Recently posted on the UroToday web site are summaries of four “state-of-the-art” lectures on prostate cancer and its management presented a couple of weeks ago at the annual meeting of the European Association of Urology is London.
Patients and advocates can access these summaries for themselves (for free) at the links given below — but you do have to register with the UroToday web site:
- Dr. Patrick Walsh, of Johns Hopkins in Baltimore, MD, discussed “Hereditary prostate cancer”, with a focus on the importance of identifying mutations that can lead to appropriate testing of individuals at high hereditary risk for prostate cancer and allow for the development of targeted therapies.
- Dr. Philip Cornford, of the Royal Liverpool and Broadgreen Hospitals NHS Trust in Liverpool, England, lectured on “EAU Guidelines on mCRPC – An Update”, addressing the increasing complexity of when and how to do what and for which patients in the management of metastatic, castration-resistant prostate cancer (mCRPC). For additional background on this topic, see pages 84-92 of the European guidelines on prostate cancer issued in 2016.
- Dr. Silvan Boxler, of the University Hospital, in Bern, Switzerland addressed “What do urologists need to know about mpMRI targeted biopsy?”, and
- Dr. Philippe Puech, of the Université du Droit et de la Santé in Lille, France, talked about “Levels of competence in mpMRI reporting” and what urologists should expect (in terms of such competence) from the radiologists who conduct and “read” such MRIs and report their findings to the treating urologist (or radiologic oncologist).
What is clear from the last two of these lectures is that uptake of multiparametric MRI scanning as a key part of the work-up of prostate cancer patients is far more advanced in Europe than it is here in the USA. Cost is certainly a key factor here, because the cost of an mpMRI scan here in America is far higher than it is in most of the rest of the developed world.
Filed under: Diagnosis, Living with Prostate Cancer, Management, Risk, Treatment | Tagged: hereditary, mCRPC, mpMRI, review, state-of-the-art |
THE "NEW" PROSTATE CANCER INFOLINK 
Regarding DR. CORNFORD’S TALK ON CRPC AND METASTASIS: ““EAU 2017 “Controversies in Metastatic Prostate Cancer”, Dr. Philip Cornford delivered the highly anticipated update of the EAU Guidelines for metastatic castration-resistant prostate cancer (mCPRC)””:
I recently finished studying the DVD videos of talks, Q&A and moderator reviews of the presentations from the 2016 Conference on Prostate Cancer in Los Angeles last September. Reading the review of Dr. Cornford’ presentation, some good points were evident, but overall I was struck by how passive this approach looked compared to a seemingly much more proactive approach advocated by prominent doctors who presented at the conference, including Dr. Charles “Snuffy” Myers, Dr. Nick Vogelzang, Dr. Eugene Kwon, Dr. Mark Scholz, and Dr. Mark Moyad, as well as others. Here are a few salient points, also including other relevant positions expressed by these physicians that contrast with the review of Dr. Cornford’s presentation.
DEFINITION OF CRPC: Dr. Cornford (and apparently the new guidelines) continue to use the standard but obsolete testosterone element of the definition of CRPC: ““Dr. Cornford reviewed the definition of CRPC, including a castrate level of serum testosterone <50 ng/mL plus either….” To many of us, that represents a failure to rigorously determine that ADT is no longer working. The level should be <20 ng/mL (with a rising PSA, etc.). Moreover, there is no mention of monitoring DHT, which is critical as it is far more potent than testosterone as a fuel for the cancer and can wreck an ADT program. Many of us are convinced that a lot of patients deemed to have CRPC would still respond well to ADT if the ADT were adjusted based on adequate testing and follow-up, such as adjusting the dosing schedule and adding needed drugs (such as an antiandrogen and/or 5-alpha reductase inhibitor drug, etc.). As a patient I find this failure to rigorously determine that the cancer is castrate resistant most disturbing! But it is not just a European problem; this failure is common in the US as well.
IMAGING: The imaging mentioned by Dr. Cornford is bone and CT scans, not specifying whether the bone scan is technetium based or the far superior NaF18 PET/CT, and with CT scans known to be relatively insensitive compared to superior technology. There is no mention of C-11 acetate or choline scans, or PSMA scans that are becoming more available, all of which are much superior for assessing lymph node and other soft tissue disease, and perhaps bone involvement as well.
