How is Prostate Cancer Treated?

For patients with early stage prostate cancer that is confined to the prostate itself, treatment options include surgery, da Vinci robotic surgery, external beam radiation therapy (EBRT), brachytherapy (LDR and HDR), CyberKnife stereotactic body radiation therapy (SBRT, sometimes called stereotactic radiosurgery), hormonal therapy and watchful waiting (active surveillance). Each of these options is explained in detail below, with descriptions of studies of their effectiveness. In such studies, patients’ PSA levels are monitored at regular intervals; elevated or increasing PSA levels indicate a possible recurrence of the cancer while continuing low PSA levels indicate the patient is “recurrence-free”. In addition, patients are periodically assessed for complications of treatment (also called “toxicities”). Complications are often graded on a scale of 1 to 5 where grades 1 and 2 complications are considered minor, grade 3 is considered moderate, and grades 4 and 5 are considered severe.


Prostate cancer surgery:
Prostate cancer surgery involves complete removal of the prostate and some of the adjacent tissues (radical prostatectomy). There are two types of surgery common for prostate cancer: open radical prostatectomy and laparoscopic prostatectomy.


Open radical prostatectomy:
There are two approaches to performing an open radical prostatectomy, a radical retropubic approach and a radical perineal approach. During a radical retropubic prostatectomy, a long incision is made in the lower abdomen and the surgeon removes the entire prostate with some surrounding tissues. Nerves in the surrounding tissues can be easily damaged during this procedure, resulting in impotence, so surgeons often use techniques to preserve the nerves around the prostate that control erections. Nerve-sparing techniques have been shown to decrease the incidence of impotence following radical prostatectomy, but there is still a high risk of impotence following surgery. The radical perineal approach involves the surgeon making an incision in the perineum, the skin between the testicles and the anus. Nerve-sparing techniques are more difficult in this approach. Patients that undergo open radical prostatectomy typically spend three to four days in the hospital and can expect to have a catheter remain in their urethra for three to four weeks to help with urination. Either surgical approach poses a significant risk of possible complications for patients, such as infection, bleeding, lengthy hospital stays, urinary side effects and impotence. In general, open prostatectomy is a highly effective modality for controlling prostate cancer, with long-term (10-15 years) overall cancer recurrence-free rates as high as 97% [2-4]. Urinary complications are common shortly after surgery, and in the long term urinary incontinence may occur in 5-15% of patients and impotence has been reported to occur in 40-80% of patients [5-7].


Laparoscopic prostatectomy: 
Laparoscopic prostatectomy is becoming more popular because it is less invasive. During this procedure, surgeons make several small incisions in the abdomen. Instruments are inserted through the small incisions and are used to remove the prostate and surrounding tissues. There is little evidence that laparoscopic prostatectomy is superior to open surgery in its ability to control the disease but it does have a reduction in complications [8-12]. Patients who undergo laparoscopic prostatectomy typically are hospitalized for one to three days, and a catheter remains in place in the urethra for 7-10 days. Most laparoscopic prostatectomies in the USA are robotic-assisted. In some reports of robotic-assisted prostatectomy urinary complications have been reduced relative to non-robotic prostatectomy (urinary incontinence has been reported in 1-20% of patients), and in studies in which modern nerve-sparing techniques can be used, impotence rates have ranged from 3-39%) [13-20].


