Dr. John Colberg, Surgical Options for Prostate Cancer
November 14, 2010

Welcome to Yale Cancer Center Answers with Dr. Francine Foss and Dr. Lynn Wilson.  I am Bruce Barber.  Dr. Foss is a Professor of Medical Oncology and Dermatology specializing in the treatment of lymphomas.  Dr. Wilson is a Professor of Therapeutic Radiology and an expert in the use of radiation to treat lung cancers and cutaneous lymphomas.  If you would like to join the conversation, you can contact the doctors directly.  The address is canceranswers@yale.edu and the phone number is 1888-234-4YCC.  This evening Francine and Lynn are pleased to welcome Dr. John Colberg.  Dr. Colberg is an Associate Professor of Surgery and Director of the Yale Uro-Oncology Program.  Here is Francine Foss.

Foss
I would like to start off by having you tell our audience a little bit about prostate cancer, what is it?

Colberg
Prostate cancer is not unlike other cancers.  It is a malignancy of the prostate gland that occurs typically in men over the age 50, although one can see it earlier in life and in fact, it has been seen in men in their 30s, but it is most common in age 50 or older.  200,000 patients are diagnosed every year.  At any one time in the United States, there are probably 5 million men that have the diagnosis of prostate cancer, newly diagnosed, or treated, and about 30,000 men die of prostate cancer every year or so.  About one in six men have a risk of developing prostate cancer in their lifetime.

Wilson
Is it possible that a patient might be very elderly and not having any symptoms at all and may die of some other cause, but if there is an autopsy done, for example, they may find prostate cancer?  How common is that?

Colberg
No question.  The issues with prostate cancer, as far as who develops prostate cancer, it is very common in the elderly, so that is one of the risk factors.  As you get older, there is a greater chance to have and develop prostate cancer.  In fact, most men, probably two-thirds of the men who have prostate cancer are 65 or older.  So yes, there are a lot of men that actually die from diseases other than prostate cancer and typically those are the men we do not go and pursue and make the diagnosis or screen for.

Foss
A lot of men have difficulties with their prostate as they get older.  How does a man know that he is at risk for prostate cancer?

Colberg
That is a great question because most of the people we find with prostate cancer today do not have any symptoms, or they do not have symptoms related to their prostate cancer.  They may have other symptoms which you were alluding to as far as an enlarged prostate gland called BPH, which is actually benign enlargement of the prostate gland, which again is very common in the same age group, so those men will presumably present with slowing of their stream, hesitancy, getting up at night, frequent urination, and those are related more to an enlargement of the prostate gland as opposed to prostate cancer, but sometimes they could have both.  It is uncommon nowadays to have someone present with symptoms from their prostate cancer. In the

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                        old days they came in with bone pain, or weight loss or malaise; symptoms we would see 20 or 30 years ago.  The typical men we see are ones without symptoms of prostate cancer but they may have symptoms related to an enlarged prostate gland or something called prostatitis, which is just an inflammation of the prostate gland with burning, frequency, or pain.

Wilson
What are some of the risk factors that are associated with this?  We know about smoking and lung cancer, for example.  How about prostate cancer?

Colberg
The three big risk factors of prostate cancer are age, meaning the older you are the greater chance you have to develop prostate cancer, race or nationality, meaning that African-Americans certainly have a higher incidence of prostate cancer and when they do develop prostate cancer and found to have prostate cancer, they tend to have a much more aggressive form of prostate cancer.  We know that people of Northern European descent have a higher incidence of prostate cancer versus someone from Asia, and thirdly is family or genetics, meaning your family history.  If you have a father, brother, or grandfather who had prostate cancer, your risk is higher.  These men had to have developed their prostate cancer at a younger age.  If your father is 80 years old and developed prostate cancer, that does not mean you have a higher risk of getting prostate cancer but if he had prostate cancer when he is 62, that puts you at a little higher risk of developing prostate cancer.

Foss
Is there an association between prostate cancer and some of these other family cancer syndromes like the colon cancer syndromes, and the lung cancer syndromes?

Colberg
Not that we know, because prostate cancer is so common. We mentioned that over 200,000 people are diagnosed a year with prostate cancer.  There is no familial or organ system type of incidence of prostate cancer and other types of cancers.

