Over the years there have been multiple debates about whether different types of androgen deprivation therapy (ADT) really do or don’t extend the survival of men with advanced prostate cancer of differing types and whether the degree to which ADT initially suppresses serum testosterone levels affects that survival. As yet, neither of these issues has been satisfactorily resolved … and they may never be.
These issues have been brought back into focus by a new paper by Klotz et al. and an associated editorial by Suzmann and Antonarakis, both recently published on line in the Journal of Clinical Oncology.
Basically, Klotz et al. state, on the basis of a post hoc, retrospective analysis of data from the PR-7 study (which compared the effects of continuous ADT to intermittent ADT in men having biochemical failure after radiation therapy or surgery plus radiation therapy) that in this study the men who had a consistent nadir serum testosterone level of > 0.7 nmol/l (about 20 ng/dl) during their first year on treatment with continuous ADT had significantly higher risks of dying as a result of their prostate cancer and were more likely to develop hormone resistance than patients whose serum testosterone level was consistently < 0.7 nmol/l during that first year on therapy.
Now it is certainly reasonable to believe this possibility. The problem is that the Klotz study really doesn’t prove the hypothesis — for all sorts of reasons that are discussed in detail by Suzmann and Antonarakis (and we strongly suggest that interested readers look at their editorial to understand their arguments in detail).
There has long been an assumption on the part of many patients — and many doctors too — that ADT extends survival and that starting ADT early is therefore a good thing for men with progressive prostate cancer. We like to remind everyone, every so often, that these two hypotheses have never actually been proven at all. There have been small studies that suggest this possibility, but no large, well-designed, randomized, double-blind trial has ever actually demonstrated that ADT alone actually extends the survival of men with prostate cancer at all. And the use of the various forms for which ADT is approved in the treatment of prostate cancer is generally limited to the palliation of pain in men with advanced prostate cancer. European guidelines on the treatment of prostate cancer do actually include the statement that, “Complete androgen blockade has a small survival benefit of about 5 percent.” However, this is, strictly speaking, an “expert opinion”.
The only use of any standard form of ADT that has actually been clearly and irrefutably shown to extend survival has been the use of 3 years of continuous ADT, with goserelin acetate combined with external beam radiation therapy, in the treatment of men with locally advanced prostate cancer (see Bolla et al. 1998).
For another set of comments on this long-running issue, see the article by Moul in the journal Cancer entitled “Twenty years of controversy surrounding combined androgen blockade for advanced prostate cancer.”
Could we actually resolve the issue of whether androgen deprivation therapy has a real and significant survival benefit, and whether that survival benefit was linked to the length of time men sustained a serum testosterone level of < 0.7 nmol/l (20 ng/dl) after initiation of therapy?
Frankly, it is no longer clear that this is possible at all, given the development of effective second-line treatments like abiraterone acetate and enzalutamide that clearly do extend the survival of men with metastatic, castration-resistant prostate cancer. The trials that would be needed today to resolve the two questions would have to be very large, very highly controlled, requiring multiple trial arms, and might take as long as 15 to 20 years to carry out! The costs would be enormous; the advancement in knowledge would likely be small; and by the time the trials were completed, we might well find that the results were irrelevant given other advances in the management of advanced prostate cancer.
If we are going to look at how to establish better ways to treat progressive and advanced forms of prostate cancer, we might do better to look at large trials in which drugs like enzalutamide are used relatively early in the treatment of men with high-risk, progressive disease after failure of localized treatment, with standard hormonal therapy replacing (or being combined with) the enzalutmide as and when the patients progress on enzalutamide alone. Such trials could also prospectively track patients’ levels of serum testosterone to see how low it goes at the onset of each type of treatment and how long it stays below certain pre-defined levels and whether that affects overall survival and/or progression-free survival.
Here are some really important facts that are worth remembering about the use of ADT:
- It is very, very effective at ameliorating the bone pain associated with late-stage, metastatic prostate cancer (as initially demonstrated by Huggins and Hodges some 75 years ago).
- Because it suppresses the normal levels of testosterone in men, it is associated with a whole series of serious adverse side effects that can vary in intensity from patient to patient and which include loss of libido, loss of erectile function, weight gain, changes in body form, gynecomastia, and effects on mental capabilities over time.
- If there is a survival benefit associated with ADT, it is small, and may only be evident in a subset of patients (who we are currently unable to define in advance).
- Early initiation of ADT introduces significant risk for early induction of the development of androgen-resistant prostate cancer cells, which has the potential to lead to early onset of metastatic, castration-resistant prostate cancer.
- Overly early initiation of ADT may therefore mean that ADT never gets the chance to be used to do the one thing we know that it is really good at — ameliorating the bone pain associated with metastatic disease!
There are good reasons why many experts in the management of prostate cancer advise their patients with progressive disease not to start treatment with ADT just because their PSA is rising, but to start ADT only if and when there are other good reasons to do so, such as a PSA doubling time of 9 months or less, or a PSA level that has risen to 50 ng/ml and/or evidence of metastatic disease (even if there is no actual pain associated with the metastasis).
Once upon a time — and not so long ago — we had nothing else at all, other than ADT, with which to treat advancing forms of prostate cancer that had progressed after treatment with surgery and/or radiation therapy. As a consequence, ADT started to be used to “manage” patients’ rising PSA levels. It did that very well … but whether this was actually beneficial is seriously open to question. Today we have many other ways to treat progressive prostate cancer, and it is high time for us to reassess exactly when it is best to start a patient on ADT. Back in the 1940s, Huggins and his collaborators were only using ADT to manage men with evident metastatic prostate cancer (most of whom also had bone pain). We had no idea what their PSA levels were. Maybe that really is the very best use of ADT (with the single exception of its combination with radiation therapy for the treatment of locally advanced disease).
Filed under: Living with Prostate Cancer, Management, Treatment | Tagged: ADT, androgen, deprivation, hormone, serum, testosterone |
THE "NEW" PROSTATE CANCER INFOLINK 
How would the Messing trial, which showed ADT + surgery far improved survival over ADT alone for LN+ patients, fit in this scheme? Or would it?
This is shocking information given the horrible side effects of ADT! Why then is ADT the “standard protocal” before application of SRT?
Dear Bob:
(1) There is an enormous difference between the short-term use of ADT in association with first-line and/or salvage radiation therapy and the long-term use of continuous ADT. Such short-term use of ADT is associated with a much lower risk for long-term side effects and may well make the difference between a remission and a cure — although this has never been proven in a randomized clinical trial.
(2) This is not exactly “shocking” information about the side effects of ADT. These side effects have been well known for years and information about them is widely available.
