Feb 08, 12 04:40AM
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Case-control studies based on data from self-reported questionnaires of people’s diets are rarely the most accurate predictors of reality. However, for what it is worth, a new study has reported that higher levels of calcium in a man’s normal diet may be associated with a lower risk for diagnosis of prostate cancer. Williams et al., [...]
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Sign in nowMike: I thought there was a study showing denomusab to be superior to Zometa, though I vaguely recall it may have been sponsored by Amgen!
Kinda late to the party on this one — it lingered way down in my inbox, and now I know why! This was a topic I looked at extensively at diagnosis, and have revisited several times in the context of advocacy.
I agree with Mike that research on this topic is very poor. Both stan rosenfeld and I have scoured the Internet to evaluate the marginal benefit of adding surgery to the mix for high-risk patients. Our conclusion is that it is somewhere between 3% and 5% in survival, largely based on talking to Peter Carroll.
The downside is that the patient bears a whole set of other surgical co-morbidities. In my own case the nomograms suggested a 70% likelihood I would need radiation and hormone therapy after surgery. Despite being an excellent candidate for surgery, I did not want to roll the dice on lousy odds, and the added benefit of surgery was not enough to entice me to suffer the risks.
As with many treatment choices, this is very much dictated by individual preference.
Denosumab is often named Prolia, and was developed as a medicine to slowly increase bone mineral density (BMD), to at least partially reverse the reduction of BMD that accompanies osteoporosis, e.g. when induced by adjuvant androgen deprivation therapy for prostate cancer. Amgen got FDA approval with some difficulty, I think less than 3 years ago. Its known side effects are non-trivial, the most dangerous but rarely occurring being osteonecrosis of the jaw (ONJ).
Now I shall stick my neck out. I am glad that the FDA will meet tomorrow to discuss this. For I don’t see how a medicine designed to reverse BMD reduction (which partially causes the osteoporotic “skeletal-related events” mentioned above, say, fractures and spinal compression) can delay the onset of metastatic disease. My quick look at the briefing document suggests that this is a problem that the FDA noted. Also, why the rebranding: from denosumab, to Prolia, to Xgeva?
Finally, a chemist in the Netherlands advised a friend of mine who has osteoporosis not to use Prolia, since (he claimed) the potential side effects are severe and it is too new to know anything about possible future problems. If this is true, how can one now justify its use as Xgeva? (An Amgen publication about Prolia’s currently approved uses can be found if you click here.</a.)
Rick:
Denosumab (Xgeva) is already approved for the prevention of skeletal-related events in men with metastatic prostate cancer. In one of those trials, denosumab was indeed more effective than zoledronic acid (Zometa). However, in this trial patients were not on drug for nearly 4 years, and the incidence of serious side effects was lower. See section 14 of the prescribing information for Xgeva. And yes, you are correct, that trial was indeed also sponsored by Amgen.
Dear George:
It is very important indeed to distinguish with care between Xgeva and Prolia, which are two different branded formulations of the drug denosumab, intended for different conditions and target audiences (which is, indeed, potentially very confusing).
Xgeva is a formulation of the agent denosumab that is given at a dose of 120 mg every 4 weeks as a subcutaneous injection. It is approved in the US and in Europe to prevent skeletal-related events (e.g., fractures) in men who already have metastatic prostate cancer.
By contrast, Prolia is a formulation of denosumab that is given at a dose of just 60 mg every 6 months as a subcutaneous injection. It is approved in the US for three indications: (a) treatment of postmenopausal women with osteoporosis at high risk for fracture; (b) treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for non-metastatic prostate cancer; and (c) treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. (I believe it has the same three approved uses in Europe, but I am less certain of this.)
You will note that the indication that Amgen is seeking for the Xgeva formulation of denosumab is for the prevention of onset of bone metastasis in men with non-metastatic, castration-resistant prostate cancer (at a dose of 120 mg given every 4 weeks). This higher dose of the drug given for a median period of near to 4 years probably accounts for the relatively high risk for ONJ seen in the Phase III trial.
I see. The difference in the dose accounts for the rebranding. That is a good reason indeed. I missed that.
Regarding “the absolute frequency of hospital admissions related to [prosate biopsy] was low and should not dissuade healthy men who would benefit from early prostate cancer diagnosis from undergoing biopsy when clinically indicated.” How would one know that one was such a man? It appears that the data say that there is no one who would benefit from early prostate cancer diagnosis.
Dear John:
Quite separately, in a variety of publications since 2009, the European Randomized Screening study has consistently shown that early detection of prostate cancer can, on average, extend prostate cancer-specific mortality.
Whether the risks (including the risks associated with biopsy and with treatment) are worth the benefit is a much debated topic. Furthermore, it is widely accepted that until we can come up with tests that can accurately differentiate between clinically significant and clinically insignificant and indolent forms of prostate cancer, it will continue to be a much debated topic.
The study described above deals only with an analysis of the risks associated with infections subsequent to actual prostate biopsy, and was never intended to address the issue you are raising. The authors’ concluding comment is an opinion, not a statement of fact.
First … Thanks for the clarification, Mike … In my eagerness to read the post (!), I missed the nuance of “prevention of onset” vs. “prevention of SREs where bone metastasis is already evident.”
The discussion is of personal interest, since I needed a bisphosphonate to accompany my own hormone therapy. I received an annual shot of Zometa because I was marginally osteoporitic and receiving 27 months of Lupron. The Zometa was clearly prescribed as a prophylactic and was very effective; combined with appropriate exercise, my BMD improved 30% over 3 years.
Looking online at men with comparable disease demographics, it seems there is a loose protocol to prescribe the standard dose of Zometa every 90 days for prevention, although I could not convince Kaiser to prescribe that frequently. I question if the FDA ruling is academic since Xgeva can still be prescribed off-label. I recognize it may have an impact on insurance reimbursement.
To answer George, I also want to relay my lay understanding of how and why these drugs work; this was provided to me by Dr. Steve Harris, a nationally recognized endocronolgist at UCSF who I know personally.
