Many men with early stage prostate cancer suffer relapse and/or die of their disease despite potentially curative surgery or radiotherapy. Early hormonal therapies are being combined with these local therapies, with the aim of facilitating local control and improving survival. In the surgical setting, neoadjuvant hormonal therapy reduces the rate of positive margins and extracapsular penetration, but most studies have failed to demonstrate an advantage with respect to biochemical progression. Further studies are needed to clarify the role of adjuvant therapy in surgical patients. In the radiotherapy setting, neoadjuvant hormonal therapy improves local control, although survival data is not available, and can be considered for stage T2b disease or higher. Adjuvant luteinizing hormone-releasing hormone (LH-RH) agonists improve both local control and survival after radiotherapy and should be offered to all patients. Currently, the LH-RH agonists are the drugs of choice for adjuvant therapy, whereas combined androgen blockade has generally been used as neoadjuvant therapy. Monotherapy with a nonsteroidal antiandrogen has considerable potential in both settings. Areas for future studies include appropriate endpoints for clinical studies, comparative drug efficacy and the effect of treatment on quality of life.

1.
Haas GP: Epidemiology of early prostate cancer. In Vivo 1994;8:403–406.
2.
Bolla M, Van Poppel H: Prostate cancer. An insight into screening and local treatment. Eur J Cancer 1996;32A:1434–1435.
3.
Brawley OW: Prostate carcinoma incidence and patient mortality: The effects of screening and early detection. Cancer 1997;80:1857–1863.
4.
Smart CR: Prostate cancer facts and fiction. J Surg Oncol 1997;66:223–229.
5.
Pettaway CA: Prognostic markers in clinically localized prostate cancer. Tech Urol 1998;4:35–42.
6.
Osin P, Crook T, Powles T, Peto J, Gusterson B: Hormone status of in-situ cancer in BRCA1 and BRCA2 mutation carriers. Lancet 1998;351:1487.
7.
Huggins C, Hodges C: Studies on prostatic cancer. I. 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.
8.
Kirby RS: Recent advances in the medical management of prostate cancer. Br J Clin Pract 1996;50:88–93.
9.
Veterans Administration Cooperative Urological Research Group: Treatment and survival of patients with cancer of the prostate. Surg Gynecol Obstet 1967;124:1011–1017.
10.
Byar DP, Corle D: Hormone therapy for prostate cancer: Results of the Veterans Administration Cooperative Urological Research Group Study; in Consensus Development Conference in the management of Clinically Localized Prostate Cancer. Bethesda, NCI, 1988, vol 7, pp 1–165.
11.
Ditonno P, Battaglia M, Selvaggi FP: Adjuvant hormone therapy after radical prostatectomy: Indications and results. Tumori 1997;83:567–575.
12.
Fair WR, Cookson MS, Stroumbakis N, Cohen D, Aprikian AG, Wang Y, Russo P, Soloway SM, Sogani P, Sheinfeld J, Herr H, Dalgabni G, Begg CB, Heston WDW, Reuter VE: The indications, rationale, and results of neoadjuvant androgen deprivation in the treatment of prostatic cancer: Memorial Sloan-Kettering Cancer Center results. Urology 1997;49(suppl 3A):46–55.
13.
Morton RM, Steiner PL, Walsh PC: Cancer control following anatomical radical prostatectomy: An interim report. J Urol 1991;145:1197–1200.
14.
Stein A, DeKernion JB, Smith RB, Dorey F, Patel H: Prostate-specific antigen levels after radical prostatectomy in patients with organ confined and locally extensive prostate cancer. J Urol 1992;147:942–946.
15.
Lukkarinen O: Surgery for the urinary tract cancer. Ann Chir Gynaecol 1996;85:202–206.
16.
Waters JS, Ross PJ, Popescu RA, Cunningham D: New approaches to the treatment of gastro-intestinal cancer. Digestion 1997;58:508–519.
17.
Brenin DR, Morrow M: Breast-conserving surgery in the neoadjuvant setting. Semin Oncol 1998;25(suppl 3):13–18.
18.
Aso Y, Homma Y, Sakamoto A, Ohasi Y: A randomized prospective study on radical prostatectomy alone versus radical prostatectomy preceded by androgen deprivation. Eur J Urol 1997;30(suppl 2):210, abstr 776.
19.
Cookson MS, Sogani PC, Russo P, Sheinfeld J, Herr H, Dalbagni G, Reuter VE, Begg CB, Fair WR: Pathological staging and biochemical recurrence after neoadjuvant androgen deprivation therapy in combination with radical prostatectomy in clinically localized prostate cancer: Results of a phase II study. Br J Urol 1997;79:432–438.
20.
Labrie F, Cusan L, Gomez JL, Diamond P, Suburu R, Lemay M, Tetu B, Fradet Y, Belanger A, Candas B: Neoadjuvant hormonal therapy: The Canadian experience. Urology 1997;49(suppl 3A):56–64.
