radiation therapy (IMRT) is a form of 3D-CRT that further modifies the radiation by varying the intensity of each radiation beam. This technique allows a precise adjustment of radiation doses to the tissue within the target area. IMRT may allow doctors to direct a higher radiation dose to the affected area and keep more radiation away from nearby healthy tissue.


Important Note

Radiation therapy works by damaging the DNA within cancer cells and destroying the ability of the cancer cells to reproduce. When these damaged cells die, the body naturally eliminates them. Normal cells are also affected by radiation, but they are able to repair themselves in a way that cancer cells cannot.


How it Works

In intensity modulated radiation therapy (IMRT), very small beams, or beamlets, are aimed at a tumor from many angles. During treatment, the radiation intensity of each beamlet is controlled, and the beam shape changes hundreds of times during each treatment. As a result, the radiation dose bends around important healthy tissues in a way that is impossible with other techniques.

Because of the complexity of these motions, physicians use special high-speed computers, treatment-planning software, diagnostic imaging and patient-positioning devices to plan treatments and control the radiation dose during therapy.

For IMRT to be effective, the anatomical position of the tumor and surrounding healthy tissues must be accurately defined. Computed tomography (CT), positron emission tomography (PET) and magnetic resonance (MR) imaging provide the necessary three-dimensional anatomical information. It's also important to accurately position and immobilize the patient during treatment.

This may be done with special head frames (if the head or brain is being treated), or with advanced imaging devices such as electronic portal imaging and scanning ultrasound, which provide daily information about the location of internal organs. Some organs, such as the prostate, move due to normal daily volume changes in the bladder and rectum. Gold seeds may be placed into the prostate to track prostate movement daily and ensure more precise targeting.

A device called a multileaf collimator adjusts the size and shape of the computer-determined radiation beams. The collimator, a computer-controlled mechanical device, consists of up to 120 individually adjusted metal leaves. These leaves move across the irradiated tissue while the beam is on, blocking out some areas and filtering others to vary the beam intensity and precisely distribute the radiation dosage.

Radiation oncologists usually administer a regimen of IMRT treatments over four to eight weeks. The total dose of radiation and the number of treatments given depend on the size, location and type of cancer; the patient's general health; and other medical therapy the patient is receiving.

As can be seen in the following image, IMRT permits the delivery of a high dose of radiation to the cancer while minimizing dose to other sensitive organs. Here multiple beams are all focused on the prostate. Each of these beams has a number of sub-beams or segments, and the intensity of each segment is varied according to the treatment plan.

The image below shows an IMRT plan for treating prostate cancer. The area in red is the prostate gland; the area in blue, the rectum. IMRT focuses high doses of radiation on the prostate while keeping the dose to the rectum at a minimum.

Transrectal Prostate Fiducial Marker Gold Seed Insertion with Ultrasound

For those who are interested in the preparation that leads to the insertion of the gold seeds, I have included the following.


How it Works

Transrectal prostate fiducial marker gold seed insertion with ultrasound guidance is a method of inserting small gold seeds into the prostate gland using a needle inserted via the rectum/back passage. Three seeds are inserted using a 17G needle and the use of an ultrasound to guide the surgeon to the correct region.

The Radiologist performing the procedure specialises in Prostate procedures, assisted by nursing staff and ultrasound technologists.


Time

The procedure will take about 30 minutes to perform but we will want to observe you following the procedure for 1 hour or so if you are an outpatient, so that you may be at the hospital for a least 2 hours - longer after sedation.


How To Prepare

Before the procedure you should have stopped any tablets or injections that may alter your blood clotting - Heparin and Clexane the day before and Warfarin for 3 days. Clopidogrel, Aspirin and most other anti-inflammatory drugs etc will need to be stopped for 10 days or more. If this has not happened or you have any questions about stopping routine medication, please see your referring doctor or ring us.

Your specialist should arrange oral antibiotics (trimethoprim [Triprim or Alprim] 300 mg at night) for the days before and following the procedure. If you have any symptoms or signs of a urinary tract infection (burning sensation when passing urine etc) please ring us.

If you wish to have strong pain relief or sedation (intramuscular or intravenous), you will need to contact us before the day of your biopsy, stay for 1 or 2 hours longer after the biopsy and have someone take you home if you are an outpatient.


What to Expect

On arrival, you will be given a laxative to empty the rectum. You should also empty your bladder at this time. You will also be given an intravenous antibiotic injection (Gentamicin 240 mg). It is necessary for you to sign a consent form to confirm that you know about the risks and benefits associated with the procedure.

After you are taken to the Ultrasound room your Prostate gland will be clinically examined (as has already been performed by your doctor). The ultrasound probe will then be inserted into your rectum and pictures taken of your prostate gland. Immediately following this, the 3 gold seeds will be inserted. This will be uncomfortable, but is not usually unduly painful. It is very important to stay still. Please do not hesitate to ask us to stop at any point if you do not want us to continue.

Following the ultrasound guided seed placement, plain x-rays of your pelvis will also be obtained.


