EVALUATION AND MANAGEMENT OF THE MAN WHO HAS FAILED PRIMARY CURATIVE THERAPY FOR PROSTATE CANCER

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The widespread use of prostate-specific antigen (PSA)–based testing has resulted in a dramatic increase in the number of men who are diagnosed with prostate cancer while it is clinically localized. Most of these men undergo potentially curative therapy such as radical prostatectomy, radiotherapy, or cryoablation. Data collected from the Surveillance, Epidemiology, and End Results program confirm that from 1983 to 1992, the proportion of men presenting with advanced disease has declined by 60% and the number of men undergoing radical prostatectomy has increased by more than 100%.65 Medicare recipients have experienced a fivefold increase in the rate of radical prostatectomy.58 As many as 30% to 50% of men undergoing radical prostatectomy and as many as 75% of men undergoing external beam radiation or cryoablation experience biochemical evidence of recurrence within 10 years.80 It has been estimated that one third of men undergoing radical prostatectomy undergo additional cancer therapy.59

The optimal strategy for the evaluation and management of patients with biochemical failure is not known. This manuscript reviews the role of PSA and imaging studies in the diagnosis and staging of recurrent disease after radical prostatectomy, radiotherapy, or cryotherapy and the role of salvage therapies for men predicted to have only local failure. Issues related to the optimal timing and form of hormonal therapy for men anticipated to harbor distant recurrent disease are also discussed.

Section snippets

Defining Disease Recurrence

Serum PSA measurement is by far the most useful and reliable test to diagnose recurrent prostate cancer after radical prostatectomy. Because serum PSA is produced almost exclusively by prostatic epithelial cells, persistently detectable (beyond the time of expectant clearance) or subsequent rising PSA levels usually indicate treatment failure. Most men with recurrent prostate cancer after surgery have detectable serum PSA levels. Conventional PSA assays such as the Hybritech Tandem-R have

Defining Treatment Failure

Measurements of PSA are now widely used as a surrogate end point to determine treatment failure and disease progression after definitive radiotherapy for clinically localized prostate cancer. Because the prostate remains in situ, failure to achieve an undetectable PSA level may not be indicative of treatment failure as it is following radical prostatectomy. Because of this fact, many different definitions have been used to define biochemical recurrence, with a resulting large variation in

Defining Treatment Failure

Failure after cryosurgical ablation has not been clearly defined. Connolly and co-workers25 described a group of 147 men who underwent primary cryoablation. At 3 months postprocedure, biopsies were performed in all of the men, and the mean PSA was 0.7 ng/mL and 1.2 ng/mL in men with negative and positive biopsies, respectively. By 12 months, the mean PSA in men with positive biopsies increased to 2.5 ng/mL, whereas the mean PSA in men with negative biopsies remained at 0.4 ng/mL. All men with

HORMONAL THERAPY IN MEN FAILING DEFINITIVE LOCAL THERAPY

The optimal timing and form of androgen ablation for men with asymptomatic local or distant recurrences following radical prostatectomy, external beam radiation, or cryoablation is a widely debated and highly controversial topic. To date, there has been no convincing evidence proving that early initiation of hormonal therapy improves long-term quality of life or survival. The majority of published studies have evaluated men with clinically advanced disease (pelvic lymph node or bony metastasis)

SUMMARY

The recurrence of prostate cancer after potentially curative local therapy is becoming a significant urologic problem. There are few prospective randomized trials, and the optimal diagnostic and treatment strategies for men who fail potentially curative therapy are not known. The experience to date seems to suggest the following as a reasonable approach.

A detectable serum PSA level (≥ 0.4 ng/mL) after radical prostatectomy is evidence of residual or recurrent prostate cancer. Men with low- or

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