These drugs do a couple of things. Firstly, they make the surface of the bone slicker so it is harder for the cancer cells to gain a grip and enter the bone structure. I also understand they promote bone growth and make it denser — the bone can be likened to Swiss cheese, and the drug works to fill in the smaller holes. This may explain why a drug prescribed to increase BMD can also prevent bone metastasis.
It seems most of us common folk still must pay our dues, years of hormone treatments until it demonstrates “biochemical failure” and then and only then are we eligible for clinical experimental trials. It seems as if the pharmas must get their money up front before we get access to potential cures.
Dear Thomas:
A lot does depend on where you are able to go to get treated. The average “local” physician is often not well integrated into the clinical trials network.
Trip Cascells has had the advantage of living in Houston, where he can go to M. D. Anderson Cancer Center. However, men like David Emerson have been making the effort for years to travel to wherever they need to go to get into trials of the very latest agents.
I have not had a biopsy at all but waited until other signs showed up to verify I had an aggressive prostate cancer. I did not like the idea at all and as the above states I reckon I did the right thing not to mention the untold risk of making it easier for the prostate to leak its dirty cancer cells to god knows where.
Dear Barry:
(1) The article referred to above says absolutely nothing whatsoever about the (utterly unproven) concept that prostate biopsy increases the risk of prostate cancer cells being disseminated outside the prostate.
(2) Your decision to not have a biopsy “until other signs showed up to verify I had an aggressive prostate cancer” may well have contributed significantly to the risk that your cancer is now incurable.
Naturally, you have a complete right to make your own decisions about how you manage your health care. However, your decisions appear to be based on a very limited understanding of medical and scientific risk related to the diagnosis of prostate cancer (as opposed to the risks for bacterial infection associated with any form of biopsy today).
Interesting, I was a heavy milk drinker all my life, and even up until age 45 I was drinking “red cap” whole milk every day! Yet, by age 65 I had had an RP.
I was very active physically, but my weight had reached 212, and for a 5 foot 10 inch body I was overweight and my Ch was at 295. So although this study says that there might be a benefit from natural calcium, and I do believe that there is validity to this finding, the bigger issue still remains … fat in men’s diets!
Asian men in Asia have the lowest rate of prostate cancer in the world. Black men in America have the highest rate of prostate cancer. But when Asian men come to this country to live, and eat our diets, their rate of prostate cancer is the same as Caucasian men! Hello! Do you hear bells going off guys? Fat, fat, fat in our diets. So calcium may be very good for us men, but from which source? Whole milk? I think not.
After watching one of my long-time acquaintances nearly die after having a prostate biopsy without any prophylactic antibiotic medication, I think it critical that physicians make sure their patients get an appropriate antibiotic regimen and refuse to perform biopsies unless the antibiotics are actually taken.
My friend said his urologist didn’t even prescribe such and he ended up losing over 30 lb after a 2-week stay in the hospital dealing with a massive E. coli infection. Of course, the doctor refutes his claim. I wonder if doctors in Europe with their socialized medical care are more inclined to get these crucial drugs into their biopsy patients than they are likely to here in the U.S.?
Dear Sitemaster:
Any update about feromoxtran-10? When are they going to reproduce it? Are there any other companies producing similar agents? Were there any major side effects that made FDA decide not to approve it?
Thanks
Dear Basha:
The reason that Combidex never got approved with the USA was complicated and had more to do with what the company that made it wanted to get it approved for than with any side effects. The trials that were carried out did not justify the precise indication that the company was seeking.
As far as I am aware, no one else is trying to get this product approved now. It is likely that the cost to get the product to market now would exceed any possible economic return on the investment.
What was the procedural protocol for preparation of the rectum, the guidance device/digit, and number of biopsy cores? The current standard seems to be TRUS-guided 12 cores, an enema, and IV antibiotic before and after. My urologist used finger-directed, 4-core, no cleanout, and ciprofloxin, which resulted in a septic infection in my case. After speaking with other patients of my urologist at a prostate cancer support meeting it seems clear that his stats for infection are significantly worse than 1%. Apparently there is no mandated minimum standard (at least in Canada).
Dear Terry:
As far as I am aware, there are no “mandated” prostate biopsy protocols anywhere in the world. There are guidelines, however. Most guidelines today appear to include recommendations for an enema, a brief oral (as opposed to intravenous) antibiotic regimen that is effective against Gram-negative bacteria such as E. coli, TRUS-guided biopsy using a biopsy “gun,” and removal of between 6 and 18 biopsy cores depending on the expertise of the urologist and the precise clinical risk/presentation of the patient.
As far as I am aware, biopsies conducted within the Rotterdam section of the ERSCP trial would have conformed to the above criteria.
The risk for infection associated with biopsy seems to be particularly high in Canada, although it is not clear exactly why this is the case.
Hmmm … All relatives on mother’s side lived into 90s except her mother, who died of cancer in her late 40s. … All relatives on father’s side died in their 60s except father’s mother, who lived to be 87?
No one ever said this sort of decision is simple!
:O)
Rick D:
Thanks for that. Your response shows how one drug can delay onset while at least partially reversing BMD reduction
There is research by Skinner and Schwartz published in Cancer Epidemiology, Biomarkers & Prevention in September 2008 that finds a positive correlation between serum calcium levels in the blood, more aggressive/higher-risk prostate cancer, and consequently, more prostate cancer-specific death. In their article titled “Serum calcium and incident and fatal prostate cancer in the National Health and Nutrition Examination Survey,” they say:
“In this prospective cohort, we observed an approximate 3-fold increased risk for fatal prostate cancer among men in the upper tertile of the distribution of serum calcium.”
I do not know if there is a direct relationship between dietary calcium intake and serum calcium, but a high calcium level in the blood is not a good thing. Personally, I have had high serum calcium for many years, make calcium deposits, and do have a high Gleason grade; I consume very little dairy, albeit a lot of leafy, dark green vegetables.
