American Cancer Center

hello my name is mark buyyounouski . i aman associate professor and director of the genitourinary cancers program in the departmentof radiation oncology at stanford university. in this series, i will be speaking about radiationtherapy for prostate cancer. my background includes a bachelor�s of sciencedegree in physics from lafayette college. a masters of science in medical physics fromcolumbia university. i received my doctorate from new jersey medical school and my radiologyoncology 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 boardfor the american brachy therapy society. held various positions within astro our internationalsociety of radiation oncology, and presently

i serve as chair of the emergent technologiescommittee. 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 legacygroup of now a larger group called energy oncology that conducts national clinical trials. this is part of the team in our departmentwho work most closely with me delivering care for prostate cancer patients, includes a physicianassistant, gu fellow, and my administrative assistant. we take personal quality care veryseriously. as part of our routine work we are sure tohelp coordinate care the best we can among patients doctors caregivers. an example ofthis is a expedited same date consultation

letter that is sent to your doctors to facilitatecommunication. we also are sure to discuss all of your treatment options and help balancethem in terms of your preferences. we try to minimize the burden of treatment by avoidingas many scheduling inconveniences as possible. i am always there to help even with the smallestdetails or emotional need. shared decision making is an emergent conceptin oncology care that, i believe is an important one. what this study showed was that patientsatisfaction was greater for patients who perceived control and experienced shared decisionmaking as part of their cancer treatment, and so when consulting with patients, i amalways sure to engage them in the process of decision making and to enhance perceptionof control in the process.

when prostate cancer is diagnosed the firstimportant 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 themost 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 rectalexam. 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 gleasonscore 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 increasein risk from low risk to intermediate risk and high risk. for example, patients in theintermediate risk group could be further sub classified as slightly on the lower end towardlower risk or slightly toward the higher end near high risk. various factors can be usedto 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 coresthat were involved with cancer or examining the length of each core that was involvedwith cancer. we can further look at the primary gleason score pattern. gleason scoring isa number based on the pattern of the cancer

under the microscope. the numbers range from6 to 10 where 6 is low, 7 is the middle 8, 9, 10 is high. this number is composed oftwo 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 gleason4, and so this can further help sub stratify risk. last you can look at how many risk factorsare present for patients with intermediate risk disease. for example, a patient withone intermediate risk factor may behave and respond to treatment differently than a patientwith 3 intermediate risk factors. slide 10: in general all patients with prostatecancer have the option of surgery, radiation therapy, or a conservative approach of justmonitoring the psa and digital rectal exams

without treatment. one caveat, however isthat as risk increases for patients who choose radical prostatectomy or radiation therapy,additional treatments may be required as risk increases for example patients who chooseto have surgery may find that they�re recommended to receive radiation therapy after, and forpatients who choose to have radiation therapy they may find they�re recommended to receiveadditional hormonal therapy in combination with radiation.slide 11: what�s important to remember a diagnosis of prostate cancer is not immediatelylife threatening, in fact 10 year survival rates show that the likelihood of dying ofprostate cancer is far less than that of dying from other causes. most common cause of deathin men especially as they age is that of cardiovascular

disease, which could be complicated by othermedical conditions, such as diabetes, and hypertension.slide 12: the standard treatments options available at stanford university, includeexternal 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 conventionalfractionation using 40 treatments or fractions over approximately 8 weeks or a moderate hypofractionatedtechnique delivering treatment in 26 treatments. this is possible because current technologyallows us to deliver a slightly higher radiation dose each day and deliver treatment over anoverall 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 forpatients with unfavorable intermediate or high risk disease, androgen deprivation therapymay 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 bea suitably for external beam technique alone using vmat, and high risk patients are oftenoptimally treatment with combinations of therapy, such as vmat hdr brachytherapy and androgendeprivation therapy. slide 14: there are two treatments, i willnot be discussing and are not available at stanford. they are proton therapy which isa form of external beam radio therapy. currently,

there are no well established advantages toproton therapy over froton therapy that is used as part of vmat, and i will not be discussinglow dose rate permanent prostate brachytherapy which is an alternative to the temporary highrate 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 radiotherapy 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 abouttreating prostate cancer with radiation therapy is that more is better . this is a collectionof phase iii randomized clinical trials, that all indicate that higher radiation dose improvesoutcome in prostate cancer. they show that

approximate in 8 to 10 gray increase in radiationdose, where is gray is the unit measure like centimeter is to length increases psa controlabout 10 per cent. slide 17: what�s more in some subgroupsof prostate cancer higher radiation dose appears to improve survival.slide 18 : in result from memorial kettering sloancancer center suggest that further doseescalation may be beneficial . slide 19 now i will prevent some conceptsabout vmat slide 20 , stanford has a long history oftreating prostate cancer. these are figures from a report from by dr. malcolm bagshawthe second chairman of the department of radiation oncology from his publication in 1965 whichwas the first to show that you could cure