Wilson
How is prostate cancer usually diagnosed?  Tell us what happens if a patient's doctor is concerned maybe about an enlarged prostate and they refer the patient to you.  What steps would you take?

Colberg
There are two reasons why men will come to see us with a concern for prostate cancer.  One is their doctor may feel an abnormality on the rectal examination. When the doctor feels the prostate with his fingers through the rectum, he may feel a lump or bump, firmness or hardness, and that does not mean he has prostate cancer, but it is something that needs to be further pursued. Much more commonly we see men come in with an elevated PSA level.  PSA is a blood sample and it has been around since 1988.  In 1989 it was approved by the FDA for screening.  This measures a protein in the blood called prostate specific antigen and it has been shown that if it is elevated it is a little bit of a red flag.  It does not mean that everybody who has an elevated PSA level has prostate cancer, but that may be a test that you want to pursue to make sure they do not have prostate cancer.  Typically the two other things that make the PSA level go up are an enlarged gland, again we talk about BPH, or some type of inflammation of the prostate gland. 

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                        The normal numbers of PSA gets a little bit confusing as to what the normal level is.  People historically have thought that a number 0 to 4 is normal.  Now we know that in younger men probably 4 is too high and for an older man 4 may be too low and that is why they came up with age reference PSA levels that take that into effect.  Also an important thing is the change of your PSA level, meaning that if you have a "normal" PSA level in the ones, and you present a year later and your PSA is three, even though it is still less than 4, that is a concern that there may be something actively going on in the prostate gland.

Wilson
If you had someone with an elevated PSA, say it was significantly elevated with an abnormal finding on their examination, and they were 72 years old, what would be the next step for that person?

Colberg
You sit down with your patient, you discuss that these are concerning findings on exam and the blood work and then the next step, if he wants to know if he has prostate cancer, would be to have a biopsy.  The biopsies are done in the office.  We use an ultrasound to guide us with the biopsy.  We do it under local anesthesia like the dentist does.  It takes 5 to 10 minutes to perform, usually results come back in 2 to 3 days depending on pathology and you get your answer.  I think that is probably the next step for someone who is 72.  If he was 82 or 85, he may not want to do that.  He may want us to just follow him, so it gets a little bit grey when you start talking about ages, but certainly a 72-year-old healthy man with a 10 year life expectancy will want to be more aggressive.

Foss
Can you just back up one minute and talk to us a little bit about the process of screening, how old should a man be when he starts getting annual rectal exams and PSAs?

Colberg
That it is a great point because the American Cancer Society has very good recommendations, and if you have a family history like we have talked about, a father or brother who developed cancer in their 60s or less and you are African-American, you should be screened somewhere between 40 and 45 with a PSA level and a rectal examination.  Everybody should be offered screening at age 50 or older with the yearly digital rectal examination and PSA level knowing that screening may lead to a biopsy, which may lead to the diagnosis of prostate cancer, so the patient is informed what his options are.

Foss
When do you use ultrasound or any other kinds of imaging studies?

Colberg
We use the ultrasound to do the biopsy because it aids us in directing where we want to put the biopsy specifically.  There are certain points in the prostate gland where more than likely the cancer is going to develop, they are not usually in the middle of the prostate, they are in the posterior zones, or posterior lateral zones, so that is where you want to target your biopsies, where 80% to 90% of the cancers will develop.  The ultrasound will tell us two things, it will tell us the size of prostate gland, so if you do an ultrasound and the prostate is really big, and it has

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                        an elevated PSA level, that may be a reason why his PSA level is elevated, but if he has a very small gland with PSA levels elevated, that is a time when you will be more concerned. It will not tell us where the cancer is, it would not tell us how big the cancer is per se, unless there is a very big abnormality in examination.

Wilson
Tell us about some of the different treatment options?

