Original study
Primary Intermittent Androgen Deprivation As Initial Therapy for Men with Newly Diagnosed Prostate Cancer

https://doi.org/10.1016/j.clgc.2011.07.002Get rights and content

Abstract

Background

The purpose of this study was to describe the long-term incidence of cancer progression and mortality in men with localized prostate cancer treated with primary androgen deprivation (AD).

Methods

A retrospective chart review, from a medical oncology practice specializing in prostate cancer, was conducted of 73 men eligible for surgery or radiation treated with induction AD. Entry criteria consisted of a minimum of 9 months of induction AD, treatment initiation before 1999, clinical stage < T3, and outcome defined as the incidence of delayed local therapy, cancer progression, cancer mortality, and mortality from other causes.

Results

Median follow-up was 12 years. Fifteen men were at low risk, 38 were at intermediate risk, and 20 were at high risk. Three men (4%) experienced metastatic disease and died of prostate cancer after 3.5, 7.7, and 11 years, respectively. Two men were in the intermediate-risk category and 1 was high risk. Nineteen men (26%) died of non–prostate cancer causes. None had metastatic disease at the time of death. Of the remaining 51 survivors, none has experienced bone metastasis. Twenty-one men (29%) required no further therapy after the first induction course of AD. Twenty-four men (33%) maintained a prostate-specific antigen (PSA) level < 5.0 ng/mL with 2 to 5 cycles of intermittent AD. Twenty-eight men (38%) underwent delayed local therapy after a median of 5.5 years. Median follow-up after local therapy was 6.2 years. Three of these men experienced subsequent rising PSA levels but none has progressed to bone metastasis. Sixteen of 20 men (80%) in the high-risk category but only 12 of 53 men (23%) in the low- and intermediate-risk categories had delayed local therapy.

Conclusions

Primary intermittent AD is feasible for men with localized prostate cancer. Men who are younger and men with high-risk disease undergo delayed local therapy more frequently.

Introduction

In the early 1990s prostate cancer treatment options were limited to surgery and radiation therapy. During that time a number of men consulted us with an interest in avoiding surgery. They perceived radiation therapy as either too toxic or ineffective. Around 1992 we tested the idea of primary androgen deprivation (AD) in 24 men with newly diagnosed prostate cancer who had a follow-up sextant biopsy after 6 months of AD. Eighteen of the 24 men (75%) showed no residual cancer.1 Further experience with longer duration AD revealed that an undetectable PSA level was almost always reached and maintained. We later found, as did others, that AD could be stopped and restarted in an intermittent fashion.2

In men with localized prostate cancer treated with initial AD, treatment selection is a dynamic ongoing process that plays out over many years. Intermittent AD, because of its intrinsically open-ended nature, leads to multiple recurrent decision points regarding when to start or stop therapy and when to initiate definitive local therapy such as surgery or radiation. These clinical decisions are made by the patient in consultation with the physician, taking into account the pace of the disease and the impact of potential treatment-related side effects.

In the present study we report the 12-year outcome of a small group of men with early-stage prostate cancer eligible for local therapy but who elected to start AD as primary treatment.

Section snippets

Materials and Methods

Systematic and exhaustive review of > 1200 patient charts was performed at a medical oncology practice specializing in prostate cancer to identify all patients meeting the following entry criteria: (1) biopsy proven prostate cancer, (2) no previous surgery or radiation therapy, (3) clinical stage < T3, (4) treatment with initial AD for at least 9 months, (5) concomitant antiandrogen therapy continued for the duration of luteinizing hormone–releasing hormone (LHRH) agonist treatment, (6)

Results

After systematic review of all charts in the practice, 73 men were determined to be eligible for study inclusion. The median follow-up was 12.0 years. Patient characteristics are shown in Table 1. The median treatment time (duration of LHRH agonist therapy) of the initial cycle of AD was 15.9 months. The median treatment for subsequent cycles averaged 12 months. The number of men in each of the D'Amico3 risk categories (assigned retrospectively) was low risk, 15; intermediate risk, 38; high

Discussion

This observational report is most relevant when interpreted in the context of its times. For example, the risk of radiation toxicity was much higher in the past. In the 1990s, men with a strong antipathy against radical prostatectomy or radiation had few alternatives.

It should be reiterated that this is a purely descriptive study. It consists of a relatively small group of men evaluated retrospectively. Care and restraint are necessary before drawing unwarranted conclusions about the

Conclusion

Our small study provides some modest preliminary evidence that primary induction AD may be feasible in men with intermediate-risk prostate cancer who are otherwise eligible for local therapy and in men with high-risk disease who are of advanced age or have significant comorbidities. Age and D'Amico risk category appear to be the most potent factors determining if delayed surgery or radiation therapy will be implemented. Younger men have more robust testosterone recovery and faster PSA doubling

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