Who would be interested in a case like mine?

June 5, 2012

I feel that I just don’t ‘fit’. I have never heard of anybody whose PCa history is remotely similar to mine. Accordingly, I find it hard to find anybody who is the least interested in my situation, or the research I have done.

I am not a doctor but, as a former technical and scientific writer and editor, I am a very experienced researcher with a great respect for accuracy and a yearning for truth and understanding.

In brief, I was diagnosed with PCa and had a radical prostatectomy in December, 2003. My urologist reported Gleason 6 with extension, clear margins. He said he though he had “got it all”.

In those days of low resolution PSA assays, my subsequent readings kept coming back as 0.1. This mystified my urologist, who told me the reading should be either <0.1 (meaning no more cancer) or should be climbing (indicating advanced cancer).

After 26 months of 0.1, my PSA began to climb. I recorded everything, and calculated the cancer’s doubling time (the PSADT). After 16 more months, my PSA was 0.8, and my PSADT was 187 days. The urologist then started me on intermittent Zoladex implants, two implants in tandem, three months apart. He told me that, in his opinion, I now had metastatic cancer.

The PSA level crashed to <0.1, resuming rising in September 2008, but at a PSADT of just 66 days.

Aided by the introduction of high resolution PSA assays, I recorded all subsequent dates and readings, and prepared graphs of the PSA behaviour. The situation was considered stable enough for my GP to take over the administration of my case. To be sure, my GP sent me to see an oncologist, who seemed irritated that I was taking up his time when all his other patients have PSA levels vey much higher than mine. Nevertheless, he took the time to hear me out, then endorsed a treatment plan whereby my treatment cycle be commenced at a progressively earlier stage (ie, at a lower value of rising PSA after it had begun rising again at the end of each cycle). By chance, it worked out that each new treatment cycle was falling just one year after the last. As each implant nominally lasts three months, I was now on Zoladex for six months, and off Zoladex for the same period.

It was at the end of the fourth such treatment cycle that I was able to detect something surprising. I was looking for a way to measure my ‘holiday periods’. For each treatment cycle, I measured the number of days between the date of the first implant (of each pair) and the date on which my PSA rose above 0.01. It was not the fact that each subsequent ‘holiday period’ was longer than the last (that was to be expected). Rather, it was the realisation that the ‘holiday period’ was increasing exponentially as the PSA value at cycle initiation decreased.

So, here I am with advanced (even metastatic) prostate cancer, with no physical symptoms whatsoever, and a PSA level that has been pushed through the floor by intermittent hormone therapy. I would love to find anybody else like that, and would be delighted to share my charts and graphs. But who would be interested in a case like mine?

June 5, 2012

Guihan,

You are not completely alone.

My similarities - radical in 2003, hormone treatment since, clean CT and bone scans today, no cancer symptoms but I have advanced PC.

My differences - Gleason 8, my PSA did not drop after radical (stayed at 6), continuous hormone treatment, PSA dropped to nadir of 0.07 after 3-4 years, PSA currently about 10.

My cancer more aggressive and further out of capsule at time of radical (despite my clean margins) - otherwise a similar pattern.

Tony Maxwell

June 6, 2012

Guihan,

I have fears like yours. I was diagnosed in May 2009 after a DRE with T3a advanced prostate cancer with evidence in the biopsie of cancer leaving the prostate ( Gleason 9). All scans for prostate secondaries have been clear ( except they found a totally independent kidney cancer which they removed - & confirmed with biopsies-after my prostate treatment). I had a double whammy. At the initial diagnosis the doctor I saw told me I probably had prostate secondaries. Prostate treatment was Brachy followed by beam radiation & ADT for 2 years. My psa never responded to my cancer before diagnosis. Was 3.5, 2years before diagnosis & 3.7 at diagnosis ( average for my age). After radiation my psa dropped to 0.02 & has been <0.03 during ADT. One year after ADT it rose to 0.04 then 0.05 before returning to <0.03 in 2 subsequent tests 2 months appart ( minimal detection level on the QLM test). Testosterone in the mean time has roared back to 20 from near zero. So it is now 18 months after the last Zoladex injection.

