Monday, August 22, 2011

The fine art of the circular argument applied to management of ...

It will likely be evident to most well-informed prostate cancer patients, support group leaders, and advocates that a man with low-risk, early stage prostate cancer (?favorable histology?) is potentially a good candidate for prostate cancer surgery. (Of course, he may well be a potentially good candidate for many types of invasive first-line treatment ? although if he has a large prostate that cannot be easily reduced down to a size, he may not be an appropriate candidate for treatment by brachytherapy.)

Such good candidates have high potential for rapid recovery of a very high level continence, and (assuming high erectile function pre-surgery and a bilateral nerve-sparing prostatectomy) they also have a high potential for good recovery of erectile function. Of course many of these men may also be good candidates for active surveillance (AS) ? particularly if they are over 65 years of age and meet the Epstein criteria (clinical stage of ? T2a; no Gleason grade 4 cancer at all; less than three positive biopsy cores; and less than 50 percent cancer in any positive core).

Lavery et al. have just reported data based on the histopathologic and functional outcomes of a series of 1,477 patients all treated using robot-assisted laparoscopic radical prostatectomy (RALP) by an single, experienced, high-volume surgeon. Specifically, the authors compared data from men who met criteria that qualified them for AS, but who opted for a RALP, to data from men who were not candidates for AS and who elected to have a RALP.

In this series of patients, the following criteria were considered essential to qualify a man as a candidate for AS:

  • A PSA level < 10? ng/ml
  • A biopsy-based Gleason score ? 6 based on a minimum of 10 biopsy cores
  • < 3 positive cores with < 50 percent tumor volume in a single core
  • A clinical stage ? T2a.

The basic results of the analysis reported by Lavery et al. showed that:

  • 352/1,477 patients met qualifying criteria for AS but opted to have a RALP.
  • 159/352 potential AS patients (45.2 percent) were upgraded.
    • 143/352 (40.6 percent) to a pathologic Gleason score of 3 + 4 = 7
    • 16/352 (4.5 percent) to a pathologic Gleason score of 4 + 3 = 7
    • There were no patients with a pathologic Gleason score ? 8.
  • 17/352 potential AS patients (4.8 percent) were upstaged to pT3.
  • Potential AS candidates were younger and had more favorable tumor characteristics (but similar preoperative functional status) compared to non-AS patients.
  • Bilateral nerve sparing was performed on
    • 96 percent of potential AS candidates.
    • 86 percent of non-AS candidates.?
  • After 12 months of follow-up in patients who received bilateral nerve sparing
    • Continence levels were superior in the potential AS cohort compared to the non-AS candidates (98 vs. 92 percent, P < 0.001).
    • Potency was equivalent between the potential AS and non-AS candidates (87 percent in each group, P = 0.89).

(Please note that the definitions of continence and potency used in this paper are not given in the abstract. We suspect that ?success? with respect to potency was not the ability to complete successful intercourse at will most of the time without the use of PDE-5 inhibitors ? i.e., drugs like sildenafil/Viagra.)

Lavery et al. conclude that, ?In addition to having the expected favorable histopathologic features, AS candidates who desire definitive therapy have a high likelihood of achieving excellent functional outcomes, perhaps superior to non-AS candidates [with respect to continence], following RALP.?

Of course there is a whole other way to look at this set of results, which is to draw entirely the opposite conclusions, and state that:

  • Younger men who were potential candidates for AS, but who elected to receive a bilateral, nerve-sparing RALP from an experienced, high-volume surgeon, had better post-surgical outcomes with respect to continence than otherwise comparable men who were not candidates for AS.
  • These same younger men who were potential candidates for AS did not have any higher level of sexual function post-surgery than those who were not candidates for AS.
  • In men who are appropriate candidates, AS can therefore be used appropriately to defer the need for surgery until the need for intervention is clear, with no significant potential for future loss of continence or sexual function compared to men who are not candidates for AS.

The need for surgery (or any other form of immediate invasive therapy) in men who are candidates for active surveillance is potentially justifiable on the grounds of oncologic outcome (elimination of the cancer). It is not even close to potentially justifiable on the grounds of short-term quality of life.

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Source: http://prostatecancerinfolink.net/2011/08/22/the-fine-art-of-the-circular-argument-applied-to-management-of-prostate-cancer/

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