Effect of Neoadjuvant Endocrine Therapy (Combined Androgen Blockade) on Normal Prostate and Prostatic Carcinoma

Abstract

The morphologic changes induced by neoadjuvant combination endocrine therapy were evaluated in prostatectomy specimens from patients diagnosed with localized prostate cancer. These patients participated in a prospective, randomized clinical trial investigating the effect of 3 months of combination therapy with flutamide and an LHRH agonist prior to radical prostatectomy versus radical prostatectomy alone. Ninety-six radical prostatectomy specimens processed according to the same protocol were evaluated without knowledge of prior treatment. Forty-seven patients were randomly assigned to the neoadjuvant combination therapy group and 49 to the control arm. Compared with the control group, several changes were strongly and significantly associated with exposure to neoadjuvant combination therapy. The nonmalignant prostatic tissue showed strong prominence and hyperplasia of the basal cell layer, accompanied by epithelial cell vacuolization and markedly reduced occurrence of prostatic intraepithelial neoplasia (p < 0.001) after combination therapy. Prostate cancer tissue, on the other hand, showed smaller nucleoli (p < 0.001), cell vacuolization (p < 0.001), rare intraluminal crystalloids (p < 0.001), higher Gleason grade (p < 0.001), lower prevalence of capsular penetration (p < 0.001), and less frequent invasion of the perineural spaces (p < 0.001) and surgical margins (p = 0.002). Tumor volume, was also reduced by more than 40% in the treated group (p = 0.007). The present findings show that preoperative endocrine combination therapy induces highly characteristic changes in both nonmalignant and cancerous prostatic tissue. Furthermore, following endocrine treatment, the surgical margins are less likely to be involved by cancer and capsular penetration is reduced.

DCE and DW MRI in monitoring response to androgen deprivation therapy in patients with prostate cancer: A feasibility study

“…This likely explains the significant reductions demonstrated by DCE MRI post-ADT, and is consistent with the findings of prior studies (17,19,20). ADT has been shown to reduce prostatic blood flow and oxygenation (17,25) and, at a cellular level, to cause nuclear shrinkage, cell vacuolization, apoptosis, and minimal necrosis in tumor tissue (26,27). Thus the reductions in DCE parameters observed at this early time point are more likely explained by the antivascular effects of ADT and endothelial cell apoptosis rather than tumor cell death.…”

Changes in extent and zonal distribution of prostatic adenocarcinoma in patients preoperatively treated with neoadjuvant endocrine therapy: Analysis on whole‐mounted prostatectomy specimens

“…Thus the Gleason score usually increases after NET. [15][16][17] In the present study, the mean Gleason score was significantly higher in the castrated group (7.8) than in the non-castrated group (5.2) (P < 0.0001). However, as previously reported by Polito et al, the proliferative activity of PCA after NET becomes low, therefore, an up-grade of the Gleason score by NET is regarded as an artifact.…”

“…Histopathologic changes induced by NET have been reported in the literature, 15,16 that is, an increase in the Gleason grade and a decrease in the prostate volume. 17 The zonal pattern of regression of PCA has never been studied systematically.…”

High-grade prostatic intraepithelial neoplasia

“…[161][162][163] This decrease is accompanied by epithelial hyperplasia, cytoplasmic clearing, and prominent glandular atrophy, with decreased ratio of glands to stroma. These findings indicate that the dysplastic prostatic epithelium is hormone dependent.…”

“…As noted above, androgen deprivation therapy and radiation therapy induce acinar atrophy and apoptosis that result in regression of high-grade PIN. 70,[161][162][163]169,[174][175][176] Chronic therapy, however, would most likely be required to prevent new high-grade PIN lesions from invading and becoming clinical prostate cancer. Although more toxicity is likely to be tolerated for the treatment agents targeted to regress or inhibit high-grade PIN, as compared to treating healthy patients to reduce prostate cancer incidence, androgen deprivation therapy has too many adverse effects in men to be clinically useful.…”