I keep asking doctors " if my psa did not reflect cancer before diagnosis why should it now?" I have had no doctor interested in my question. They all say there must be a psa rise if you have problems. I have been searching for other detection methods. I have heard of 2. There is a blood test at the PA hospital in Brisbane that detects cancer cells in the blood stream. I have asked for that & been rejected. I beleive there is a special MRI test being set up in Brisbane at the Wesley as well to detect bone metastases.

In my case i could be boxing at shadows - my wife certainly thinks so. Catch 22. No one is interested in my case as no positive scans & no psa rise. I feel fit & well. Being a chemical engineer & witnessing plenty of bum lab results over the years I am very suspicious.

Tony Brown

June 6, 2012

Thank you, gentlemen, for so kindly sharing your details. Yes, there are clearly common elements in our stories, but I suspect it is the differences that define our individual situations.

Tonymax, I was interested to learn that your current PSA level is around 10, and that you remain symptom-free.

Tonybrown, your posting describes how your testosterone levels were able to soar whilst your PSA levels remained curiously low.

These postings throw some light on a remark made by my oncologist, who told me there is a “major disconnect” between PSA levels and the level of disease. I had not known what to make of that remark, and continued to imagine that my PSA readings were a reliable analogue of the extent of my own cancer. I am now starting to see why our own cases are never quite like anybody else’s.

Well. If PSA and PCa do not always march in step, I wonder if tracking my testosterone levels would provide more reliable information. I have never had these assayed, and have no idea what the readings would mean for me.

I now find myself even more interested in that recently-reported research involving common soil-dwelling bacteria. These may have the potential to act like tiny Trojan horses, seeking out every last PCa cell and destroying it with its chemical payload. Now, wouldn’t THAT be nice!

June 6, 2012

Hi Guihan,

There is such research being carried out - nanotechnology by Australians ( who have been snapped up by US drug companies I beleive so we won't see the light of day for many years ( after US patients). It maybe on this website ( I don't use it enough to find my way around yet). Sounds just what we need - all of us.

EnGenIC- company started by Dr Himanshu Brahmbhatt & Dr Jennifer MacDiarmid on nano bacterial ( EDV)transfer of Chemotheraphy chemicals into Cancer solid tumours(Breast,Prostate,Kidney) . 1st experimented on Natural products on Kidney tumours. First paper in Cancer Cell, "Bacterially derived 400nm particles for encapsulating & cancer Cell targeting Chemotheraputics. http://www.cell.com/cancer-cell/abstract/S1535-6108%2807%2900090-6

pilot studies on dogs with lymphoma 2007 very successful.

So hopefully give it 5 - 10 years & if any of us survive with the current drug cancer blocking technology that long we can be treated.

June 10, 2012

Guihan

Thanks for sending me the Excel spreadsheets and graphs.

One question I have:

I know that for each session off the treatment you lowered the re-start PSA target to lower than the last one.

What were the actual targets that you set?

Jim

June 16, 2012

I would also be interested in the target re-start PSA figures (and the actual re-start figures).

SuperFred

June 20, 2012

Guihan

Thanks for sending me the Excel spreadsheets and graphs.

One question I have:

I know that for each session off the treatment you lowered the re-start PSA target to lower than the last one.

What were the actual targets that you set?

Jim

Jim, I had read that at least one specialist was applying the principle of recommencing (Zoladex) treatment when the post-breakout PSA had risen to half the value of the previous treatment cycle. Having said that, it should be remembered that that specialist (like so many others) was dealing with much higher PSA levels than mine. My case presented extra difficulties because my levels were so low. Yes, I began the recurring treatment with the initial aim of halving the previous value each time. I soon found that very difficult to achieve, partrly because of the low values, and partly because my PSADT (doubling time) had shortened dramatically since starting the Zoladex therapy.

Mathematics to the rescue. Each treatment cycle swiftly took my PSA levels down below my lab's lowest reportable level. Accordingly, 0.01 became my breakout level (when the level started to climb again). The threel evels reported by the lab that signalled breakout had occured were 0.8, 0.17 and 0.1. To facilitate comparison, I had to calculate the date on which my breakout value of 0.01 occurred. I did this by juggling the PSADT value and the start date of the exponential projection, For each treatment cycle, I discovered that there was only one doubling time and one start date that produced a projection curve that exactly matched my subsequent PSA levels. By this process, I was able to calculate both the breakout date and the PSADT for the PSA rise following each tratment cycle.

