Abstract

Recent work has demonstrated the return of hormone sensitivity after palliative chemotherapy in androgen independent prostate cancer. We wished to establish whether a similar phenomenon existed in patients with no exposure to chemotherapy. A review of "hormone resistant" patients who had received salvage brachytherapy for localized prostate cancer after previous external beam radiotherapy was undertaken. Three patients with subsequent biochemical relapse responded to the rechallenge with hormonal treatment. The series of patients presented here demonstrates this phenomenon occurs after salvage brachytherapy with no exposure to chemotherapy. Recovery of sensitivity is demonstrated both to androgen deprivation and to androgen receptor antagonism. The recovery of hormone sensitivity was surprisingly durable, ranging from eight months to over twenty-one months. Hormone sensitivity may be recovered after salvage brachytherapy. Potential mechanisms underlying these observations are discussed and the likely central role of the activity of the androgen receptor highlighted. The relevance of these findings to the management of advanced prostate cancer is considered including thoughts on the practice of intermittent anti-androgen therapy.

Highlights

  • Prostate cancer is unique amongst malignancies in that its initial growth is dependent on the presence of intrinsic androgens

  • Recurrent or metastatic disease is typically first treated with hormonal manipulation: strategies include testicular androgen deprivation by either bilateral orchidectomy [2] or administration of a luteinizing hormone releasing hormone (LHRH) agonist [3], and treatment with anti-androgens such as flutamide to compete with testosterone for the androgen receptor binding site [4]

  • Patients were eligible for inclusion in this review only if they had previously been treated with conventionally fractionated external beam radiotherapy (EBRT) to 68-72Gy, had subsequently developed biochemical relapse and had initially responded to hormonal treatment before developing androgen resistance

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Summary

Introduction

Prostate cancer is unique amongst malignancies in that its initial growth is dependent on the presence of intrinsic androgens. Whilst mutations in several tumor suppressor genes have been described and are thought important in the establishment of a clonal population of cells, development of clinically significant cancer requires an androgenic drive to cellular proliferation [1]. This necessary androgenic drive provides therapeutic targets which may be exploited to inhibit the growth of prostate cancer. Resistance to androgen suppression invariably develops: cells accumulate further genetic abnormalities and proliferate despite low testosterone levels at a median interval of 12-16 months after initiation of endocrine treatment [5]

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