prostate cancer with radiation. he knew thatthe best way to concentrate radiation in the prostate was to use a arc base technique andhe accomplished this by using a lazy susan type device with patients standing on it andmimicking a rotisserie type motion where patients were rotated while radiation was directedto 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 islying flat on his back immobilized with a device holding his legs still, while the machinerotates around focusing radiation at the prostate. patient doesn�t see the radiation, theydon�t smell it they don�t see it, patient does not feel sick or nauseous and has norestrictions during treatment. overall treatment

times takes about 2 to 3 minutes.slide 22: while the machine is rotating a device called the multileaf collimator isadjusting the shape and size of the radiation beam to ensure that it is conformal to theprostate concentrating the radiation inside while minimizing the exposure to the surroundingnormal tissues, such as the rectum and bladder. what you can see here on the right is a contourof the prostate shown in red while the radiation is concentrated inside which is the whiteappearance. slide 23this is an illustration in how theradiation is concentration in a around the prostate and seminal vesicles. on the leftyou can see a description of the anatomy showing the prostate bladder rectum, seminal vesiclesand proximal portions of the penis called

the penile bulb and corporal bodies. on theright is topography map of the radiation dose similar to an elevation map where toward thecenter represents the greatest radiation dose. what radiation oncologist do is devise thedelivery of radiation that concentrates the radiation in side while sparing the normalsurrounding tissues. slide 24: this accomplished with a simulationor mapping procedure. stanford university patients are simulated with a cat scan andan mri to create a map of where the radiation will go . what i do as the physician is drawon that map each of the various structures that are important for the treatment planningsuch as the prostate the rectum bladder erectile tissues bowel and any structures that aresensitive.

slide 25: it is customary to use ct scanningfor this mapping procedure, this is standard throughout the country. however, you see canthat these pictures may sometimes be difficult to interpret.slide 26: at stanford we routinely use mri scans because we can achieve much greaterdefinition of the target and normal tissues. slide 27: in addition to creating best mappossible to deliver the radiation is ensuring that we hit the prostate every day. this isroutinely accomplished with the use of implanted gold fiducial markers, they are small goldseeds the size of a dry grain of rice that are planted in the prostate with a proceduresimilar to the biopsy, although not as traumatic. here you can see on the left three green circlesthat represent the location of the gold seeds,

on the initial mapping procedure, each daybefore your treatment lying on the table, an x-ray is performed to visualize the goldseeds that appear as small white dots. the therapist job of positioning you on the tablebefore treatment begins is to simply align the little dots and the little green circlesto ensure that the prostate is on the mark before we begin. slide 28: similarly this can be achieved withthe use of a cat scan equipment enables us to to a cat scan before each treatment andthis 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 scheduledto come in to the department on a wednesday

where the gold makers are implanted into theprostate, the cat scan and mri are required for the mapping procedure. two weeks lateryou would return to receive their first treatment which is then delivered monday through friday5 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 attributedto the swelling and inflammation of the bladder, prostate and rectum. these side effects areoften easily controlled with over the counter anti-inflammatories, such as ibuprofen. it�stypical for patients to report increases in daytime and nighttime urinary frequency orurgency. they may experience mild discomfort

or burning with urination as well. patientsfind that they sometimes have an increased number of bowel movements or looser bowelmovements. 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 regimensand activities. additional side effects in the months and years following radiation therapyare also possible. it is very typical for patients to report a greater sense of urinaryurgency, this usually means that they time their restroom visits accordingly. go to thebathroom before leaving the house and upon arriving at their destination and commonlystop 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�tget 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. keepin mind permanent rectal and bladder injury requiring serious treatment such as surgeryis a rare consequence of radiation therapy. slide 31 erectile dysfunction is an oftenasked consequence of radiation therapy treatment. recent evidence suggest that one out of fivepatients suffer a decline in erectile dysfunction following a course radiation therapy. erectiledysfunction after radiation therapy is most commonly related to impair blood flow to theproximal portion to the penis near the prostate.

this type of erectile dysfunctions respondsfavorably to medications like cialis or levitra, and is effective in 7 out of 10 men in helpingto improve erectile dysfunction. slide 32: the erectile tissues are easilyidentifiable on mri which we use standardly at stanford. this allows us to better sparethe erectile tissues by imposing dose constraints in the treatment planning process. we arehopeful that further lowering the dose received by the erectile structures we will furtherimprove erectile function in the future. slide 33: the next part of this discuss willfocus on brachy[t1] therapy slide 34. prostate brachytherapy is radiationfrom the inside out this is achieved by planting hollow needles into the prostate with ultrasoundguidance through the skin between the scrotum

and the anus.slide 35: at stanford our prostate brachytherapy program is centered on a real time ultrasoundbase high dose rate technique. this technique has several advantages over permanent lowdose rate brachytherapy. the radiation exposure is temporary and there are no implanted radioactiveseeds left behind, which means there are no restrictions to your children. because noloose radioactive seeds are left behind there is no risk that these seeds can move to otherparts of the body. the radiation therapy delivery is also improved, we can achieve a greaterconcentration of radiation in the prostate and better conform the radiation to treatproblematic areas such as cancer that has penetrated through the capsule of the prostateor penetrated the veseminal vesicles. radiation

