The role of CT scanning in assessment of progression of men with CRPC

A newly published paper in the journal Cancer seems to be implying that every man with castration-resistant prostate cancer who progresses from non-metastatic to metastatic status (based on a bone scan or other indicators) should also be given a CT scan because of risk for soft tissue metastasis.

The new paper by Hanyok et al. (based on data originally presented earlier this year at the annual meeting of the American Urological Association) explored the prevalence of soft-tissue metastases in patients with non-metastatic castration-resistant prostate cancer (nmCRPC or M0 CRPC) at time of evidence of progression to metastatic castration-resistant prostate cancer (mCRPC or M1 CRPC).

The authors looked at data from a cohort of 232 men all of whom progressed according to these criteria, and whose progression was documented as a consequence of a bone scan or a CT scan. All relevant bone scans and CT scans given 30 days before or 30 days after the diagnosis of mCRPC were reviewed.

Here are the core findings of the study:

  • Compared to the patients who underwent only a bone scan (n = 114), patients given a CT scan (n = 118)
    • Were more likely to have received primary treatment for their prostate cancer (P = 0.048)
    • Were older (P = 0.013)
    • Has less recently developed metastases (P = 0.018)
  • Of the patients given a CT scan
    • 52/118 (44 percent) had soft tissue metastasis, including
      • 20 visceral metastasis (in 17 percent of the patients)
      • 41 lymph node metastases (in 35 percent of the patients)
    • 35/118 (30 percent) had no sign of metastasis to bone
  • Only the patients’ PSA levels were predictive of soft-tissue metastases based on a univariate anaylsis (odds ratio [OR] = 1.27; P  = 0.047).
  • No statistically significant predictors of visceral metastases were found on the same univariate analysis.
  • A higher PSA level was associated with an increased risk of lymph node metastases (OR = 1.38; P = 0.014).
  • Having received primary treatment was associated with a decreased risk for lymph node metastasis (OR = 0.36; P = 0.015).

The authors conclude that their data suggest

… there is a relatively high rate of soft-tissue metastasis (44 percent) among CRPC patients undergoing CT at the initial diagnosis of metastases, including some men with no bone involvement. Therefore, forgoing CT during a metastatic evaluation may lead to an underdiagnosis of soft-tissue metastases and an underdiagnosis of metastases in general.

What is not clear from the abstract of this study, however, is:

  • What caused some men to be given both a bone scan and a CT scan
  • What caused some men to be given only a bone scan
  • What caused some men to be given only a CT scan

It would also be helpful to know how many of the men in this study had

  • TxN0M1 disease, broken  down into two subsets
    • Metastasis to bone alone (but no positive lymph nodes)
    • Metastasis to soft tissue alone (but no positive lymph nodes)
  • Tx N1M1 disease, broken down into three subsets
    • Metastasis to bone and to the lymph nodes, but no other soft tissue metastasis
    • Metastasis to soft tissues and to the lymph nodes but no bone metastasis
    • Metastasis to bone and to lymph nodes and to other soft tissues

Such data may be provided in the full text of this paper, but are not evident in the abstract. There are some data related to these questions in the data presented at the AUA annual meeting (but that study is based on a smaller total number of patients)

It would appear to be relatively simple to conduct a prospective study in which one gave serial bone scans and an appropriate CT scans to every man in a cohort who was thought to be in transition from non-metastatic to metastatic disease and then asked his physicians to

  • First, evaluate the patient’s situation and future treatment based on the bone scan and other customary data alone (without the CT scan data)
  • Second, re-evaluate the patient’s situation and future treatment based on the added information provide by the CT scan

Such a study would quickly demonstrate what percentage of patients would need to have their treatment changed on the basis of the CT scan. If it was more than about 5 percent, then this would be a strong indicator that all patients in such a transition should be routinely getting both a bone scan and a CT scan. If it was less than about 5 percent, then the question arises whether there really are other indicators that might be strongly suggestive of the need for a CT scan in carefully selected patients.

