Management of men with bone metastasis over time

A new review article in issue 2 of Everyday Urology addresses the topic of bone mets, quality of life, and related factors in the management of advanced and metastatic prostate cancer over time.

The article by Dr. Neal Shore is entitled “Bone metastases and mortality in prostate cancer: can we be doing more?“, and the full text is available on the UroToday web site.

This article may be of interest to a lot of readers who have advanced disease, but do remember that it has been written for urologists as opposed to patients, so some of it gets complicated.

6 Responses

  1. I read this paper and found it informative — providing many useful facts and several excellent graphs, and nicely current.

    I am a bit puzzled by the discussion and Table 1 regarding imaging to detect bone metastases. Based on a paper by the well-known prostate cancer physician E. D. Crawford, MD, the text states:

    “… In terms of cost-effectiveness, the RADAR group recommends conventional bone scintigraphy using technetium 99 (99mTc) and abdomen/pelvis/chest computed tomography (CT) as imaging modalities for initial testing [22]….”

    That struck me as an arguably obsolete or sub-optimal recommendation. The next sentence, based on the same paper by Dr. Crawford and a different paper by Dr. P. J. Koo and Dr. Crawford adds the following:

    “… Other novel imaging modalities are available (Table 1), and the RADAR group suggests using plain radiography, magnetic resonance imaging (MRI), and 18F-sodium fluoride (NaF) with positron emission tomography (PET) or CT (particularly for detection of osseous metastases); these tests should be conducted at the physician’s discretion when necessary, as they may be needed to clarify equivocal lesions [22 23]. (see Table 1)….”

    Table 1 displays a striking difference in effectiveness, with the technetium-99 scan with only 78% sensitivity and 48% specificity, and with the CT scan with only 74% sensitivity and 56% specificity for bone metastases, in very sharp contrast with three of the other choices, led by the Na18F PET/CT scan boasting a sensitivity of 100% and a specificity of 97%.

    I’m curious why the RADAR group would recommend the old scans these days. (At some point I have had all of the scans discussed in this comment.)

  2. Dear Jim:

    The answer to your puzzlement is simple. Look at the very first sentence of your two quotes. It begins, “In terms of cost effectiveness …”. The authors of the paper are looking at this issue in terms of the costs associated with stopping all testing with traditional bone and CT scans and replacing them with Na18F PET/CT scans. It would cost a very large fortune. PET scanning is way more expensive than bone scans and CT scans.

  3. Follow-up to cost-effectiveness explanation by Sitemaster

    I did suspect that cost effectiveness was the answer, and thank you for your assessment, but the cost/value question really looks different from the perspective of a worried patient.

    My Tc-99 scan back in early 2000 showed some spots that were evaluated as arthritis and a long-ago injury, with no metastases, which pleasantly surprised the doctors and me based on my initial highly unfavorable presentation. However, the doctors did caution me back then that it took about 10% of cancer involvement at a bone site for the Tc-99 scan to pick up an indication of likely cancer, so I was aware of limited sensitivity and therefore the possibility of stealthy bone metastases (about 9% or lower cancer involvement, but, of course, growing). (Ditto for my CT scan about the same time: while negative, I was advised the scan needed cancer to have grown to about the size of a pea for the radiologist to rate the scan as positive, and this again allowed for the possibility of stealthy soft-tissue metastases for my case. I also had a ProstaScint at Johns Hopkins in early 2000, which was ambiguous: negative except for a “suspicious” spot in the anterior tip of the liver, an unlikely spot for an initial met, leading me to always — with a nod towards hope — regard that “suspicious” rating as likely an artifact. My electronic medical record was not so optimistic, labeling my case as Stage IV cancer.) All these results gave me and my wife guarded confidence that I would likely live for another 5 years or so, the prognosis I received from two well-regarded urologists. At the time, that was very good news!

    Cost is a consideration for my family but not a show-stopper, and my wife and I would have been grateful for the advanced bone and soft-tissue scanning technologies now available, and we would have been willing to squeeze our resources and pay for them had they been available back in 2000. A dozen years later, thanks to advancing technology, the negative readings I got around 2012 for bone and soft tissue metastases boosted our morale and opened the way to a confident shot at radiation, going for a cure, which seems to have been successful at the 3.5-year point of follow-up. Even if one or both scans had turned out the other way and been positive, my wife and I would have been confident in choosing other tactics, which suggests that these scans have value.

