AUA 2006 - Prostate Cancer Localized III Discussed Poster Session

UroToday.com - Interesting topics in this section included investigations to evaluate the appropriateness of focal therapy, the natural history of treated disease and the outcomes of some significant clinical trials. Barber et al [ABST 1573] evaluated the characteristics of patients with a single positive core with regard to contralateral disease. The single core was defined as 40 percent or less, or 5mm or less, of one core among 6-12 cores of tissue. These were collected from 1999 to 2004. 129 cases were identified and 46 (35.6%) underwent a radical prostatectomy. The average tumor volume was 1.15 cc's and the largest tumor focus was on the ipsilateral side of biopsy. However 89% of cases demonstrated tumor on the contralateral side and one forth of these had high grade disease. These data suggested that a 6-12 core biopsy may be insufficient to rule out contralateral disease. Another perspective is that greater stringency in defining a single core (smaller percentage of core positive or absence of high grade tumor) as informative for ipsilateral disease is needed.

In an evaluation of 961 radical prostatectomy specimens, tumor foci were ranked according to size Ohori, et al [ABST 1574] Mean tumor volume for the largest site was 2.13 cc with significantly reduced volumes for the next several lesions(0.39,0.17,0.09, 0.04 cc's) in succession. 16% of cases demonstrated extracapsular disease and over 85% of these where associated with the largest lesion. Only 18% of lesions in patients with a PSA under 10 were unifocal, yet in the majority of such patients, treatment of this lesion would eradicate 80-90% of the significant tumor. The authors suggest that there may be some role for unifocal therapy for disease control in specific situations.

Longitudinal recurrence of PSA after radical prostatectomy was described by Allaf et al [ABST 1582] who analyzed the biochemical progression of 3521 radical prostatectomy patients treated from 1986 to 2005. With a mean follow up of 7 years the biochemical failure rate was 13%. 60.9% of failures occurred within 5 years and 91% and 97% occurred within 10 and 15 years. Patients with favorable pathological features failed later and only 23.8% of biochemical recurrences had occurred by 5 years. These data suggest that the vast number of biochemical failure will manifest themselves over the first 10 years of follow-up.

Docetaxel is now the standard for the therapy of hormone refractory, metastatic prostate cancer. Major areas of research are now aimed at improving outcomes in these patients by augmenting this platform with other agents or investigating whether this platform can be shifted to earlier stage disease. Kibel et al, [ABST 1587] described a multi-institutional trial of weekly docetaxel for high risk patients after radical prostatectomy. Risk was assessed by a multivariate hazards model and those patients with a greater than 50% risk of biochemical or clinical recurrence. 77 patients were enrolled and at a median follow up of 28 moths 63% of the patients' demonstrated progression. Median progression free survival was 16 months compared to a predicted 10 months. Four of seven deaths were attributable to prostate cancer. Grade I-II toxicity in the absence of greater toxicity was noted in 70% of patients yet 26% had grade III toxicity and one GI bleed and a case of pulmonary fibrosis and death from pneumonia may have been treatment related. These data suggest that adjuvant docetaxel in prostate cancer is feasible. The toxicity can be significant yet is generally tolerable. Progression free survival appears longer than predicted by nomogram. Based on these data an adjuvant phase III trial has been initiated.

The potential side effects of androgen deprivation therapy have become increasingly of concern as a larger proportion of men without bone metastatic disease remain on therapy. Changes of bone mineral density and increased fracture risk are of significant concern. Casey et al [ABST 1590] reported on a trial of 200 men with bone metastasis negative disease who received either goserelin acetate every three months for one year or goserelin acetate and 4mg of zoledronic acid on the same schedule. The primary end point was the BMD change in the lumbar spine from baseline over this period and other bone sites were also measured. An interim analysis of 80 patients demonstrated a 2% decrease in BMD in those patients receiving goserelin alone and an average 4% increase in patients receiving zoledronic acid and goserelin. These data suggest that this combination can prevent bone loss in those patients receiving hormonal therapy.

Supported by an unrestrictional educational grant from Sanofi-Aventis

By S.Bruce Malkowicz, MD

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