Of course the expanding availability of newer types of full body imaging test may also make all such questions moot over the next decade.

8 Responses

  1. I thought bone scans and CTs were always done together. It surprises me that they might not be. Recent evidence (CHAARTED) implies that the number of visceral plus bone metastases is an important differentiating factor. Since CTs are relatively cheap, why would they not do it whenever a bone scan is indicated?

  2. My bet would be that CT scans and bone scans are always done together at major medical centers where insurance is usually paying the bills. These data were generated from studies using the SEARCH database (i.e., the VA Medical Centers, where every penny counts).

  3. This is just another reflection of a most logical, bur unfortunately too often not practiced, paradigm: “You should know where the prostate cancer is before treating it.” Seems obvious, no?

  4. Jon,

    I think it varies with the situation. Given the limitations of modern technology and the nature of prostate cancer, that is often not possible, or may not be all that useful in some cases. Prostate cancer is often micrometastatic and multifocal — small bits of it may be scattered around an area or may be systemic. Even when we can see a tumor in, say, the prostate, the prostate bed or a pelvic lymph node, it makes sense to treat the entire area and not just what we can see. On the other hand, a bone scan and a CT scan are our basic tools for detecting metastases and deciding on whether radical treatment would be useful for unfavorable risk orostate cancer, and whether lymph node dissection or radiation may be worthwhile.

  5. Period of Study: 2000 – 2013 – Significant Technology Advances

    I’ve read the linked items, and the study was based on men with non-metastatic castration-resistant prostate cancer (nmCRPC or M0 CRPC) (etc.) identified between 2000 and 2013. That caught my attention because my own high-risk case was identified weeks before New Year’s Day 2000. This study brought to mind how greatly technology has advanced over this time span, a phenomenon alluded to by Sitemaster.

    In early 2000 my post-biopsy work-up included a standard (technetium) bone scan, a CT scan, and a ProstaScint scan at Johns Hopkins. None of them found even a single metastasis (one suspicious spot but in an unlikely place for a single metastasis), despite an initial PSA of 113.6 and an overall challenging presentation. Skipping forward about a decade (during which I was treated solely by intermittent ADT3 with supporting medications and lifestyle tactics), in 2011 I had a much more reliable Na18F1 PET/CT scan for bone metastasis, and in 2012 a feraheme Ultrasmall Superparamagnetic Iron Oxide (USPIO) MRI/CT scan for lymph metastases (both negative). My impression is that ProstaScint scanning is now obsolete, though it is still in use in some places.

    Also, in the earlier years, prostate cancer that was resistant to ADT was defined in most places by rising PSA despite a testosterone level of 50 ng/dl or lower, and my impression is that that definition is still widely accepted. The abstract did not state the definition, so I’m assuming it was that one. I have been convinced by certain doctors that the T level after adequate ADT should be less than 20 ng/dl, with higher levels indicating likely inadequate suppression of testosterone — an indication for alteration of ADT, and that DHT should also be checked. DHT can run wild despite T suppression, and DHT is a far more potent fuel for the cancer than T. In other words, men judged resistant by the 50 ng/dl standard may be just under-treated and not really resistant. It is clear that many physicians stick to the older definition.

  6. Dear Jim:

    The older, formal definition of effective suppression of serum T levels requires serum T to be < 50 ng/ml (and no higher). In addition, in order to be defined as castrate resistant, a man must not only have a rising PSA level while on treatment with an LHRH agonist, he must also have a rising PSA level again, subsequently, after some form of standard second-line androgen deprivation therapy (most commonly the addition of an antiandrogen to the LHRH agonist and subsequent antiandrogen withdrawal when the PSA rises while the patient is on the LHRH and the antiandrogen).

  7. What surprised me most was the level of visceral metastasis at 17%. This strikes me as high. Thoughts?

  8. Rick:

    I don’t think this is necessarily that high. I have long suspected that a lot of men don’t get CT scans routinely, and if they don’t get the CT scan they are highly unlikely to be identified with visceral metastasis.

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