gms | German Medical Science

Objectives: Patients with locally advanced prostate cancer (PCA) as defined by invasion of the seminal vesicle, positive lymph nodes or Gleason grade 8-10 harbour an increased risk for systemic relapse following even extended radical prostatectomy. Androgen deprivation has been considered as adjuvant treatment in the majority of these patients. However, despite endocrine manipulation, most of the patients will relapse after 3-5 years as has been shown in a recent analysis. Since metastases may develop in different organ systems – lymph nodes, visceral organs, skeletal system – we initiated a multimodal adjuvant treatment protocol including androgen deprivation, docetaxel and zoledronate.

Patients and Methods: Between 3/2004 and 9/2005 15 patients with high risk PCA were included in the protocol. High risk PCA was defined by a ≥ 70% of systemic relapse within the following 7 years according to the postoperative Kattan nomograms. Adjuvant androgen deprivation with LHRH-analogues and zoledronate was started immediately; adjuvant chemotherapy with docetaxel was started 6 weeks postoperatively. Zoledronate was applied at 4mg at 4 weeks intervals for 2 years; docetaxel was given at 75mg/m2 for 6 cycles at 3 weeks intervals. Dose reduction was performed for any grade 3/4 toxicity. PSA serum levels were followed at each cycle and 3-monthly afterwards, quality of life was evaluated by the EORTC QLQ-30 questionnaire. Primary study endpoint will be prolongation of time to progression, time to symptomatic progression, safety and quality of life.

Results: Mean age of the patients was 62 (39-65) years; mean initial PSA level was 11.9(4.6-52) ng/ml. The mean number of applied cycles was 5.1 (4-6) with 12 patients receiving 6 cycles, 2 and 1 receiving 2 and 1 cycle, respectively. 5 (33%) patients experienced WHO grade 3 hematotoxicity, 6 (40%) experienced WHO grade 2-3 diarrhoe, and 8 (53.3%) patients experienced significant fatigue. None of the patients developed septic fever, cardiotoxicity or neurotoxicity. Quality-of-life was significantly reduced in all domains analysed during treatment but recovered within 3 months after the end of therapy. After a mean follow-up of 9.5 (3-19) months, none of the patients experienced PSA-recurrence.

Conclusion: Adjuvant treatment with androgen deprivation, docetaxel and zoledronate of high risk PCA following radical prostatectomy is feasible with a tolerable spectrum of side effects. Currently, follow-up is too short to draw any conclusions with regard to oncological control. For the future, high risk patients should be randomised in the ongoing AUO protocol.