Dear Tarhoosier:
The Messing trial involved a small number of patients (98 in total, as opposed to the 220 patients originally projected), all of whom were high risk at the time of their initial treatment because they had been found to have of lymph node positive disease (with a pathological stage of pTxN1M0) at the time of initial surgery. While the trial showed a positive result in terms of a clear benefit from immediate ADT, the authors themselves state that, “We must stress that these results are applicable only to the particular subgroup of patients in our study — namely, men who underwent radical prostatectomy and lymphadenectomy and were found to have metastatic prostate cancer in the excised lymph nodes.”
There is no question in my mind that there may well be a subset of men for whom early ADT can provide a survival benefit compared to delayed ADT, and that this subset may well include many of the men diagnosed and treated by Messing et al. But these patients were hardly typical of the average patient today, who is often encouraged to start ADT long before there is any evidence of node-positive or other forms of micrometastatic (let alone metastatic) disease.
It is also worth noting that at a median follow-up of 7.1 years, the patients in neither of the two arms of this trial had actually reached median overall survival, which raises other questions about the validity of the data from this trial. In other words, even in the observation arm only 18/51 patients had died at the time of completion of the trial. Whether this is important or not is hard to determine. What is also interesting is that even in this trial, started back in 1988, most of these high-risk patients were living for 7+ years even with delayed androgen deprivation!
I had 6 months of Lupron and had very bad SEs. I can’t imagine 3 years on it. I was not saying I was shocked about the SEs but shocked that I was told it was necessary to have ADT before and during SRT when there apparently is no proven benefit for most people, and given that it is standard protocol I’m sure many men are put through ADT unnecessarily. The reason given is that ADT helps IMRT be more effective.
Bob,
ADT is not part of the standard protocol for SRT. It’s a very difficult decision for the patient and doctor to discuss on a case-by-case basis. It may be beneficial with high Gleason scores or rapidly rising PSAs, but its optimal use in all settings requiring SRT has yet to be defined.
Bob:
Allan’s description of the role of ADT in SRT is mine too. It is not a standard protocol but needs to be assessed and discussed on a case by case basis — and it is rarely an easy decision.
After brachytherapy for T2aN0M0 Gleason 6 disease in 2012 at age 62 I had a metastasis to L5 9 months later. My urologist in South Africa where I currently live told me the only treatment was continuous ADT for life. I opted to travel back to the States to M. D. Anderson for a second opinion. They did a 6-month, short course of ADT followed by EBRT to the spot on L5. A year later my PSA is 0.2 and I am on no treatment. Like Bob, the side effects of the ADT were terrible for me. I am so glad I followed my instincts and went to M. D. Anderson for another opinion. There are probably lots of urologists worldwide who still are telling patients that ADT for life is their only choice after a metastasis. Get a second opinion!
ADT SIDE EFFECTS AND COUNTERMEASURES — A FAVORABLE VIEW
As a long-term patient on ADT (14 years of IADT3 to April 2014), I am glad Sitemaster published this report, but I have a much different perspective on some of the issues. I’ll start with what is a much-needed comment on the side effect exchange between Bob and Sitemaster:
• Bob, on March 19, 2015 at 1:17 pm said:
“This is shocking information given the horrible side effects of ADT! Why then is ADT the ‘standard protocol’ before application of SRT?”
• Sitemaster, on March 19, 2015 at 1:41 pm said:
“Dear Bob:
“(2) This is not exactly ‘shocking’ information about the side effects of ADT. These side effects have been well known for years and information about them is widely available.”
• Bob, on March 19, 2015 at 2:52 pm said:
“I had 6 months of Lupron and had very bad SEs. I can’t imagine 3 years on it. I was not saying I was shocked about the SEs but shocked that I was told it was necessary to have ADT before and during SRT when there apparently is no proven benefit for most people, and given that it is standard protocol I’m sure many men are put through ADT unnecessarily….” (plus comments not directly relevant to my point below by Allen and Sitemaster)
As a now savvy, experienced veteran of ADT, familiar with some of the key literature and experts, I’m confident making these points:
— Tolerance of ADT varies considerably among patients, ranging from virtually no burden — even for libido and EF, to major burden; a few patients can’t tolerate ADT or can only barely tolerate it even with countermeasures. Their solution is to stop ADT and try something else. Most patients will tolerate intermittent ADT well for the periods needed, with the help of countermeasures.
— Each side effect varies over patients in its incidence (most of us only experiencing a subset of the more likely side effects, not all of them), time of onset, and degree of mildness-severity. While side effects were not the focus here, I am frustrated that so many discussions of side effects do not address these very important aspects.
— Countermeasures have been proven that are at least somewhat effective, often highly effective, for the side effects. I have been a vigorous and successful user of countermeasures. Relief is certainly not total, but I have been well satisfied.
— Information on side-effects of ADT and countermeasures is far from new. Much of the key technology was known by 1999, shortly before I became aware of it, though the technology has improved further since then. I am frustrated that so many doctors do not seem aware of the side effects or the countermeasures, also failing to advise their patients. My impression is that the medical oncologists are generally considerably better informed about ADT side effects and countermeasures than are urologists. For instance, while known before 1999, the bone density issue was not in the education book for the medical oncology annual meeting until the early-mid 2000s and for the urologists a year or two later. A good source for information on countermeasures, in layman’s terms, is Invasion of the Prostate Snatchers, a book by Ralph Blum and Dr. Mark Scholz, MD (a medical oncologist).
— For a substantial majority of patients, side effects of triple ADT are reversible during the vacation phase of IADT3 or final cessation of ADT in the adjuvant role. My belief, based on statements by doctors who appear to be expert in ADT use, is that the side effects of most kinds of ADT (such as single agent and two agent) are also reversible. Some of the factors that make the side effects more permanent are a single very extended period of ADT, several long courses of ADT, advancing age — especially at about 70, and combinations of these factors. Countermeasures can improve the odds of recovery from side effects as well as helping during ADT therapy.
For patients facing ADT, I recommend asking what the doctor knows about side effects and countermeasures. If the doctor does not seem savvy, it might be a fine idea to find another doctor who knows this territory.
Bob, would you mind sharing your experience with side effects, including whether you were advised about them ahead of time and whether you were advised about countermeasures ahead of time or as you experienced side effects?