21.
Schulman CC, Debruyne FMJ, Forster G, van Cangh PJ, Witjes WPJ: Neoadjuvant combined androgen deprivation therapy in locally confined prostatic carcinoma. Three years of follow-up of a European multicentric randomised study. Br J Urol 1997;80(suppl 2):259, abstr 1015.
22.
Soloway MS, Shairifi R, Wajsman Z, McLeod D, Wood DP, Puras-Baez A: Radical prostatectomy alone vs. radical prostatectomy preceded by androgen blockade in cT2b prostate cancer – 24-month results. Br J Urol 1997;80(suppl 2):259, abstr 1013.
23.
Aus G, Abrahamsson PA, Ahlgren G, Hugosson J, Lundberg S, Schain M, Schelin S, Pedersen K: Hormonal treatment before radical prostatectomy: A 3-year follow-up. J Urol 1998;159:2013–2016.
24.
Goldenberg SL, Klotz LH, Jewett MAS, Srigley J, Barkin J, Mador D, Fradet Y, Chin JL, Paquin JM, Laplante S: Randomized, controlled study of neoadjuvant reversible androgen withdrawal therapy for prostate cancer. J Urol 1996;156:873–877.
25.
Klotz LH, Goldenberg SL, Buillock M, Srigley J, Jewett MA, Mador D, Fradet Y, Barkin J, Chin J, Paquin JM, Lapalante S: Neoadjuvant androgen ablation prior to radical prostatectomy (CUOG P-92). 24-month post-treatment PSA results. Br J Urol 1997;80(suppl 2):266, abstr 1045.
26.
Labrie F, Cusan L, Gomez JL, Diamond P, Suburu R, Lemay M, Tetu B, Fradet Y, Candas B: Downstaging of early stage prostate cancer before radical prostatectomy: The first randomized trial of neoadjuvant combination therapy with flutamide and a luteinizing hormone-releasing hormone agonist. Urology 1994;44:29–37.
27.
Vaillancourt L, Tetu B, Fradet Y, Dupont A, Gomez J, Cusan L, Suburu ER, Diamond P, Candas B, Labrie F: Effect of neoadjuvant endocrine therapy (combined androgen blockade) on normal prostate and prostatic carcinoma. Am J Surg Pathol 1996;20:86–93.
28.
Schulman CC, Debruyne FMJ, Forster G, van Cangh PJ, Witjes WPJ: Neoadjuvant hormonal blockade before radical prostatectomy: 3–4 years’ follow-up evaluation of an European multicentric randomized study. Eur Urol 1998;33(suppl 1):135, abstr 538.
29.
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. Urology 1997;49(suppl 3A):65–69.
30.
Soloway MS, Shairifi R, Wajsman Z, McLeod D, Wood DP, Puras-Baez A: Randomized prospective study comparing radical prostatectomy alone versus radical prostatectomy preceded by androgen blockade in clinical stage B2 (T2bNxM0) prostate cancer. J Urol 1995;154:424–428.
31.
Montironi R, Schulman CC: Pathological changes in prostate lesions after androgen manipulation. J Clin Pathol 1998;51:5–12.
32.
Voges GE, Mottrie AM, Fichtner J, Mappes C, Storkel S, Stockle M, Hohenfellner R: Maximum androgen deprivation prior to radical retropubic prostatectomy in patients with stage T3 adenocarcinoma of the prostate. Eur Urol 1995;28:209–214.
33.
Lee F, Siders DB, McHugh TA, Solomon MH, Mayman DM: Neoadjuvant androgen ablation therapy prior to radical prostatectomy: Results of a 3-year follow-up. Endocr Relat Cancer 1996;3:171–177.
34.
Garnick MB, Fair WR: First International Conference on Neoadjuvant Hormonal Therapy of Prostate Cancer: Overview Consensus Statement. Urology 1997;49(suppl):1–4.
35.
Gleave M, Goldenberg SL, Jones E, Bruchovsky N, Sullivan L: Biochemical and pathological effects of 8 months of neoadjuvant hormonal therapy – An update on 125 consecutive patients. Br J Urol 1997;80(suppl 2):259, abstr 1016.
36.
McLeod DG, Johnson CF, Klein E, Peabody JO, Coffield S, Soloway M and the Lupron Depot Neoadjuvant Study Group: PSA levels and the rate of positive surgical margins in radical prostatectomy specimens preceded by androgen blockade in clinical B2 (T2bNxM0) prostate cancer. Urology 1997;49(suppl 3A):70–73.
37.
Schulman CC, Wildschutz T, Zlotta AR: Neoadjuvant hormonal treatment prior to radical prostatectomy: Facts and open questions. Eur Urol 1997;32:41–47.
38.
