According to the 2004 American Cancer Society report, approximately 230,000 cases of prostate cancer are diagnosed each year in the U.S. and about 30,000 deaths result from the disease annually. Cancer of the prostate is the second most common cause of cancer death among American men after lung cancer. Although 1 in 6 men will develop prostate cancer, only 1 in 32 will die from this disease.

There is no single direct cause of prostate cancer. However, there are several known risk factors. These include: age, race (African American men have a higher risk for unknown reasons), nationality (Asian men for example have a lower risk), diet (red meat and dairy products have been implicated), lack of exercise, and family history of prostate cancer. Several studies have suggested that some dietary supplements such as vitamin E and Lycopene can perhaps reduce the chance of developing prostate cancer.

Over the past decade, better understanding of the complex biology of prostate cancer has led to an earlier diagnosis, and advances in technology have resulted in improvements in treatments such as radiotherapy. While many areas within the field of prostate cancer remain controversial and several questions are still unanswered, standard therapies such as surgery or radiation therapy for localized disease are the benchmark against which all other novel treatment modalities must be compared to. Patients who want further reading should go to the American Cancer Society website at www.cancer.org.

The following is a brief overview of some of the important facts relating to the diagnosis and therapeutic options for patients with newly diagnosed localized prostate cancer.

What are the symptoms of prostate cancer?

For the most part, prostate cancer has no warning symptoms in its earliest stages. Older men may experience urinary frequency, but this is more likely due to enlargement of the prostate gland known as BPH (benign prostatic hypertrophy) rather than prostate cancer. Pain or bleeding is also not commonly associated with the early stages of prostate cancer.

How is prostate cancer diagnosed?

Prostate cancer is commonly suspected if there is either an elevated PSA (prostate specific antigen) level in the blood or an abnormal finding, such as a nodule, on digital rectal exam (DRE). However, the diagnosis of prostate cancer can only be confirmed by a positive biopsy.

Prostate biopsies are typically performed by a urologist on an outpatient basis. During this procedure a trans-rectal ultrasound probe is used to guide a needle gun that removes several small tissue samples from different regions of the prostate gland. In the typical patient 10 to 12 samples are taken.

Based upon microscopic examination of the biopsy samples, the pathologist assigns a tumor grade using the Gleason scoring system. The Gleason score provides a measure of the potential aggressiveness of the tumor which is an index of how fast the tumor is likely to grow. The Gleason score consists of two numbers, each one ranging between 1 (nearly normal) and 5 (most abnormal). The grades of the two most common cell patterns in the cancer are added together to form the Gleason 'sum' (e.g. 3+4 = Gleason sum of 7). The higher the Gleason sum (which ranges from 2 to 10) the more aggressive the cancer. A Gleason sum of 6 or lower is sometimes referred to as 'low grade', a sum of 7 referred to as 'intermediate grade', and a sum of 8 or higher referred to as 'high grade'.

A Gleason sum of 6 or lower is sometimes referred to as 'low grade', a sum of 7 referred to as 'intermediate grade', and a sum of 8 or higher referred to as 'high grade'. In addition to the biopsy, other factors that are used to assess or stage patients include the PSA level and the DRE findings, which are assigned a T-stage.

In addition to the biopsy results, other factors are used to assess or ‘stage’ patients, such as PSA level and DRE findings. Together, these findings are assigned a T-stage.

The T-stage is defined as follows:

T1c: the prostate gland feels normal on DRE (ie. no nodule) but the PSA level is elevated
T2a, b or c: a nodule is felt on DRE (the letter a or b is given if the nodule is on one side of the gland, c if it is felt on both sides)
T3: there is suspicion of cancer spread outside of the prostate capsule based upon DRE

Sometimes, additional diagnostic tests such as a bone scan, CT, or MRI are performed depending on the physician's estimate of risk.

