Hello my name is Mark Buyyounouski . I am
an Associate Professor and Director of the Genitourinary Cancers Program in the Department
of Radiation Oncology at Stanford University. In this series, I will be speaking about radiation
therapy for prostate cancer. My background includes a Bachelor�s of Science
Degree in Physics from Lafayette College. A Masters of Science in Medical Physics from
Columbia University. I received my Doctorate from New Jersey Medical School and my Radiology
Oncology Residency was conducted at Fox Chase Cancer Center in Philadelphia. Nationally,
I have contributed to various societies. I�ve served as secretary and treasurer to Board
for the American Brachy Therapy Society. Held various positions within ASTRO our International
Society of Radiation Oncology, and presently I serve as Chair of the Emergent Technologies
Committee. I am a member of the Genitourinary Committee for the American Board of Radiology,
and I participate in a group called the Radiation Therapy Oncology Group, which is a legacy
group of now a larger group called Energy Oncology that conducts national clinical trials. This is part of the team in our department
who work most closely with me delivering care for prostate cancer patients, includes a physician
assistant, GU fellow, and my administrative assistant. We take personal quality care very
seriously. As part of our routine work we are sure to
help coordinate care the best we can among patients doctors caregivers. An example of
this is a expedited same date consultation letter that is sent to your doctors to facilitate
communication. We also are sure to discuss all of your treatment options and help balance
them in terms of your preferences. We try to minimize the burden of treatment by avoiding
as many scheduling inconveniences as possible. I am always there to help even with the smallest
details or emotional need. Shared decision making is an emergent concept
in oncology care that, I believe is an important one. What this study showed was that patient
satisfaction was greater for patients who perceived control and experienced shared decision
making as part of their cancer treatment, and so when consulting with patients, I am
always sure to engage them in the process of decision making and to enhance perception
of control in the process. When prostate cancer is diagnosed the first
important step is accessing the aggressiveness of the cancer, its likelihood of spreading,
and risk of occurrence. This is done commonly using a risk gratification model, where the
most common one used is that of National Comprehensive Cancer Network. It utilizes three major factors,
the PSA level from the blood test, the Gleason Score, which is a number from the biopsy,
and the T stage, which is an evaluation of the prostate in tumor from the digital rectal
exam. Cancers are then classified as low risk, intermediate risk, or high risk. For example,
a patient with a PSA level of 15, and the T2b tumor on digital rectal exam with a Gleason
score of 8, would be categorized as high risk. Despite this strict categorical classification.
However, most times in real life risk behaves more as a continuum.
What this slide attempts to illustrate is the gradual process by which cancers can increase
in risk from low risk to intermediate risk and high risk. For example, patients in the
intermediate risk group could be further sub classified as slightly on the lower end toward
lower risk or slightly toward the higher end near high risk. Various factors can be used
to further sub classify risk. Factors such as the volume of the cancer can be examined.
There are various ways to do this including determining the percentage of biopsy cores
that were involved with cancer or examining the length of each core that was involved
with cancer. We can further look at the primary Gleason score pattern. Gleason scoring is
a number based on the pattern of the cancer under the microscope. The numbers range from
6 to 10 where 6 is low, 7 is the middle 8, 9, 10 is high. This number is composed of
two parts a primary pattern which comprises most of the cancer, and a secondary pattern.
When a patient has a Gleason score 7 the primary pattern can be either Gleason 3 or Gleason
4, and so this can further help sub stratify risk. Last you can look at how many risk factors
are present for patients with intermediate risk disease. For example, a patient with
one intermediate risk factor may behave and respond to treatment differently than a patient
with 3 intermediate risk factors. Slide 10: In general all patients with prostate
cancer have the option of surgery, radiation therapy, or a conservative approach of just
monitoring the PSA and digital rectal exams without treatment. One caveat, however is
that as risk increases for patients who choose radical prostatectomy or radiation therapy,
additional treatments may be required as risk increases for example patients who choose
to have surgery may find that they�re recommended to receive radiation therapy after, and for
patients who choose to have radiation therapy they may find they�re recommended to receive
additional hormonal therapy in combination with radiation.
