Your sitemaster is gradually “coming back to life” after a rather unpleasant week that included his trip to the GU Cancers Symposium (when he should probably have been in his bed at home). So here is the quick summary from Orlando.
There was no significant “breaking news” at this years’ GU Cancers Symposium; no exciting data from Phase III trials; and a limited amount of truly actionable data from Phase II studies. From that perspective the meeting was a “down year”. Everyone is still waiting to see what comes out of the Prostvac trial … although a couple of “little birds” were also suggesting forthcoming announcements of some interesting outcomes from the next phase (Arm G) of the STAMPEDE trial in the UK (the addition of abiraterone acetate/Zytiga + prednisone to the “standard of care”).
So, with that context, the two most interesting components of the meeting from a clinical prostate cancer perspective were:
- The opening session on “Active Surveillance for Prostate Cancer” and
- Dr. Charles Drake’s lecture on “Immunology of Prostate Cancer”
The opening session used Howard Wolinky’s clinical experience of 6 years on active surveillance as a backgrounder for the various lectures and discussions. And it is clear that adoption of active surveillance as a first-line management strategy is already far more advanced in Canada and in the UK than it yet is here in the United States. There are all sorts of reasons for this, including:
- Sociocultural factors
- The “nationalized” health care systems in place in the UK and Canada
- The greater and easier access to MRI technology in the UK
- The US medico-legal culture
- The system of financial benefits in the US that favors immediate treatment (from a physician perspective)
- A higher degree of “cancer-phobia” in the US
However, it is also clear that a huge corner has, in fact, been turned, and many, many men who would have been operated on or radiated without a moment’s serious thought 5 or 10 years ago are now being advised to consider active surveillance as a standard form of first-line management for low- and very low-risk forms of prostate cancer. thus allowing them to avoid all of the potential side effects and complications of unnecessary, immediate treatment, while simultaneously ensuring that such treatment is easily available and accessible if it seems to be necessary 1, 2, 5, or even 10 years later.
The session included Dr. Laurie Klotz’s evaluation of the state of guidelines regarding the treatment of prostate cancer in the UK, Canada, and the USA; Dr. Freddy Hamdy’s review of the data from the ProtecT trial; Shonit Ponwani’s update on the role of MRI scanning in the diagnosis and management of prostate cancer in the UK; Lorelei Mucci’s commentary on the role of genetic and genomic tests in the selection of patients from active surveillance; and of course Howard Wolinsky’s own comments on the importance of appropriate communication between physician and patients and the continuing education of the patient so that he understands that active surveillance, when appropriately carried out, really is a high-quality management strategy and not just a sophisticated form of “watching and waiting”.
It will probably take another 5 to 10 years before we have “standardized” active surveillance into the management of low-risk prostate cancer here in America to the degree that has already been accomplished in the UK and in Canada. It is easier to make such changes within nationalized health care systems, but progress is being made, and The “New” Prostate Cancer InfoLink is delighted to see that change.
Dr Charles Drake’s lecture on the immunology or prostate cancer presents us with a very different challenge.
Dr. Drake is an unabashed enthusiast and advocate for the application of immunobiological science to the treatment of progressive and advanced forms of prostate cancer. And his enthusiasm can be infectious. He knows every detail of which he speaks and every nuance of the differing agents that have been and are being explored … from sipuleucel-T/Provenge and ipilimumab/Yervoy to the latest PD-1 inhibitors. And let us be very clear that immunologic forms of therapy are going to have a significant role to play in the future management of higher-risk forms of prostate cancer. But … there are some serious “buts”.
The available data on the effectiveness of treatment of prostate cancer using immunobiological forms of care and treatment are limited. Sipuleucel-T is still the only form of immunobiological treatment that has ever been approved for the treatment of prostate cancer. It was approved back in 2010 for the treatment of men with asymptomatic or minimally symptomatic, metastatic, castrate-resistant (hormone refractory) prostate cancer. In such patients it provided a 4.5-month survival benefit compared to a placebo, but at a cost that is now > $100,000 per course of treatment. And treatment with sipuleucel-T is associated with a list of common side effects, some of which are distinctly serious (e.g., bladder pain; bloating or swelling of the face, arms, hands, lower legs, or feet; bloody or cloudy urine; body aches or pain; chest pain; chills; confusion; cough; diarrhea; difficult, burning, or painful urination; difficulty with breathing; difficulty with speaking up to inability to speak; double vision; sleeplessness; and inability to move the arms, legs, or facial muscles).