Risk Groups

Using all information available, the risk of extra-prostatic disease (either by direct extension of cancer through the prostate 'capsule', or by the spread of the cancer to skeleton or other organs) can be estimated. Although in reality there is a continuous spectrum of risk, assigning specific risk groups allows us to think more clearly about the best medical management for an individual patient. A common classification scheme used is as follows:

Low Risk: T1c or T2, PSA<10, Gleason sum of 6 or lower
Intermediate Risk: T1c or T2, PSA 10-20, Gleason sum of 7
High Risk: T3 or PSA>20 or Gleason sum of 8 or higher

What treatment options are available? What factors influence treatment choice?

The treatment options available to patients with prostate cancer depend upon their risk group. The principal options include: surgery, external beam radiation, and brachytherapy (alone or in combination with external beam radiotherapy). What follows is a very brief outline of these individual options.

Surgery

Surgery, otherwise known as radical retropubic prostatectomy, refers to the surgical removal of the entire prostate gland and possible sampling of nearby lymph nodes. This operation typically lasts 3 to 4 hours, requires general anesthesia, and a 3-day hospital stay. Recovery at home usually lasts several weeks, the first two weeks of which a Foley catheter (inserted through the urethra into the bladder) is used. Potential long-term side-effects include a low risk of urinary incontinence and erectile dysfunction.

External beam radiotherapy

External beam radiotherapy consists of daily doses of radiation given on an outpatient basis for a total of 7-8 weeks. Each daily dose lasts about 15 minutes. Modern external beam radiotherapy is usually referred to as 3-dimensional (3D) conformal or intensity-modulated radiotherapy (IMRT). IMRT utilizes beam-shaping to dynamically reshape the outlines and intensity of the radiation field, thereby allowing the dose of radiation to be sculpted (conformed) to a target much better than with conventional radiation techniques. By limiting irradiation of normal tissues, injury to these structures is lessened and it becomes possible to increase (escalate) the dose of radiation administered to a tumor. Potential side-effects include the temporary symptoms of rectal and urinary irritation, and long-term erectile dysfunction.

Brachytherapy

Brachytherapy (permanent seeds) consists of a closed procedure under general or spinal anesthesia whereby radioactive seeds are placed within the prostate gland. Long needles are inserted through the area of skin between the legs into the prostate under the guidance of a trans-rectal ultrasound. A temporary Foley catheter is rarely needed. Patients are usually discharged home on the same day. Potential side-effects include symptoms of urinary irritation which can last for 6 months, and long-term erectile dysfunction.

It is important to realize that there are currently no randomized trials comparing one treatment option to any other, and therefore there is no conclusive data favoring any specific therapy. However, based upon a multitude of retrospective published series, all of the treatment options are currently thought to be equivalent in terms of cure rates. These treatments differ primarily in terms of their technical nature and potential side effects. Patients who are eligible for all of these options have an important personal decision to make with the help of their physicians.

Based upon the patient's risk group, there are some generally accepted recommendations regarding optimal treatment for a given situation. The following provide only general guidelines - a full recommendation depends on many more factors and can only be made in conjunction with a physician.

For Low Risk patients, all treatment options are available (ie. surgery, external beam radiation, or brachytherapy).
For Intermediate Risk patients, the only difference from what was described above is the possible addition of 4 months of hormone therapy prior to and throughout radiotherapy. Brachytherapy is also less likely to be recommended to such patients.
For High Risk patients surgery is generally not an option. Hormone therapy is added to external beam radiation therapy, including a prolonged course after irradiation. Moreover, in such patients the fields of radiation are expanded to include the pelvic lymph nodes. Brachytherapy is not recommended.

What is CyberKnife radiotherapy and how might it help prostate cancer patients?

The CyberKnife belongs to a new class of radiotherapy techniques called IGRT (image-guided radiotherapy). The CyberKnife is unique in that it uses a compact linear accelerator (LINAC) mounted on an image-guided robotic arm to deliver multiple beams of high energy x-rays to a target. The ability of the CyberKnife to shape the profile of radiation to conform to the patient's individual anatomy allows for maximum sparing of surrounding normal tissues. The CyberKnife accomplishes this by accurately cross-firing approximately 150 beams of radiation at the target from multiple directions.

The CyberKnife technology represents an improvement upon the most advanced conventional radiation therapy techniques, Intensity Modulated Radiotherapy (IMRT). Similar to IMRT, the CyberKnife can produce a highly conformal dose distribution which 'matches' the shape of the prostate and spares adjacent normal anatomy (bladder and rectum).

