Objectives: To evaluate the long–term effects of 3–month neoadjuvant hormonal treatment in patients treated by radical prostatectomy for locally confined prostate cancer.Methods: We report the results of 402 patients (220 with a clinical T2 tumor and 182 with a clinical T3 tumor) of whom 192 randomly received neoadjuvant total androgen deprivation using a LHRH analogue (goserelin) plus flutamide for a period of 3 months and 210 underwent radical prostatectomy only.Results: ‘Clinical downstaging’ was seen in 30% of cases in the neoadjuvantly treated group (NEO). ‘Pathological downstaging’ occurred in 7 and 15% of cases in the direct radical prostatectomy (DP) group and the NEO group, respectively (p<0.01). In patients with clinical T2 as well as in patients with clinical T3 tumors, a significant difference in the number of positive margins was shown in favor of the NEO group (cT2, p<0.01; cT3, p = 0.01). This advantage, although there was a trend in favor of the NEO group, specifically in cT2 tumors, did not translate in a significantly better PSA progression rate (p = 0.18). However, when evaluating the local control rate in cT2 tumors, we observed local recurrence in 3 of 102 (3%) patients in the NEO group versus 12 of 114 (11%) patients in the DP group. The difference is statistically significant (p = 0.03). In the cT3 group, this difference was not statistically significant (NEO group: 15 of 87 (17%), and DP group: 21 of 95 (22%) patients; p = 0.41).Conclusions: In this study, the clinical revelance of pathological downstaging and the lower percentage of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor is not confirmed by a lower PSA progression rate. However, this study indicates that there may be a trend that this advantage in favor of the NEO group directly translates into a better local control rate in clinical T2 tumors. Better local control in cT2 tumors is only going to be of relevance if subsequently you can show that there is a better survival for these patients. Unfortunately, this article reports a study which is not yet mature enough to show relevant information. Presently, neoadjuvant therapy should not be given outside clinical research settings.

Keywords:
Prostatic neoplasms, Prostatectomy, Hormone antagonists, Flutamide, Goserelin
1.
Partin AW, Oesterling JE: The clinical usefulness of prostate specific antigen: Update 1994. J Urol 1994;152:1358–1368.
2.
Epstein JI, Pizov G, Walsh PC: Correlation of pathological findings with progression following radical prostatectomy. Cancer 1993;71: 3582.
3.
Huggins C, Hodges CV: Studies on prostatic cancer: The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941;1:293–297.
4.
Lee HHK, Warde P, Jewett MAS: Neoadjuvant hormonal therapy in carcinoma of the prostate. BJU Int 1999;83:438–448.
5.
Schulman CC, Wildschutz T, Zlotta AR: Neoadjuvant hormonal treatment prior to radical prostatectomy: Facts and open questions. Eur Urol 1997;32:41–47.
6.
Witjes WPJ, Oosterhof GON, Schaafsma HE, Debruyne FMJ: Current status of neoadjuvant therapy in localized prostate cancer. Prostate 1995;27:297–303.
7.
Witjes WPJ, Schulman CC, Debruyne FMJ: Preliminary results of a prospective randomized study comparing radical prostatectomy versus radical prostatectomy associated with neoadjuvant hormonal combination therapy in T2–3 N0 M0 prostatic carcinoma. The European Study Group on Neoadjuvant Treatment of Prostate Cancer. Urology 1997;49:65–69.
8.
Hermanek P, Sobin LH: TNM Classification of Malignant Tumors, ed 4. International Union Against Cancer. Heidelberg, Springer, 1987, pp 124–125.
9.
Aus G, Abrahamsson P–A, Ahlgren G, Hugosson J, Lundberg S, Schain M, Schelin S, Pedersen K: Hormonal treatment before radical prostatectomy: A 3–year followup. J Urol 1998;159:2013–2017.
10.
Labrie F, Dupont A, Cusan L, et al: Downstaging of localized prostate cancer by neoadjuvant therapy with flutamide and lupron: The first controlled and randomized trial. Clin Invest Med 1993;16:499–509.
11.
Goldenberg SL, Klotz LH, Srigley J, et al: Randomized, prospective, controlled study comparing radical prostatectomy alone and neoadjuvant androgen withdrawal in the treatment of localized prostate cancer. J Urol 1996;165:873–877.
