High Risk Prostate Cancer

Prostate cancer can be divided into low risk, intermediate risk, and high risk.  This is important to know because the treatment options are different.  In the categories below, I included my own categories of percent of biopsy cores which contain cancer.

Low Risk  (~ Stage 1)

  • PSA less than 10, and
  • Gleason Group 1 (Gleason 3 + 3)
  • No nodule felt or small nodule felt on digital rectal exam

Intermediate Risk  (~ Stage 2)

  • PSA 10 – 19.9, or
  • Gleason Group 2 or 3 (Gleason 3+4 or 4+3), or
  • There is a large nodule felt, or tumor is felt on both sides of prostate

High Risk  (~ Stage 3)

  • PSA 20 or higher, or
  • Gleason Group 4 or 5 (Gleason 4+4, 4+5, 5+4, or 5+5), or
  • Tumor is found to be outside of the prostate gland (stage 3)
  • There are suspicious lymph glands (very high risk, stage 4A)

Generally, CyberKnife by itself is an excellent treatment for low risk prostate cancer.  It can also be used in many cases of intermediate risk especially when there is just a single intermediate risk factor present.  However, for patients with high risk prostate cancer and for patients with multiple intermediate risk factors, using CyberKnife by itself may be under-treatment.  It may be better to combine it with hormone therapy and some longer duration conventional radiation therapy.

Sometimes it is difficult to tell if an intermediate risk cancer should be treated with CyberKnife alone, versus with CyberKnife + hormone therapy + conventional radiation therapy.  The Decipher test can be very helpful in this regard.  This test is done on the biopsy samples you already had done, examines the RNA, and can divide the cancer into low, intermediate, and high risk.  If it is low risk we can do CyberKnife alone, and if it is high risk we will do the combination therapy.

Triple Combination Therapy

In high risk cases I usually recommend triple combination therapy with a reduced dose of conventional radiation (IMRT), along with with a CyberKnife “boost”, and some hormonal therapy.  This strategy is based on the excellent results from triple therapy using high dose rate (HDR) brachytherapy + IMRT + hormonal therapy.

Ingredient #1: Hormonal Therapy

Hormonal therapy, also known as androgen deprivation therapy (ADT), lowers the testosterone in your body, taking away some of the fuel for prostate cancer.  Usually we use Lupron injections for anywhere between 6 to 24 months.  We typically use 3 month injections – a single injection will lower the testosterone for 3 months, and every 3 months another injection is given.  Lupron doesn’t start lowering the testoerone for a couple weeks after the first injection is given, so sometimes for the very first injection we use Firmagon (degarelix) which is a 1 month injection with a rapid onset, or else we add Casodex for the first month.  We start the hormone therapy 3 months before the radiation is started, which will start to shrink the cancer, lower the PSA, and get the cancer “primed” for the radiation.   Hormone therapy by itself cannot cure cancer but when combined with conventional radiation (IMRT) it can increase the cure rate of IMRT.   After 6 – 24 months we stop the injections, and your testosterone levels will gradually rise back up to normal.   While on hormonal therapy you may experience some temporary “male menopause” symptoms including hot flashes, lack of sex drive and erections, and weight gain.  Those symptoms should reverse within some months after stopping the injections.

Ingredient #2: Conventional Radiation (IMRT)

This is a reduced dose of IMRT.  Instead of 9 weeks of treatment, 5 weeks is used.   Larger areas are treated then we would treat with CyberKnife: an extra zone of tissue surrounding the prostate is treated, the seminal vesicles may be included, and the pelvic lymph nodes may be included.

Ingredient #3: CyberKnife Boost

This is a reduced dose of CyberKnife.   For example, instead of 5 treatments, 2 – 3 may be used.  These treatments have a very high dose per treatment and are targeted to the prostate gland with a narrow zone of surrounding tissue along with any tumor extension outside of the prostate.  When the IMRT and CyberKnife components are added together the total effect against the cancer should be greater than if we gave CyberKnife alone or IMRT alone.

Schedule for Triple Combination Therapy

  1. Initial staging scans are required, including CT scans and bone scan.
  2. Hormonal therapy is started with a Lupron injection.  We allow this to shrink the cancer for 3 months before going on to the next steps.
  3. Three months after starting hormone therapy you return for your next injection and to start the radiation process.
  4. Gold marker seeds and SpaceOAR are placed.
  5. Mapping occurs with a CT simulation and MRI of the pelvis.
  6. The following week, a CyberKnife boost of 3 consecutive days is given
  7. The week after IMRT is started to the prostate gland +/- lymph glands.  This takes 25 treatments, 5 days a week, for 5 weeks.
  8. The total radiation therapy process therefore takes about 1 week for mapping, and 6 weeks (28 treatments) for radiation.
  9. Hormonal therapy is continued for a total duration of 6 to 24 months.

This is the schedule that I use.  Note that other doctors may prefer to use slightly different numbers of treatments, may do the CyberKnife and IMRT in the opposite order, may have a longer gap between the CyberKnife and IMRT, may use different lengths of hormonal therapy, and may require more than one CT-simulamapping.

Results of Triple Combination Therapy

A study by Anwar in 2016 gave 2 fractions of CyberKnife along with 25 fractions of IMRT to 48 patients.  A complete article is available online. This study only included patients with intermediate and high risk prostate cancers. 71% of patients had high-risk. At the 5-year mark the rate of cancer control was 83%.


An important principle of treating high risk cancer is to combine multiple treatments together.

Instead of the CyberKnife boost, many centers use a brachytherapy boost with a permanent seed implant or high dose rate (HDR) brachytherapy.  This is a very effective strategy.  However, we think CyberKnife gives similar dosage as HDR but is easier on the patient and has the ability to more easily target cancer which extends beyond the prostate gland.

Alternatively some men start with surgery (prostatectomy).  We then see on the pathology report if the cancer was contained within the prostate gland, if the surgical margins were clear, and if the PSA went down to 0.0 afterwards.  If not, then we would typically recommend some followup IMRT for 7 weeks often with some hormonal therapy.  This IMRT starts about 3 – 4 months after the surgery, to allow sufficient healing.  EORTC 22911 study looked at the benefits of giving followup radiation therapy to men who underwent surgery but were found to have cancer extending outside the prostate gland or had positive margins.  Those who did not have radiation had a 55% PSA control rate at 5-years, and those who received radiation had a 77% PSA control.