GENETIC TESTING: There is no mention of genetic testing except for a lone reference to AR-V7 mutations, which are mentioned as a problem but not as a treatment guide. Not all conference presenters in Los Angeles were onboard with genetic testing; notably Dr. Kwon was unenthusiastic. But at the conference Drs. Myers and Vogelzang made clear that they used genetic testing as part of their kit of important tools.
TREATMENT OF CRPC PATIENTS: This is from the summary: ““In summary, patients with CRPC should not receive treatment outside of a clinical trial until they are metastatic. Treatment decision making is largely based on patient performance status.” The concept in Dr. Cornford's talk is to wait for metastases to become evident rather than to look for them early (such as with the C-11 choline or acetate or PSMA scans) and, if the spread is oligometastatic (just a few, especially three or fewer), wipe them out if possible, typically with spot radiation or surgery. The Wait And Get Clobbered Strategy is very different from the proactive strategy presented at the 2016 conference.
There should be a high demand for MRI service which should in turn create a lower price due to providers moving in to create a healthy supply of service but, because the urology community does not want to recognize this as a valid methodology, the price remains high .
Dear Jim:
Just because there are researchers investigating other forms of therapy for CRPC does not make the EAU guidelines “wrong”. And actually I would entirely agree with Dr. Cornford and with the EAU guidelines that “patients with CRPC should not receive treatment outside of a clinical trial until they are metastatic.” We have no established form of effective treatment for non-metastatic CRPC, and so the most appropriate form of therapy for a man who has non-metastatic CRPC is, actually, to participate in a clinical trial — the question is which one. The fact that physicians like Snuffy Myers offer their patients what many would consider to be unproven forms of therapy don’t make that correct.
I would also point out that just because you want to use differing definitions of certain criteria does not make you correct and ther EAU guidelines committee wrong. These guidelines on treatment of non-metastatic CRPC represent the collective viewpoint of a group of pretty experienced and high-profile European physicians and are actually relatively close to those issued by the NCCN as well.
I would also point out that things like choline-11 scans (while far more widely available in Europe than they are in the USA) are still only available at a small number of academic facilities. Guidelines aren’t written to help these facilities; they are written to provide guidance for the average urologist or medical oncologist at the average medical center in Europe.
After many years of listening to you make this sort of criticism, I would note that there are no data from Drs. Myers, Kwon, Scholz, or Moyad that the forms of treatment they offer extend survival or even quality of life over what you choose to describe as “Wait and Get Clobbered”. I therefore find your comments increasingly irritating since they reflect your personal biases rather than any actual data. Since Dr. Vogelzang is co-chairman of the SWOG prostate cancer trials committee, I know that his priority, whenever possible, is, in fact, to enter appropriate patients into such trials.
You are, of course, entitled to do exactly what you want to do as an individual patient, but I respectfully suggest that this type of criticism that is based entirely on your personal viewpoints is at best unhelpful and largely unconstructive. If you want to help find a better form of treatment for non-metastatic CRPC, you would do better to encourage men with this form of progressive prostate cancer to actually enter clinical trials.
“After many years of listening to you make this sort of criticism”. That has to be encouraging for those of us early on a journey where this is one path (next PSA result in 2 hours). So I look around and find this, which which I guess must be you. So well done, may you continue to be a PITA for the next several years at least, and I quote Wordsworth:
“… they whose hearts are dry as summer dust; Burn to the socket.” Haha: Sorry, Sitemaster…
Dear Jerry:
Actually I suspect that there is a rather different dynamic in play here, which is that the radiology community sees mpMRI as a potentially high profit form of scan. Thus, they have set the price high. The consequence is that payers are reluctant to cover the cost and urologists are stuck in the middle because. although many of them might wish to have patients get mpMRIs, their patients’ insurance will not cover the costs without a great deal of effort (if at all). The people who have the power to drive the costs down are not the urologists. They are the payers. And the payers are probably less than enthusiastic about covering the costs of tens of thousands of mpMRIs every year.
Dear blogollum:
As I said to Jim, he (and you) are entitled to follow whatever plan you want to to treat your own personal cases of prostate cancer, and I encourage everyone to do that. There are no rights and wrongs when there are no good data. However, giving people to believe that the forms of treatment offered by a small subset of the medical community outside clinical trials are necessarily in some way “better” than standard practice, without any data to support such recommendation, is inappropriate and misleading.
