Wednesday’s news: October 15, 2008

There is a significant number of new reports today, addressing such issues as: data from a large series of robotic prostatectomy patients; the importance of positive surgical margins and their management; the significance of number of positive lymph nodes in N+M0 patients; evolving models of the role of testosterone in prostate cancer progression; and data on the clinical use of the investigational LHRH antagonist degarelix.

Patel et al. have added to the surgical knowledge base about robot-assisted laparoscopic prostatectomy (RALP) with publication of data from a series of 1,500 consecutive cases, all carried out by a single surgeon. The study is entirely focused on the perioperative and immediate postoperative results of the procedure (i.e., events occurring during and immediately after the surgery itself) and does not address longer-term outcomes. However, the authors report that the average (mean) time from skin incision to fascial closure (the time that the surgeon was present) was 105 minutes. The mean blood loss  was 111 ml (with a range of 50-500 ml). Almost all patients (97 percent) were discharged 1 day after the procedure. The overall complication rate was 4.3 percent with no deaths. The positive margin rate (PMR) was 9.3 percent overall, with PMRs of 4 percent for pT2, 34% percent for pT3, and 40 percent for pT4 patients. We believe that this is the lowest published rate of positive surgical margins to date. The lowest rate reported by Yossepowitch et al. (see below) in the recent review is only 11 percent.

Yossepowitch et al. have reviewed the significance of positive surgical margins (PSMs) in the surgical treatment of localized disease. They emphasize a number of critical points, as follows: PSMs in radical prostatectomy specimens are uniformly considered an adverse outcome. Attention to surgical detail is essential to minimize rates. Radiation therapy is the only established treatment with curative potential for patients with PSMs who are destined to have progressive disease. However, they also note that a randomized trial comparing immediate postoperative radiotherapy to salvage radiotherapy in patients with PSMs is critically needed before definitive recommendations can be made regarding appropriate treatment. It should also not be forgotten that patients with a post-surgical PSM do not, in fact, always have progressive disease.

Briganti et al. have reported intesting data on the significance of the number of positive lymph nodes at the time of initial treatment on the cancer-specific survival (CSS) of prostate cancer patients. According two this study, patients with only 1 or 2 positive lymph nodes have a significantly better CSS than patients with > 2 positive lymph nodes (84 vs. 62 percent) based on a 15-year follow-up of 703 N+M0 patients treated between 1988 and 2003. They suggests that this may be significant to prostate cancer staging and perhaps to the stratification of patients in future clinical trials.

Morgentaler and Traish have reviewed available literature in order to assess the accuracy of the traditional belief that prostate cancer development and progression over time is dependent on serum testosterone (T) levels. This belief has been challenged by recent negative studies in non-castrated men. Their goal was to offer a beeter basis for our understanding of the relationship between prostate cancer progression and  serum T levels that would be consistent with current evidence and founded on established biochemical principles of androgen action within the prostate. They conclude that “there is a limit to the ability of androgens to stimulate” prostate cancer growth. They describe a model of androgen-to-androgen receptor binding that may be able to account for the dramatic effects seen with castration as well as the minor impact of T administration in non-castrated men.

Gittelman et al. have just published the results of a Phase II clinical trial of the investigational LHRH antagonist degarelix in the management of 127 men with histologically confirmed prostate cancer. They conclude that, “Degarelix treatment for 1 year resulted in a fast, profound and sustained suppression of testosterone and prostate specific antigen with no evidence of testosterone surge. Degarelix was well tolerated.” We note, however, that 6 patients (4.7 percent) withdrew from this trial as a result of adverse events. The results of Phase III clinical trials of degarelix are currently awaited with considerable interest.

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