IMPORTANCE OF PSA NADIR IN MANAGING ADT
This study adds to the body of research supporting the notion that achievement of a low PSA nadir is important for successful ADT. This idea has been around for a long time. My own goal after diagnosis of a life-threatening case in December 1999 was a nadir of < 0.05 maintained for a year under ADT3 therapy, which would be evidence I could reasonably try intermittent ADT. (Conversely, failure to achieve that nadir would have been a basis for adding other tactics or changing course. For me personally, it was not at all clear that I would make it, but I did.) This tactical use of such a low nadir was based on clinical experience in medical oncology practices dedicated to prostate cancer that were treating many patients with well-advanced prostate cancer.
The best published practice I know of on this point has involved Drs. Stephen Strum, Mark Scholz, and Richard Lam, and their team mates. They used a lower cut-point, finding that the ability to achieve that threshold of < 0.05 made a difference. (Over time they relaxed the requirement of holding that level for a year. At least one other expert wants the PSA to be < 0.01.) They published their most pertinent results in Urology in 2007. The striking finding was that the PSA nadir cut-point of 0.05 or lower was an extraordinary indicator for prostate cancer-specific mortality. Men with a higher nadir had an 11.6 fold greater risk of death from prostate cancer!
This team has described how they use the nadir to keep men on ADT, with intermittent therapy strongly favored, or redirect them to other tactics. In the past, that often meant fairly early chemo, but now the whole field of ADT is undergoing great change because of the new and very potent drugs now available, as well as advanced imaging and radiation techniques.
JUST PALLIATION OR ACTUALLY COUNTERING PROSTATE CANCER
The article above includes this text: “… and the use of the various forms for which ADT is approved in the treatment of prostate cancer is generally limited to the palliation of pain in men with advanced prostate cancer.”
There is an important subtlety in this text that I’ll bet not many of us appreciate: the value and role of an approved drug often extends well beyond its approved “indication,” meaning area of use.
While the text indicates that the “approval” for a number of ADT drugs was for palliation — “relief from pain” instead of “treatment” — knocking back the disease, the savvy oncology community I follow regularly uses ADT to treat prostate cancer. In fact, as an example, one of the newer ADT drugs — Firmagon (degarelix) — is actually approved for treatment (see the product prescribing information). This is also true for Zytiga and Xtandi. As I understand it, fresh approvals for extended applications for many drugs are not attempted because: (1) the safety profile is already well and favorably established; (2) new trials are almost always very expensive and time consuming (many years); and (3) patents will often have expired before the new approval, thereby nullifying the sponsoring company’s advantage in gaining an approval.
SUGGESTION FOR TESTING SURVIVAL ADVANTAGE OF ADT
The article states that the survival advantage of ADT is small: “… If there is a survival benefit associated with ADT, it is small, and may only be evident in a subset of patients (who we are currently unable to define in advance) ….”
The expert medical oncology community I follow enthusiastically believes that the advantage is great, rather than small, and that the advantage is experienced by many men rather than a small subset, but they have not been able to launch the kind of Phase III clinical trials that would prove their point, as Sitemaster notes.
A key problem is that there is no sure way of knowing whether those of us with long-term success on intermittent ADT treatment would have died if not treated. Here’s the rough suggestion: use PSA doubling time (PSADT) as a method for projecting nominal death from prostate cancer without treatment, and compare that to actual survival. PSADT is often known or can be inferred for patients who have one of the kinds of prostate cancer that poses a deadly threat. While PSA is not an ideal predictor of prostate cancer mortality, a nominal threshold PSA level might be usable as a proxy for death. For example, based on research, a level could be selected that would be associated with high likelihood of death. I don’t know what that level would be; perhaps 2,000; perhaps 6,000. The point is the projected time for the conjectural untreated patient to reach that level, based on the doubling time of the actual patient on ADT/IADT, could be compared with whether the actual patient was alive beyond that time. Longer actual survival than projected would indicate a survival advantage for ADT.
ADT AND DEVELOPMENT OF ANDROGEN-RESISTANT PROSTATE CANCER CELLS
Many of us — especially those of us diagnosed well over a decade ago — for whom early or primary ADT seemed like the best option have probably been concerned that we might be just setting ourselves up for early development of androgen-resistant prostate cancer. Back then, the typical advice about success on ADT was that it would only work for a short time, such as 18 to 24 months. Even then that advice was based on a false understanding of important research, such as Dr. David Crawford’s 1989 study, but nonetheless the misunderstanding was quite common. I heard it about my own case from respected doctors, and I heard it echoed many times from highly regarded urologists.
The article reflects this view as follows: “… Early initiation of ADT introduces significant risk for early induction of the development of androgen-resistant prostate cancer cells, which has the potential to lead to early onset of metastatic, castration-resistant prostate cancer….” It is important to bear in mind that “ADT” is not a single entity but rather a group of related approaches with important differences. I personally believe that the statement is probably true about single agent ADT — by a drug such as an LHRH agonist or by orchiectomy. However, there is research that suggests that two and three agent ADT — not only sharply limiting testosterone but also holding down DHT and blocking the androgen receptors (fuel ports for the cancer cells) — substantially delays or prevents development of androgen-resistant cells.
Unfortunately, I am not aware of conclusive research supporting early combined and triple blockade.
On the other hand, the issue is probably moot as new drugs are profoundly recasting the options for ADT. For instance, one major practice is now using Firmagon (degarelix, an LHRH-antagonist) instead of the older LHRH agonists, thereby achieving a far more rapid and deeper decline in testosterone, arguably giving the cancer much less time to mutate and survive ADT. Other drugs like Xtandi (enzalutamide) are moving into use earlier in the course of the disease, and, because of their much greater potency compared to older options like bicalutamide and flutamide, are producing clearly superior results. Some of these new drugs work well together, and consequently some patients are already enjoying marvelous improvement with durable complete remissions being reported.
Dear Jim:
I think it is important to note a number of points about your “Just palliation …” comment above.
— The reason that degarelix (Firmagon) is approved for the “treatment” of prostate cancer as opposed to a specific clinical use is that the clinical trials carried out to gain its approval only ever showed that its effect on lowering PSA over a 12-month period was at least as good as that of leuprolide acetate. The manufacturer never even demonstrated that degarelix could palliate pain in men with prostate cancer. “Treatment” is a general term that in no way implies a survival benefit. It is used commonly by the FDA and other regulatory agencies when a specific clinical benefit has not been established but a potential clinical benefit is believed to have been demonstrated.
— Extensive trials were conducted between the late 1980s and the late 1990s to try and demonstrate that the LHRH agonists and the antiandrogens actually had a survival benefit. The only trial that ever actually showed such a really significant effect was the Messing trial (see above) — in a very highly identified subset of patients. Thus it is misleading to imply that the older “standard” forms of ADT might never have sought such an indication. Their manufacturers very definitely did.