I would also note that Jim has, for years, clearly had a relatively unusual form of prostate cancer that has been extremely highly responsive to IADT. The vast majority of patients initially diagnosed with what was almost certainly micrometastatic, node-positive prostate cancer, a Gleason score of 4 + 3, a PSA level of > 100 ng/ml, and a PSA doubling time of 2-3 months, would not have responded as well as he has to the treatments he has received. I have pointed this out over and over again to Jim over most of the past 10 years. There is a relatively small subset of patients who respond like this to IADT (17 years and counting in Jim’s case). It is important for others to appreciate that his case is atypical.
Yes; in the end we are all in a non-statistically-significant sample set of one and Jim does look like an outlier. And there is quackery, no doubt. This site is great in helping avoid it and I see the occasional warning is useful. Bloody disease; not straightforward.
Like Jim (for whom I have high regard since I know he involves himself in research and deep study regarding our prostate cancer and reasonable treatment) I have never seen myself as having “clearly” a “relatively unusual form of prostate cancer” because I have been successful in controlling/managing my prostate cancer with ADT/IAD for now over 24 years. I chalk up my success as I also believe is Jim’s success in our personal “taking-the-bull-by-the-horns” by our personal research and deep study of our insidious disease and those physicians we have come to highly regard for the results they have achieved. We have learned what can work as well as what may not work and have chosen our paths of treatment in consort with our local medical oncologists as well the success of some of the top medical oncologists, urologists, radiation oncologists in the nation who have specialized specifically in prostate cancer and its appropriate treatment among which are those whom you apparently choose not to accept but we do (Myers, Scholz, Strum, Liebowitz, Kwan, Dattoli, to name a few). The key, folks, is to get busy and research and study your prostate cancer so you empower yourself with sufficient knowledge to work with your treating physician to determine your best treatment for your status rather than simply “doing as the doctor orders.” I have found way too many physicians from urologists to radiologists to medical oncologists who have little knowledge regarding prostate cancer. Keep up the good work, Jim!
Yes, I’m “atypical”, an outlier for survival with likely micrometastatic disease
– Some evidence (Scholz/Strum team) supporting Sitemaster’s statement in reply to blogollum of April 18, 2017 at 7:52 am
I live with a sense of continuing awareness that I am most fortunate to be alive, and also to be in good shape at nearly 74 years of age. Hopefully my story will help people see what is possible, though, in my circumstances, not what was then likely. However, with more modern treatments, I believe a substantially larger portion of patients in difficult circumstances will likely achieve similar success.
First a brief note of clarification about my case:
— Before imaging, I was considered likely metastatic, though only a ProstaScint scan at Johns Hopkins in early 2000 showed a “suspicious” area in the “anterior tip of the liver”, an unlikely location that would have to have been a “skip metastasis” and could have been an artifact in the hard-to-read ProstaScint images, with technetium (Tc) bone and CT scans negative;
— After imaging I was considered to have likely micrometastases, as neither the Tc nor CT scans were sensitive to small metastases and the ProstaScint technology was a challenge for radiologists, not capable of ruling out small mets, which were deemed likely based on my case characteristics, as noted by Sitemaster;
— The CT evidence was that I was not node positive (but with seminal vesicle involvement per DRE);
— My PSA doubling time, determined from three 5-finasteride vacations from ADT as the time from a PSA of 5 to a PSA of 10, was in the range of 3 to 4 months instead of 2 to 3, which is an important difference. (I was on Lupron so fast after my first PSA that there was no time for typical evidence of a PSA doubling time.)
The best evidence I know of comes from a study by the Scholz, Strum, and colleagues team published in Urology in 2007. Their practice took a look back at all their patients treated with ADT2 (an LHRH agonist plus an antiandrogen, not triple ADT) prior to 2000 who had a PSA less than 100 (median 9.6, with overall risk in the intermediate zone), a negative bone scan, and adequate records. 160 men met these criteria. It’s likely that most of these patients, perhaps the vast majority, were also free of soft tissue (nodes, etc.) metastasis and micrometastases; yet, as noted below, many of them did not fare well.