There is a fair amount of discussion and research discouraging consumption of animal protein, especially dairy; one example is Ornish’s research. The China Study by T. Colin Campbell has an extensive bibliography.
This discussion has raised another question and that is, “Can abiraterone be taken with food?”
This is a somewhat controversial area, so I will give my opinion as a pharmacologist rather than as a doctor.
The manufacturer’s prescribing instructions for abiraterone (see section 5.4, Food Effect) state clearly that it should not be taken with food:
“ZYTIGA® must be taken on an empty stomach. Exposure of abiraterone increases up to 10-fold when abiraterone acetate is taken with meals. No food should be eaten for at least two hours before the dose of ZYTIGA® is taken and for at least one hour after the dose of ZYTIGA® is taken. Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17- and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state.”
This is because the clinical data for this disease indication has been conducted at a dose of 1 g daily taken without food.
It is worth re-stating the fact that abiraterone is an exceedingly potent drug, so that it has always surprised me when such high doses (1 gram) of abiraterone acetate are used. Abiraterone is five times more potent than letrozole (Femera), an aromatase inhibitor used to treat breast cancer, which is taken at a daily dose of 20 mg. So why isn’t abiraterone taken at a dose of 20 mg. The main reason is the poor uptake of abiraterone acetate in the un-fed state. Abiraterone acetate has been specially formulated as the acetate to help increase intestinal absorption and bioavailability through absorption by digestion. Without food digestion, there is poor absorption. The main reason for such high doses is therefore due to the very poor absorption of abiraterone acetate by the intestine in the un-fed state. Given on an empty stomach, only about 5% of abiraterone is absorbed by the intestine, so for a 1 g (1000 mg) dose only about 50 mg is absorbed and the remaining 950 mg is excreted. What a waste of drug when 95% is excreted. It would make far better sense if the absorption of the drug can be increased somehow, as is found when the drug is taken with food. Abiraterone was designed as an orally active drug, and as such was designed to be absorbed with food. When abiraterone is taken with food, the absorption increases dramatically — by 10-fold. The area under the curve (AUC) exposure is a measure of the volume of the drug absorbed into the bloodstream and this increased 10-fold when abiraterone was administered with a meal. So it is important to realise that the concentration of abiraterone in the body increases 10-fold when taken with food. In this way a 100 mg dose will deliver the same amount of drug as a 1000 mg dose without food. This means a dose as low as 100 mg could be taken with food to deliver the same pharmacological effect as 1000 mg without food.
Since it appears that some clinicians are already administering abiraterone with food, it should be borne in mind that a single tablet dose of 250 mg taken with food will deliver 2.5 times more drug than 4 tablets taken without food.
There is little doubt that this is a complex issue. The precise source of the dietary calcium and the capacity of individuals to metabolize products containing calcium are likely to to have high relevance to the exact risks involved.
Thanks Dr. Potter. This is very helpful for people.
… and here’s another excellent and free resource available online with a very good reference list.
Small correction: It’s not double-blind because it’s an open label study, so both patient and doctor know who is getting which medication. A study may be placebo controlled or controlled with a treatment of known efficacy and still be double-blinded.
Dear Allen:
Thank you. You are, of course, technically correct, but I think you may be making a distinction that would escape the understanding of the average patient.
Hello Doctor,
My father is 71 years old; no history of prostate cancer. His PSA 11.6 in November and 17.0 ng/ml in December. The urologist suggested a biopsy for him. He had a heart bypass 8 years ago and he has diabetes and high blood pressure. My question is, are there any side effects of biopsy?
Hi Sangita,
Yes, like all invasive procedures, prostate biopsy is associated with a range of risks, including bleeding and infection, which can include sepsis (bacteria getting into the blood stream). Your father can review these risks with his doctor(s) so he can make an informed decision and consent.
Arnon
I have been on a Zytiga/prednisone regime for almost 2 months now. The treatment seems to be having little or no effect and my PSA continues to rise. Admittedly I have a very aggressive PCa (Gleason 10, Stage IV mCRPC).
I would be very interested in trying smaller doses, say 250 mg taken with food and will approach my oncologist about this at our next meeting. I have little hope that he will go along with this because of the general reluctance of physicians to expose themselves to litigation. So if he opposes the idea, I believe I will experiment on my own with reduced dosage plus food. I believe I have very little to lose by doing so. The advanced state of my disease leaves me very few options to
explore. Thank you Dr. Potter for your information. That and some of
the testimony of readers will help me make a final decision.
Dear Frank:
Thedre does appear to be some variation in how long it can take the effects of abiraterone acetate to “kick in” individual patients. Regardless of what you and your oncologist do (or don’t) agrees to do about the dose level, let’s hope that you start to see a drop in your PSA level some time in the next 30 days or so.
My husband still feels bad 4 weeks after LRP. Is this normal?
His results were fabulous, all organ contained; cancer was very small and found through PSA. Surgeon said he was able to save nerve bundles. He is continent except for a few “stress incontinence events.” He has moderate abdominal bloating and some back/flank type pain which bothers him and I know worries him. His bowel pattern has changed.
He has gone back to work (desk work) but sits a great deal of time at home, complaining of discomfort and swelling. Cialis 5 mg/day but nothing in the erection department. I am very frustrated and not sure if this is to be expected, depression, or being “whiney”. This is our first health crisis. Surgeon follow-up vist in 4 weeks.
My husband has talked with office nurse, but is told all is moving as expected. Thanks for your help!
Hi P,
Unless your husband is 30 years old, then the lack of erections at 4 weeks post-op, especially since he has other physical discomforts, is not at all surprising. It also has no particular prognostic significance and you may not want to work into anxiety with it.
Back pain is not uncommon in the first few days if the patient has been lying in bed a lot. This is especially true in men who have chronic back pain, which can be exacerbated by bed rest. On the other hand, flank pain is less common, although it can represent muscle spasm and ache. However, at a month post-op, and especially if flank pain is stationery (doesn’t move about as you would expect if it was from intestinal gas; which raises the question of if he’s constipated) and/or is associated with nausea/vomitimg/loss of appetite and/or is getting worse, then it unusual and would warrant serious attention and, at the absolute least, informing his surgeon.