— I was very careful to point out in the original commentary that both abiraterone acetate (Zytiga) and enzalutamide (Xtandi) most certainly do extend survival in men with metastatic, castration-resistant prostate cancer, and that is clearly reflected in their indications. Whether they would have the same effect in men with earlier stages of prostate cancer is currently being tested.
Dear Jim:
It has been shown over and over again in medicine that just because physicians (even most physicians) believe something doesn’t make it true. Just as there is a subset of physicians who believe that ADT has a survival benefit, there is a whole other group of physicians who believe (based on some rather good scientific evidence) that overly early use of ADT may actually accelerate the onset of castration-resistant prostate cancer in at least a subset of patients.
Unfortunately, the study you suggest wouldn’t prove anything one way or another. Why? Because you are correct, neither PSA levels nor PSA doubling times have ever actually been shown to correlate to risk for prostate cancer-specific death. Plenty of men die with mCRPC without their PSA levels ever reaching anything like 2,000 or 6,000 ng/ml, and it would be unethical to defer treatment that long in any patient anyway.
Dear Jim:
I am sorry, but in your last post above you are comparing oranges to apples.
When Crawford et al. did their trials back in the late 1980s they were treating men with severe, advanced, metastatic prostate cancer. Patient survival from onset of such a diagnosis was routinely 18 to 36 months.
In the article above I am talking about the use of ADT in men who have (commonly) progressed after either surgery or radiation or some combination of the two and have a low and often very slowly rising PSA — maybe even <0.2 ng/ml. The Hopkins group showed years ago that men with a PSA doubling time of 15 months or higher had no significant benefit from the early use of standard forms of ADT. We also know that the side effects of ADT can be highly debilitating.
What on Earth is the justification for starting a standard form of ADT alone in a man with non-metastatic, progressive disease, a PSA of anything under 20 ng/ml, and a PSA doubling time of anything like 18 months or higher? If such a person wants to enter a clinical trial of some other potential form of treatment, that's a quite different question, but I don't understand the concept of exposing oneself to a treatment that comes with high risk for debilitating side effects and that has no known benefit on either quality or quantity of life in a man with no sign of at least node-positive disease! If such a patient wants to "manage his PSA level", then he could do that for quite a while with a drug like dutasteride (Avodart) … with a far lower risk for all the side effects of standard ADT.
With respect to the use of degarelix, very few patients are actually treated long term with this drug. It is usually used up front to drop the patient's PSA and serum T as fast as possible, but (because degarelix injections are customarily quite painful and have to be given every month) most patients are rapidly switched over to a standard LHRH agonist after initial degarelix treatment.
Drugs like enzalutamide and abiraterone acetate are indeed in clinical trials for use earlier in the treatment of selected groups of patients with prostate cancer. Whether there will be any evidence of a real clinical benefit from such treatment is unknown at this time. There may be or there may not. The fact that they can induce durable remissions is hardly a surprise. Whether they will have a long-term impact on survival when used earlier in the disease course is a whole other question and utterly unknown at this time. It is wrong to imply that such patients are "enjoying marvelous improvement" when we have very limited data to support any such conclusion.
Jim:
By far the worst SE from Lupron was pain in joints and fatigue. Next came night sweats and bowel issues — the latter due I’m sure due to SRT as well. Total ED and lack of libido were also problems but ED was a problem pre-RP due to finasteride and tamsulosin I was taking for BPH. Now I have libido and T is back to normal, but I still have total ED. The other issue I still have is fatigue which necessitates a daily nap.
Bob
I should have disclosed that I was stage pT3bN0M0 post-RP, Gleason 4 + 5 = 9. Ten nodes were dissected, all clear, and the positive margin found at the base was Gleason 7. I’m hoping that the lower Gleason score at the positive margin was helpful in terms of SRT being able to eliminate any prostate cancer at that location. To my knowledge, a separate analysis of the involved seminal vesicles was not done but I assume they would have been Gleason 9 also. Did these characteristics make me a good candidate for ADT?
Dear Bob:
Anyone with the characteristics you describe (positive seminal vesicles, a positive surgical margin of Gleason 7, and Gleason 9 disease overall) has at least three characteristics of high-risk disease post-surgery. If your original PSA was also > 10 ng/ml, then you would have had another suggestive characteristic. Having said that, the fact that 10/10 lymph nodes were negative tends to suggest that the cancer had not progressed very far at the time of your surgery.
Whether you were a “good” candidate for ADT may be debatable; certainly you were a strong candidate if your goal was a cure, and I think that many clinicians would have recommended at least a short course of neoajuvant ADT along with the radiation therapy in a case like yours.
Dear Sitemaster:
At age 69, my biopsy was two of six cores positive for prostate cancer with Gleason 9 on right side only, one 10% and the other 40%. Since my prostate was only 33 g due to finasteride, only six cores were deemed necessary. My PSA at biopsy was 6.6 but really like 13.2 due to finasteride. So before treatment I was staged pT1c. Radiation oncologists said I needed ADT then IMRT. Surgeons said RP was also a good option for me. So wanting to avoid ADT and IMRT due to length of treatment and perceived side effects, I went for RP. But PSA never reached zero. At 2 months post-RP it was 0.1, at 5 months 0.2, and at 8 months 0.3 ng/ml, so I started Lupron and then 68.2 gy of IMRT/IGRT over 38 sessions. I had two 22.5 mg shots; my serum T level went down to < 3 and I felt awful so I stopped. PSA post-treatment has been < 0.1 (undetectable) for three tests in a row. My urologist thinks I won't have recurrence due to the gradual way PSA increased post-RP, plus SRT concentrated on positive margin at base. Do you think his optimism is justified?
Dear Robert:
If I am understanding you correctly, it has been about 2 years since your original diagnosis and about 9 to 12 months since you completed your radiation therapy. Yes?
There are never any guarantees for any patient who is initially diagnosed with Gleason 9 disease. On the other hand, your urologist certainly has good reason to take a positive attitude to your response to the radiation therapy. Can I make you a promise that you will never have a recurrence? No, I can’t. However, optimism is certainly the best policy under the circumstances … but that optimism needs to be tempered with a level of reality, and so you do need to keep getting those PSA levels measured at least every 4 months or so. Should your PSA ever start to rise again, there are other options than the Lupron.
Sitemaster,
What options other than hormone therapy are you referring to for Robert if his PSA starts a to rise? Since he is still hormone sensitive, Provenge isn’t approved by insurance. Chemo is not an attractive option. The newest drugs like Zytiga and Xtandi are hormone therapy drugs. Are you referring to these?
