The Friday news reports (Part B): February 13, 2009

The second set of reports in today’s news commentaries encompasses new nomograms, possible new biomarkers, a specific subtype of prostate cancer, and the “hedgehog” signaling pathway.

Rosenzweig et al. have reported that the addition of the levels of two specific proteomic biomarkers to preoperative PSA levels could be used to develop a model with statistically significant value for predicting prostate cancer recurrence in men who underwent radical retropubic prostatectomy (RRP). The two specific biomarkers (P1 and P2) were discovered using mass spectrometric analysis of serum from 52 patients with recurrent disease and 52 patients who had no biochemical recurrence 5 years after RRP. The identities of the P1 and P2 markers have been tentatively determined.

Skinner and Schwartz are reporting that the level of ionized serum calcium (as opposed to total serum calcium) is associated with higher prostate cancer mortality, and that the ionized seroum calcium level may also have potential as a biomarker for prostate cancer risk. More information on this study is available in a media release from Wake Forest University Baptist Medical Center.

Kattan et al., recognizing that recent literature suggests that surgeon experience is a factor in outcomes to radical prostatectomy (RP), have developed and internally validated nomograms to predict the probability of disease recurrence, both preoperatively and postoperatively, with adjustment for standard parameters plus surgeon experience. Their study cohort included 7,724 eligible prostate cancer patients treated by a total of 72 surgeons. For each patient, surgeon experience was coded as the total number of cases conducted by the surgeon before the patient’s operation. However, according to the internal validation, surgeon experience seems to have had a quite modest effect, especially postoperatively.The “New” Prostate Cancer InfoLink is tempted to wonder whether this result is affected by the fact that the 72 surgeons involved were all practising (or training) at some of the most highly regarding urologic surgery centers in the USA, and therefore all 72 surgeons involved would be expected to achieve and maintain very high standards.

Froehner et al. report the results of an external attempt to validate a “recently published” nomogram developed to predict the 10-year survival probability of men selected for radical prostatectomy (RP). A total of 1,910 consecutive patients who underwent RP from 1992 to 2004 were included.  The 10-year survival probability was estimated for each individual patient, using this recently published nomogram. Even including the prostate cancer-related mortality (accounting for 5.1 percent at 10 years), the 10-year overall survival rate in our sample was somewhat greater than predicted by the nomogram (84.9 vs 81.9 percent, P = 0.0222). Subgroup analyses revealed that this difference was attributable to a greater than predicted survival in patients with a Charlson score of 0 and aged ≥ 70 years (87.9 vs 74.7 percent, P < 0.0001). The authors conclude that clinicians using this nomogram should be aware of a possible underestimation of survival in healthy men aged ≥ 70 years selected for RP.Unfortunately we are unable to tell from the paper’s abstract exactly which 10-year survival nomogram the authors were attempting to validate.

It has long been understood that there were almost certainly different “types” of prostate cancer, based on genetic and other characteristics. Identification of a subtype of prostate cancer associated with the ETS fusion gene was initially reported by Tomlins et al. In a new article, Demichelis et al. have now published further information that helps to define a distinct molecular subtype of prostate cancer based on the presence of ETS gene rearrangements.

The so-called “hedgehog” signaling pathway is being intensely investigated as a possible target for development of new drugs to treat many forms of cancer. A recent article by Chen et al. has reviewed the potential of hedgehog-blocking agents in conjunction with androgen deprivation (ADT) in treatment of patients with advanced forms of prostate cancer. Chen et al. note that because of the ability of androgens to modulate the expression and release of hedgehog ligands, and the activity of the autocrine hedgehog signaling pathway in certain prostate cancer cells, chronic ADT might create a hedgehog signaling environment in the region of the tumor that could ultimately impact on the long-term effectiveness of the ADT.

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