Slide 11: What�s important to remember a diagnosis of prostate cancer is not immediately
life threatening, in fact 10 year survival rates show that the likelihood of dying of
prostate cancer is far less than that of dying from other causes. Most common cause of death
in men especially as they age is that of cardiovascular disease, which could be complicated by other
medical conditions, such as diabetes, and hypertension.
Slide 12: The standard treatments options available at Stanford university, include
external beam radio therapy, which is delivered with a volumetric modulated arc technique,
which is a form of intensity modulated radiotherapy or IMRT. This is delivered in either conventional
fractionation using 40 treatments or fractions over approximately 8 weeks or a moderate hypofractionated
technique delivering treatment in 26 treatments. This is possible because current technology
allows us to deliver a slightly higher radiation dose each day and deliver treatment over an
overall shorter period of time. Patients are often advised about the benefits of brachytherapy.
At Stanford, we use a high does rate or HDR temporary prostate implant technique and for
patients with unfavorable intermediate or high risk disease, androgen deprivation therapy
may be used which can be delivered from duration anywhere from 4 months to 36 months.
Slide 13: In general as the risk of prostate cancer increases there is treatment intensification,
you can see that by the layering effect in which patients with low risk disease may be
a suitably for external beam technique alone using VMAT, and high risk patients are often
optimally treatment with combinations of therapy, such as VMAT HDR brachytherapy and androgen
deprivation therapy. Slide 14: There are two treatments, I will
not be discussing and are not available at Stanford. They are proton therapy which is
a form of external beam radio therapy. Currently, there are no well established advantages to
proton therapy over froton therapy that is used as part of VMAT, and I will not be discussing
low dose rate permanent prostate brachytherapy which is an alternative to the temporary high
rate dose brachytherapy. I will be discussing this a little further detail.
Slide 15: I will also be discussing two treatments, HDR mono therapy and stereotactic body radio
therapy are being offered as part of clinical trial at Stanford.
Slide 16: Over the last two and a half decades the most important thing we have learned about
treating prostate cancer with radiation therapy is that more is better . This is a collection
of phase III randomized clinical trials, that all indicate that higher radiation dose improves
outcome in prostate cancer. They show that approximate in 8 to 10 gray increase in radiation
dose, where is gray is the unit measure like centimeter is to length increases PSA control
about 10 per cent. Slide 17: What�s more in some subgroups
of prostate cancer higher radiation dose appears to improve survival.
Slide 18 : In result from Memorial Kettering SloanCancer Center suggest that further dose
escalation may be beneficial . Slide 19 Now I will prevent some concepts
about VMAT Slide 20 , Stanford has a long history of
treating prostate cancer. These are figures from a report from by Dr. Malcolm Bagshaw
the second chairman of the Department of Radiation Oncology from his publication in 1965 which
was the first to show that you could cure prostate cancer with radiation. He knew that
the best way to concentrate radiation in the prostate was to use a arc base technique and
he accomplished this by using a lazy susan type device with patients standing on it and
mimicking a rotisserie type motion where patients were rotated while radiation was directed
to the prostate. It was a very cleaver technique and was monumental in our field.
Slide 21 This is a video of a patient receiving VMAT today, as you can see the patient is
lying flat on his back immobilized with a device holding his legs still, while the machine
rotates around focusing radiation at the prostate. Patient doesn�t see the radiation, they
don�t smell it they don�t see it, patient does not feel sick or nauseous and has no
restrictions during treatment. Overall treatment times takes about 2 to 3 minutes.