Arnon
Democratic trials.
When the whole world became a small thing thanks to comunnication and the Internet, why is there still no international register of patients with mCRPC. Why are all trials are not multi-center?
I am a patient with mCRPC. I am facing many difficulties to enter in trials. Why do I want to enter into such a trial? Because in this events are the most advanced drugs against cancer.
I have recently been diagnosed with prostate cancer. I am 57.
It appears to me after my reading of the quite similar Swedish trial, now augmented by the preliminary PIVOT data, that radical prostatectomy has very little benefit to anyone beyond the urologist. While I scheduled a surgery at Johns Hopkins, I am having serious buyer’s remorse. If I can find instead a nice randomized controlled trial for some therapy with minimal side effects that would calm down my poor frightened wife, I think that’s where I would like to wind up. Let’s face it, we’re all going to die. I think I’d rather spend the rest of my life having sex and control of my bladder, rather than hoping to be the one out of 14 men who might benefit from radical prostatectomy.
Thanks for breaking these data down into the raw numbers. It’s nearly impossible for me to draw any conclusion from hazard ratios, which is the only way I’ve seen these data presented elsewhere.
To Fuller et al.
Were the CyberKnife treatments followed up with hormone treatments?
Dear Paul:
It kinda depends on the exact nature of your diagnosis. If you join our social netwoek we might be able to give you some assistance in considering your opportunities.
Dear John: As far as I can tell from the abstract of the poster by Fuller et al., no, none of these patients received any form of hormonal therapy.
These numbers can’t be right.
There were 731 men enrolled.
If 48% of the population died, that’s 351 men.
If “7.1% of those who died … or probably died of prostate cancer” that’s 7.1% of 351 = 25 prostate cancer deaths total.
So after 10 years, only 25 men out 731 died of prostate cancer? And half of the 731 weren’t treated?
Something isn’t right.
Testosterone is associated with heart disease. Testosterone is associated with prostate cancer. Is testosterone the cause of both?
P,
I’m not sure of your husband’s age or general health, but 4 weeks post-op is certainly not long enough to be concerned about an erection.
I had DaVinci prostate removal 2 years ago (nerve sparing and localized cancer contained in the capsule) by an excellent surgeon. It took 2 months for total continence to return, and about the same for some rectal pain to subside. To this day an erection without some sort of mechanical intervention is not possible. Shots will do it with no problem, but I do not tolerate those well. I personally prefer a vacuum pump, which does well. I am now — after 2 years — capable of achieving a slightly firm appendage on my own, but it is not sufficient for intercourse. I am 54 years old and in great health and fit. The point is that everyone is different and the recovery period for each will be different. Be patient and support your husband as much as possible through his recovery. There are many ways of achieving closeness and intimacy without the actual act. If you both are anxious, then ask about the injections, because they do work, but don’t let your husband get discouraged because his recovery doesn’t happen as quickly as you or he think it should.
Greg
Dear Paul:
The formal results of this trial have still not been published (which is really rather embarrassing in my personal opinion since it is now > 8 months since these data were initially presented). However, these are the data reported by the principal author of the study; he has given the same data at other presentations, and there is no reason to believe they are inaccurate.
You do need to appreciate that the 10-year mortality rate among men diagnosed with low- and intermediate-risk prostate cancer in the PSA era is really extremely low indeed, which is precisely the point behind the conclusions from this study. Why are we aggressively treating men with a reasonable life expectancy of 10 years and less who are actually highly unlikely to die of prostate cancer when they are much more likely to die of other age-related problems first?
Since I moved to a rural area I have become more aware of access as an issue. There is also a lack of access to primary care MDs. Hospitals in the area have been opening satellite office for primary care but specialty care is much more difficult. Makes sense to me. Men are less likely to go to a primary doctor in rural areas, Therefore they are more likely to be diagnosed with later stage disease. Not sure it is distance to urologist or lack of access to primary care doctors, lack of health education/screening programs, or possibly a cultural difference in rural men? Nice start in identifying an issue in a specific group of men though.
I have been diagnosed with prostate cancer (3 + 3 = 6/10) and (3 + 3 = 6/10) so I am considering treatment options. I also have an atonic neurogenic bladder and so I have to catheterize myself in order to urinate. Should this condition affect my choice of cancer remedy? Thank you.
Thomas,
Have a look at this discussion thread on the social network.
Arnon
We now have a number of HIFU studies reporting biochemical (PSA based) recurrence free survival at five years. My recollection is that they all indicate that HIFU is not an effective first-line treatment, even in men diagnosed with low-risk prostate cancer. The success rates reported for low-risk men seem similar to what we would have expected if those men had taken an active surveillance approach, suggesting that HIFU is adding little or nothing to success.
How do the strong advocates of HIFU explain these discouraging findings? (I’m aware that some centers for HIFU and advocates report results that look good at the 1- and 2-year time points but do not report available results from the same series that turn discouraging at the 5-year point and later.)
What’s good about this trial — beyond the tight design and good population size — is that the subjects weren’t a bunch of Gleason 6s and 7s that would have survived even if they had been treated by a witch doctor.
These guys were all palpable tumors, T2s, T3s and T4s.
Jim:
I would characterize this a rather different way.
It seems to me that there are significant numbers of men who do appear to get good outcomes from HIFU at 5 years, with low to minimal rates of complications. There are also men who get not-so-good or poor results from HIFU because either they get good oncologic results with significant side effects or they get poor oncologic results (with or without significant side effects).
The problem is that we don’t seem to able to know up front who will and who will not do well in order to apply HIFU primarily to those who will benefit the most and with the least risk of complications. This is nothing new in the world of prostate cancer. We see the same problem with almost every form of active primary therapy. And on top of this is the issue of whether the people who do do well on HIFU are, in fact, the men who would have done as well or nearly as well on active surveillance, which is a separate question.
