ASCO 2006 - GU Oral Presentation: Prostate Cancer

UroToday.com - At the GU Oral Presentation, six prostate cancer abstracts were presented.

Stephenson, et al. presented a model for determining durable benefit of salvage external beam radiation therapy for post-prostatectomy patients with biochemical progression. The authors used multivariable Cox proportional hazard regression analysis in examining data on 1540 patients who underwent salvage external beam radiation therapy. The primary endpoint of the study was disease progression, either biochemical or clinical. The 5-year progression-free probability was 38% and the 10-year progression-free probability was 19%. The nomogram consisted of the following variables: pre-radiation therapy PSA, Gleason score at prostatectomy, neoadjuvant androgen deprivation, negative surgical margins, PSA at the time of biochemical progression, PSA doubling time, and regional nodal metastases. The concordance index for the nomogram was 0.68. The authors concluded that the nomogram reliably predicts outcome of salvage radiation therapy in patients with biochemical progression after prostatectomy.

Da Silva, et al. presented a randomized trial of continuous versus intermittent maximum androgen blockade (MAB) in patients with locally advanced or metastatic prostate cancer. A total of 766 patients were enrolled. After an initial induction of MAB, patients with significant reduction in PSA were randomized to continuous or intermittent MAB. Estimated 5 year survival was 51% for the continuous MAB group versus 53.8% for the intermittent MAB group (p=not significant). There was no statistically significant difference in objective or subjective progression between the 2 groups. Sexual activity and resultant quality of life were better in the intermittent MAB group. The authors concluded that intermittent androgen ablation should be an option for patients.

Patients with stage D2 prostate cancer are treated with androgen ablation therapy. SWOG 9346 (INT-0162) is an intergroup randomized trial of continuous versus intermittent androgen ablation therapy in patients with D2 prostate cancer. While the final results of this trial are forthcoming, Hussain et al. reported on the significance of the absolute PSA value after patients completed 7 months of induction androgen ablation. 1345 patients with D2 prostate cancer were included in this analysis. 1134 patients achieved a normalized PSA (<= 4.0 ng/mL) and 604 patients had an undetectable PSA at the end of induction. The median overall survival was 13 months for patients who did not normalize PSA, 44 months for patients with normalized but not undetectable PSA, and 75 months for patients with an undetectable PSA (these differences were statistically significant). The authors concluded that the absolute PSA value after 7 months of induction androgen ablation is a strong predictor of survival.

One of the drawbacks of androgen ablation therapy is loss of bone mineral density. Michaelson, et al. presented the results of a randomized trial in which 44 men with nonmetastatic prostate cancer undergoing androgen ablation therapy were randomized to receive an annual dose of zolendronic acid 4 mg by intravenous infusion or placebo. The primary endpoint was the effect on bone mineral density as measured by DEXA scan at one year. Patients who received the annual zolendronic acid had significantly increased bone mineral density of the total hip and spine at 1 year of follow-up. However, the study did not report on the impact of treatment on actual skeletal complications.

For patients who develop hormone refractory prostate cancer, systemic cytotoxic chemotherapy may play an important role. TAX 327 randomized patients with HRPC to docetaxel on an every 3 week schedule, docetaxel on a weekly schedule, or mitoxantrone (all arms included prednisone). TAX 327 demonstrated a survival advantage to docetaxel when administered on an every 3 week schedule. An ancillary analysis of TAX 327 was reported by Berthold et al. in which the authors determined the association between pain scores, quality of life scores, and PSA response in patients treated on this study. This study demonstrated that pain and quality of life were associated with PSA response, and pain response was an independent predictor of survival.

Beer et al. reported on the role of intermittent chemotherapy in the management of patients with HRPC. ASCENT was a multi-institutional randomized phase III trial comparing docetaxel plus DN-101 with docetaxel plus placebo. In this trial if patients had an excellent response to initial chemotherapy, they could elect to stop therapy with the option of further treatment in the future at the time of PSA progression. Eighteen percent of patients entered the intermittent phase of the treatment protocol. The median duration of the first chemotherapy holiday was 16 weeks. Upon resumption of docetaxel-based therapy on evidence of progression, 85% of patients demonstrated either a PSA response or stable disease. The promising results of this first prospective report of intermittent chemotherapy in HRPC should lead to further investigation of this approach.

Supported by an unrestrictional educational grant from Sanofi-Aventis.

By David Vaughn, MD

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