Some more interesting insights from the annual meeting of the SUO

Reports on the UroToday web site this morning give us some interesting points of view on some of the more debated issues affecting the future of prostate cancer research and treatment and “on the agenda” yesterday at the annual meeting of the Society for Urologic Oncology (SUO) in Washington, DC.

In his Huggins Medal lecture yesterday, Dr. Joseph Smith of Vanderbilt University apparently indicated that he was expecting to see major changes in the role of the urologic oncologist and the urologic surgeon over the next decade. These included the ideas that:

  • 10 years from now, open surgery for prostate cancer will probably never be carried out any more.
  • There is likely to be a significant decrease in the numbers of radical prostatectomies carried out each year here in America.
  • Urologic surgery as a subspecialty will become significantly more refined, will need to be applied more selectively, and will require more advanced technical skills.
  • Management options for care of patients will expand to allow for true multidisciplinary management.
  • Just being a good surgical technician will no longer be sufficient to be a competent urologic surgeon (although Dr. Smith was careful to point out that in his opinion it never really has been).

A presentation by Dr. Daniel Moreira looked at findings about the potential link between chronic prostate inflammation and prostate cancer tumor grade (based on data from 889 men enrolled in the REDUCE trial. All the eligible patients were aged between 50 and 75, had a cancer-negative prostate biopsy result at baseline, but were then found to have prostate cancer 2 years later. Moreira et al. report that, based on their study:

  • Acute forms of inflammation alone were found in just 1 percent of patients at baseline with prostate cancer at their 2-year biopsy
  • Acute and chronic forms of inflammation were found in 10 percent of patients at baseline.
  • Chronic forms of inflammation aloone were found in 60 percent of patients at baseline.
  • 70 percent of the patients had low-grade tumors.
  • 30 percent of the patients had high-grade tumors.
  • Compared to patients with no prostate inflammation at baseline, those with chronic prostate inflammation had a lower risk of high-grade disease (odds ratio [OR] = 0.68, p = 0.016) on multivariate analysis.

They also concluded that there was no association between acute inflammation and subsequent cancer grade.

Finally, Dr. Himisha Beltran provided attendees with a current overview on molecular and histological heterogeneity affecting the development and progression of  prostate cancer.

Prostate cancer is a multifocal disease with wide clinical variability between patients.  From a patient perspective the key points that Dr. Be;ltran made in giving this presentation were that:

  • No one single genomic mutation has been shown to predict cancer prognosis. (It is the way multiple mutations affect the development of the disease that is important.)
  • Risk stratification is highly dependent on the tumor tissue available for testing and on which tissue is tested if tissue is available from more than one tumor in a specific patient.
  • The “dominant” lesion or lesions may not be the largest tumors or even the ones with the highest Gleason scores, because “dominance” is much more likely to be dependent on molecular biological features of specific tumors.

Much of this information is not new in and of itself. However, it all adds to the complexity of how to be able to asses, for an individual patient, what his long-term risk is over time (which of course affects how he should be managed), and it places greater emphasis on the need to appreciate the molecular and clonal heterogeneity of prostate cancer both across cohorts of patients with differing genetic backgrounds but also among the tumors to be found in individual patients.

11 Responses

  1. Beltran’s study raises important questions about the efficacy of focal therapy. It confirms an earlier case report from Johns Hopkins that found: “the lethal clone arose from a small, relatively low-grade cancer focus in the primary tumor, and not from the bulk, higher-grade primary cancer or from a lymph node metastasis resected at prostatectomy.” Focal therapy, as currently practiced, is dependent upon there being an identifiable dominant lesion.

  2. Dear Allen:

    I think a better way to be looking at this is whether focal therapy is really appropriate at all unless there is good reason to believe that such therapy can and will eliminate all evident cancer in the prostate because all cancer appears to be confined to highly defined and limited areas of the prostate.

    While some have indeed suggested that it may be acceptable to eliminate only a dominant lesion (and leave behind small, lower grade, non-dominant lesions), this has certainly not been accepted by the urology community as a whole, nor even by a number of those who have been investigating the potential clinical applicability of focal therapy.

  3. ‘The “dominant” lesion or lesions may not be the largest tumors or even the ones with the highest Gleason scores, because “dominance” is much more likely to be dependent on molecular biological features of specific tumors.’

    What this says to me is that Gleason score, and any post-surgery upgrading, must mean a whole lot less than the typical patient understands.

    Advances in biopsy targeting are providing more specific Gleason details that may not really mean very much?

  4. Allen.

    Just glanced at the Hopkins study.

    First, it is only one case. More importantly, the lethal clone arose from the “primary” tumor.

    Why would focal therapy not have not worked in this case, as focal always destroys the primary tumor?


  5. Dear Mike:

    There was a reason that I emphasized the word “may” in this statement. Frankly I don’t really think we know what any of this means yet. And in saying that I am specifically including the experts in the molecular biopsy of prostate cancer!

  6. Doug,

    Yes — I identified it as a case study and pointed out this new study confirmed it. You are confusing the terminology. “Primary tumor” refers to the tumor that spawned off the clones. Focal therapy does not necessary ablate the primary tumor, it ablates the largest, highest grade tumor, which is called the “index tumor.”

    Focal therapy depends on the “index tumor” hypothesis: that the “primary tumor” is the same as the “index tumor.” That hypothesis states that there is a single tumor from which clones spawn off and that that tumor is identifiable by its size and grade. Focal therapy then treats only that identified index tumor and not any other tumors that are smaller and lower grade, which as it turns out, may be the actual source of the clones. Beltran’s study calls that hypothesis into question.

    We don’t yet know how to identify which men have index tumors that are controllable with focal therapy, or how to identify the primary tumor when they are not one and the same.

  7. Dear Allen:

    I would again point out that one form of focal therapy restricts treatment to the index lesion. However, the term “focal therapy” can also be used to encompass forms of therapy in which all cancer (and all tissue) within a specific segment of the prostate is ablated, regardless of how many tumors are within that segment. It can also encompass the focal treatment of more than one specific cancer lesion within the prostate (although it is unusual to individual target lesions in both lobes of the prostate. In focal therapy one would usually treat only cancers in one lobe or the other.

  8. They usually call it “hemi-ablation” when they fully ablate one lobe. The issue is the same, however — at pathological examination, the cancer often has microscopic foci in both lobes even when it was detected in only one lobe at biopsy. In most focal (rather than hemi-ablation) ablation trials I’ve looked at, limits were set on the number of detected lesions — typically two. The question remains — are the targeted tumors the ones responsible for the spread of the cancer?

  9. Yup … I’m not trying to understate the risk factors at all. My only point is that one has to be very clear what different centers mean when they use the term “focal” therapy because it is all over the map. I know of papers where the heading says “focal therapy” but the actual paper then describes partial ablation of an entire lobe of the prostate (“hemiablation”), half of one lobe, or less than half of one lobe. Conversely there are most certainly papers in which the term “focal therapy” is used to mean what you are using it to mean — ablation of the index lesion while knowingly not treating one or more other small foci of Gleason 6 disease.

  10. Allen and Sitemaster,

    My doctor, who does only focal therapy (laser), destroys all visible tumors and suspicious lesions.

    I would guess the odds of destroying the “primary” tumor are pretty good, under that scenario,

  11. A prostatectomy is not a 100% guarantee even when done early. How much do the odds change with a focal therapy, however defined?
    Maybe a little, maybe a lot for an individual. It is like playing poker when you do not know the house rules until the game is over. Study the cards you can see, weigh your risks and rewards, and do not look back. You will never know the outcome of a path you did not take.

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