Dear Dr. Krongrad,
I was diagnosed with prostate cancer in October, 2005. My minimally invasive surgery 2 months later was very successful. My PSA since then has remained less than 0.1.
My question, however, is not about me. It’s in regard to a friend of mine who was diagnosed with early stage prostate cancer about 2.5 years ago. I don’t know what his PSA was at the time, nor do I recall his Gleason score or exactly what stage his cancer was, but during his “watch and wait,” period, he has had a few biopsies and several PSAs. The PSA levels have steadily decreased. Because his most recent PSA was down to less than 1.0, his primary care physician told him that he’s now probably cancer-free. Is this possible? Could a biopsy, or repeated biopsies, somehow remove the cancer? Does cancer ever disappear without treatment?
Tom
Tom,
Not too likely, even as his overall risk is low (as implied by a low PSA).
Arnon
I don’t understand the interpretation. Surely, improvements in detection and diagnosis of prostate cancer from 1972 to early 1990s would reduce PYLL, not show an increase?
Why should nerve-sparing surgery have an effect on PYLL?
My opinion for the later fall? More prostate cancer awareness and availability/use of PSA testing and DRE examination..
I’m just reporting what the authors claim. Don’t shoot the messenger!
Re: “Why should nerve-sparing surgery have an effect on PYLL?”
When the outcome is better for the patient, more patients will tend to have the surgery. Back in 1991, my 64-old father chose radiation instead of surgery because my mother apparently stated very emphatically that “our sex life is not over”. Thankfully my father’s PSA is still undetectable, over 20 years later.
??? I would use a popular online acronym for incredulity if it wouldn’t raise undue suspicion regarding my commitment to ladylike decorum …
Really, this is meaningless drivel without demographic, policy, and clinical context. My people (social scientists) call this, “I’ll do (say, think) anything to get enough journal articles published to get tenure” writing. It’s pointless, it’s meaningless, it’s misleading, it’s distracting, and it means the folks who put it out were wasting their time on this rather than improving their skills as clinicians, thus contributing to increasing the mortality (and certainly morbidity) rates they claim to be concerned about.
Enough with this nonsense! Epidemiologists, psychologists, sociologists, and demographers don’t try to treat urogenital disease. Why in the world are a bunch of urologists trying to measure the extent of impact of urogenital disease on the population and the effects of these diseases, and the effects of treatment of these diseases, on people’s quality of life? Get back to your real jobs!
Hype and non-disclosure; view TV adds for radiation treatment.
Dear Amy!
I googled this website because I couldn’t sleep.
I’m in my late 30s with three children. Before my partner was diagnosed and treated for prostate cancer, we had been having frequent fights and arguments over my sex refusal. It all started when I found out he was cheating with me constantly with different women but I stayed on because of my children. Now it’s worse because I can’t seem to get intimate with him but he blames me and calls me names and says that I’m the cause of him having had the disease and that I also caused him not to have an erection anymore ‘cos I’ve refused him sex.
I’m drained emotionally. Is it true? That I’m the cause? I just find having sex with him repulsive. I have forgiven him but I just get turned off. What do I do? I’m confused! Please advise.
*****
Amy replied as follows:
Dear Elizabeth:
First, it is extremely clear that you and your husband have a very real problem. And so do your kids.
Second, the very real problem has nothing to do with his prostate cancer and everything to do with the state of your relationship. You didn’t “cause” him to have prostate cancer. You are not the reason he can’t get erections. And his prior behavior is where the problem began. (I am of course “taking your side” in my perception of the problem, because I assume you are telling me the truth. I am sure that your husband would tell me a quite different story.)
Third, arguing with each other about what has caused the problem is not going to resolve it. You and he need to make some decisions about what you actually want to do. The fact that you and he aren’t getting along (to put it mildly) has already affected the children. If you think that they don’t know that Mom and Dad are constantly fighting with each other, you are wrong. Of course they do. They can “smell it.” It’s in the air.
The real issue here is whether the two of you really want to stay together or whether you need to be honest that you don’t. If it’s the latter, then you need to find a way to restructure your lives in ways that will free each of you from what sounds like a near to impossible situation while at the same time ensuring that the kids are able to get on with their lives and understand that you and their Dad are also getting on with yours too. This may well have some economic ramifications for all concerned, and you and your husband are only going to be able to decide how to resolve this issue if you can stop fighting about the “substitute” problem and deal with the real one.
So first and foremost, you and your husband need to decide whether you still love each other and want to stay together (“for better for worse, for richer for poorer”; i.e., not just because of the children). If you do, then you need to stop fighting and work out what the implications are. If you don’t, then you both need to work out and agree on what you are going to do to make sure that you can put the needs of the kids at the top of the priority list while you decide how to separate your lives.
Sometimes in life one finds out that what one has got isn’t what one signed up for. Then one is faced by a very hard decision. Am I willing to do whatever it takes to change the situation for the better, or am I going to just suppress my own needs and put up with the situation because I don’t know what else I can do? I know which side of that question I would come down on myself, but I am not you … and I can’t make these decisions for you.
I hope this helps … if only a little bit.
Amy
I think that denial by the doctor that his/her treatment caused the observed side effects should be added to this list.
Dear Joe:
I think that is more complicated. One would need to know whether there is good evidence that a specific treatment was in fact associated with occurrence of the actually observed side effects. If it is, then the doctor should be advising the patient of this before the patient decides to accept such treatment.
Does anyone have any idea when this would be available in Canada?
One ethical notion seems to be missing from the talk and, I guess, the survey. I was given two treatment options and explicitly excluded from a third, with a quickly-stated reason that did not satisfy me. This occurred because of a failure (perhaps not intentional) to inform me of a condition under which the third option would be applicable. No lie was involved, just a sort of incompleteness. I obtained a second opinion in another country, in secret. I was right. (1) The third technique was applicable, given that condition. (2) The third technique is part of a combination treatment that seems to be at least as effective as the two I was offered. I was informed as to why this is so, and told which oncological papers were used to motivate the doctors’ advice to go for the combination. I did, and further reading, on this site and elsewhere, supported the advice.