    Sadly, several thousand dollars of copay responsibility is a show-stopper for many patients. I have met a number of such patients in my Us TOO group. It is good we have the old stand-by scans that provide a fair amount of information for those patients, even with the loss of a substantial proportion of sensitivity and a large proportion of specificity.

    Thanks again for your knowledgeable reply.

  4. Does Paper Suffer a Bit from a Surgeon’s (Urologist’s) Viewpoint?

    We would all want a surgeon to perform surgery rather than having the work done by a medical oncologist, but when it comes to cases that are beyond surgery, my own impression that has been polished over many years is that doctors whose main therapy is drugs — oncologists — are aware of valuable advances that may not register on a surgeon’s radar.

    Reflecting on this worthy paper by a urologist, I realized that the author had not included one of the exciting new drug treatments for bone metastases. This drug is known by several names, but its brand name is Xofigo®, and it was known for years as Alpharadin during some of its development. Shouldn’t Xofigo® have been mentioned in this paper? I see no reason why not and would welcome other viewpoints. (Xofigo® links a powerful alpha particle radiation source which is preferentially absorbed by calcium and therefore seeks out prostate cancer in bone specifically, delivering its potent but short-distance therapy, and thereby minimizing injury to healthy tissue.)

    Again reflecting, it seems the useful statistics/graphs on prognosis for prostate cancer in bone that are provided give us a good snapshot of the survival situation in the fairly recent past, but not a good indicator of our current situation in which we have impressive new drugs, such as Xofigo®, as well as imaging and other know-how that enables us to use them effectively. For instance, Figures 2 and 3 are a pair of graphs that show progression from bone to multiple metastatic sites and the effect on overall and cancer-specific mortality. Both graphs report Kaplan-Meier projections to the 60-month point. However, 60 months, or 5 years, subtracted from 2016 is 2011, and some of our exciting prostate cancer medications were not even on the scene in 2011, including Xofigo®, which was approved by the FDA in May of 2013 –- a date recent enough that relatively little impact of Xofigo® would likely be reflected in Figures 2 and 3. Similarly, Zytiga® (abiraterone) was not approved by the FDA until the end of April, 2011, and Xtandi® was not approved until August 2012.

    Of course it takes a while for drugs to become widely adopted in practice after they are approved, and therefore their impact on survival statistics lags their dates of approval. Indeed, the 3,857 patients whose cases were used for Figures 2 and 3 had presented with metastatic prostate cancer between 1991 and 2009 and were included in the Surveillance Epidemiology and End Results-Medicare database (Gandaglia et al., 2015). It seems likely that few if any of these patients would have been treated with Xofigo®, Zytiga® or Xtandi®.

    Therefore, perhaps the prognosis statistics for overall and cancer-specific survival that are presented in the paper should be regarded as floor level, with modern drugs encouraging us to expect superior results.

    All this said, from my savvy but layman’s perspective, this paper provides ample food for thought, useful snapshots in time of key clinical statistics, and sound conclusions about the evolution of prostate cancer over time, which underlines the importance of changes in treatment approaches as the disease evolves into bone metastasis.

  5. Dear Jim:

    I think I should note that Dr. Neal Shore is actually a urologic oncologist and not simply a urologist, and is considered by many to be highly knowledgeable on the subject of the treatment of advanced forms of prostate cancer (including treatment with drugs like sipuleucel-T (Provenge), abiraterone acetate (Zytiga), etc.)

    The potential role of radium-223 acetate (Xofigo) in the treatment of anything other than castration-resistant prostate cancer (and mostly metastatic, CRPC at that) is generally considered by nearly everyone to be very limited at this time (since we have very limited data on it efficacy and safety in any patients other than CRPC). From that perspective, its value in delaying the progression of advanced and high-risk prostate cancer to date is minimal, because it has generally been used as a “treatment of last resort” to either manage bone pain or prevent progression of bone pain (like other systemic radiation therapies before it, e.g., strontium-89).

    Whether radium-223 might have a really significant value in delaying the progression of high-risk forms of advanced prostate is, as yet, unclear, and I would suspect that that is much more likely to be the reason why Dr. Shore chose not to address that use of this product in this article.

  6. Spoke to Bayer the other day. Should the Xofigo work as hoped and all the metastases disappear, they could possibly return in say 3 to 5 years. At this time, you can not get another round of the drug through Medicare. FDA only approved it for one time use.

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