Colberg
This is where it gets very delicate as far as options are concerned.  The same option may not be ideal for every patient you see.  It is not like breast cancer, colorectal cancer, or lung cancers where the algorithms are worked out as far as if you present with X, you get Y and Z.  Prostate cancer is very individualized; the disease is heterogeneous. Cancer in one man may not be the same as in another man.  We look at several things when you talk about treatment for prostate cancer, a patient's age, a patient's health, PSA level, clinical exam based on what you feel during the rectal examination, what we call the Gleason score, what the pathology is under the microscope from the biopsies, and ultimately it depends on the patient's wishes and what he would like to do.  But essentially there are three options.  He can have some form of radiation therapy, which is either giving external beam radiation therapy, where he would come in every day Monday through Friday for usually about 8 weeks where they get radiation to the prostate area, or they can have another form of radiation therapy called brachytherapy which is little pellets that are implanted in the prostate gland and it is kind of a one shot deal where they are placed under anesthesia.  The patients come in one time and the radiation therapy is released over a couple month period depending on what type of implant you get, typically we use either iodine or palladium, and the seeds stay there forever, but the radiation therapy is released over a 2 month period.  That can be done in combination with we call hormonal therapy, depending on what type of grade a tumor you have. The Gleason score and the grade is based on the system of 2 to 10, ten being the worst and 2 being the best.  Most patients are 6s and 7s.  They get what we call hormonal therapy which is an injection that drops the level of testosterone; sometimes you do not need hormonal therapy.  Some people will combine the radiation therapy both external beam and seeds together and that depends on exactly what type of grade the tumor is and the clinical stage.  The other option is to do surgery, and surgery is to remove the prostate gland with the seminal vesicles which are little structures behind the prostate gland and you also take out lymph nodes at the same time, and thirdly, something which is getting more and more interest is something called active surveillance.  We know that everybody who has prostate cancer does not die of their prostate cancer.  We know that the vast majority actually do not.  Only 30,000 people die of prostate cancer a year and 200,000+ get it a year, so there is certainly a difference between the incidence and the mortality, so there is a sliver of patients, maybe 20% of patients who actually do not need treatment for their prostate cancer.  The problem is how to identify those patients you can safely follow without treatment.  There have been lots and lots of studies looking at who can be followed safely without treatment, on a protocol called active surveillance versus ones who should not and those patients who decide to not be treated are followed very closely.  They get blood samples three times a year, they get exams three times a year, they get repeat biopsies, usually after one year and then if everything is unchanged, we will do it every

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                        two to three years, but it requires a very compliant act of an actively involved patient who desires to do this and often times that is very difficult.  You tell a 65-year-old man he has prostate cancer and that we probably do not need to treat them, they can be followed, a lot of men will be attracted to that option, but often times they are not.

Foss
There must be some significant downsides to some of these therapies.  Could you talk a little bit about that?

Colberg
I think that has been the Achilles' heel for prostate cancer treatment since the first prostatectomy was done in the 30s and 40s.  The real complication from surgery, and we can talk further about it, is incontinence, the inability to control urine, and also something called erectile dysfunction.  Both of them are measurable, percentage wise, usually incontinence, depending on who you talk to and how you define it, may be on the order of 5% to 20%.  Erectile dysfunction is more difficult because it is a harder thing to get at, it may be depending upon age, the younger you are the better you do, and what your function is before the operation.

Wilson
We are going to take a short break for a medical minute.  Please stay tuned to learn more information about prostate cancer with Dr. John Colberg.

Wilson
Welcome back to Yale Cancer Center Answers.  This is Dr. Lynn Wilson and I am joined by my co-host Dr. Francine Foss.  Today we are joined by Dr. John Colberg and we are discussing prostate cancer.  John, before the break you were talking about some of the side effects such as erectile dysfunction, go ahead and continue that conversation with us.

Colberg
We talked a little bit about surgery and the way we do the operation. The way a man becomes impotent or loses erection after the operation is a fact that the prostate is kind of enveloped by certain nerves that supply the vessels that result in an erection in a man, so when you take the prostate out, you try to preserve those bundle fibers on the sides of the prostate gland and depending on the tumor and where it is located, will depend on if you can save one or both or neither of the nerves.  Certainly, the better outcome is the one where you try to preserve both

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                        bundles. After the operation, the man may not get erections for 3 months to 6 months.  It may take 12 months to 18 months to actually get some function back.  Often times, what we will do is we will begin the man on oral medication.  Typically, the ones we use are Viagra, Cialis, and Levitra.  If that does not work, there are other treatments we can use, there are vacuum erection devices, we can use injection therapy where we actually inject medication into the penis with a liquid medication that allows them to obtain an erection for a period of time.  If all those fail after a period of time, the last option would be something called an implantation, or penile prosthesis.  Again, the important part of who is going to get erections after the operation is the younger you are the better you do and also what your status is before the operation.  If you have a man who is 70 years old having difficulty getting erections before the operation, there is a very good chance he is not going to keep his erection no matter what type of a perfect operation you do, but if you have a 50 year old man who has good erections before the operation, then he should do quite well, and those numbers vary.  For the younger man their potency rate after the operation should be 70% or 80% or higher, if you are 70 years old, that number is well below 20% or 30% probably.