Early Breast Cancer Trialists’ Collaborative Group: Systemic treatment of early breast cancer by hormonal, cytotoxic or immune therapy. Lancet 1992;339:1–14.
39.
Andriole GL: Adjuvant therapy for prostate cancer patients at high risk of recurrence following radical prostatectomy. Eur Urol 1997;32(suppl 3):65–69.
40.
Seay TM, Blute MC, Zincke H: Radical prostatectomy and early adjuvant hormonal therapy for pTxN+ adenocarcinoma of the prostate. Urology 1997;50:833–837.
41.
Wirth M, Frohmüller H, Marz F, Bolten M, Thieb M: Randomized multicenter trial on adjuvant flutamide therapy in locally advanced prostate cancer after radical surgery. Br J Urol 1997;80(suppl 2):263, abstr 1033.
42.
Wirth M, Frohmüller H, Marx F, Bolten M, Theiss M: Adjuvant antiandrogenic treatment after radical prostatectomy in stage C prostate cancer – Preliminary results of a randomized controlled multicenter trial. J Urol 1997;157(suppl):335, abstr 1308.
43.
Roach M: Neoadjuvant therapy prior to radiotherapy for clinically localized prostate cancer. Eur Urol 1997;32(suppl 3):48–54.
44.
Zelefsky MJ, Harrison A: Neoadjuvant androgen ablation prior to radiotherapy for prostate cancer: Reducing the potential morbidity of therapy. Urology 1997;49(suppl 3A):38–45.
45.
Galbraith SM, Duchesne GM: Androgens and prostate cancer: Biology, pathology and hormonal therapy. Eur J Cancer 1997;33:545–554.
46.
Raghavan D: Adjuvant systemic therapy of prostate cancer. Semin Oncol 1995;22:633–640.
47.
Pilepich MV, Krall JM, Al-Sarraf M, John MJ, Scotte Doggett RL, Sause WT, Lawton CA, Abrams RA, Rotman M, Rubin P, Shipley WU, Grignon D, Caplan R, Cox JD: 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.
48.
Candas B, Gomes JL, Cusan L, Diamond P, Laverdiere J, Labrie F: Effects of neoadjuvant and adjuvant combined androgen blockade associated to radiation therapy on serum PSA. Br J Urol 1997;80(suppl 2):259, abstr 1017.
49.
Laverdiere J, Gomez JL, Cusan L, Suburu ER, Diamond P, Lemay M, Candas B, Fortin A, Labrie F: 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.
50.
Porter AT, Elhilali M, Manji M, Grignon D, Thomas G, Kostashuk GE, Eapen L, Danjoux C, Ago T, MacLennan I, Morris J, Laverdiere J, Laplante S: A phase III randomized trial to evaluate the efficacy of neoadjuvant therapy prior to curative radiotherapy in locally advanced prostate cancer patients. Proc Am Soc Clin Oncol 1997;16:315, abstr 1123.
51.
Duchesne GM, Bloomfield D, Wall P: Identification of intermediate-risk prostate cancer patients treated with radical radiotherapy suitable for neoadjuvant hormone studies. Radiother Oncol 1996;38:7–12.
52.
Schultheiss TE, Lee WR, Hunt MA, Hanlon AL, Peter RS, Hanks GE: Late GI and GU complications in the treatment of prostate cancer. Int J Radiat Oncol Biol Phys 1997;37:3–11.
53.
Pilepich MV, Krall JM, Sause WT, Johnson RJ, Russ HH, Hanks GE, Perez CA, Zinninger M, Martz KL: Prognostic factors in carcinoma of the prostate – Analysis of RTOG study 75–06. Int J Radiat Oncol Biol Phys 1987;13:339–349.
54.
Pollack A, Zagars GK, Kopplin RN: Radiotherapy and androgen ablation for clinically localized high-risk prostate cancer. Int J Radiat Oncol Biol Phys 1995;32:13–20.
55.
Bartelink H, Rubens RD, van der Schueren E, Sylvester R: Hormonal therapy prolongs survival in irradiated locally advanced breast cancer: A European Organization for Research and Treatment of Cancer randomized phase III trial. J Clin Oncol 1997;15:207–215.
56.
Arcangeli G, Saracino B, Micheli A, D’Angelo L, Pansadoro V, Cruciani E, Marchetti P: Radiotherapy with or without androgen deprivation in the treatment of localized adenocarcinoma of the prostate. Am J Clin Oncol 1998;2:1–5.
57.
Anderson PR, Hanlon AL, Movsas B, Hanks GE: Prostate cancer patient subsets showing improved bNED control with adjuvant androgen deprivation. Int J Radiat Oncol Biol Phys 1997;39:1025–1030.
58.
Zagars GK, Johnson DE, von Eschenbach AC, Hussey DH: Adjuvant estrogen following radiation therapy for stage C adenocarcinoma of the prostate: Long-term results of a prospective randomized study. Int J Radiat Oncol Biol Phys 1988;14:1085–1091.