Slide 22: While the machine is rotating a device called the multileaf collimator is
adjusting the shape and size of the radiation beam to ensure that it is conformal to the
prostate concentrating the radiation inside while minimizing the exposure to the surrounding
normal tissues, such as the rectum and bladder. What you can see here on the right is a contour
of the prostate shown in red while the radiation is concentrated inside which is the white
appearance. Slide 23This is an illustration in how the
radiation is concentration in a around the prostate and seminal vesicles. On the left
you can see a description of the anatomy showing the prostate bladder rectum, seminal vesicles
and proximal portions of the penis called the penile bulb and corporal bodies. On the
right is topography map of the radiation dose similar to an elevation map where toward the
center represents the greatest radiation dose. What radiation oncologist do is devise the
delivery of radiation that concentrates the radiation in side while sparing the normal
surrounding tissues. Slide 24: this accomplished with a simulation
or mapping procedure. Stanford University patients are simulated with a cat scan and
an MRI to create a map of where the radiation will go . what I do as the physician is draw
on that map each of the various structures that are important for the treatment planning
such as the prostate the rectum bladder erectile tissues bowel and any structures that are
sensitive. Slide 25: It is customary to use CT scanning
for this mapping procedure, this is standard throughout the country. However, you see can
that these pictures may sometimes be difficult to interpret.
Slide 26: At Stanford we routinely use MRI scans because we can achieve much greater
definition of the target and normal tissues. Slide 27: In addition to creating best map
possible to deliver the radiation is ensuring that we hit the prostate every day. This is
routinely accomplished with the use of implanted gold fiducial markers, they are small gold
seeds the size of a dry grain of rice that are planted in the prostate with a procedure
similar to the biopsy, although not as traumatic. Here you can see on the left three green circles
that represent the location of the gold seeds, on the initial mapping procedure, each day
before your treatment lying on the table, an x-ray is performed to visualize the gold
seeds that appear as small white dots. The therapist job of positioning you on the table
before treatment begins is to simply align the little dots and the little green circles
to ensure that the prostate is on the mark before we begin. Slide 28: Similarly this can be achieved with
the use of a cat scan equipment enables us to to a cat scan before each treatment and
this is done on a weekly basis just as a double check on quality assurance measure.
Slide 29: Here is a typical schedule for a patient receiving VMAT you would be scheduled
to come in to the department on a Wednesday where the gold makers are implanted into the
prostate, the Cat Scan and MRI are required for the mapping procedure. Two weeks later
you would return to receive their first treatment which is then delivered Monday through Friday
5 days a week no weekends or holidays for either 26 or 40 treatments.
Slide 30: Shown here are a list of potential side effects of a course of radiation therapy.
Side effects that occur during and immediately following radiation therapy are largely attributed
to the swelling and inflammation of the bladder, prostate and rectum. These side effects are
often easily controlled with over the counter anti-inflammatories, such as ibuprofen. It�s
typical for patients to report increases in daytime and nighttime urinary frequency or
urgency. They may experience mild discomfort or burning with urination as well. Patients
find that they sometimes have an increased number of bowel movements or looser bowel
movements. Mild fatigue is also possible especially as the days and weeks of treatment add up.
Patients have no restrictions and are encouraged to continue their daily exercise regimens
and activities. Additional side effects in the months and years following radiation therapy
are also possible. It is very typical for patients to report a greater sense of urinary
urgency, this usually means that they time their restroom visits accordingly. Go to the
bathroom before leaving the house and upon arriving at their destination and commonly
stop to use the restroom along the way. However, it is important to remember that leaking urine,
laughing, sneezing, coughing, lifting heavy objects is not expected after radiation therapy.
Patients sometimes report leaking one or two drops of urine in their shorts, if they can�t
get to the bathroom in time because they are in unfamiliar surroundings or not near a bathroom.