My principal aim became to start the next treatment cycle just as soon as the lab reported my PSA was starting to rise again. In the end, my graphs were providing me with such reliable information that I was able to work out in advance when the PSA level was due to break out. My graphs were also telling me that, not only was there nothing to be gained by allowing the PSA to rise to some arbitrary value before resuming therapy, but there was an exponential benefit in NOT allowing the PSA to rise.

Each of my Zoladex implants has a nominal life of three months. It seems I respond very well to Zoladex, and my graphs tell me that I can now have just one Zoladex implant every six months. This is still intermittent therapy, but it has been tailored to my case, and my graphs are telling me that, as long as the treatment keeps working, I will never again see a PSA level above that breakout level of 0.01.

June 21, 2012

Hi Guihan,

I assume your cancer is one that does not result in a psa response ( or very little pas response to have such low psa readings). It appears some prostate cancers are in this catagory. That is my worry because my psa never responded to the presence of cancer. In my case the treatment was radiation so I still have some normal prostate tissue left but also have a very low psa (<0.03). So the presence of metastases in you gives only a small response to psa. But your scans do not detect metastases. It appears from talking to others there are many men out there who have a psa response but no evidence in scans they have metastases. This is a big black hole that does not seem to be covered by the medical profession. Hence the drive to find other indicators that psa.

It also appears that Zoladex continues to operate on you to suppress testosterone for 6 months & not 3 months. When I went off zoladex it was over 9 months before I registered testosterone. So in your case by having a zoladex injection every 6 months that maybe enough so that you never generate testosterone. So really you are on continuous ADT. If so then perhaps you are aware of the next stage which is all the things that can happen to men medically without testosterone. There are many articles on this site that cover this situation & many men who are in this catagory.

Regards Tony B

June 21, 2012

Hi Guihan,

I assume your cancer is one that does not result in a psa response ( or very little pas response to have such low psa readings).

Regards Tony B

Tony, I don't think I have any evidence that my PSA level and my level of cancer acvity are not related. My PSA may, in fact. be an accurate analogue of my cancer activity. The reason my PSA levels have never climbed too high is that I have always had a Zoladex implant at an early stage. Having said that, the doubling time of my PSA is only about 67 days (suggesting my cancer is doubling more than five times every year). I have little doubt that, if I were to let this genie out of its bottle by discontinuing my implants, my disease would soon become uncontainable.

June 21, 2012

Guihan, I think you are right & your treatment seems logical. I agree it seems silly to let the cancer grow when you can suppress it as soon as you have indication of cancer growth. But the difference with you is the low level of psa response compared with most men. And that makes arbitary limits on psa before you start treatment silly. But the other factor that effects the psa rise frequency is how rapidly testosterone ( the food of prostate cancer ) comes back in your body as zoladex dissappears. And that is complex. It certainly isn't a linear response. So rate of psa rise may be effected by testosterone concentrations. Having a zoladex every 6 months in your case may suppress testosterone enough but maybe not completely. Are you measuring testoserone response of the cancer ( psa) indirectly as well as cancer growth? Are you aware of the long term effects of very low testosterone? Osteoperosis, heart problems, diabetes etc?

Regards, Tony

June 22, 2012

Guihan, I think you are right & your treatment seems logical. I agree it seems silly to let the cancer grow when you can suppress it as soon as you have indication of cancer growth. But the difference with you is the low level of psa response compared with most men. And that makes arbitary limits on psa before you start treatment silly. But the other factor that effects the psa rise frequency is how rapidly testosterone ( the food of prostate cancer ) comes back in your body as zoladex dissappears. And that is complex. It certainly isn't a linear response. So rate of psa rise may be effected by testosterone concentrations. Having a zoladex every 6 months in your case may suppress testosterone enough but maybe not completely. Are you measuring testoserone response of the cancer ( psa) indirectly as well as cancer growth? Are you aware of the long term effects of very low testosterone? Osteoperosis, heart problems, diabetes etc?

Regards, Tony

Thanks for that, Tony. That is the sort of question that is rolling around in my head at the moment. I have been watching my PSA like a hawk, but I had never had any measurement of my testosterone levels. I had also been unable to find any printed data describing what usually happens to testosterone levels during the clurse of intermittent hormone therapy.