Thanks,
Jerry
Jerry:
What I said was not that there were options other than hormone therapy but that there were options other than Lupron.
Some men respond differently to different LHRH agonists; some men do very well on an antiandrogen alone; and some men manage their progressive prostate cancer by the use of transdermal estrogen patches.
“If there is a survival benefit associated with ADT, it is small, and may only be evident in a subset of patients (who we are currently unable to define in advance).”
If this is true, that’s a lot of wasted Lupron and a lot of needless sore butts in the last 75 years.
I, for one, am a IHT guy and at minimum ADT represents “doing something” in the fight against advanced prostate cancer. So, perhaps over the decades patients, doctors, and families have been using these drugs psychologically. Meaning, we’ve been using them to think we’re making a difference. And as a prostate cancer guy myself, I get it.
I’m optimistic that ADT does have a survival benefit, but happier there are newer drugs and therapies already available and new ones coming down the pike.
Dear Jerry:
There is little doubt in my mind that a lot of unnecessary ADT has been given to a lot of men over the years — but mostly since the early 1990s, when men and their urologists started to “manage their PSA levels.” Before we had PSA testing, these drugs were really only being used in men with metastatic disease or men assumed to have at least micrometastatic disease or who had evidence of positive lymph nodes.
Since you were a high-risk patient almost from day 1, with just a very small amount of metastatic disease in your pelvis, you are in the category of patients for whom there is a much greater possibility that ADT (intermittent or otherwise) really does have a survival benefit, but we don’t have data that really proves this.
I just wanted to add my agreement with the Sitemaster that there is no evidence to support early initiation of lifelong ADT after biochemical-only recurrence after definitive therapy. Last year at the 2014 ASCO Conference, Garcia-Albeniz et al. presented an analysis of this which has now been published. Their analysis of 2,096 cases in the CAPSURE database showed that there was no significant difference in survival between those who initiated ADT within 3 months of biochemical failure compared to those who waited for a diagnosis of metastasis, symptoms, or a short PSA doubling time. This represents an increase in quality-of-life years without penalty, and perhaps, as the Sitemaster suggests, may slow down the time to castrate resistance. The non-inferiority of the waiting approach would have to be proved in a randomized clinical trial.
The downside of this approach is that the patient may feel a loss of control because he is not actively doing anything to forestall his cancer’s progression. It is very hard to wait patiently and do nothing. Perhaps what is needed is a distinctive protocol similar to active surveillance, including frequent PSA testing, biennial PET scans, and questionnaires to help monitor symptoms.
I hate the term “ADT” without specific identification of the composition/ingredients. The range of coverage and therefore the effectiveness and side effects makes these discussions almost meaningless. I can’t take Lupron because it caused severe heart problems the first month (don’t take a 3-month shot to start), atrial fibrillation, and other side effects, but I have done great with Casodex and Avodart. All are considered ADT, but the results vary greatly. Sitemaster we need your help on clarifying these discussions and definitions.
Allen:
Renowned doctors like Snuffy Meyers have an interesting take on recurrence after first-line treatment, as I’m sure you are aware. He hated the side effects of ADT, which he was on for 18 months, and seems to support using anything but. He is a big supporter of Avodart and also feels that ultrasensitive PSA testing is very important in order to start treatment quickly. I believe he thinks that the delay in taking action caused by non-sensitive PSA tests is very problematic in terms of avoiding metastases. Others think that there is no benefit to ultrasensitive tests and that starting as soon as there is a PSA uptick in the hundredths of a point makes no difference in delaying or stopping metastases. My surgeon was at the other end of the spectrum feeling that nothing should be done until mets occur, then blast with radiation. Wow!
Does it really make sense to restart treatment when there is no sign of or symptoms of cancer and does it make a difference what age the patient is?
Is there any consensus on type of tests after treatment and when to start treatment?
Bob
Dear George:
Re the term ADT … While I agree with you that the term ADT encompasses many different types of treatment, any attempt to be absolutely specific under all circumstances would be impossible, just as being absolutely specific about how each surgeon performs a radical prostatectomy is impossible. We need general terminology to encompass general concepts. When specificity is necessary and we have the available information, we do try to be specific.
Dear Bob:
(1) No, there is no consensus on the types of tests that should be carried out as tools to determine exactly when to restart treatment in a man with a rising PSA. Why is there no consensus? Because there is no really good evidence to support consensus. Everyone thinks that you should monitor the PSA levels of patients with prostate cancer post-treatment. The differences come over how, how often, and what one should do as a consequence of the available data.
(2) In my entirely personal opinion, no, it makes no sense to start ADT in a man with no other indications of risk other than a very low and slowly rising PSA … but that’s a personal opinion and others are entirely entitled to disagree with it if they want to. But I prefer disagreement on the basis of actual data.
(3) I really don’t like the use of the term “renowned” for any physician until they have really proven that they are entitled to that form of recognition (which is often only evident after they are dead). Dr. Meyers is certainly “well known” to many in the prostate cancer community, but then so are Dr. Walsh, Dr. Scardino, and many others. Dr Meyers also has all sort of opinions that many other “well known” clinicians who specialize in the management of prostate cancer would disagree with entirely. Dr. Meyers is, of course, entirely entitled to his opinions … but without real proof, that’s what many of them are — opinions.
Dr. Meyers is not well known nor is he renowned…However, Dr. Myers is very well known in the PC community. Just kidding with you here….
I believe Dr. Myers has survived for some 16 years with mets which have been in remission, so he is doing something worth considering. I know my urologist thinks a lot of his expertise. Maybe not renowned but very bright and well regarded in the prostate cancer community, which owes a lot to him for educating the community on ways to fight recurrent prostate cancer.
SKETCH OF LOGICAL, EVIDENCE-BASED TEST FOR SURVIVAL BENEFIT TO ADT
Thank you Sitemaster and others for sticking with the various aspects of this interesting and important discussion. I’m focusing here on the survival benefit issue, referring back to my comment of March 20, 2015 at 8:58 pm, SUGGESTION FOR TESTING SURVIVAL ADVANTAGE OF ADT, which basically called for looking at usually lethal levels of PSA compared to projected levels of PSA for patients with rather short doubling times who were on ADT. The idea was that if ADT patients were likely to survive well beyond that time, then that was evidence for a survival advantage for ADT. Personally, I’m convinced that the medical oncologists I follow who have large practices with many patients facing challenging cases (including short PSA doubling times) and monitor those patients closely have become convinced that ADT frequently extends life well beyond what would otherwise be projected. Hence, they believe strongly in ADT for appropriate cases.
