Evaluation and management of the man who has failed primary curative therapy for prostate cancer.

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 (> or = 0.4 ng/mL) after radical prostatectomy is evidence of residual or recurrent prostate cancer. Men with low- or moderate-grade cancers (Gleason score < 7), with capsular penetration, or with positive surgical margins in whom disease recurs more than 2 years after radical prostatectomy with a PSA doubling time greater than 12 months seem likely to harbor a local recurrence and are the only good candidates for salvage therapy. Unless there is a palpable recurrence, transrectal ultrasound and biopsy are generally not recommended, and CT scanning and bone scintigraphy usually do not provide helpful information. The role of monoclonal antibody scanning is currently investigational. Men with high-grade tumors (Gleason score > or = 7) or with seminal vesicle or lymph node involvement in whom disease recurs within 2 years of radical prostatectomy are most appropriately observed or treated with early hormonal therapy. Men who do not achieve a PSA nadir of 0.5 ng/mL or less within 2 years of radiotherapy are very likely to harbor residual disease. For young healthy men who are willing to accept a substantial risk of impotency, urinary incontinence, and bladder neck contractures, salvage radical prostatectomy is a reasonable option if the preradiation tumor characteristics are acceptable (PSA < 10 ng/mL, Gleason score < or = 6) and if the current PSA is less than 10 ng/mL. Salvage cryotherapy may result in substantial morbidity and should only be offered on an investigational basis. Other men failing radiation may be observed or treated with hormonal therapy. There is seldom a role for repeat biopsy. Because the optimal time to begin hormone therapy is still not known, early or delayed treatment are both reasonable options. Testicular androgen ablation by orchiectomy or LHRH agonists is considered standard therapy. Combined therapy with an antiandrogen does not seem to be beneficial for all patients and should not be routinely used. Sexually active men in whom preservation of potency is important can be offered an investigational regimen such as a 5-alpha-reductase inhibitor combined with an oral antiandrogen or intermittent LHRH agonist therapy. It is hoped that the results of ongoing randomized trials and future research will establish efficient and effective practice guidelines to evaluate and treat men who have failed potentially curative therapy for localized prostate cancer. This remains a very important and controversial topic that will challenge many practicing urologists.

Effect of ejaculation on serum total and free prostate-specific antigen concentrations.

OBJECTIVES: Measurement of total serum prostate-specific antigen (PSA) is widely used as an aid to early detection of prostate cancer. Measurement of the ratio of free to total PSA may increase the specificity of PSA testing. To improve specificity further, other factors that may cause transient increases in PSA, such as ejaculation, have been identified. We prospectively studied the effect of ejaculation on total and free PSA levels and examined whether changes induced by ejaculation would affect recommendations for performing prostatic biopsy. METHODS: We measured the baseline total and free serum PSA levels and obtained measurements 1.6, and 24 hours after ejaculation in 20 volunteers (mean age 59 years). All men had baseline PSA levels less than 4.0 ng/mL. We used repeated-measures analysis of variance to test for changes in total, free, and percent free PSA after ejaculation. We also calculated the proportion of men with PSA levels greater than the expected biologic variability at each timepoint. RESULTS: The mean total, free, and percent free serum PSA increased 1 hour after ejaculation. Mean total PSA levels remained significantly increased 6 and 24 hours after ejaculation. Mean free PSA decreased to baseline levels by 6 hours after ejaculation, and percent free PSA returned to baseline by 6 hours after ejaculation and then decreased below baseline by 24 hours. When normal biologic variation was accounted for, 40% of men, at 24 hours after ejaculation, had total PSA levels above the baseline level. Similarly, 24 hours after ejaculation, the percent free PSA remained above baseline level in 10% and below baseline level in 35% of the men. CONCLUSIONS: Both total and free PSA increase immediately after ejaculation, with differing rates of return to baseline levels. PSA testing within 24 hours after ejaculation may lead to an erroneous interpretation of the results of both total and percent free PSA measurements in a small proportion of men.

Racial differences in a prostate cancer screening study.

PURPOSE: We attempted to determine whether black men have a higher prostate cancer prevalence and more advanced disease. MATERIALS AND METHODS: We screened 17,157 white and 804 black men 50 years old or older by serum prostate specific antigen measurement and digital rectal examination. We recommended biopsy when either test was suspicious. RESULTS: Black men had a higher prevalence of elevated prostate specific antigen (13.1 versus 8.9%) and cancer (5.1 versus 3.2%) than white men, and a higher prevalence of clinically but not pathologically advanced cancer. Fewer black men in lower income zip codes complied with recommendations for biopsy. CONCLUSIONS: In our screening study black men had a higher prevalence of detectable cancer. However, unlike in clinical studies there was no striking racial difference in advanced cancer stage at diagnosis.

Longitudinal screening for prostate cancer with prostate-specific antigen.

OBJECTIVE: To determine for the first 4 years of serial prostate-specific antigen (PSA)-based screening trends in compliance, prevalence of abnormal screening test results, cancer detection rates, and stage and grade of cancers detected. DESIGN: A community-based study of serial screening for prostate cancer with serum PSA measurements. SETTING: University medical center. SUBJECTS: A total of 10 248 male volunteers at least 50 years old who were screened at 6-month intervals for a minimum of 48 months. MAIN OUTCOME MEASURES: The proportion of men who returned for serial screening, the proportion with elevated PSA levels, the proportion with newly elevated PSA levels, prostate cancer detection rates, and the distribution of tumor stages and grades at diagnosis. RESULTS: At 48 months, 79% of volunteers returned for screening. During this interval there was a decrease in the proportion of volunteers with serum PSA levels higher than 4.0 ng/mL (from 10% to 6%-7%), in cancer detection rates (from 3% to <1%), and in the proportion with clinically advanced cancer (from 6% to 2%). In men who underwent surgery, the proportion with high-grade cancer decreased (from 11% to 6%), and the proportion with pathologically advanced cancer was proportionately reduced but not significantly reduced (from 33% to 27%). CONCLUSIONS: With serial PSA-based screening, the proportion of men with abnormal test results decreased, and the prostate cancer detection rate decreased to near the reported population-based incidence rate. There was also a shift to detection of cancers at an earlier clinical stage and detection of lower-grade cancers. If PSA screening is ultimately shown to be beneficial, then appropriate cost-benefit analyses will be required to determine how the shifts in cancer detection rate and cancer stage will affect the economics of serial PSA-based screening.