For this reason its common report wearing a pad in their short for confidence. Keep
in mind permanent rectal and bladder injury requiring serious treatment such as surgery
is a rare consequence of radiation therapy. Slide 31 Erectile dysfunction is an often
asked consequence of radiation therapy treatment. Recent evidence suggest that one out of five
patients suffer a decline in erectile dysfunction following a course radiation therapy. Erectile
dysfunction after radiation therapy is most commonly related to impair blood flow to the
proximal portion to the penis near the prostate. This type of erectile dysfunctions responds
favorably to medications like Cialis or Levitra, and is effective in 7 out of 10 men in helping
to improve erectile dysfunction. Slide 32: The erectile tissues are easily
identifiable on MRI which we use standardly at Stanford. This allows us to better spare
the erectile tissues by imposing dose constraints in the treatment planning process. We are
hopeful that further lowering the dose received by the erectile structures we will further
improve erectile function in the future. Slide 33: The next part of this discuss will
focus on Brachy[T1] Therapy Slide 34. Prostate brachytherapy is radiation
from the inside out this is achieved by planting hollow needles into the prostate with ultrasound
guidance through the skin between the scrotum and the anus.
Slide 35: At Stanford our Prostate Brachytherapy Program is centered on a real time ultrasound
base high dose rate technique. This technique has several advantages over permanent low
dose rate brachytherapy. The radiation exposure is temporary and there are no implanted radioactive
seeds left behind, which means there are no restrictions to your children. Because no
loose radioactive seeds are left behind there is no risk that these seeds can move to other
parts of the body. The radiation therapy delivery is also improved, we can achieve a greater
concentration of radiation in the prostate and better conform the radiation to treat
problematic areas such as cancer that has penetrated through the capsule of the prostate
or penetrated the veseminal vesicles. Radiation therapy given at a high dose rate is more
lethal to the cancer cells. Another advantage of the Stanford HDR technique is the use of
ultrasound for treatment planning. This is a newer technology not widely available. It�s
important because it eliminates the need for a CT scan. Traditionally CT scans have been
used to design the HDR treatment. Ct scans are problematic however, because they require
moving the patient from the operating table to a stretcher and the CT scan. All of this
movement opens the door for the needles which were carefully placed in the prostate to move.
Using ultrasound we have very high confidence that the needles are exactly where we intend
them to be. Slide 36: This slide illustrates the ability
to concentrate radiation within the prostate using various radiation therapy techniques.
On the top left you can see a VMAT technique, the two top right techniques are proton techniques
and on the bottom on the left low dose brachy therapy and on the right high dose brachy
therapy. These pictures are very similar to a topography map for elevation, you can see
that the radiation is best concentrated in and around the prostate with HDR
Slide 37: This figure illustrates the effectiveness of dose rate on cancer cell killing. Each
curve represents a different rate of radiation delivery. You can see that there are fewer
surviving cancer cells with high dose rate as compared to low rate brachy therapy. Slide 38: Here you can compare the image quality
of ct base versus ultrasound based imaging for treatment plan.
Slide 3: This slides illustrates how it is possible to implant a seminal vesicle that�s
cancerous, on the right you can see a needle implanted directly within the cancerous seminal
vesicle. This gives us great confidence that we can concentrate the dose within the tumor
Slide 40: Prostate brachytherapy is the same day outpatient procedure performed under general
anesthesia. Patient are asked to undergo routine pre-admission testing including EKG, chest
ray and blood work. After arriving at the hospital patients are transported to our operative
suite in the Radiation Oncology Department. General anesthesia is administered and a urinary
catheter is placed in the penis. Patients are positioned supine with their legs up as
shown here, an ultrasound probe is inserted in the rectum and pictures are captured and
transferred to monitors for the treatment team.
Slide 41: Together with the team of physicist the treatment team is devised based on the
needle placement and your ultrasound imaging. Each hollow needle is then connected to a
catheter which is connected to the delivery device. Remote after loader contains a radioactive
source of iridium, this is connected to a cable which is connected to a motor, the computer
software controls the motor to drive the cable and the source in and out of each catheter
and hollow needle into your prostate, where it pauses temporarily radiating the prostate
from the inside out. The entire treatment takes about 10 minutes. Upon completion of
the treatment the needles are removed and the patient is transferred to the recovery
area. Once the effects of anesthesia have worn off the urinary catheter is removed.
Once the patient is able to urinate he is discharged home. Usually mid to late afternoon.