I’ll suggest a candidate PSA threshold for such use as a proxy for survival time based on this paper by Scher et al., available in full free online. Figure 3 includes a plot of PSA level versus survival time, and a best fit line indicates survival of about a year for patients with a PSA of 2,980. It also indicates many other points for patients in the study, but I’m using 2,980 as kind of a near-worst-case scenario. (I understand I’m ignoring the circumstances of the study such as treatment beyond just ADT, but I’m taking this graph as an indicator of the near outer limits of PSA in lethal cases for the purpose of exploring my logical test. I’ve heard of one report — by Dr. Eugene Kwon — of a patient with a PSA of 25,000 who substantially recovered.) Sitemaster, in your comment of March 21, 2015 at 8:25 am you noted that “Plenty of men die with mCRPC without their PSA levels ever reaching anything like 2,000 or 6,000 ng/ml, and it would be unethical to defer treatment that long in any patient anyway.” Of course I understand that and agree, but that does not prevent us from using such figures as a useful benchmark, if the logic is sound. (As an aside, we could even use a considerably higher PSA benchmark as those of us with rapid PSA doubling will have projections that quickly surmount even higher figures, where the odds of survival are even lower.)
Based on this, I’m suggesting use of the projected time, based on baseline PSA at the time ADT is started and PSA doubling time, to exceed a PSA of 2,980, plus a year as noted above, as the benchmark time for testing whether ADT extends survival. Therefore, for a patient diagnosed with a baseline PSA of 113 and a PSA doubling time of 4 months, it would take four doublings, or 16 months (about a year and a half), to exceed that level (3,616 at that time), and we’ll add a year — per the graph in the paper as described above — to estimate a survival benchmark of 28 months, or about 2.5 years. (These figures are pretty close to my own case.) If a patient on ADT alone exceeds that time, that suggests that ADT is extending survival. In my own case, for example, I had achieved a survival duration of 13 years 4 months, far beyond 28 months — all on just intermittent ADT, mostly ADT3 — when I started radiation in March of 2013; if I were a subject in such a study as I’m proposing, I would be counted as a success as I had exceeded the survival benchmark (by a long shot).
My impression is that well-done ADT is typically successful in extending survival for men who can achieve a low nadir, such as 0.05, on ADT, but you and others who are respected doctors have a different view, and we need some kind of test other than a trial, as such a trial is impractical.
A Lot More Consensus Among Dr. Myers, Me, Sitemaster and Allen Than Has Surfaced So Far On When To Start ADT
Hi once again Bob, Allen, Sitemaster and fellow participants. (And thanks for your patience and endurance, Sitemaster!) As this issue is important, it is worth revisiting to increase the recognized area of agreement/decrease the area of disagreement. Bob, I’ll reply to your post of March 23, 2015, at 3:08 pm as it reflects a misconception of Dr. Myers views — particularly your phrase “start treatment quickly”, and I can clarify that. You wrote, replying to Allen:
“Renowned doctors like Snuffy Meyers have an interesting take on recurrence after first-line treatment, as I’m sure you are aware. He hated the side effects of ADT, which he was on for 18 months, and seems to support using anything but. He is a big supporter of Avodart and also feels that ultrasensitive PSA testing is very important in order to start treatment quickly. I believe he thinks that the delay in taking action caused by non-sensitive PSA tests is very problematic in terms of avoiding metastases.”
Actually, while Dr. Myers is a big fan of catching recurrence early where the recurrence looks dangerous, he is right in line with some of the statements made by Sitemaster and Allen, which are consistent with research by Johns Hopkins on the severity of recurrence. These statements include:
– Sitemaster wrote to you on March 23, 2015 at 4:36 pm:
“Dear Bob:…
(2) In my entirely personal opinion, no, it makes no sense to start ADT in a man with no other indications of risk other than a very low and slowly rising PSA…”
– Allen wrote to you on March 23, 2015 at 1:26 pm:
“I just wanted to add my agreement with the Sitemaster that there is no evidence to support early initiation of lifelong ADT after biochemical-only recurrence after definitive therapy ….”
(A note here Allen: for a long time Dr. Myers has been a proponent of intermittent ADT.)
I believe I am correctly representing Dr. Myers views when I state the following as his thinking and practice, based on my long-term reading of his newsletters, attending talks at least annually, my own consultation with him about my case, and viewing some of his video blogs:
— Assess the degree of risk of recurrence early, including likelihood and potential severity, using ultrasensitive tests for surgery patients, and where appropriate using imaging and perhaps other techniques.
— Consider potential for seriousness using published research such as (but not only) that published by Johns Hopkins’ (then) Dr. Freedland, and team (which homed in on PSA doubling time — with 15 months and longer being one clue of safety, time to recurrence up to or greater than 3 years, and Gleason of less than 8 or 8 and higher), and updates that basically dissolved the recurrence time as likely not independent of PSA doubling time. Dr. Myers actually favorably focused extensively on the Freedland research in one of his newsletters.
— For patients who appear to have a substantial risk of recurrence or actual recurrence but no indication of a serious recurrence, suggest an anti-cancer growth regimen that chiefly involves lifestyle tactics. At one point, pomegranate juice or extract looked good as one prominent element, and I believe it still looks pretty good despite one adverse and concerning study. Fairly mild drugs like finasteride and dutasteride may be part of the program. Imaging may or may not be worthwhile depending on case circumstances, along with other assessment technologies. Note the objective of avoiding major treatment if possible, consistent with Sitemaster’s, Allen’s and my own views.
— For patients appearing to face likely serious prostate cancer recurrence, employ an anti-cancer growth program early, but also assess the case in more detail, such as with imaging, genetic testing, etc., and intervene early. That intervention might involve radiation after surgery. It might include spot radiation for oligometastatic disease. It might involve ADT, and if so degarelix is often, these days, an early part of the arsenal he uses. Other approaches are also on the table.
In sum, while Dr. Myers would often be intervening in some manner much earlier than some other physicians, he would not be applying a one-size-fits-all early ADT program to all patients, and he would try to avoid ADT or other major therapy if that were a sound option. Thus, we have a substantial amount of consensus.
Degarelix and tolerance of injection
Hi Sitemaster. I’m replying to your post of Sitemaster, on March 21, 2015 at 9:03 am said:
“… With respect to the use of degarelix, very few patients are actually treated long term with this drug. It is usually used up front to drop the patient’s PSA and serum T as fast as possible, but (because degarelix injections are customarily quite painful and have to be given every month) most patients are rapidly switched over to a standard LHRH agonist after initial degarelix treatment….”