Side Effects

One of the advantages of performing the procedure under ultrasound guidance is to decrease the risk of damage to adjacent organs; however side effects and complications may still occur from this procedure.

For a day or so following the procedure you may notice MINOR pelvic discomfort or pain. MINOR blood staining of your urine/bowel motions may last for up to a week or so.

For a month or so following the procedure, you may notice blood staining in your ejaculate.


Possible Complications

If any of the following main complications develop:

• Severe infection (symptoms include feeling generally unwell, raised temperature, shivers etc most commonly manifested in the first 24-72 hours.)


• Urinary Retention (inability to pass urine for 8 hours or more.


• Profuse bleeding from the rectum or penis.

Contact your referring specialist IMMEDIATELY and proceed to the Emergency Department.

Infection develops in approximately 1 in 100 procedures and urinary retention/profuse bleeding occur in less than 1 in 1000. Spread of infection to the spine and death from infection is rare.


Afterwards

Following the procedure, for your comfort it is recommended that you should rest for the next 24 hours although you may undertake light activity. You may have minor discomfort over the 24 hours for which you may take paracetamol, but NOT aspirin. Depending on what sort of work you do, you may need to arrange a day’s sick leave.

Prostate 'Gold Seeds' Improve Radiation Treatment

Today I attended my first appointment with the newest member of my healthcare team - 'Dr T' - my Radiation Oncologist. The appointment lasted for over 90 minutes - I finally got to ask, and have answered, ALL of my questions!!

Firstly, I want to talk about the 'new' technique that I will be undergoing in terms of my radiotherapy - sometimes referred to as 'gold seed technology'.

Gold seed technology is a fairly recent innovation in Australia and is only available in a (very) limited number of places. Fortunately for me, my radiologist is one of the few 'experts' who not only possess such technology, but have become very conversant with it's usage.

Now, some history...


November 2005

A new treatment method for prostate cancer patients undergoing radiation therapy that more accurately and effectively targets the cancer while minimizing side effects is now available in Australia.

Fiducial markers, or "gold seeds," are non-radioactive markers that are placed in the prostate. Because it is natural for the prostate to move around in the pelvic cavity, depending on how much liquid a patient has consumed and other factors, it can be challenging to locate the prostate precisely during radiation therapy.

Unlike brachytherapy, which uses radioactive seeds to treat the cancer, gold seeds simply allow the prostate's location to be tracked on a daily basis using X-ray imaging to ensure treatment accuracy. Only a handful of health care organizations offer this treatment in Australia.

Previously, physicians had to leave a margin of error when locating the cancerous tissue because it was difficult to target the exact location of the prostate before the gold seed technology emerged. During this process, healthy tissue may have been exposed to radiation.

Gold seed technology allows the physician to know exactly where the prostate is at any given time. Therefore, a higher dose of radiation can be delivered to a more precise area, while minimizing exposure to nearby healthy tissues.


Gold Seeds Help Pinpoint Prostate Cancer

WCVB-TV 04.07.2006

BOSTON -- Prostate cancer is the most common cancer among American men. One in six men will be diagnosed with the disease in his lifetime.

NewsCenter 5's Heather Unruh reported Friday that treating it can be tricky -- even a slight movement of the prostate can alter the effectiveness of radiation and potentially damage healthy tissue.

Now, doctors at Mount Auburn Hospital are using new technology to pinpoint prostate cancer with the help of some very tiny but very precious metals.

A tiny gold seed is helping doctors treat Joe Crowley's prostate cancer.

"I feel good about the treatment," Crowley said.

The gold seeds are actual gold, but they are not radioactive. Instead, they serve as markers for radiologists attempting to locate and treat the often hard-to-target prostate.

"In the past, our solution was very simple. You simply enlarge the area you're treating to make sure the target is going to be fully covered by the radiation -- but in the process, we were exposing more normal tissue to the radiation and increasing the risk of injury," Mount Auburn Hospital's Dr. Anthony Abner said.

With Gold Seed technology, [a number of] seeds are placed around the prostate. Using X-ray imaging, doctors can then monitor the location of the seeds. If the seeds have moved, the prostate has moved, and they can alter the radiation accordingly.

"The benefit is that we can dramatically reduce the amount of normal tissue that's hit by the radiation. By doing so, we can actually use higher doses of radiation with better cure rates," Abner said.

The treatment is less painful and more accurate than other options, such as balloon dilation and ultrasound. But it does require almost daily monitoring, which means many trips to the radiologist -- a price Crowley said he is willing to pay.

"It's a little lengthy, but I think I have 34 treatments, but hopefully they'll go by fast and I'll pick up where I left off," Crowley said.

While it's too soon to know exactly how much Gold Seed technology is improving prostate cancer outcomes, doctors said that patients report feeling better during treatment, having fewer side effects and fewer long-term complications.


The implications for me are ...

• I can benefit from the higher doses of radiation , without the risk of 'other organ damage'!


• I can also receive a variation of the 'whole-pelvic' treatment described in an earlier post - safely.

We'll look at this in more details in my next post.