It has long been known that men with apparently localized prostate cancer can relapse many years after radical prostatectomy and/or other forms of treatment that appear to have been curative. A new study from researchers at the University of Washington appears to throw some more light on why this may occur.
Morgan et al. sought to determine if epithelial-like cells — commonly known as disseminated tumor cells (DTC) — identified in the bone marrow of patients after radical prostatectomy are in any way associated with later biochemical recurrence.
They took bone marrow aspirates from three different groups of men, as follows:
- The first group comprised 569 men known to have prostate cancer and scheduled for radical prostatectomy.
- The second group included just 34 healthy men with PSA levels < 2.5 ng/ml who were used as a control group.
- The third group consisted of 98 patients with no evidence of disease (NED) after radical prostatectomy.
Using sophisticated technical means to evaluate the presence of DTC in the bone marrow extracts, the authors demonstrated the following results:
- DTC were present in bone marrow extracts of 408/569 patients (72 percent) prior to shceduled radical prostatectomies.
- Also in the patients scheduled for radical prostatectomy, there was no evidence of correlation between the presence of DTC and pathologic stage, Gleason grade, or preoperative PSA level.
- In the control group, 3/34 men (8.8 percent) demonstrated the presence of DTC.
- In the patients with NED after radical prostatectomy, DTC were present in 56/98 (57 percent).
- DTC were detected in 12/14 NED patients (86%) after radical prostatectomy who subsequently suffered biochemical recurrence.
- The presence of DTC in NED patients was a strong independent predictor of biochemical recurrence (hazard ratio 6.9).
As the authors point out, the fact that > 70 percent of men scheduled for radical prostatectomy had DTC detected in their bone marrow prior to surgery suggests that these cells escape very early in the disease process. Indeed, the fact that 3/34 men in the control group also showed the presence of DTC in their bone marrow, despite the fact that they had no other apparent indicator for prostate cancer, may indicate just how early such transfer of DTC to the bone marrow can occur.
What is going on here?
We all develop cancerous cells in various organs on a regular basis. In the vast majority of cases, these cells are appropriately eliminated by our immune systems. However, if some of these cells get transferred to bone marrow as DTC, they may be better protected from the immune system in some way, allowing the possibility of expression of disease much later on.
In the case of men who have a diagnosis of localized prostate cancer that requires treatment, the risk for transfer of DTC into the bone marrow is clearly going to be higher, because the immune system has already failed to eliminate the cells that led to formation of the primary tumor. In such men, treatment will not eliminate the DTC, and the possibility of biochemical recurrence some time later is significantly increased, because treatment hasn’t eliminated all possible sources of such recurrence.
Some researchers are liable to suggest that this may be a reason to consider bone marrow transplanation (BMT) as follow-up therapy after definitive treatment to eliminate the primary tumor. The “New” Prostate Cancer InfoLink suspects that we are a long way from taking such suggestions seriously for the vast majority of prostate cancer patients. BMT is still a relatively high-risk form of therapy. However, given the data presented by Morgan et al., we wouldn’t be at all surprised to see small numbers of younger patients with clear evidence of DTC in bone marrow undergo BMT post-surgery on an investigational basis within a few years.
Filed under: Living with Prostate Cancer, Management, Treatment | Tagged: biochemical recurrence, disseminated tumor cells, DTC |
THE "NEW" PROSTATE CANCER INFOLINK 
Just last evening a doctor presenting to the prostate cancer support group I attend remarked on this same subject: of how it is becoming increasingly (depressingly!) clear that prostate cancer may spread earlier than anyone thought it might, and that one’s Gleason score might not be as good a predictor of that as had been hoped. That would explain how so many “successful” surgeries or radiation treatments later result in the cancer reappearing. The surgery or radiation probably didn’t “fail.” It likely did what it could. But what it couldn’t do is reach those little sleeper cells hiding out in bones far from the prostate. You do have to give cancer credit for being as ingenious as it is! Of course when it “wins” we both die, but I’m not sure it cares about that.
This is a very interesting study … and a bit unsettling. So, this side of an unlikely marrow transplant, if one were tested and DTC were found, what would the treatment options be? Probably not much until PSA started rising?
