ASCO 2011 Annual Meeting, 3—7 June 2011, Chicago
Treatment options for prostate cancer
Professor Otis Brawley (American Cancer Society, Atlanta, USA)
The first thing is, in terms of prostate cancer screening, we have one study, a European study, that suggests that prostate cancer screening saves lives; we have an American study that suggests it does not. We have the PIVOT trial of prostate intervention versus observation trial which was presented in the abstract at the American Urological Association and it questions how good early prostate cancer treatment with radical prostatectomy is versus observation. The answer is we still don’t know a lot of things about prostate cancer that we desperately need to know about. I firmly believe that in terms of screening men need to know that there is a controversy and need to understand that some of the risks are proven, but some of the benefits are starting to be proven as well and men need to weigh the benefits and the risks and make a decision that they’re comfortable with.
In terms of prostate cancer prevention, we’ve had the prostate cancer prevention trial with finasteride, the reduced trial with dutasteride, both of which show 5-alpha reductase inhibitors decreased risk of getting prostate cancer, but both imply that diagnosis of high grade tumours may be higher. Now we don’t think that these drugs are causing higher grade tumours, we think that they are making it easier for those high grade tumours in small size to be diagnosed. So men need to know all these things and then make a decision about what’s right for them.
And how do you present that little paragraph in language that I understand, having left school sixty years ago with not very great qualifications. I’ve not got a job, I’ve now got a pension and, you know, am I caring?
It’s a tough question. I think what we need to tell men is we do not have really definitive proof yet that prostate cancer screening saves lives. We have studies that suggest that it might but we have studies to suggest it might not. We know that a good proportion of men who are diagnosed with prostate cancer have a kind of cancer that was never going to bother them, but we are going to treat them and they are going to get needless treatment and they are going to be cured but they didn’t need to be cured. And then a man needs to go with his gut feeling. If he is very concerned about prostate cancer, if his personal experiences are people in the family or friends who have died of prostate cancer, he might legitimately choose to be screened. If he is less concerned about prostate cancer he might decide not to get screened for prostate cancer.
That was very eloquent, as usual. Now let’s discuss the treatment issues, because you have to have that discussion.
Linked to the last paragraph, because you are talking about the treatment option, where are you to agree to have the treatment; because you have seen people with bony metastases dying in pain? It shouldn’t happen nowadays. How do you go about that discussion? I mean you are a real expert at this and you must be better than I am at it. You have a number of options, and how do you lay them on the line?
If a man is diagnosed with prostate cancer, I first encourage him to make sure that his biopsy is reviewed by at least two pathologists and that those pathologists are people experienced in assigning a Gleeson score and describing the tumour. Some men, depending on their age, depending on the percentage of cancer that’s in the biopsy and the grade of the cancer, might very well choose to be watched for a while, perhaps get a PSA every six months and re-biopsy it after a year or two years. In the United States men really tend not to want to be watched, they are very impatient; in Europe I think people are much more tolerant of being watched.
They are less trusting of doctors.
Hmm. And now when the time comes that a man needs to be treated, be it immediately or deferred, and I know some people who have deferred the decision successfully for 15 or 20 years, when the decision to be treated is made I really think men need to look at all the various treatment options, be it surgery, external beam radiation, which can be given through a couple of different modalities now. In the United States we are even using proton beam now to treat prostate cancer, as well as seed therapy, radioactivity palladium and radioactive iodine seeds. Cryotherapy is an option; I personally don’t like cryotherapy. I think men need to understand all of those different options, all the various side effects. I think, quite honestly, the most important thing is that the man chooses a treatment that he likes with a doctor that he trusts. And I encourage men to go talk to doctors who do all the various therapies and then, if they are going to get treated, go with their gut feeling about what they feel comfortable with.
Multidisciplinary teams exist and flourish in this part of the world?
Multidisciplinary teams are starting to really come together in prostate cancer. For years in the United States we had the urologists in one camp where most of the patients were; when they got very sick the medical oncologists would get involved; the radiation oncologists were the third camp. Now you actually see people talking to each other. When you go to the major cancer centres it’s not unusual for the patient to see a urologist, medical oncologist and radiation oncologist all in one visit and have this conversation about treatment, sometimes with all of them present.