I don’t know what this sort of incomplete range of choice is called in ethics. I do know, that in the current state of scientific uncertainty and insufficiency of statistical data in prostate cancer research, full discussions of all applicable options is desirable. Where I came from, however, the private insurers and health ministry limit “discussions” with patients to 10 minutes, making extensive conversations nearly impossible. In my present country of residence, each discussion lasted for at least half-an-hour, and others were held when I felt they were needed. All were highly informative.
Hi Tony,
The second article in hypertext (by Nick Mulcahy) stated that the test was “already approved and marketed in Europe and Canada.”
What a useless report. Where are the data?
Dear John:
If you want to study all of the data, click on “Shafique et al.” in the commentary above and it will take you to the full text of the article with all the relevant data.
Having had prostate cancer and had 37 radiation therapy sessions I thought all was well. Now I read this, and makes me feel a lot better (NOT!!!!!)
Dear Tony:
(1) Sooner or later we are all going to die! (2) If you had no actual signs or symptoms of prostate cancer prior to your treatment (i.e., your cancer was only found because of an elevated PSA level), this study shows your risk of all-other-cause mortality is now the same as that of a man who never had prostate cancer in the first place.
Aloha Sitemaster,
The initial conditions were such that localized treatment of the prostate would leave potential prostate cancer that might exist outside the prostate. There was no discussion of potential side effects. Three weeks into the 8-week treatment, I tried to quit as going to the toilet (both #1 and #2) was very painful. Was persuaded to continue and given pain meds by the radiation oncologist. During the following months my log shows a max of 44 trips to toilet in 48 hours. Bladder bleeds wherever it is touched inside. Two and a half years and several cauterizations later to control rectal bleeding, extreme pain began whenever I needed to urinate; I was on pain management for 1.5 years. The radiation oncologist was in denial of the problem. I have been using a suprapubic catheter since October 2010 to bypass the urethra. The urethra appears to have a wound that will not heal. When bleeding got bad, I started mild HBOT; 6 months later I was able to stop pain management. Now, preparing for uro-ostomy. The mild HBOT helped a lot but is not healing the open wound. The urologist feels that bladder is not usable for the long term.
Long story, short story, still feel that other treatment options would not have been a better option to keep me alive.
Should have made the decision for plumbing realignment earlier.
Joe
Dear Joe:
While I sympathize with your problem, I don’t think this is really an ethical issue as much as it is one of less than high quality medical practice at several point along your journey.
Why would this be a mystery? I expect that people in poor health are more likely to get cancer and treatment will degrade their health even further. Thus this group is more likely to die of any cause than the group that has not had these health-degrading events.
Dear John:
That is certainly one of several possible interpretations. Whether it can be justified by the available data is a completely different issue. You are making multiple assumptions.
This is no surprise to me at all. African American men have the highest rate of prostate cancer in the U.S., but they also have a terrible diet, consisting of too many fat products. So heart problems and adult-onset, type 2 diabetes are two factors that can cause death other than prostate cancer.
What amazes me is the lack of a good, in-depth study of all men, all races, here in the U.S. Diets, smoking, alcohol use, drug use, genetics, type of work, drinking water contamination (i.e., high levels of arsenic, etc.) are just some of the factors that should be gathered. Certainly now, in 2012, there must be a considerable amount of data that can be gathered, which could ultimately point doctors in a direction to find a cause and effect hypothesis. Small numbers in these studies are not statistically significant enough to warrant any eurekas (in my humble opinion)
I can give you “some” data, not statistically significant because I am only one data point. My cholesterol level rose higher and higher as I approached 62 until it hit a high of 295 and my weight hit 212 for a frame of 5 feet 10 inches. After I retired (engineering desk job), my weight dropped to 180 and my cholesterol level to 205; triglycerides were the bad guys in my case as HDL was high and LDL was withing limits soon afterwards. But by then my PSA was at 6.1 and biopsies showed cancer. Fats in our diet are certainly a factor, but, what role is it playing in prostate cancer? Primary or secondary effect? Where are the studies? I would like to plot on a graph every known cholesterol level of edvery prostate cancer patient at the time they were diagnosed.
Neither the article, nor the include 5+ year data on erectile function for all men or men disaggregated by age. If brachytherapy were genuinely producing significantly different outcomes in regard to quality of life measures, billboards would be plastered and radiologists would have ponied up for a Super Bowl ad. Just more marketing bologna.
All I know is that I am doing 200 percent times better .
Yery interesting — albeit anecdotal; it is certainly true in my case because I have had high cholesterol levels since I started measuring them in my early 30s!
A missing variable might be that healthy Scottish diet — deep fried Milky Ways, haggis, sausage and chips, English breakfasts; however, much porridge you eat, I doubt it can compensate!
One serious note … If you look at the Shafique study, do not be confused … cholesterol levels are measured the European way (in mmol/l) as opposed to in US units (mg/dl). You will see a reference to the highest association found in the second highest cholesterol quintile between 6.1 and 6.9 mmol/l; this correlates to approx. 235 to 270 mg/dl in US units. (I am fortunate to own a precious cholesterol conversion table!)
Thanks for the reply. That gives me hope since his PSA levels have come down a lot since starting on Lupron or hormone therapy.
Dave
PLEASE NOTE: We have just discovered that the full text of this article is available on line on the web site of Dr. Tewari’s institution. A careful reading of the full paper makes it clear that sexual potency was being defined as “the ability to have sexual intercourse” as opposed to the ability to have a high level of sexual perfomance.
Indeed, the authors claim to have “calculated” the patients’ level of sexual satisfaction.
Some day, everything is gonna be different.
Wouldn’t it be nice if FDA (web) published their decision on approving the test, ideally with at least citations to supporting data, published studies, any comments on the test, etc.?
If they have published anything like that, I sure can’t find it.