12.
Laverdière J, Gomez JL, Cusan L, et al: Beneficial effect of combination hormonal therapy administered prior and following external beam radiation therapy in localized prostate cancer. Int J Radiat Oncol Biol Phys 1997;37: 247–252.
13.
Pilepich MV, Sause WT, Shipley WU, et al: Androgen deprivation with radiation therapy compared with radiation therapy alone for locally advanced prostatic carcinoma: A randomized comparative trial of the Radiation Therapy Oncology Group. Urology 1995;45:616– 623.
14.
Jhaveri FM, Klein EA: How to explore the patient with a rising PSA after radical prostatectomy: Defining local versus systemic failure. Semin Urol Oncol 1999;17:130–134.
15.
MacFarlane MT, Abi–Aad A, Stein A, Danella J, Belldegrun A, deKernion JB: Neoadjuvant hormonal deprivation in patients with locally advanced prostate cancer. J Urol 1993;150: 132–134.
16.
Narayan P, Lowe BA, Carroll PR, Thompson IM: Neoadjuvant hormonal therapy and radical prostatectomy for clinical stage C carcinoma of the prostate. Br J Urol 1994;73:544–548.
17.
Têtu B, Labrie F, Dupont A, Monfette G: Histopathological effect of combination therapy on normal prostate and prostatic adenocarcinoma, in Labrie F, Lee F, Dupont A (eds): Early Stage Prostate Cancer: Diagnosis and Choice of Therapy. Amsterdam. Elsevier Science, 1989, pp 63–75.
18.
Wojno KJ, Epstein JI: The utility of basal cell–specific anti–cytokeratin antibody (34 beta E12) in the diagnosis of prostate cancer. A review of 228 cases. Am J Surg Pathol 1995;19: 251–260.
19.
Gleave ME, Goldenberg SL, Jones EC, Bruchovsky N, Sullivan LD: Longer duration of neoadjuvant hormonal therapy prior to radical prostatectomy in clinically confined prostate cancer: biochemical and pathological effects. Mol Urol 1997;1:199–204.
20.
Trachtenberg J: Neoadjuvant androgen ablation prior to radical prostatectomy: Quantum leap or hope unrealized? Curr Opin Urol 1996; 6:254–257.
21.
Srougi M, Kaufmann JR, Nesrallah A, Leite KR: High Gleason score predicts poor pathologic outcome after neoadjuvant androgen deprivation for locally advanced prostate cancer. Mol Urol 1998;2:195–199.
22.
Soloway M, Sharifi R, Wajsman Z, et al: radical prostatectomy alone vs. radical prostatectomy preceded by androgen blockade in cT2b prostate cancer–24 months results. J Urol 1997; 157:A619.
23.
Rabbani F, Bastar A, Fair WR: Neoadjuvant hormone therapy before radical prostatectomy: Update on phase II and III Memorial Sloan–Ketterin Cancer Center Trials. Mol Urol 1998; 2:151–156.
24.
Klotz LH, Goldenberg SL, Bullock MJ, Srigley JR, Laplante S, and the Canadian Uro–Oncology group. Neoadjuvant cyproterone acetate (CPA) therapy prior to radical prostatectomy reduces tumour burden and margin positivity without altering 6 and 12 month post–treatment PSA. Results of a randomised trial. J Urol 1996;155:A356.
25.
Gleave ME, Goldenberg SL, Jones ES, et al: Biochemical and pathological effects of 8 months of neoadjuvant androgen withdrawal therapy before radical prostatectomy in patients with locally confined prostate cancer. J Urol 1996;155:213–219.
26.
Gleave ME, Goldenberg SL, Jones ES, Bruchowsky N, Sullivan LD: Long–term neoadjuvant hormone therapy prior to radical prostatectomy: Analysis of outcome by preoperative risk factors. Mol Urol 1998;2:171–177.
27.
Fair WR, Aprikian A, Sogani P, Reuter V, Whitmore WF: The role of neoadjuvant hormonal manipulation in localized prostate cancer. Cancer 1993;71:1031–1038.
2000
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.