Do you see any possibility ever of having a head on randomised trial but for the prostate cancer patients who want therapy between, let’s say, a minimum invasive surgery and minimum invasive radiation therapy; so CyberKnife versus robotic?
Well you know the problem is technology has changed so quickly. The PIVOT trial, which was radical prostatectomy versus observation, was started in 1992, took quite a while, they had to go through about 12,000 patients in order to get less than 1,000 enrolled. So many men didn’t want to compute it and make a decision about observation. And then you had the follow on and now after about 15 years we’ve got follow up with 12–13 years median. The end result is I think many of these questions have got to be answered using some kind of validated surrogate marker. Any study that we wanted to do right now looking at radiation versus surgery is going to take 15 years to get an answer, and 15 years from now we are going to be using a totally different kind of radiation. You know, proton beam was not used to treat prostate cancer just 5 years ago.
On the other hand, some of these new gimmicky therapies, for me protons are still a gimmick, they seem to sneak into the armamentarium without the sort of strict evaluation that a medical device, like a drug or a hormone or a vaccine, would have to undergo.
You are absolutely correct, and part of that is people wanting new technology. We see this with the Da Vinci robot as well as with proton beam: hospitals wanting to provide the latest technology and wanting to attract patients because they have the latest technology. This is actually very, very worrisome, for example with the Da Vinci robot, it’s a great machine if the operator, the surgeon, who is actually using the machine is well skilled in it. And outcomes with a well skilled surgeon are the same or perhaps even better as outcomes with someone who does the conventional open prostatectomy. But the number of surgeons who are really, really good and skilled at using the robot is actually quite small. I am also worried, by the way, that in the long term we are going to have a generation of urologists who are afraid to operate in the traditional format when traditional surgery is actually necessary.
Now, we were talking in Lyon about the late effects of management of prostate cancer which are put down to androgen exposure and to over-zealous and maybe misconceived application of androgen targeted therapies. We are now seeing deaths in men who do not have prostate cancer any longer but they are dying of cardiovascular disease and all sorts of things. How are we going to resolve that?
Well one of the things we are very concerned about is there’s now at least half a dozen studies in the literature that show that lupron, zoladex, all of these androgen blocking drugs, cause increased rates of diabetes, cardiovascular disease as well as sudden death. We really are concerned that over use of those drugs, there are some appropriate uses in prostate cancer but there are some prostate cancer patients who perhaps have no evidence of disease except a rise in PSA, who have been put on these drugs and actually may be harmed. Some of the studies actually suggest that we are literally causing an early demise of some of our prostate cancer patients and there is actually concern in the United States that overuse of these drugs has actually led to a decrease in the prostate cancer death rate by causing people to have heart attacks and die.
Before they die of the prostate cancer?
Before they die of their prostate cancer; tremendous concern. Also a special problem in the United States is we now have studies to show that as Medicare reimbursement for these GNRH analogues went down, inappropriate over-prescription of these drugs also went down.
OK, the new generation of drugs in the castration resistant patients now, abiraterone?
Oh, one cannot be other than excited.
It’s a bit early?
Yeah, abiraterone you have to be tremendously excited about that. I actually have some excitement as well for the vaccine provenge. You know, this is a wonderful time in prostate cancer medicine. I have been doing prostate cancer for now nearly 25 years and we actually seem to have things that work. It started with taxotere and prednisone, now about 10 years ago, but we’ve gotten other things now that are seemingly wonderful. Now some of the advances, you know, taxotere and prednisone, increased median survival by 3-4 months; provenge increased median survival by 3-4 months. Those seem like small incremental advances but they are advances and I remember when we had none, and so I think abiraterone is even better and I think we are going to see a few other things coming down the pipe and some very exciting times to be in prostate cancer medicine.
It’s very exciting having you here again, but there is a big meeting out here at ASCO and we had better get on. Thank you very, very much indeed Otis.
Oh this has been fun, thank you.
All the best.