Degarelix was available by the time of my fourth round of ADT, but I was not at all eager to use it because of the concern about pain that you related above. I had heard that the injection was like a punch in the stomach, but lasting for many hours. (Lupron was the main leg of my ADT3 during the fourth round, as it had been for the previous three rounds.)
Recently I read a comment by Dr. Charles Myers, who now uses degarelix frequently to achieve a very rapid and profound decrease in testosterone, quite superior to Lupron or other LHRH-agonist drugs, and then maintain it. He stated that proper administration, according to the label, is very important in reducing injection discomfort. He believes that many health professionals are simply short-cutting the injection process and thereby causing many patients a lot of unnecessary pain.
Years ago there was a similar issue with infusing the bone density drug Zometa: a slower infusion did a lot to relieve discomfort. Even with Lupron, my own experience is that injection higher up in the muscle is much more tolerable than lower down.
HUGE FLAWS IN GARCIA-ALBENIZ STUDY RE EARLY OR LATE ADT
This is a rebuttal to Alan’s post of March 23, 2015 at 1:26 pm in which he wrote:
“I just wanted to add my agreement with the Sitemaster that there is no evidence to support early initiation of lifelong ADT after biochemical-only recurrence after definitive therapy. Last year at the 2014 ASCO Conference, Garcia-Albeniz et al. presented an analysis of this which has now been published. Their analysis of 2,096 cases in the CAPSURE database showed that there was no significant difference in survival between those who initiated ADT within 3 months of biochemical failure compared to those who waited for a diagnosis of metastasis, symptoms, or a short PSA doubling time. This represents an increase in quality-of-life years without penalty, and perhaps, as the Sitemaster suggests, may slow down the time to castrate resistance. The non-inferiority of the waiting approach would have to be proved in a randomized clinical trial.”
Hi Allen,
I’m with you and Sitemaster that lifelong ADT is not a good choice for most who recur after definitive therapy, and my impression as someone who has followed ADT developments closely for more than 15 years is that there is a broad consensus behind that view. For many recurring patients, the recurrence is so mild that no treatment is ever necessary, and I see that too as a consensus view.
However, I sharply disagree that waiting for symptoms is a wise approach. I’ll leave that for now but want to focus on that Garcia-Albeniz research involving 2,096 cases from the CAPSURE database because that is profoundly flawed and useless research regarding the early versus late issue! Here’s why.
Background: The researchers wanted to investigate “the optimal timing to start androgen deprivation therapy (ADT) in prostate cancer patients with rising prostate-specific antigen (PSA) as the only sign of relapse ….” Here’s their method: “We emulated such trial by assigning patients to the ‘immediate’ strategy if they initiated ADT within 3 months of PSA relapse and to the ‘deferred’ strategy if they initiated ADT when they presented with metastasis, symptoms or a short PSA doubling time.” These were patients with rising PSAs after definitive treatment with clinical stage <= T3a and no known lymphatic or distant metastases; two thirds had a Gleason of 6 or lower, and the average (mean) time to recurrence was just over 3 years at 37.4 months, but with wide variation about that average (standard deviation only slightly shorter at 34.2 months). “Mean follow-up from primary treatment was 91.4 (SD 48.4) months” — or about 7½ years. As their yardstick they used survival (not clear from the abstract whether overall or prostate cancer-specific survival) and their results were that “The adjusted mortality hazard ratio for immediate versus deferred ADT was 0.91 (95% confidence interval (CI), 0.52–1.60), which would be translated into a similar 5-year survival (difference between groups: −2.0% (95% CI: −10.0 to 5.9%).” They conclude this with the statement that “prostate cancer patients undergoing immediate ADT initiation within three months after PSA-only relapse had similar survival to those who deferred ADT initiation within 3 months after clinical progression.”
But let’s look at the flaws. First, the follow-up, which was from primary treatment, which was likely pretty close to the date of diagnosis for most, was about 7½ years. While it is not clear when the patients were initially treated, as of 2008, nearly 100% of prostate cancer patients in the US were alive at 10 years since diagnosis, and about 93% — all comers, including those already metastatic at diagnosis — were alive at 15 years since diagnosis. (It’s even better now at 94% per the American Cancer Society.) That means there would have been extremely few deaths at the 7½ year mark of follow-up. Basically, those deaths would almost surely have come from men already metastatic at diagnosis, but with stealthy metastases, as they would have been excluded if metastases were detected, per the study protocol. The very wide confidence interval results for the hazard ratio — ranging from a possible “true” low of 0.52, meaning half the survival of the deferred ADT group, to a possible “true” high of 1.60, more than half again better than the survival for the deferred group — hint at the shaky nature of the data. The results are all over the map!
Here’s another big flaw: all patients with short PSA doubling times were assigned to the deferred group, presumably even if they got ADT quickly after treatment, even within 3 months of relapse. That means you likely have some pretty risky patients in the deferred group, but there is no information about how large this rapid PSA doublingtime group is. While you would think the group given “immediate” ADT would have the riskier patients, we can see that a portion of unknown size of risky patients was assigned to the deferred group. What this underscores is that we really don’t know much, at least from the abstract, about the average riskiness of cases assigned to the two groups, and it is likely that such riskiness drives mortality more than anything else. Compound that with follow-up that is clearly inadequate for the mortality outcome measure, and you have an analytic mess.
I see no way that this study tells us anything useful regarding whether it is safe to defer ADT for men with risky recurrences. (As we agree, men without risky recurrences are better off avoiding ADT; they don’t need it.)
Dear Jim:
No one is disputing the fact that degarelix can lower PSA faster than an LHRH agonist. However, I am aware of an awful lot of patients treated by very highly skilled urologic oncologists who would dispute Dr. Myers claims about “unnecessary pain”. According to the product prescribing information (which you reference above) this pain can be expected in 35 to 44 percent of patients (depending on the dose administered), compared to slightly more than 1% of patients being given Lupron. And that is the prescribing information that you say Dr. Myers is following, and which was created based on the outcome of the clinical trials.
I appreciate the clarification re when to start ADT after BCR post-RP and SRT/ADT. I was concerned that the simple PSA tests I have been getting at Labcorp, wherein < 0.1 is termed "undetectable" would not give me early enough warning of recurrence so I could take action. As a pT3bN0M0 , Gleason 9 guy, I'm at high risk and maybe a little paranoid. But so far so good.
Jim:
Sorry for the late response to your 3/20 query re pre-ADT discussion with urologist. Basically I was told I’d get hot flushes but not much more. Aching joints was not mentioned and that was my biggest side effect.