However, the CyberKnife differs from IMRT significantly in that it is much more spatially precise in delivering radiation. Because of such accuracy the CyberKnife enables a course of radiotherapy to be ‘hypofractionated’.

Hypofractionation

Hypofractionation refers to a course of radiation during which the number of treatments is reduced while simultaneously increasingly the size of the daily dose. A conventional course of external beam radiotherapy for the prostate consists of 37 daily treatments, each of 200 cGy (a cGy is a measure of radiation dose) delivered over a period of two months. This regimen is standard and is used for nearly all cancers. It is based upon the fact that normal tissues are more sensitive to the size of the daily dose than are tumor cells. Thus, in order to minimize damage to normal tissues, the size of the daily dose is chosen to be small. This is true of all tumors with the exception of prostate cancer where the situation is reversed: prostate tumor cells are more sensitive to the size of the daily dose relative to normal tissues. This unique biologic response to radiation for prostate cancer has only recently been understood and has led to the conclusion that hypofractionated radiotherapy would be a more effective way to deliver radiation. Indeed, using a hypofractionated course of radiation (with daily doses of around 500 to 700 cGy) would: a) yield higher cure rates, b) produce fewer acute side effects, and c) keep the late side effects at the same level as conventional radiotherapy regimens.

What is the patient process for CyberKnife treatment of prostate cancer?

After an initial physician consultation, the following steps would ensue:

Placement of fiducials
CT scan of the abdomen and pelvis about one week later
CyberKnife treatment beginning about one week after the CT scan

Fiducial placement

Three tiny gold seeds, also known as fiducials are placed in the prostate gland during an outpatient procedure by the urologist using trans-rectal ultrasound. These fiducials are readily visible with a pelvic x-rays. The CyberKnife's image-guidance system uses these gold seeds to precisely localize and track the spatial position of the prostate at the start of and throughout each daily radiation treatment. Once implanted, these seeds will remain in the prostate permanently.

The procedure to place fiducials is very well tolerated and similar to a prostate biopsy. In fact, patients typically report less discomfort with placement of these seeds than with the biopsy procedure itself. An x-ray of the pelvis in a patient who has had these gold seeds placed within the prostate is shown below from both a left and right perspective.

CT Scan

Following placement of the fiducials, the patient will return about one week later. A custom body mold (called an ‘alpha cradle’) is fitted to each patient so as to minimize movement during CyberKnife treatment. While lying in the body mold, a patient will next undergo a CT scan. The CT information is then downloaded to the CyberKnife computer where it is used by physicians and medical physicists to develop a customized treatment plan based on the patient's specific anatomy. The treatment plan establishes the number, intensity, and direction of radiation beams the CyberKnife will administer to the prostate gland.

CyberKnife Treatment

Once treatment planning is completed, the patient is scheduled to return for 5-8 daily CyberKnife treatments. Each day the patient lies comfortably on the treatment table in the body mold while the CyberKnife delivers the appropriate dose of radiation. After each daily treatment which lasts around 30-40 minutes, the patient returns home.

What are the side effects of CyberKnife radiotherapy?

The potential side effects of CyberKnife radiosurgery for prostate cancer are similar to those experienced with standard courses of radiation therapy using conventional techniques. However, because one can minimize the physical margins of radiation to the target (ie. prostate) with the CyberKnife and thus spare more adjacent healthy tissue, the occurrence and severity of side effects from CyberKnife radiotherapy should be reduced compared to conventional radiation techniques.

What are the side effects of conventional radiation therapy for prostate cancer?
The symptoms following conventional prostate radiation treatment are classified into early and late side effects.

Early (acute) side effects are those experienced during the first few months after treatment. They include: urinary urgency and frequency, nighttime urination, mild burning with urination, rectal urgency, increased frequency of bowel movements, or irritation of hemorrhoids. These are usually temporary and resolve gradually once treatment is completed.
Late side effects are those that may persist for months or may even be permanent. These include erectile dysfunction.

Can the Cyberknife be used to treat prostate cancer?

Yes.