59.
Bolla M, Gonzalez D, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Gil T, Collette L, Pierart M: Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med 1997;337:295–300.
60.
Pilepich MV, Caplan R, Byhardt RW, Lawton CA, Gallagher MJ, Mesic JB, Hanks GE, Coughlin CT, Porter A, Shipley WU, Grignon D: Phase III trial of androgen suppression using goserelin in unfavourable prognosis carcinoma of the prostate treated with definitive radiotherapy – Report of RTOG protocol 85–31. J Clin Oncol 1997;15:1013–1021.
61.
Fellows GJ, Clark PB, Beynon LL, Boreham J, Keen C, Parkinson MC, Peto R, Webb JN: Treatment of advanced localised prostatic cancer by orchiectomy, radiotherapy, or combined treatment. A Medical Research Council Study. Urological Cancer Working Party – Subgroup on Prostatic Cancer. Br J Urol 1992;70:304–309.
62.
Lawton CA, Winter K, Byhardt R, Sause WT, Hanks GE, Russell AH, Rotman M, Porter A, McGowan DG, DelRowe JD, Pilepich MV: Androgen suppression plus radiation versus radiation alone for patients with D1 (pN+) adenocarcinoma of the prostate (results based on a national prospective randomized trial, RTOG 85-31). Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 1997;38:931–939.
63.
Walsh PC, Partin AW: Treatment of early stage prostate cancer: radical prostatectomy; in DeVita VT, Hellman S, Rosenberg SA (eds): Important Advances in Oncology 1994. Philadelphia, Lippincott, 1994, pp 211–223.
64.
Pound CR, Partin AW, Walsh PC: The natural history of progression to metastases and death due to prostate cancer in men with PSA recurrence following radical prostatectomy. J Urol 1998;159(suppl):334, abstr 1283.
65.
D’Amico AV, Whittington R, Malkowicz B, Schulktz D, Tomaszewski JE, Wein A: Prostate-specific antigen failure despite pathologically organ-confined and margin-negative prostate cancer: The basis for an adjuvant therapy trial. J Clin Oncol 1997;15:1465–1469.
66.
Rabbini F, Sullivan LD, Goldenberg SL, Stothers L: Neoadjuvant androgen deprivation therapy before radical prostatectomy: Who is unlikely to benefit? Br J Urol 1997;79:221–225.
67.
Dijkman GA, Debruyne FMJ, Fernandez del Moral P, Plasman JW, Hoefakker JW, Idema JG, Sykes M: A randomised trial comparing the safety and efficacy of the Zoladex 10.8-mg depot, administered every 12 weeks, to that of the Zoladex 3.6-mg depot, administered every 4 weeks, in patients with advanced prostate cancer. Eur Urol 1995;27:43–46.
68.
Townsend MF, Sanders WH, Northway RO, Graham SD: Bone fractures associated with luteinizing hormone-releasing hormone agonists used in the treatment of prostate carcinoma. Cancer 1997;79:545–550.
69.
Tunn UW: Intermittent endocrine therapy of prostate cancer. Eur Urol 1996;30(suppl 1):22–25.
70.
Kaisary AV: Compliance with hormonal treatment for prostate cancer. Br J Hosp Med 1996;55:359–366.
71.
Iversen P, Tyrrell CJ, Kaisary AV, Anderson JB, Baert L, Tammela T, Chamberlain M, Carroll K, Gotting-Smith K, Blackledge GRP: Casodex (bicalutamide) 150-mg monotherapy compared with castration in patients with previously untreated nonmetastatic prostate cancer: Results from two multicenter randomized trials at a median follow-up of 4 years. Urology 1998;51:389–396.
72.
Delaere KP, Van Thillo EL: Flutamide monotherapy as primary treatment in advanced prostatic carcinoma. Semin Oncol 1991;18:13–18.
73.
Caffo O, Fellin G, Graffer U, Luciani L: Assessment of quality of life after radical radiotherapy for prostate cancer. Br J Urol 1996;78:557–563.
74.
Altwein J, Ekman P, Barry M, Biermann C, Carlsson P, Fossa S, Kiebert G, Kuchler T, McLeod D, Porter A, Steineck G: How is quality of life in prostate cancer patients influenced by modern treatment? The Wallenberg Symposium. Urology 1997;49(suppl 4A):66–76.
75.
Fossa SD, Woehre H, Kurth KH, Hetherington J, Bakke H, Rustad DA, Skanvik R: Influence of urological morbidity on quality of life in patients with prostate cancer. Eur Urol 1997;31(suppl 3):3–8.
76.
Hanks GE: Long-term control of prostate cancer with radiation. Past, present and future. Urol Clin North Am 1996;23:605–616.
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.