Bone scan ok... now what??

Hello all,

Due to a rising PSA, our radiation oncologist suggested a bone scan to see what was happening. This was done several days ago, and the scan was clear, ie, no mets found. This is good news indeed, however, now we are wondering why the PSA numbers are still rising and doubling fairly quickly.

This is a very frustrating condition!!!

Yaamba
Sorry for your guy's predicament! Unfortunately he's very high risk like I am albeit with much higher volume than me. Since he still has his prostate, you don't know the extent of spread outside. PSA at these levels are too low to find bone mets. As suggested you need MRI and CT pet scans to find the mets. And you need to find a medical oncologist and talk to a RO who specializes in PCa about IMRT to lymph nodes, the likely place of PCa. Best wishes!
Bob

Sorry you both have to deal with this. The way that the bone scan works is that they inject you with a radioactive "dye" that then concentrates on any active cancer on the bones. They then use a fancy Geiger counter to find any hot spots. It will also concentrate on areas where you had broken bones, Arthritis, etc. It will not tell out about soft tissue. Initially my bone scan was negative but my CT scan was positive for lymth node.

I can only give you a couple of things to ask for your next appointment.
1) CT or MRI scan. It would be great if that was done before your oncologist. If possible, have them scan more than just the pelvic area. Doing so will literally take less than a minute and it could help rule out migration to the lungs, etc. Hopefully they can determine if it is coming from the prostate or another source.
2) Secondary treatment. Based on what has already been done surgery is not really an option. Unfortunately, I am weak in that area of information.
3) If the CT scan shows possible cancer in the pelvic lymph nodes (usually the first place cancer moves), what options are available?
4) Relook at the bone scan. I had a lot of hot spots on my scan, but they corresponded to areas where I have arthritis. It is possible that one of those hot spots may of been cancer instead.

Wish you both the best and I hope others can give you additional advice.

Yaamba,
a 68Ga PSMA PETCT is the only scan which can show anything at this low PSA.Of course if you have the possibility.
Having all my MRIs, CT,BONE scans clear,PSMA PET CT found 2 lesion....PSA=0.27
Wish you all my best!

If you can get a PSMA PET/CT this would usually show the mets if there are any. Then can radiate these and bring down the PSA value this way or, as Allen suggested, start with ADT.

George

Yaamba,

I would suggest getting a newer type of scan, such as the
Gallium 68 PSMA PET/CT as already mentioned by others, to determine if the cancer is still at the local/regional level.
If so, it may still be curable.

PSMA scans are being done in trials, as well as other newer scans.

If you go this route, make sure that the trial will release the findings and CD disk to you. Some scan trials will not give you the results!

Bobby Mac

George-

The OP was diagnosed with high volume GS9 and had EBRT with a brachy boost, so there is little likelihood that it is locoregional. I assumed he had whole pelvic radiation already. So any mets are likely to be distant ones.

By "patient expectations must be reasonable" (and it breaks my heart to say this) I meant that the patient must understand that radiation to isolated mets is probably pointless - it doesn't stop the cancer, and it probably doesn't even slow it down. Detectable mets start appearing slowly in its early metastatic stages. What you didn't quote from that same article is the study that showed that after 5 years of playing whack-a-mole with mets, 85% still kept having detectable distant mets.

I have often seen that patients, perhaps yourself, misunderstand how metastases work. There are millions of cancer cells in the bloodstream. Sometimes they plant themselves (usually in bone) and start to replicate, slowly at first. It can take years for those mets to be large enough to be visible on a scan, and there are certainly many more cells in circulation that are completely undetectable, except perhaps to a CellSearch analysis. Detectable mets are, and always will be, the tip of the iceberg.

More importantly, we have recently learned that delaying hormonal therapy doubled mortality. So delaying start of hormone therapy to go on a pointless hunting expedition may be harmful.

I like Dr Kwon, I even had lunch with him once, but don't mistake a presentation to a group of patients for medical evidence. I recall a presentation at PCRI where he showed case studies of complete met resolution with cabozantinib and hailed it as the new cure. It turned out not to have any benefit at all. I don't fault him for that -- I know he was just trying to give people hope rather than despair. But we can't get stuck on yesterday's hope. We move on to the next hope. Cabo didn't work. Oligometastatic treatment doesn't seem to work. But early hormone therapy does. Early docetaxel does when there are numerous mets. We just learned that there is a benefit to Zometa+Celebrex. I am very hopeful about systemic nuclear medicine, immunotherapy, and the right combination of growth factor inhibitors. The new hopes keep coming.

Wow! You guys have me really thinking. Talk about a roller coaster of emotions. I really do appreciate the time and effort you have taken to explain much of this, particularly in such a way that it is understandable and not jargonized and in medicese (medical language).