Foss
If you opt to have the surgery or the brachytherapy, are there effects on erectile function?

Colberg
Yes, I think that the difference between surgery and radiation therapy is the fact that men who have radiation therapy actually have fairly good erections maybe during and after the radiation therapy if there are not on hormonal therapy and then over the years maybe 2 to 3 years their erections kind of dwindle down, so the lines kind of cross with radiation and surgery probably 3 to 5 years after the original treatment.  So the erections in radiation patients are usually quite good initially, but then they get worse over time as opposed to surgery, where they start out poorly and they get better overtime.

Foss
What are the complications of the hormonal therapy?

Colberg
The big complications for short term hormonal therapy are hot flashes, so the decrease of testosterone level, the man will feel warm when he's cold and cold when he's warm.  They will have these hot flashes or sweating episodes.  It probably happens in half the patients and some can be just minor, some can be very debilitating.  The other issues are that you will lose your sex drive or libido because you do not have a testosterone level.  Once he stops the hormone shots, the testosterone level will come back and both those symptoms will get better, that's for short term treatment.  If you are on it long term, there are lots of other issues of bone density, loss of muscle mass, cognitive issues, anemia, that is when you are on it for years and years and years and typically a man with localized prostate cancer is not on it more than six months to a year typically for radiation therapy.

Wilson
John, what about incontinence?

Colberg
Yes, that is the other issue with surgery, not so much as with radiation therapy because radiation

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                        therapy, both seed implants and radiation therapy, it is usually the opposite.  The man may have difficulty urinating perhaps, they have a slowing of their streams, they have some hesitancy, they may actually not be able to urinate at all, as opposed to surgery where he has trouble controlling the urine.  That is based on the fact that they have two sphincter mechanisms ones at the bladder neck and one at the pelvic floor.  When you take the prostate out, you are relying on the pelvic muscle to keep control of your urine and it is developed differently in different men so that when you take the catheter out after the operation, usually a week or 10 days, these men will have difficulty urinating, often times they will be incontinent for days.  They will wear six or eight diapers a day, but they slowly get control over the urine and that may take a week, it may take a month, it may take six months, or a full year.  Usually men improve, so if I see a man back from the operation a month or two after the operation and he is leaking like it will do when the catheter comes out, I get concerned, but if he says, listen I am 50% better or 30% better, then I am not so worried that he will get control of his urine.  Men will always have what we call stress incontinence when they cough or sneeze, or pick up something heavy, they may squirt a little bit of urine, but the incontinence rates are kind of difficult to tease out, but usually somewhere around 5% if you do a lot of the surgeries, if you do not do a lot of the surgeries and only do 1 to 2 a month, that number may go up to 15% to 20%.

Wilson
Just a real quick question, on average, how many nights are patients in the hospital for if they have the operation?

Colberg
The way we do the operation, and most of them are done today not with an incision but with what we call robotic, laparoscopic or assisted robotic prostatectomy using a system called da Vinci System, and those men, at least my patients, probably 90% or plus will go home the next day, versus 5 year or 6 years ago when we did an open operation, we made an incision, those men typically were in the hospital 2 to 3 nights.

Foss
Can you explain the da Vinci System to us?

Colberg
Initially the first step in this was to do it purely laparoscopically where you put instruments in to the body and you did the operation like you did an open operation, but through small incisions.  Now, there is a robotic system where the surgeon operates arms of this robot from a remote position in the same room but across the room, you control a camera and 2 arms with an assistant and actually do the same operation but through much smaller incisions, so you make usually 6 small incisions with a camera and you can do the operation like you would do an open one.  The advantages of a robotic prostatectomy are less pain, less time at the hospital, less time with a catheter, minimal blood loss, and the results seem to be comparable, meaning incontinence, impotence, and ultimately cancer control, meaning the patient does as well with that operation versus an open operation.