External beam radiation therapy: 
Radiation therapy is a non-invasive procedure that uses low doses of radiation to kill prostate cancer cells. Prior to treatment, CT and MRI images are taken to determine the exact location of the prostate and surrounding structures. A treatment plan is then created to deliver the radiation to the prostate and some of the surrounding tissue. It is necessary to irradiate some of the surrounding healthy tissue during this treatment because there is a significant amount of variability in the day-to-day location of the prostate and because the prostate can move inside the body from the effects of gas in the rectum and fluid in the bladder, which cause uncertainties in the exact position of the prostate. Each treatment session lasts several minutes and is painless. Treatments are typically delivered on an outpatient basis, five days a week, for seven to 10 weeks. These external beam radiation therapy (EBRT) treatments can be delivered with three-dimensional treatment planning, delivering radiation to the prostate typically through 5-7 coplanar beams, and intensity modulated radiotherapy (IMRT), whereby the dose is modulated through each of those beams. Published outcomes of prostate cancer treatment by EBRT include 5-year cancer recurrence-free rates as high as 97% [21-24]. In a recent report of 10-year outcomes of IMRT, recurrence-free rates were 81% for low-risk and 78% for intermediate-risk patients [25]. Studies have shown that by 3 years approximately 3-5% of patients will have experienced moderate to severe urinary toxicities and 2-14% of patients will have experienced moderate to severe rectal toxicities [26, 27]. Impotence has been reported in 35-54% of patients [28-31].


Brachytherapy is an invasive procedure that delivers radiation to the prostate from a source that is implanted within the prostate. There are two approaches to brachytherapy treatments, low dose rate (LDR) brachytherapy and high dose rate (HDR) brachytherapy.


LDR brachytherapy:
In LDR brachytherapy, small radioactive seeds about the size of a grain of rice are placed into the prostate and remain there permanently. Typically, 40 to 100 seeds are placed into the prostate through a needle, which is inserted through the skin. To relieve discomfort, the procedure is done using spinal anesthesia or general anesthesia. The procedure may require overnight hospitalization. The seeds emit low dose radiation to the prostate over several weeks or months, and the patient is radioactive while the radiation is being emitted by the seeds. LDR brachytherapy publications report long-term cancer recurrence-free rates ranging from 83-96% [32-36]. Patients may experience low rates (0-8%) of moderate to severe urinary and rectal side effects [26, 27, 37]. Sexual dysfunction has been reported in 30-45% of patients [37, 38]. Sexual quality of life has been reported as better than that of surgery [39]. In very rare situations, the seeds have become dislodged from the prostate, enter the blood stream and migrate to other distant organs, but this does not typically pose health complications.


HDR brachytherapy:
HDR brachytherapy involves administration of high doses of radiation to the prostate over a short period of time. Typically, an HDR brachytherapy procedure involves insertion of 12 to 20 hollow needles containing catheters, which are inserted through the skin and into the prostate. Spinal anesthesia is usually given and the procedure often requires overnight hospitalization. After the catheters are in place, a CT scan and/or MRI are taken to confirm the exact location of the catheters, prostate and surrounding tissues. A treatment plan is then created and a radioactive source is placed through the catheters to allow radiation to reach the prostate. The radioactive source remains at a location in the prostate for five to 15 minutes and is then removed. Often the treatment occurs over several days and the catheters are removed after the last treatment. Studies have shown that HDR brachytherapy results in recurrence-free rates at 5-8 years of 89-97%, with rates of urinary, rectal and sexual function side effects that approximate those obtained with LDR brachytherapy [37, 40-42]. Nevertheless, this procedure can be painful and difficult for patients to undergo because of its invasiveness.


Hormonal therapy: 
Male hormones, known as androgens, are produced normally by men and help support the growth of prostate cancer cells. The goal of hormonal therapy is to decrease the amount of these specific hormones produced, in order to control the growth of the prostate cancer cells. Hormonal therapy is usually prescribed in combination with other treatments, including external beam radiation therapy, brachytherapy or before surgery to help shrink the size of the tumor. Side effects associated with hormonal therapy can include decreased libido, impotence, hot flashes, osteoporosis and breast tenderness [43].


Watchful waiting/Active surveillance: 
Prostate cancer is often a slow-growing cancer. Doctors may recommend that a patient receive no immediate treatment, instead just closely monitoring the patient with PSA testing and rectal exams. Some men, especially those who are older or have other health problems, may never need prostate cancer treatments; for a recent review see Freedland [44].


Stereotactic Body Radiation Therapy:
Radiosurgery devices, such as the CyberKnife Robotic Radiosurgery System, offer patients a new option for the treatment of prostate cancer called stereotactic body radiation therapy (SBRT) whereby radiation is delivered in four to five sessions.