Mind you, my husband - apart from wanting to detach himself more and more from social company - is quite happy plodding along in the garden, going to the gym daily, and entertaining the grandchildren, especially this weekend with the footy finals happening. He does not "appear" to be unduly concerned, and his optimism shows in subtle ways, e.g. planting a fruit tree yesterday that we both know will not fruit for another 5 years minimum.

I am getting the message you are saying that -

* due to the high volume cancer in the prostate in 11 out of 12 cores
* Gleason 9 in 10 cores, Gleason 7 in one core, and one core clear
* the fact that he has already had hormone treatment, High dose Brachy (which he likened to feeling like a rotisseried chicken),
* six weeks of External Beam Radiation - and this WAS around the whole pelvic area, because I remember the little tattoos that he was branded with.

So, correct me please if I am wrong.... there is little apart from hormone therapy that will have any benefit for him if the PSA keeps rising the way it has - doubled in six months.

I am not being morbid, just realistic. My husband and I have very different characteristics. I face things head on, sometime bull at a gate, whilst he is very laid back and easy going. I am the one who is on this forum and occasionally tell him about posts, while he listens and then goes on reading his book, or mowing the lawn.


So... when we see oncologist, listen carefully, but go for hormone treatment???? Or perhaps a trial of some sort?

I look forward to any replies.

My husband is also GL 9 who failed surgery. He had the F18 PET/PSMA test in a test trial at Hopkins that showed micro mets in the bones a week or so after a bone scan only showed two. So if you could get one of the more sensitive scans mentioned you might know more. I think, though, that Tall Allen is right and it's better to start treatment ASAP.

We spent a lot of precious weeks NOT getting treatment while my husband was sent for test after test. Three other scans taken elsewhere also showed two very tiny suspicious lymph nodes. That, to me, bears out what Tall Allen says about how metastases work. Yet, the Hopkins team recommended spot radiation to the bone mets and ADT. They also suggested looking into the ORIOLE trial they were conducting involving SBRT to bone mets. That was surprising given their cutoff seemed to be three bone mets and my husband had at least five. He is now on ADT and undergoing radiation.

Your husband sounds a bit like mine - much more laid back and just will do what the doctors say. I'm so glad this forum is here as it is very supportive and informative. I think hormone therapy is where you might start with the MO and he will probably suggest treatment/trial options from there. The good thing is you can bring those suggestions here for advice. Wishing you the best.
Chris

Palliative treatment of mets is quite a different thing from treating them in the hope of slowing the disease down. Absolutely there is a role in palliative treatment. But there is no role for spot treatment of all mets, just the ones likely to cause trouble.

You said "However, it's these tips that can be lethal." No. All metastases can be lethal eventually, whether they are big enough to be seen or not. Metastases are already systemic by the time they get to the bone. The ones you see are a small fraction of all those that are there. The only way to delay progression is by systemic therapy.

Neither Decaestecker and Berkovic nor anyone else have shown a benefit to playing "whack-a-mole." 5-year survival of 90% or higher is exactly what we expect anyway after the early discovery of mets. They did NOT show that there was any benefit to their treatment. In fact, the data show that distant mets almost always are discovered within 5 years of such treatment.

While I am hopeful that cytoreduction (debulking) of the primary tumor in the prostate may be beneficial, there has never been anything to suggest that eliminating the visible mets is anything but useless.

In my support group, a man who failed RP and SRT, paid for an expensive PET scan, and found mets in several locations around his body. His RO, who is an expert at SBRT, refused to treat them. He found an RO who would. After completing adjuvant hormone therapy,his PSA was up higher than it was before, and they discovered more mets on an ordinary bone scan.

You are much better off pursuing systemic therapies.

George-

The man in my support group had a C-11 Acetate PET scan at a PSA of 2.0, and it is pretty good at that PSA. He was not and still is not castration resistant. He has undetectable PSA now that he's gone back on ADT. The new mets only appeared after he came off his adjuvant ADT.

You seem to be confusing the idea of local control with control of the cancer. They are totally different. SBRT to mets provides excellent local control, and that can be important if the met is causing pain or is large enough that the bone integrity is compromised. However, there is no evidence that it does anything to control the cancer. It will just pop up in more and more places.

The thing you have to understand is the natural history of prostate cancer. It almost always forms visible mets only very slowly at first, but later that process accelerates. This seems to be because there are biochemical changes that the micrometastases undergo that make them increasingly virulent. Also, the non-visible mets seem to alter the bone tissue to make it more accommodating to growth.

There was early hope that oligometastatic prostate cancer treatment might be beneficial. But with longer follow-up, those hopes dissipated. So far, all the studies have been very small and lacking controls. Ost's meta-analysis (accumulated experience of all previous research) last year showed that, while SBRT provided good local control, the distant mets kept coming. By 5 years, 85% had new distant mets detected, and then started on permanent ADT. There are some randomized trials exploring it further, and perhaps they will identify some men in whom it can delay progression, but so far the evidence is not in its favor. But if you want to zap some mets, and they are not in places where radiation might damage organs, I don't see harm in doing that.