Dear Dave:
Since much of the information provided by commercial companies seeking approval of products that they want to bring to market is considered to be proprietary information, the FDA is commonly proscribed from publishing or making any of that information publicly available! Only the company that owns the data has the right to do that (unless they are willing to waive that right).
I would love to hear the authors of this study and the low-dose brachytherapy study respond to the Health Affairs lying article referenced earlier this week.
Again, one wouldn’t expect a sociologist or psychologist to provide valid counsel on treatment of prostate cancer, so why in the world would urologists imagine themselves skilled in measurement of human perception. “Calculated” patients’ level of sexual satisfaction indeed!
The more palliative care can be integrated with other treatments the better.
I have been astounded many times over during my going-on 6 years of being treated for prostate cancer that comments of mine along the lines of “I am losing my mind!”, or “This hurts a lot”, or “Surely there must be a way to relieve these symptoms” fell on deaf ears, and I was sent home to deal with that pain, confusion, concern, etc. on my own as best I could. That is just crazy! There are certain words that when a doctor or nurse hears them from a patient should trigger an automatic response of additional care, and never just a “Have a nice weekend!”
Just so that we are very clear, lapatinib has never been submitted for approval by the manufacturer for any prostate cancer indication, and the results currently available from Phase II trials of lapatinib in advanced forms of prostate cancer are varied. There are four ongoing trials of lapatinib in the treatment of prostate cancer, but none of these are Phase III trials, and it seems highly unlikely that the manufacturer intends to seek an approval for the use of lapatinib in the treatment of prostate cancer.
Thanks, Sitemaster. That brings me up to date. I was thinking about a report on this site, some time ago. I noticed it because when that article appeared here, the use I mentioned had just been rejected by the Health Minister, who accepted the advice of the quango. Right after that, the main Dutch researcher on lapatinib was said to be furious at this decision. He remarked that residents of the Netherlands who feel they need lapatinib for breast cancer have no choice except to fight the decision in court. I’ve no idea what if anything has happened since then. My hunch about prostate cancer was a mere educated guess. There’s not one word about it in the Dutch documents that I have seen.
Perhaps the Indian government should subsidize the cost of this drug for their citizens who can’t afford it, rather than steal it. India is trying to establish a robust pharmaceutical industry and could open themselves to trade war-type actions, such as having the sale of their drugs banned in the US. No doubt the US based pharmas would lobby for this type of action if the issue can’t be resolved another way. Many thieves justify their actions based on the excuse “They charge too much.”
Thank you, thank you, thank you, for getting the word out! We need more things like this to bring public awareness to prostate health and prostate cancer issues!
I see even more troubling stuff right here on American soil. Here are two examples:
(1) Viagra was slated to come off patent this year, but a judge has ruled that Pfizer re-patented the drug for use for ED. (Its original use was for luminary hypertension and that patent was going to expire in April.) The newer patent was deemed valid so we are to pay 25 bucks a pill for another decade (or thereabouts). I expect Pfizer to find another use for it at that time and re-patent it again.
(2) Here in Las Vegas, 3 years ago, a doctor started re-using syringes on patients, causing a hepatitis outbreak. He was arrested and has been in custody awaiting trial. Was he sued by the patients? Nope … too poor to sue after being arrested. So. The makers of propofol were sued by a single patient for 500 million bucks and he won. Why? Because the bottles the drug came in were too big and would tempt a criminally minded doctor to reuse syringes and drugs. One patient 500 million bucks and 110 more patients to go that are also suing the pharmaceutical company and not the doctor. Propofol is a very common drug and I am certain that the folks that will pay this tab are we the American patients.
Two examples as to why we should never expect any help from lawyers to lower drug prices … LOL!
Thieves? Maybe you should actually read the law before passing your comment. The Indian controller general of patents, designs and trademarks is following the law even if it has invoked a rarely used provision. The provision exists for a reason, all that Bayer can do is argue that this may not meet the criteria for the law to be invoked; something that they will find very difficult to do.
I am 71 and in excellent condition. I had a PSA of 7.0 in september. Biopsy showed seven cores with cancer. Highest core is Gleason 9 (4 + 5) with two others at 8 and one 7 and three 6. All high ones are on left side of prostate. Bone scan showed no spreading. MRI suggests that seminal vesicles “may” be involved. I am now on 6 months of Lupron preceded by a month of Casodex. MY PSA now is 0.07 so this treatment is working well. I am seriously considering HDR with IMRT but concerned about radiation side effects. I am really concerned about RP surgery and its even more scary side effects.
How long can I go with only Lupron with regular 3 month PSA checks?
IS HDR and IMRT my best chance of living a long time?
Thanks
Gene
I had a kidney scan a few weeks ago and they said I should receive a letter soon. I received a letter today confirming I need to see a urologist. Should I be worried about this?
*****
Amy replied as follows:
Dear Claire:
Just take one step at a time. Go and see the urologist, but make sure you write down all your questions before you go so that you remember to ask them all. This might turn out to be absolutely nothing … but it also might tun out to be important. What I am sure about is that it is a waste of your time to “worry” about it until you know what the problem is … if there really is one.
Look at the issue this way … It’s not like someone phoned you and said, “This is an emergency and you need to come to the hospital now!” They have simply advised you to go see a specialist, and I have to assume that you originally had some type of problem that caused your primary care doctor to send you to get a kidney scan.
There is one other thing I am sure about too. You don’t have prostate cancer! You can’t, ‘cos women don’t have prostates!
Amy
Gene:
Please join our social network, where we can address all of your questions in more detail. What I can tell you here is that surgery is not usually appropriate for men of your age; that some form of radiation therapy would likely be a good option in your case; that HDR + IMRT is certainly one appropriate type of radiation therapy; and that the side effects of radiation therapy today are far less serious than they used to be 10 and 15 years ago because the radiation can now be targeted with much greater accuracy.
Hi. My husband is 52 years old. His doctor ran a PSA test last year and it was elevated. He was told to re-test in 3 months, which he did. It was even higher. They tested again and still high.
They ordered a biopsy, which he had done and they found nothing yet his last PSA test was 6 ng/ml.