And the costs and side effect profiles with many of the other new forms of immunotherapy are going to be equally problematic. In his lecture Dr. Drake referred frequently to the occurrence of grade 3 and grade 4 side effects in ongoing or recent trials of immunotherapeutic drugs or drug combinations in the treatment of advanced prostate cancer. (A grade 5 adverse reaction is death, so a grade 4 adverse reaction is pretty darn serious.)
Your sitemaster is concerned that we may see the approval (here in the USA, over the next few years) of a number of immunological drugs for the treatment of prostate cancer which offer limited survival benefit, at very high cost, with 30 to 50 percent risk for serious grade 3 and grade 4 adverse reactions. This would mean that, yes, for those who do well, there may well be an extra year of life, but to accomplish that extra year of life you are actually risking very serious complications associated with treatment — quite apart from the cost factor. Few of the patients receiving treatment with these drugs are going to be living with a truly high quality of life for extended periods of time.
The “New” Prostate Cancer InfoLink is all too aware of the attraction of the argument that any drug that offers a survival benefit should be approved because it offers “hope” and “choice” to patients. However, we are also equally aware of the failure of our healthcare system to advize patients thoroughly of the risks they may be taking when they decide to use some of these new classes of drug. We know that (at least as of today) they actually cure a very small number of patients; they induce serious consequential side effects in many (up to and including death); and (rather like the ads one sees for certain types of weight loss system) the best results “are not typical” and can’t be relied upon.
Enthusiasm and advocacy for what one believes in as a research scientist is one thing. We do not fault Dr. Drake for that. However, the day-to-day clinical use of the types of products he and others have been working on will be a great deal more likely if there is a risk/reward equation that shades strongly in favor of actual patients and their families as opposed to the researcher and the drug manufacturer.
Filed under: Living with Prostate Cancer, Management, Treatment | Tagged: active, Cancers, genitourinary, immunotherapy, surveillance |
THE "NEW" PROSTATE CANCER INFOLINK 
It would seem that Dr. Klotz (from the report on Urology Today) has made a landmark statement this time around in saying he thinks the current study results support doing active surveillance (AS) only on patients with Gleason 3 + 3 disease and not on those with Gleason 4 disease because of the higher risk of metastases and death with Gleason 4 disease. He went on to say that doing AS on patients with Gleason 4 disease requires the utmost care and caution.
This conclusion of Dr. Klotz seems like a very big deal because he up to now has been the advocate of more flexible AS protocols, and now he has drawn a line in the sand and basically said he has been wrong with these looser protocols.
This is a real step forward towards a more unified and simpler way of doing AS that has the potential of better serving the patient from a morbidity and survival standpoint.
Perhaps this site would like to say more about Dr. Klotz’s recent statements.
Thank you.
Dear Walter:
Actually what Dr. Klotz said at this meeting is by no means new at all. He has been saying this for quite a while, and what he said is entirely in line with the active surveillance guidelines issued on December 10, 2014, by Cancer Care Ontario (of which Dr. Klotz was one of the key authors), i.e., more than 2 years ago. The CCO guidelines were also endorsed, with some minor modifications, by the American Society for Clinical Oncology early in 2016 (see here for the details).
The problem is not what Dr. Klotz said. The problem is that whoever was reporting on his presentation for UroToday implied that he was saying something new. He wasn’t!
The guidance available from the CCO and the ASCO guidelines represents a very “safe” form of applying active surveillance in that the priority is both to avoid risk for progressive disease to the greatest degree possible while also avoiding initiation of unnecessary treatment in the men most likely not to need it. However, at the end of the day only an individual patient can make his own decision about that risk/benefit equation. Exactly how little Gleason pattern 4 cancer (and the genomic makeup of that Gleason pattern 4 cancer) that can be monitored with a high degree of safety is still completely unknown. And Dr. Klotz would be among the first to agree with that.
Sitemaster,
Thank you for allowing open discussion of issues like this one on AS, so that others can have more complete information to make their own informed decisions, as you say.
The good thing that seems to have come out of all this AS discussion is that more and more people are accepting of the fact that maybe Gleason 4 patients do not belong in AS unless other risk stratification can be done in those cases such as by genetic analysis to render this a more justifiable approach in such cases.