SBRT for Oligometastatic Recurrence

What can be harmful, however, is delaying the start of hormone therapy. We now have level 1 evidence that early hormone therapy leads to longer survival than waiting. Because hormone therapy will interfere with the detection of mets, some men might delay starting ADT in order to hunt for mets. Consider the relative and known benefits:
• ADT kills many more cancer cells, seen or unseen, than SBRT to a few mets ever could
• While neither is curative, ADT has been proven to extend survival, while it is extremely dubious that SBRT does.

In one of the references you cited, the author wrote : "The evidence for treatment of oligometastases in prostate cancer is weak based on the study designs being all nonconsecutive case series (Level 3iii)" Why pin hopes on weak evidence when there's strong evidence that early systemic treatment increases survival?

Gemlin said...
Isn't it so that sometimes metastasis lead to further metastasis (all mets do not have to come from the primary tumor)?

If you followed the recent discussions of genetic heterogeneity vs. homogeneity, you will understand that most metastases within a single man are genetically similar. This points to a common origin, at least for most mets, and the place they came from was a source (at one time) within the prostate. Once that source cancer acquired the ability to become metastatic, thousands, if not millions, of metastatic cells were unleashed into the serum. Metastatic cells continue to evolve and become more virulent, and more able to clump and attach themselves anywhere.

Do some travel from one detectable met to establish a new met? Probably so. But it really doesn't matter much - there are already millions of cells available for that purpose.

The metastases are there whether or not you can detect them with any scan. If you pick off a few, more and more will grow. There is no evidence that it slows it down or adds to survival at all. This isn't something one can win with a pea-shooter. In contrast to picking them off like that, nuclear medicine has some systemic treatments like Xofigo, Sr 89, Lu-177-PSMA, Ac-225-PSMA, etc. And of course, hormone therapy is our first option.

George-

Not all research is alike. In research terminology, there are "levels of evidence." Level 1 evidence - which means large randomized clinical trials - are the only ones that prove anything. "Proof" means this - now we know what is likely to happen is they use treatment X vs. if they don't use it. When we learn something that is Level 1 evidence, it can be practice changing. The Duchesne study was level 1 evidence.

The Duchesne study found that, among men whose curative options have been exhausted, 11% died within 5 years if they started ADT immediately, but 20% died within 5-years if ADT was delayed - the death rate nearly doubled if ADT was delayed.

This confirms an earlier randomized clinical trial where patients were follow-up for a much longer time (14.6 years) among men with locally advanced prostate cancer. Among those who received bicalutamide immediately, the death rate was 23% lower compared to those who only received standard of care.

www.ejcancer.com/article/S0959-8049(15)00288-9/abstract

In the studies you cited, The Schroeder study is not really relevant. It was among men diagnosed with LN mets who had never received any treatment. The study was underpowered, which means the statistical significance doesn't prove or disprove their hypothesis. Even so, early treatment reduced the hazard of death by 22%, and survival was 1.5 years longer if they started early treatment.

The Studer study has nothing to do with this issue, it just says that the time to death is faster when the PSA is higher or doubling quickly (not very surprising). The Wong study was just a database analysis (level 3 evidence - which should only be used to suggest further studies) among men who were lymph node positive after RP. Read what they wrote: "Because observational studies should be considered hypothesis-generating studies, these results should be validated in a prospective fashion in a similar patient population."

Now, I went to the trouble of explaining all this because I think it is perilous to make claims not supported by evidence, especially where there is high quality (Level 1) evidence.

As far as zapping distant mets is concerned, there is no Level 1 evidence to support it, but the data are increasingly showing it is an ineffective approach. You are misinterpreting is what Ost is actually saying. He is right that there is a prolonged "progression-free interval" of about 3 years when men were detected to have 3 or fewer mets utilizing advanced detection techniques. Because all of the men had the SBRT, and none didn't, he can't say that the treatment caused any delay. In fact, what likely caused the delay was what is called "lead time bias." Lead time bias occurs when men are screened with advanced techniques early in their progression. So the time to progression, which we know is slow at first anyway, only seems to be longer; in fact, it was only detected earlier.

I have nothing against patients doing this when it is safe. I do understand the feelings of desperation, and the need to feel that one is actually doing something. I only care when patients put off starting ADT - which has level 1 evidence that starting it earlier has a real survival advantage.

However, if you want to ignore evidence and go with your hunches -- I truly hope it works for you. You have no way of ever knowing if it worked, or if it would have been just the same without treatment. But I can see you are hoping it will do something, and I hope so too.