Wilson
This is a somewhat newer technology, John, and any kind of surgery is complicated, could you comment on the importance of the operator's experience?  Is this something that you can watch a

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                        couple being done and you are pretty good at it, or do you have a sense that it is something that you should do quite a few times with supervision, tell us about the learning curve?

Colberg
I will give you some numbers. In 2003, 2004 there were about 400 robotic prostatectomies done in the whole United States.  This year 85% of all prostatectomies, probably somewhere between 60,000 or 70,000, will be done by robotic system, it is a technology that takes some learning, has a learning curve, but it is not as great as doing pure laparoscopy.  I have done probably over a thousand open prostatectomies before I learned the technique.  You need to observe the patients, you need to have proctored cases, meaning people who have experience come and help you do your first three to ten to twelve, depending on what your hospital requires, and then basically you do your operations by yourself.  Anatomy is anatomy, it is the same anatomy, it is just different tools and skills.  There is a learning curve and I think that just like any type of operation in urology, the more you do the better you are at them, the better results you have, and the better outcomes you have.

Foss
Are there specific men that may not be eligible for this approach?

Colberg
I would say for every 20 robotic prostatectomies, I do one open prostatectomy and that is based on if the patient had a significant amount of prior surgeries, colon surgeries, prior bladder surgery, prior prostate surgery, maybe he has got a really big prostate gland and it may be difficult to do robotically, but it is becoming very, very uncommon to do an open proctectomy.

Foss
And this does not require general anesthesia, is that correct?

Colberg
No, they have the same anesthesia as for an open prostatectomy.

Wilson
We have talked about a lot of details, John.  Tell us a little bit about the program itself.  How can patients come to Yale, where are they seen, how does multidisciplinary care work?  Give us some comments along those lines.

Colberg
Probably by early next year, we will all be located on the fourth floor of Smilow Cancer Hospital.  Right now, I am still seeing patients in the Physician's Building on Howard Avenue.  We have a team of radiation oncologists, medical oncologists, radiologists, and pathologists that will be centralized on the fourth floor in Smilow, so we will be seeing patients all at the same time, so that if you need help with medical oncology, radiology or radiation oncology, we will all be able to look at the patient and give them the best care, hopefully in one visit or minimal visits.  We have a tumor board that meets twice a month, where we discuss all the patients, and again, the patients are shared mutually so that they get the best outcome and the best treatments.

Foss
Can you talk about supportive care for the patient and their family as they go through this process?

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Colberg
It is really important and probably not something we have done a great job with historically, but certainly now my patients go the 15th floor of Smilow Cancer Hospital to a brand new floor.  There are social workers, there is nursing, and my resident staff is there. We try to meet all the non medical day to day issues of the patient so that they are able to, when they go home, have supportive care as far as visiting nurses, so that they have a little more support staff and structure for when they go home and take care of themselves.

Wilson
Are there clinical trials that are available for patients, and what do you see in the next five to ten years down the road for patients with prostate cancer?

Colberg
There are clinical trials and I think where we focus a lot of clinical trials is on the patients who we have not done very well with using just one form of treatment whether that is radiation therapy or surgery, where we find a patient that may be an operative candidate, radiation therapy candidate, but maybe that is not enough, maybe they need more treatment before or after. So one area that we are working on is what we call the high risk patient, the patient that even though you may think it is still confined to the prostate gland, the radiation or surgery may not alone help. And the other patient is obviously the patient who has developed metastatic disease where the prostate cancer has come back after surgery, it has come back after radiation therapy, and you try to treat them with different types of chemotherapy or hormonal therapy and that is where I think that we are starting to make a little bit of inroad with.

Dr. John Colberg is an Associate Professor of Surgery and Director of the Yale Uro Oncology Program.If you have questions for the doctors or would like to share your comments, visit yalecancercenter.org, where you can also subscribe to our podcast and find written transcripts of past programs.  I am Bruce Barber and you are listening to the WNPR Health Forum on the Connecticut Public Broadcasting Network.