Neoadjuvant androgen blockade prior to prostatectomy: A retrospective study and critical review

Abstract

The treatment of locally advanced prostatic cancer is controversial, as there are several possible treatment options. The aims of temporary androgen deprivation prior to radical prostatectomy are to achieve downgrading and downstaging of the tumor, an increase in local control, a decrease in morbidity and operative sequelae, a decrease in the time to progression, and an improvement in survival.A retrospective study has been carried out on 100 patients who underwent radical prostatectomy between 1988 and 1992. Forty patients received androgen deprivation therapy followed by prostatectomy, while the remaining 60 acted as controls, undergoing prostatectomy alone. Treated patients had a 40-50% reduction in prostate volume after 3 months, facilitating dissection of the prostate, reducing intraoperative blood loss, and reducing operation time. Of these 40 treated patients, one third showed clinical downstaging; one patient staged initially as T 2 B was downstaged to PTO.The proportion of patients with positive surgical margins was 32% in the group treated preoperatively, compared with 57% in untreated patients. Treated patients also recovered full continence more rapidly after the operation than patients who underwent prostatectomy alone.After androgen blockade, serum PSA levels returned to normal (<4 ng/ml) in 37 of the 40 patients. Of these patients, 22 had undetectable serum PSA levels (<0.25 ngiml), showing a definite reduction in tumor activity. PSA levels after 3 months of neoadjuvant hormonal treatment might play a useful predictive role in selecting patients before radical prostatectomy, since 86% with undetectable PSA had tumors confined to the gland (T2/B2), while patients who still had PSA > 4 ng/ml all had stage T3-T4 tumors.Although downstaging was confirmed pathologically in only 13% of patients, this is of significance when the total number of patients with locally advanced prostate cancer is considered and, therefore, may have implications for survival in the future. Prospective randomized studies should provide conclusive information on the potential benefit of this approach.

Neoadjuvant hormonal therapy prior to radical prostatectomy: promises and pitfalls

“…However at 48 months follow-up, no differences in PSA recurrence rates were apparent. 26 Several smaller nonrandomized studies by Sassine and Schulman 27,28 and by Ha È ggman et al 29 also reported 40 ± 50% decreases in positive margin rates when groups of patients pretreated with 3 months of NHT were compared to historical controls. In contrast, reports on small cohorts of patients with cT 2 or cT 3 tumors by Mcfarlane et al 11 and Oesterling et al 12 suggested no improvement in pathologic outcome following short-term NHT.…”

AP-1, but not NF-κB, is required for efficient steroid-triggered cell death in Drosophila

“…21,22 For example, glucocorticoids regulate cell death in the central nervous system, sex steroids control cell death in the ovary, and progesterone can inhibit cell death in breast cancer cells. 23 ± 25 Steroid hormones have also been used for treatment of prostate and breast cancers 26,27 and extensive efforts are underway to alter apoptotic signaling pathways in order to control other diseases, including viral infections, autoimmune diseases, and neurodegenerative disorders. 28 ± 30 We are studying the fruit fly, Drosophila melanogaster, as a model system for defining the hormonal regulation of programmed cell death.…”

Stellenwert der neoadjuvanten Therapie vor radikaler Prostatektomie

“…Eine Senkung der Rate positiver Absetzungsränder kann somit als prognostisch wichtiges Kriterium für den Erfolg einer neoadjuvanten Hormontherapie gewertet werden. Wie in ⊡ Tabelle 1 dargestellt, findet sich eine signifikante Reduktion positiver Absetzungsränder in der Mehrzahl der publizierten Studien [1,14,11,22,39,34,45]. Die Ergebnisse von Bellavance u. Fradet [3] konnten sogar einen Vorteil einer maximalen Androgenblockade gegenüber einer einfachen Hormonblockade im neoadjuvanten Setting zeigen.…”