Slide 4: Several studies have shown the intensification dose escalation of HDR brachy therapy is beneficial
in curing prostate cancer. Slide 4: This slide show the experience from
the Peter MacCallun[T2] Cancer Institutes in Australia. When HDR is used there is an
approximate 10 per cent benefit PSA control was observed for 5 years.
Slide 44: A similar benefit was observed at Memorial Sloan Kettering Cancer Institute
in New York. Slide 45: In this review found that optimal
survival and biochemical control was achieved when HDR was used compared to LDR and external
beam treatment alone. Slide 46: These observations are most likely
related to the ability of HDR to further escalate dose. This hypothesis that combining VMAT
and HDR to up the dose in order from 90 to 100 gray. This is roughly 10 to 20 gray more
than is achievable using an external beam technique alone rather with VMAT
Slide 47: This is a typical schedule for a patient undergoing combined VMAT and HDR.
Slide 48 Patients undergoing HDR may also experience additional side effects, bleeding
is possible, there is also risk of infection, but antibiotics are used during and after
the implant. There is a small risk that patients may require a urinary catheter beyond the
day of the procedure. Slide 4: Following the completion of radiation
therapy patients are followed on a periodic basis with PSA levels and digital rectal exams
(34:42) Slide 50: This slide represents 2 populations of patients. On the bottom PSA
for patients whose cancer appears to be controlled, on the top PSA levels of patients whose prostate
cancers returned. You can see following radiation therapy PSA levels declined to some low level
less than 1 after about 2 years. At that point PSA levels usually remain stable and low.
For patients whose have prostate cancer return they may begin to appreciate after an initial
decline PSA a very gradual increase after about 1-2 years, this is usually the first
that the prostate cancer is returning. If PSA levels raise concern about recurrence
then typically you begin looking for prostate cancer with scans and bone scan. If these
indicate spread the next appropriate treatment is hormonal therapy. For patients whose scans
are negative a re -biopsy of the prostate looking for persistence of prostate cancer
may be appropriate. This is appropriate for patients who are considering a second treatment
to the prostate. Second treatments of the prostate may include surgery, brachytherapy
or cryo surgery. Slide 50 (repeat) If PSA levels raise concern
about reoccurrence then typically you would begin looking for prostate cancer with scans
such as CAT scan and a bone scan if these indicate spread the next appropriate treatment
is hormonal therapy. For patients whose scan are negative a re -biopsy of the prostate
looking for persistence of prostate cancer may be appropriate. This is appropriate for
patients who are considering a second treatment to the prostate. Second treatments of the
prostate may include surgery, brachytherapy or cryo surgery. Slide 51: For patients who receive hormonal
therapy the pattern of PSA after treatment is different. While hormonal therapy is being
delivered PSA levels should be zero, when hormone therapy stops the PSA is expected
to rise although gradually and minimally. If the PSA levels continue to rise this may
signal a return of prostate cancer and warrant further investigation. In this figure the
lower curve show PSA for patients who have control of their prostate cancer without recurrence.
The upper curve shows PSA for patients are were later found to have recurrence of PSA.
Slide 52: This final sessions we will discuss two clinical trials at Stanford
Slide 53: There are two emerging treatments for prostate cancer at Stanford University.
The first is the use of high dose rate brachy therapy alone for the treatment of prostate
cancer and the second is stereotactic body radio therapy or SBRT. At Stanford a clinical
trial is being conducted that allows patients with low intermediate prostate cancer to be
treated with HDR monotherapy alone, without the use of supplemental external beam radio
therapy Slide 54: The hope is that we can deliver
adequate amounts of radiation dose to the prostate with an HDR technique in order to
eliminate the need for an external beam radiotherapy compound. This significantly shortens the
overall treatment time and reduces the burden of treatment.
Slide 55: Similarly stereotactic body radiotherapy an external beam technique may be possible.
Soon a clinical trial for patients with low risk prostate cancer will be available for
patients to receive treatment on an every other day basis over approximately two weeks Thanks you listening to this informational
session. I hope you have found it helpful. [T1]