If you think about this in quality of life terms, the presence of DTC signals high potential for a biochemical recurrence, but not when and not how aggressively. In that sense it is similar to the knowledge that having had a heart attack, one is always at elevated risk for another … but when, and how aggressively? Who knows!
A biochemical recurrence with a PSA of 0.4 ng/ml at 78 years of age, 10 years after initial treatment, with a PSA doubling time of 12 months would mean that by age 90 one might have a PSA of about 800 ng/ml — but still no clinical symptoms of metastatic prostate cancer, and that’s assuming one lived that long.
When I read this it was like I heard I had cancer all over again. I am 43 and had RP with organ-confined Gleason 6 prostate cancer. I have no chance of beating this if this study is true. If 72 percent had DTC, then I most certainly am destined for recurrence sometime in the next 30 years. Why aren’t they testing everyone for this before treatment?
Chris: You can’t draw a conclusion like that from these data. They don’t support such a conclusion.
The presence of DTC in 70 percent of patients who have an RP is not a 70 percent guarantee of disease recurrence. The percentage of patients who have a recurrence within 5 years after first-line therapy is actually only about 15-20 percent, and the longer the patient goes without a recurrence, the higher the likelihood that no recurrence will occur.
Application of the Kattan nomograms to your specific case could easily suggest that you have a 99 percent probability of remaining disease free at 10 years and higher. Click here to find and use the nomogram. You will need to know your PSA at diagnosis, your year of treatment, and how long you have been disease free (in addition to your Gleason score). I am assuming that you had negative surgical margins, no cancer in the seminal vesicles, and no cancer in the lymph nodes. In other words you were a relatively low risk patient.
Oh … and the reason they aren’t testing everyone for this is as follows: (a) they have only just demonstrated it; (b) the test required to demonstrate it is expensive, often painful, and complicated; and (c) most men treated today with localized disease are at minimal risk for such recurrence. The presence of DTC signals the possibility of a risk, not some sort of guarantee of it. And it does explain why some men can unexpectedly have a recurrence as much as 15 or 20 years after their initial treatment, but such events are rare. Most recurrences are much more predictable, because they occur in men who started out at high risk for recurrence at the time of diagnosis.
Mike. My PSA at Dx was 2.76. Everything was negative. Totally contained. Only issue to me was path. report showed a small amount in every lobe. Tumor volume rated as “moderate.” I had RP by Partin at J.H. and he tells me he thinks I will make it into his 30 year survivor numbers. I just can’t seem to believe it with everything I read. Any you know, it’s cancer. Thanks for your response.
I understand the relatively low risk of PC recurring in most people who are at lower risk to begin with. In my case, I had PSA doubling in 8 months (3.6 to 8.0), T3a, dirty margins, followed by IMRT. And PSA “undetectable” after nearly a year … but I figure that the chances of recurrence in the next 5 years is pretty good. I wouldn’t be as concerned except that my type was diagnosed as “quite agressive.” The new study just verifies that there are no guarantees in any case.
Chris: So if I assume you had an RP last January 2008 and that you have been “disease free” for 13 months, the the Kattan nomograms give you a 10-year probability of disease-free survival of 98 percent, and the longer you are disease free, the higher the probability of remaining disease free. Also, I have known Alan Partin since I had to ask his permission to put the original Partin tables on line back in the 1990s. If he says he thinks you’ll be one of his 30-year survivors, my guess is you probably will be.
Harvey: You are clearly at significantly greater risk for recurrence than Chris is. I can’t estimate your risk by using the Kattan nomograms without knowing your Gleason score, but if you use the link I told Chris about, you can do it for yourself very easily. On the other hand, you just never know. There are people like you who respond really well to the radiotherapy and just go into complete remission. You need to remember that statistics don’t apply to individuals, only to groups of individuals.
Mike,
I believe that this is a very significant discussion and needs to be brought up on the “Social Site”. It is very depressing and scarey. One wonders if there is any real chance of beating cancer because of the DTC. However, whether there is or there is not a chance, we still have to go on as if there were a chance. I know of no other way to live my life. I am not going to give up, but this is tough news to swallow. Sort of makes me gag and wonder why I am still fighting. But … for me … most of the time I love a good fight, even when the scales have been just tipped by the above article. It makes me fight harder. We really need to share this Mike. Thanks, George
‘Tis done. See Disseminated tumor cells — coping with the reality.