Bob
Dear Sitemaster:
I still have not seen an answer to my question as to whether ultrasensitive PSA tests are necessary for guys like me with Gleason 9 and pT3b after RP, then ADT and SRT after PSA rose from 0.1 to 0.3 in 8 months post-RP. PSA has been < 0.1 ng/ml (" undetectable") since SRT was concluded last July based on PSA tests out to one tenth of a point by Labcorp. My urologist doesn't believe in ultrasensitive testing. Is PSA doubling a valid and actionable measurement below 0.1 (i.e., is 0.01 to 0.02 considered "doubling")?
Dear Jim,
I think you misunderstand the study, or perhaps I misunderstand your points. This was an analysis of a rather large database of cases, not a randomized clinical trial. They didn’t take an arbitrary point in time to assess results, instead they simply reported what the actual results were. The men in the database who started ADT within 3 months of primary treatment failure had no better survival than men who waited for rapid PSA doubling time, metastases or symptoms.
The fact that the hazard ratio confidence interval is wide and crosses 1.00 is actually the point that the study makes, rather than a flaw. It’s telling us that survival is not predictable based on the timing of ADT initiation.
Men who presented with rapid PSA doubling times, metastases, or symptoms immediately after primary treatment were assigned to the “deferred” group because that’s the whole point of the study — that beginning ADT when one of those events occurs gives no worse outcomes than beginning it in the absence of those events.
You don’t have to jump through hoops and make all kinds of assumptions to guess at average survival times, there are actual statistics. Researchers at Johns Hopkins found that the median time to metastases was 8 years from the time of PSA level elevation. After men developed metastatic disease, the median time to death was 5 years. The CAPSURE database was begun in 1995, so there are many men in it with follow-up as long as 20 years — well beyond the timeframe needed to observe differences in those effects. If there were a survival benefit, it would have shown up by now — the survival curves would have begun to diverge long ago.
Dear Bob:
You hadn’t actually asked any question when you left your prior message, so I didn’t know you were looking for an answer. :O)
(1) No … ultrasensitive PSA testing is really not that useful after ADT and salvage radiation. Why? Because very small variations in the PSA levels of men like that are quite common and can’t be used to determine what needs to be done. The important thing would be a series of two or more increases in your PSA level (e.g., from < 0.1 to 0.1 to 0.2 to 0.4, etc.).
(2) PSA doubling times can really only be assessed as having clinical value for PSA levels of 0.1 ng/ml and higher. No one has ever carried out a large enough study of PSA doubling times in men with lower PSA levels (e.g., 0.01, 0.02, 0.03, etc.) based on ultrasensitive PSA data to know whether these are really meaningful in any patients, let alone in men who have been given second-line treatment like ADT + salvage RT.
(3) Clearly a rise in the PSA from 0.01 to 0.02 is a "doubling" of the PSA level, but I wouldn't give it much credibility unless the PSA continues to rise (e.g., to 0.04 and then 0.08). At that point it would be possible to assess a patient's PSA doubling time if the PSA was rising consistently using an ultrasensitive PSA test. However, because of (2) above, it would still be hard to know whether it should change the course of the patient's care.
Mike,
I have been meaning to write for a long time. This article, as well all that you write, is the most outstanding on the internet for coverage of prostate cancer. I admire the work you are doing!
Stan (Rosenfeld)
Thank you Stan … That is very kind of you …
I’m glad this discussion has resurfaced in that I am now on the threshold of more treatment decisions caused by quick doubling of my PSA (from < 0.1 to 0.1, to 0.4 to 0.7 over 7 months) after coming off 6 months of Lupron last December along with SRT last June/July. I had an OORP in September 2013.
So I recently had an 18F PET scan and a colonoscopy which found no cancer. I read in HealingWell of guys who have had success (complete remission) with radiation to lymph nodes at the Dattoli Cancer Center after being scanned at Sand Lake Imaging, who were using feraheme off label up until a while ago. They now are using morphologic imaging, 3-T MRI, and 18F PET scans. When I asked why they stopped using feraheme they said they were looking for a less costly treatment for the patient inasmuch as feraheme was not covered by insurance and cost the patient ~ $1,500.
Getting to the issue of more hormone therapy, Dattoli is recommending that, after I am scanned (no matter what the results of the scans), I go on Casodex, Avodart, dostinex, transdermal estradiol and Trelstar or Lupron. If metastases are found, I would get more radiation to attempt, once again, to get a "cure".
I would appreciate any and all comments on whether these scans are likely to be effective and the need for all of the hormone and related therapy being recommended. As a reminder, I am age 71, Gleason 4 + 5 = 9, and stage pT3bN0M0.
Bob
Dear Bob:
With a PSA level of 0.7 ng/ml, I don’t think anyone can give you an entirely accurate assessment of whether you have metastasis or micrometastasis based on available scanning techniques today. The risk for both false negative and false positive results is too high.
What was your PSA post-surgery when you were initially given SRT + ADT? And what was radiated: your prostate bed alone or the prostate bed and other areas of pelvic tissue?
Dear Sitemaster:
My PSA at Bx and pre-ORRP PSA was 6.6, but I was on finasteride, so PSA was probably more like 13.2. My PSA post-op was 0.1 at 2 months, 0.2 at 5 months, and 0.3 at 8 months, at which point Lupron and SRT (IMRT/IGRT) of 68.2 Gy over 38 sessions to prostate bed only was administered. Since 10 nodes were removed during surgery, all benign, no SRT was applied to the nodes. For this reason, I’m thinking that radiation to the nodes could be safely administered if metastases are found there. No scans, including 3-T MRI, bone scans, 18F PET have ever found prostate cancer. I’ll take blood tests again in 3 weeks, including an ultra-sensitive PSA, prior to going down to Orlando to LSI.
Dear Bob:
So if your PSA was something like 13 at diagnosis; you had Gleason 9 prostate cancer at surgery; you had an almost immediate recurrence post-surgery; and another almost immediate recurrence post SLT after you stopped a short course of Lupron, I am very dubious that your problem is a localized recurrence. It sound much more like a case of a distant micrometastasis that has responded to the Lupron therapy but was unaffectewd by any radiation to date. Quite how distant is also an unknown because it is probably too small to be visible on any available scan at present.
You are going to need to do whatever you feel comfortable doing, but I see little point in the ultrasensitive PSA test. You have a rising PSA with a PSA doubling time of the order of 3 months. Knowing whether your PSA has risen to 1.0 or 1.003 the next time you get it tested isn’t going to change anything.
I do also think you need to be very assiduous at working with the people at SLI with regard to the results of any imaging test they choose to use. As I mentioned before, the risk for false positive and false negative results is significant in a man with a PSA level of < 2 ng/ml.