therapy given at a high dose rate is morelethal to the cancer cells. another advantage of the stanford hdr technique is the use ofultrasound for treatment planning. this is a newer technology not widely available. it�simportant because it eliminates the need for a ct scan. traditionally ct scans have beenused to design the hdr treatment. ct scans are problematic however, because they requiremoving the patient from the operating table to a stretcher and the ct scan. all of thismovement 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 intendthem to be. slide 36: this slide illustrates the abilityto 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 techniquesand on the bottom on the left low dose brachy therapy and on the right high dose brachytherapy. these pictures are very similar to a topography map for elevation, you can seethat the radiation is best concentrated in and around the prostate with hdrslide 37: this figure illustrates the effectiveness of dose rate on cancer cell killing. eachcurve represents a different rate of radiation delivery. you can see that there are fewersurviving cancer cells with high dose rate as compared to low rate brachy therapy. slide 38: here you can compare the image qualityof ct base versus ultrasound based imaging

for treatment plan.slide 3: this slides illustrates how it is possible to implant a seminal vesicle that�scancerous, on the right you can see a needle implanted directly within the cancerous seminalvesicle. this gives us great confidence that we can concentrate the dose within the tumorslide 40: prostate brachytherapy is the same day outpatient procedure performed under generalanesthesia. patient are asked to undergo routine pre-admission testing including ekg, chestray and blood work. after arriving at the hospital patients are transported to our operativesuite in the radiation oncology department. general anesthesia is administered and a urinarycatheter is placed in the penis. patients are positioned supine with their legs up asshown here, an ultrasound probe is inserted

in the rectum and pictures are captured andtransferred to monitors for the treatment team.slide 41: together with the team of physicist the treatment team is devised based on theneedle placement and your ultrasound imaging. each hollow needle is then connected to acatheter which is connected to the delivery device. remote after loader contains a radioactivesource of iridium, this is connected to a cable which is connected to a motor, the computersoftware controls the motor to drive the cable and the source in and out of each catheterand hollow needle into your prostate, where it pauses temporarily radiating the prostatefrom the inside out. the entire treatment takes about 10 minutes. upon completion ofthe treatment the needles are removed and

the patient is transferred to the recoveryarea. 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 beneficialin curing prostate cancer. slide 4: this slide show the experience fromthe peter maccallun[t2] cancer institutes in australia. when hdr is used there is anapproximate 10 per cent benefit psa control was observed for 5 years.slide 44: a similar benefit was observed at memorial sloan kettering cancer institutein new york. slide 45: in this review found that optimalsurvival and biochemical control was achieved

when hdr was used compared to ldr and externalbeam treatment alone. slide 46: these observations are most likelyrelated to the ability of hdr to further escalate dose. this hypothesis that combining vmatand hdr to up the dose in order from 90 to 100 gray. this is roughly 10 to 20 gray morethan is achievable using an external beam technique alone rather with vmatslide 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, bleedingis possible, there is also risk of infection, but antibiotics are used during and afterthe implant. there is a small risk that patients may require a urinary catheter beyond theday of the procedure.

slide 4: following the completion of radiationtherapy 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 psafor patients whose cancer appears to be controlled, on the top psa levels of patients whose prostatecancers returned. you can see following radiation therapy psa levels declined to some low levelless 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 initialdecline psa a very gradual increase after about 1-2 years, this is usually the firstthat the prostate cancer is returning. if psa levels raise concern about recurrencethen typically you begin looking for prostate

cancer with scans and bone scan. if theseindicate spread the next appropriate treatment is hormonal therapy. for patients whose scansare negative a re -biopsy of the prostate looking for persistence of prostate cancermay be appropriate. this is appropriate for patients who are considering a second treatmentto the prostate. second treatments of the prostate may include surgery, brachytherapyor cryo surgery. slide 50 (repeat) if psa levels raise concernabout reoccurrence then typically you would begin looking for prostate cancer with scanssuch as cat scan and a bone scan if these indicate spread the next appropriate treatmentis hormonal therapy. for patients whose scan are negative a re -biopsy of the prostatelooking for persistence of prostate cancer

may be appropriate. this is appropriate forpatients who are considering a second treatment to the prostate. second treatments of theprostate may include surgery, brachytherapy or cryo surgery. slide 51: for patients who receive hormonaltherapy the pattern of psa after treatment is different. while hormonal therapy is beingdelivered psa levels should be zero, when hormone therapy stops the psa is expectedto rise although gradually and minimally. if the psa levels continue to rise this maysignal a return of prostate cancer and warrant further investigation. in this figure thelower 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 stanfordslide 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 prostatecancer and the second is stereotactic body radio therapy or sbrt. at stanford a clinicaltrial is being conducted that allows patients with low intermediate prostate cancer to betreated with hdr monotherapy alone, without the use of supplemental external beam radiotherapy slide 54: the hope is that we can deliveradequate amounts of radiation dose to the prostate with an hdr technique in order toeliminate the need for an external beam radiotherapy

compound. this significantly shortens theoverall 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 forpatients to receive treatment on an every other day basis over approximately two weeks thanks you listening to this informationalsession. i hope you have found it helpful. [t1][t2]