The effect on tumour and prostate volumes of a 3-month course of neo-adjuvant hormone therapy was studied using computerised planimetry on serially sectioned specimens obtained by radical prostatectomy. Fifty-four specimens from patients not receiving pre-treatment were compared to 38 specimens from patients given the gonadotropin-releasing hormone (GnRH) analogue triptorelin for 3 months before the operation. Glandular volume and volume of the index tumour was determined. To determine the position of the index tumour within the gland, the centre of mass of the tumour was identified and the distance to the gland margin calculated. This value (M(1)) represents the sum of the tumour radius and the various amounts of normal tissue. The amount of surrounding tissue could be approximated by correlating M(1) to the corresponding tumour volume.Results: The two groups differed significantly in total gland volumes, but not in tumour volumes. M(1) was strongly correlated to the tumour volume in the treatment group (r = 0.73), whereas in the control group the correlation was found to be significantly weaker (r = 0.44), indicating that there was less tissue surrounding the tumour in the pre-treated group. In a multiple regression analysis of all 92 patients, index tumour volume was found to be associated with total gland volume, DNA ploidy pattern, tumour grade but not whether or not pre-treatment was given. This study found that the volumes of the single largest tumour focus were not significantly affected by hormonal pretreatment, and that ''the prostate condenses around the tumour rather than that the tumour shrinks back into the prostate''. However, the precise relationship between tumour epithelial volume and stroma with or without neo-adjuvant hormonal pre-treatment remains to be clarified.
OBJECTIVE To measure the area distribution of epithelial and mesenchymal components in the prostate of patients with localized prostate cancer after temporary androgen deprivation. PATIENTS AND METHODS Surgical specimens from 38 patients treated with the gonadotrophin-releasing hormone agonist triptorelin for 3 months before radical prostatectomy were examined (group I). Specimens from a second group of 54 patients who underwent the same surgical procedure with no prior therapy were used as controls (group 2). The specimens were serially step-sectioned and whole-mount tissue sections prepared. The epithelial, smooth muscle and connective tissue components were stained separately with immunohistochemical and histochemical techniques, respectively. Using colour-based image analyses, the tissue components were classified into three categories, displayed in different colours. The percentage of tumour areas occupied by cancer epithelial cells, connective tissue and smooth muscle was determined. RESULTS In specimens from group 1, the cancer epithelium was sparse and scattered throughout the tumour area. A mean (SD) of 21 (11)% of the area was occupied by cancer cells, compared with 40 (11)% in the corresponding material from group 2 (P < 0.001). The connective tissue/smooth muscle ratio in stroma (about 1:1) was similar in both groups. CONCLUSIONS Neoadjuvant hormone treatment of patients with localized prostate cancer was associated with a marked reduction in tumour density and thus in the total amount of cancer epithelium.
Prostatectomy was performed in 48 patients with localized prostate cancer. Before surgery, they had been treated with the GnRH agonist triptorelin for 3 months. Specimens from the largest tumor focus (n = 6.3 + 3.6, mean + SD) were analyzed with regard to the DNA ploidy pattern. The results were compared with those obtained in a previous investigation of 54 patients who were subjected to surgery without hormone pretreatment. In both series, about 50% of the tumors showed a diploid DNA ploidy pattern, the rest being nondiploid. Ploidy heterogeneity, i.e., a mixture of diploid and nondiploid ploidy patterns in the single largest tumor focus, was found in 36% of the cases compared to 48% in the previous report (NS). In 13% of the tumors, all samples revealed a nondiploid DNA ploidy pattern as compared to 6% in the previous report (NS). In both series, needle biopsy examination (1/patient) prior to prostatectomy was associated with a significant and similar underestimate of the chromosomal aberration. In conclusion, despite the marked histopathological changes previously reported, there is no evidence that neoadjuvant triptorelin treatment during 3 months has any effect on the DNA ploidy pattern.
Objective To examine the effect of pre-operative androgen deprivation on the progression rate of malignancy in patients operated on for localized prostate cancer.Patients and methods A total of 53 patients received no hormone therapy (group 1) and a further 38 patients (group 2) received the generic releasing-hormone agonist triptorelin during the 3 months before surgery, The patients in group 1 had T1b-T2 tumours, whereas 12 of those in group 2 had clinical stage T3 tumours. Despite this, the surgical specimens from the patients in group 2 showed a rate of cancer invasion of the surgical margins 20% lower than those from the patients in group 1. After prostatectomy, the patients were followed for 3 years by repeated analyses of prostate-specific antigen (PSA) in serum.Results During the follow-up, the PSA level exceeded the upper threshold (0.6 ng/mL) in 16% of the patients in group 1 and in 43% of those in group 2 (P < 0.05). This difference was mainly related to the pre-treatment stage of the tumour. Some of the patients in group 1 received post-operative radiotherapy but this was not reflected in their PSA levels. Of the patients in group 1 and 2, 4% and 14% respectively (P > 0.05), developed symptoms from skeletal metastases.Conclusion There was no evidence that pre-operative hormone therapy slowed the progression of prostate cancer.
The effects of 3 months treatment with the GnRH agonist triptorelin as a neoadjuvant to total prostatectomy in 40 men with localized prostatic cancer have been evaluated. The study included 1 patient with a stage T1b tumour, 25 patients with stage T2 tumours and 14 with stage T3 tumours. The patients were examined by digital rectal examination, transrectal ultrasound before and after treatment. Serum testosterone and prostate-specific antigen (PSA) levels were followed. The totally removed prostate gland was step-sectioned at 5-mm intervals and the whole-mount sections were assessed for tumour pathology stage (pT stage). Triptorelin treatment resulted in a significant decrease in total gland and tumour volume and in a reduction in the serum levels of PSA and testosterone. In comparison with the findings from a previous study, in which neoadjuvant treatment was not used, it appears that the proportion of tumours invading the margins of the surgical specimen decreased.
Androgen deprivation with triptorelin treatment prior to total prostatectomy gave the opportunity of studying consequent morphological changes in the surgical specimens from 38 men with localized prostatic cancer. Multiple core-needle biopsies were taken prior to treatment and compared to the step-sectioned surgical specimens. The histological changes in the prostate following androgen deprivation include glandular atrophy, nuclear pyknosis, cytoplasmic vacuolation, squamous metaplasia and an increase in the relative amount of stroma. None of these changes could be correlated to pretreatment tumour grade, nor to the volume of the residual tumour. A positive correlation was found between tumour grade prior to therapy and volume of residual tumour after treatment. The treatment was not associated with downgrading of the malignancy. On the contrary, in 16% of the cases, foci of a higher grade were found in the surgical specimens compared to the pretreatment core-needle biopsies.