We don’t know what to do. What could cause his PSA levels to be so elevated with no evidence of cancer?
Hi Cindy,
Please understand that PSA is a non-specific test, for which reason one moves to a biopsy to establish a diagnosis. At 6 ng/ml, the PSA indicates a risk of approximately 25% of a positive biopsy, with a laundry list of other things possibly explaining the negative 75%. The only question now is if to repeat a biopsy, which reflects index of suspicion that depends upon such things as family history, prostate size, findings of atypia on the first biopsy, and the like. This is a question best addressed by your husband’s urologist.
Arnon
In response to Doug Miller …
Rather than the Indian government subsidizing the drug, maybe Bayer should consider two-tier pricing for lesser-developed markets, or offer some other form of subsidy in order to protect its patent.
At the very least, no man should get tested without being informed about the high odds of getting a treatment that does not improve his survival. If, however, the small chance of lowering the risk of dying from prostate cancer is acceptable, then and only then should screening occur. Importantly, however, the editorial points out the potential problems with the European study, namely, that differences in treatment are the reason for their findings rather than the screening itself. Also, the US trial cannot be ignored.
Too bad this research did not tease out the statistics showing the likely benefit of PSA screening in younger than the 55-69 age study population. It would seem logical that baseline PSA screening would catch those younger victims and early treatment would significantly reduce cancer-specific mortality in this younger age subset whose normal life expectancy would be much higher than those included here.
We have two prostate cancer survivors in my support group who were PSA diagnosed with operable cancer in their 40s. Without that screening they would most likely be dead by now from prostate cancer.
I’ve made this point before, but it is inappropriate to put any weight on the statistical insignificance of the effects of all-cause mortality. The European study simply does not have sufficient size to detect such effects.
If one looks at Figure 1 in the paper, we find that 72,891 men were in the screening group, of whom 299 died from prostate cancer, and 13,917 died from all causes; 89,352 men were in the control group, of whom 462 died from prostate cancer, and 17,256 died from all causes.
If one calculates rates: the screening group had 0.410% die from prostate cancer versus 0.517% who died in the control group, so the prostate cancer death rate declined by 0.107%. If one looks at overall mortality rate, the screening group had 19.093% die from all causes versus 19.312% in the control group. This is a decline of 0.219%, which is actually over twice the decline in prostate cancer deaths. In other words, if one believed the point estimates, there is no sign that non-prostate cancer mortality changes somehow “offset” the prostate cancer mortality effects.
Yet the difference in prostate cancer death rates is statistically significant between the two groups, whereas the difference in overall mortality is not even close to being statistically significant. Why is this? The intuitive reason is that, statistically, it is much easier to detect the larger, relative change from a 0.517% death rate from prostate cancer to a 0.410% death rate from prostate cancer than the much smaller, relative change from a 19.312% death rate to a 19.093% death rate, even though the absolute change in mortality is actually somewhat larger in all-cause mortality.
If I take these data, and the actual sample sizes, and ask the following question: what would be the probability in a sample of this size in the treatment and control groups, with a baseline all-cause mortality rate of 19.312%, of detecting a decline by 0.107% to 19.205%, at a statistical significance level of 95%, the answer is, the probability would be only about 8%. In other words, the sample sizes are simply not big enough to make it at all likely that we could detect statistically significant all-cause mortality declines of the size of the observed prostate cancer mortality declines.
If I asked instead, how big a sample, with equal numbers in the treatment and control group, would I need to have an 80% probability of detecting an all-cause mortality decline from 19.312% to 19.205%, at a statistical significance level of 95%, what statisticians call a “power” of 80%, the answer is, I would need 2.35 million in the treatment group, and 2.35 million in the control group. This is far larger than any likely sample sizes we will ever get in prostate cancer screening studies, even if we do a meta-analysis to pool all results across all studies.
Therefore, in debating this issue, the issue of statistically significant effects on all-cause mortality is a red herring, a distraction. The fact that they found nothing statistically significant in all-cause mortality means nothing because the study was simply not designed to be large enough to detect such effects at the likely magnitude that we might expect.
It also is of interest to compare differences in prostate cancer mortality in the treatment vs. control groups vs. differences in actual treatments that could cause serious side-effects.
Table 9B in the supplements to this paper shows that of the 6,963 men diagnosed with prostate cancer in the screening group, 1,600 received only “watchful waiting” as a treatment. In the control group, of the 5,396 diagnosed with prostate cancer, 861 received “watchful waiting” as a treatment. Presumably this is related to the fact that the screening group had, on average, prostate cancer diagnosed at an earlier stage. There is also a higher percentage of the control arm that received hormone therapy.
Therefore, the percentage of men who actually received some treatment other than watchful waiting is (6,863 – 1,600)/72,891 = 7.358%. In the control arm, the percentage of men who actually received some treatment other than watchful waiting is (5,396 – 861)/89,352 = 5.075%. So an extra 2.273% received some treatment other than watchful waiting due to the screening assignment.
The percentage of men who died from prostate cancer was 0.410% in the screening group versus 0.517% in the control group, a decline of 0.107%.
If one calculates the ratio of (a) the extra percentage receiving treatment other than watchful waiting to (b) the extra percentage not dying from prostate cancer, the ratio is 21.4.
In other words, for every man who does not die of prostate cancer during the follow-up period because of the screening random assignment, there are a little over 21 men who must be treated in some way other than watchful waiting, and who in many cases will get side effects. I think this gives a little different picture than the headline numbers from the latest European study paper. If we’re concerned about the ratio of treatment side effects to lives saved, we should focus on this ratio, rather than the ratio of prostate cancers detected to lives saved.
These numbers reflect 23% of the screened group who had prostate cancer being assigned to watchful waiting only. But the European study also reports that 60% of the screening group with cancer was considered to have a low-risk cancer, versus 42% of the control group. If a higher percentage of the low-risk group could be persuaded to adopt active surveillance, I suspect the ratio of men treated to lives saved would drop.