I will be seeing my GP for implant number 10 on 24th July, and I will ask him then to start monitoring those testosterone levels. I suspect the levels don't get very high, if facial hair growth is any measure. I could stop shaving for a week, and I am sure nobody would notice any difference. Nevertheless, life is full of surprised, so I would like those figures. On the other hand, I don't even know what would constitute a normal testosterone reading for my position. I'll ask my GP to help sort that one out.

Regarding the risk of osteoporosis, I suspect that not being on continuous Zoladex probably helps. However, given the choice of some bone density loss or letting my fast-doubling PCa genie out of its bottle, the bone density will just have to take its chances!

June 22, 2012

Hi Guihan, The whole purpose of ADT seems to be to get testosterone to zero if possible. So you cannot have your cake & eat it i.e. enough T to keep bodily functions going but not feed cancer. it is all or nothing. Many men use Zoladex plus abdrogen scavengers in combination ( ADT2 & ADT3) because there is some research that indicates some cancers morph to produce their own T & they want T as close to zero as possible. So they use T scavengers as well as suppress the production in the testes ( which is what Zoladex does). The adrenal gland can also produce T & there are tests of that because I just had one. So it seems to me one reason for your psa increase maybe due to small levels of testosterone because you have stretched out the injection frequency to double the recommended. Others with more knowledge might comment. There was some discussion in the teleconference this morning about continuous vs intermittant ADT & latest research picked up by Jims search engine suggests intermittant leads to a shorter life span than continuous. This is the reverse of popularly held medical opinion. Your treatment may be a cross between the 2. Not sure what levels of T you need to get bodily benefits but I bet the cancer gets more. That is the dilemma of current advanced treatment. We are basically having testoserone eliminated to stop cancer growth but that has very harmfull effects long term on the body. With some men these are quite rapid effects. Oh for a chemical/drug treatment that attacks the cancer & not just suppresses or eliminates T! Then there are treatments that try & replace the T with hormone that does not grow the cancer such as oestrogen ( with all those effects)! Tony B

June 24, 2012

Hi Guihan, the subject of testosterone levels during ADT arose at the last advanced prostate cancer sufferers teleconference last Friday. I think this link gets the article. http://www.nejm.org/doi/full/10.1056/NEJMc1010187

June 25, 2012

Hi Guihan, the subject of testosterone levels during ADT arose at the last advanced prostate cancer sufferers teleconference last Friday. I think this link gets the article. http://www.nejm.org/...56/NEJMc1010187

Thank you, Tony. This was exactly the information I needed to take with me when I see my doctor. He has always been highly supportive of my input, and I feel sure he will agree to:

(1) changing my Zoladex implants to one every 24 weeks (which I feel is appropriate in my particular case);

(2) adding a testosterone test to my 12-weekly PSA blood tests; and

(3) helping me monitor new research in the field of intermittent and continuous ADT.

June 25, 2012

Brian, you have not reported the results of a bone scan after your PSA started rising.

If your bone scan is clear, you seem to be in the same boat as several other men. That is, some time after your primary treatment, your PSA started rising, showing active prostate cancer, but with no metastases. Treatment guidelines in this area seem to lack evidence, and your doctor may be choosing between observation and ADT based on their clinical judgement.

If your bone scan does show metastases, your doctor has two studies to consider, both earlier reported on our website:

Intermittent ADT not good for metastatic disease, which reports:

Continuous vs. intermittent androgen deprivation therapy for metastatic prostate cancer, by Langenhuijsen et al. ; and

Price to Pay for Intermittent ADT in Advanced Prostate Cancer, which reports:

Intermittent (IAD) versus continuous androgen deprivation (CAD) in hormone sensitive metastatic prostate cancer (HSM1PC) patients (pts): Results of S9346 (INT-0162), an international phase III trial, by Hussain et al.

In the first paper, Langenhuijsen et al. report that metastatic patients whose PSA dropped below 0.2 ng/ml on ADT had:

53% risk of progression after 2 years of intermittent ADT
31% risk of progression after 2 years on continuous ADT.

and conclude " Therefore, IAD is not a good treatment option for many metastatic prostate cancer patients."