The research team looked at various characteristics and endpoints including whether the nadir on ADT2 was greater than 0.05, whether the PSA doubling time was greater than 12 months, Gleason score, stage, baseline PSA greater than 20, age, and death from prostate cancer. (They were early adopters of ultrasensitive PSA testing, which is now widely accepted.) Median follow-up was 10 years. (My case characteristics were less favorable as my PSA at baseline was greater than 100, in the exclusion zone for this study (used for comparison to more current practice) and far above the median PSA of 9.6. (While I have talked and communicated at times with Drs. Strum and Scholz, I have never consulted them formally.)
During the 10 years of median follow-up, 42% developed CRPC, which I never developed through 14 years of ADT until radiation in 2013 (or afterwards). Also, 42% developed bone metastases (but not all the same men, as 19 of the patients with bone metastasis never developed CRPC). Therefore, 67 men (CRPC) plus 19 additional men (bone metstasis but no CRPC), or 86 men, equaling 54%, developed either CRPC and/or bone metastasis (neither of which I developed). At 10 years of median follow-up, one quarter of all 160 patients had died from prostate cancer, and at least nine were alive but with metastatic disease. (Figure 1) In summary, even with what was probably excellent treatment, there was a very substantial amount of progression and death.
I’m also an outlier in time to reach a PSA nadir of 0.05 or lower, which this paper indicates is a key clinical characteristic for prognosis and treatment decision making. “… After 6 years, the minimal period of follow-up, 81% of men with a high PSA nadir greater than 0.05 ng/mL had disease progression. In contrast, only 8% of men with a low PSA nadir had disease progression. (Table 1) …. After a median of 10 years of follow-up, the prostate cancer-specific mortality was dramatically higher greater in men with a high PSA nadir (Fig 2B). Of 32 men with high PSA nadirs, 25 (78%) died compared with only 14 (11%) of 128 men with low PSA nadirs …” (time to death: 4 years versus 7 years, respectively) (Results section) The median time to nadir (at any PSA level) was 4 months, with 83% achieving 0.05 in 6 months, and 97% in 8 months. It took me 20 months to get there, so I was quite an outlier! (It reminds me of the joke about the man who walks into the bar with a singing pig, and the bartender remarks that the pig doesn’t sing very well. But the trick is to be able to sing at all.)
The Scholz/Strum practice had announced the thrust of these results informally in the early 2000s, and for many months my wife and I did not think I would make it to 0.05. In fact, they were then advocating that patients get to < 0.05 ng/ml and maintain that for a year (since relaxed to just getting to < 0.05) before taking a vacation from the LHRH agonist and antiandrogen, at that time also with Proscar that would be continued during the vacation. But my PSA kept steadily dropping once I added Proscar to Lurpon and Casodex, and I eventually managed to keep below < 0.05 for a year, even hitting < 0.01 before starting the welcome vacation.
Why me? There’s no certain way of knowing what worked for me as I was doing everything I thought would help. In 2000 the Strum/Scholz practice excitedly found that their patients who had been on ADT3 instead of just ADT2 had done a lot better (published in A Primer on Prostate Cancer, Strum and Pogliano), and at the 10-month point since starting ADT I was on ADT3 by adding Proscar, thereby moving from ADT2 to ADT3. I was also on bone density protection (then Fosamax), and was using lifestyle tactics (Mediterranean diet, exercise, avoiding high stress where possible) and supplements to aid my cause. In fact my wife was strongly encouraging me to consume a can of processed tomatoes (lycopene source) every day, which got old, and I was downing 14 bags worth of green tea daily. I also took selenium and gamma tocopherol vitamin E, both now out of style, vitamin D3 with calcium, other supplements, and fish oil.
I, my wife and my spiritual buddies also prayed a lot.
Dear Chuck:
Sorry it took a couple of days to find your post and put it up. However, …
As you will see, Jim has just agreed with me that his case has, in fact, from the very beginning, been more than a little unusual … which was the point I was trying to make.
It’s not a matter of me “not accepting” what the physicians you refer to recommend to and do with their patients. This whole conversation is based on what Jim said he thought ought to be in the European guidelines. Treatment guidelines are based on high quality evidence, but … There is no high-quality evidence to support the forms of therapy that have worked for you and Jim … so they aren’t going to be recommended in clinical guidelines. That’s all.