In the second abstract, Hussein et al. reported to the recent American Society of Clinical Oncology (ASCO) annual meeting (2102) that:

For men with metastatic disease whose PSA at treatment start was higher than 5 ng/ml, but dropped below 4 ng/ml after the first 7 months of ADT survived a median (average) of:

5.1 years if treated with intermittent ADT
5.8 years if treated with continuous ADT.

Separating the men's results according to whether they had less metastatic disease (no spread beyond the spine, pelvis and lymph nodes) or more widespread metastatic disease (spread to the ribs, long bones, and/or liver and lungs) led to an interesting result for men with less metastatic disease:

For men with metastatic disease that had not spread to the ribs, long bones, and/or liver and lungs), and whose PSA at treatment start was higher than 5 ng/ml, but dropped below 4 ng/ml after the first 7 months of ADT survived a median (average) of:

5.2 years if treated with intermittent ADT
7.1 years if treated with continuous ADT.

Although these abstracted figures may make the case seem simple here, it is still a complex decision for you to make with your doctor. Two of the authors of the second paper advise:

... that clinicians discuss the findings with patients. Dr. Higano said that the decision on how to proceed with ADT in an individual patient is complex. "It has to come down to educating patients about the risks and benefits," she said.

June 26, 2012

Thank you, Jim. That summation is very useful.

I believe I had a bone scan just before my radical prostatectomy in December, 2003. I assume nothing was found. My disease appeared to be confined to the prostate, but with “an extension”. I took this to mean the cancer had broken out of the capsule and into surrounding tissue. The urologist removed what he thought he needed to, and the pathology reported “clear margins”. He told me he thought he had “got it all”. The first indication that was not the case was when my PSA readings kept coming in at 0.1 instead of <0.1. My PSA remained at that level for nearly three years.

In August 2006, my PSA started to rise, and I calculated the doubling time at 187 days. By September, 2007, with my PSA passing 0.8, my urologist informed me that “It’s metastatic”, and started me on interrupted 3-month Zoladex implants (two in tandem, three months apart, followed by a break until my PSA got to some level he had in his mind).

Following the second implant in December, 2007, my PSA was undetectable, but it started rising again in September, 2008. Fortuitously, my lab. had improved the resolution of their PSA assays, and I was able to plot the PSA rise and calculate the doubling time at an earlier stage. I was shocked to discover that my post-Zoladex doubling time had crashed to just 66 days.

This was now a very dangerous genie, but those Zoladex implants kept pushing it back into its bottle. My primary concern became to determine when it should be administered, and how frequently I needed the implants. I decided to have my GP administer my case, and he was happy to work with me in conducting some studies. It was during those studies that I discovered that, the lower my PSA was when I had the implant, the longer my “holiday period”. It turned out to be not a linear equation, however. It appeared that there was an inverse exponential relationship between the PSA level at the start of the treatment cycle and the length of the holiday period. In other words, there was a clear benefit in NOT allowing the PSA to climb to some arbitrary level (as is still advocated by some specialists) before resuming treatment. The lower the PSA at implant time, the (much) greater the holiday period.

That finding supports the concept of continuous ADT as opposed to interrupted ADT, but with the important rider of dosage. Drugs like Zoladex can have serious side-effects, so it was obviously important to try to determine the minimum regular dose necessary to keep my PSA below measurable levels (0.01 in my case). For me, this looks like being one 3-month implant every six months. To make my therapy more continuous, I suppose that an ideal solution for me would involve one half-strength 6-month Zoladex implant every six months. Still, as long as Zoladex keeps working for me (nearly five years to date), I will be very content to keep doing what I am doing.

June 26, 2012

Brian

Do you think it would give you a better idea of what is happening if you had, at least for your next 'off' period, more frequent testosterone/PSA measures?

Jim

June 26, 2012

Hi Guihan, I wonder what the supplier of Zoladex thinks about this Issue? Your testosterone level on your current Zoladex dose every 6 months would be interesting. There wouldn't be too many people in your circumstance but I may be one of them if my psa starts to rise due to my previous history of low psa with advanced cancer. So basically you have been on an unusual but continuous ADT for 6 years. Assuming testosterone is at castrate levels which it should be. The other issue is after approx 3 years ADT the testes usually atrophy so will not produce testosterone again ( that is a danger for many men when they get off ADT) so in your case what is happening? So maybe you don't need Zoladex which just stops the testes but something else?