Many young men with prostate-specific antigen (PSA) screen-detected prostate cancers may be candidates for active surveillance.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Little is known as to the potential for over-treatment of young men diagnosed with prostate cancer. We show that for men aged ≤55 years with PSA screen-detected disease, 45% of the tumours are classified as very low risk and 85% of these have favourable pathology, yet most are actively treated. These findings raise the spectre of over-treatment for a group of men likely to be affected by treatment side-effects. OBJECTIVE: To identify a population of young men (aged <55 years at diagnosis) with very-low-risk prostate cancer (stage cT1c, with prostate-specific antigen [PSA] density of <0.15 ng/mL/g, Gleason score ≤6, and ≤2 positive biopsy cores with <50% tumour involvement) that may be candidates for active surveillance (AS). PATIENTS AND METHODS: We queried a Department of Defense tumour registry and hard-copy records for servicemen diagnosed with prostate cancer from 1987 to 2010. Statistical analyses were undertaken using Fisher's exact and chi-square testing. RESULTS: From 1987-1991 and 2007-2010, PSA screen-detected tumours diagnosed in men aged ≤55 years rose >30-fold. Data for a subset of men (174) with PSA screen-detected cancer were evaluable for disease risk assessment. Of the 174 men with screen-detected disease, 81 (47%) had very-low-risk disease. Of that group, 96% (78/81) selected treatment and, of 57 men undergoing radical prostatectomy (RP), the tumours of 49 (86%) carried favourable pathology (organ confined, <10% gland involvement, Gleason ≤6). CONCLUSIONS: Nearly half of young men with PSA screen-detected prostate cancer are AS candidates but the overwhelming majority seek treatment. Considering that many tumours show favourable pathology at RP, there is a possibility that these patients may benefit from AS management.

Increasing low risk prostate cancer incidence in United States Air Force servicemen and selection of treatments.

PURPOSE: Periodic Health Assessments have been mandated for United States Air Force servicemen since the mid 1990s. Thus, we determined whether United States Air Force prostate cancer incidence rates increased thereafter and how these tumors segregate into low and intermediate/high risk categories. We also identified treatment choices. MATERIALS AND METHODS: We queried the Department of Defense Automated Central Tumor Registry for prostate cancer diagnosed in United States Air Force servicemen between 1991 and 2008 to determine incidence rates, disease risk category and treatments. RESULTS: Age adjusted rates in white active duty servicemen diagnosed for the most recent period of 2005 to 2008 increased 3-fold relative to the rate in the earliest period of 1991 to 1994. A similar trend was evident in black servicemen. Relative to the Surveillance, Epidemiology and End Results population prostate cancer rates in active duty United States Air Force men between 1995 and 2008 were significantly increased for the 2 racial groups. A significantly greater proportion of active duty servicemen than retirees (62% vs 40%) presented with low risk disease, defined as prostate specific antigen less than 10 ng/ml, Gleason sum less than 7 and clinical stage T1a-T2a. Of those with low risk disease significantly more active duty servicemen elected curative surgery than retirees (93% vs 53%). CONCLUSIONS: Prostate cancer incidence rates in United States Air Force servicemen have increased with time, exceeding rates in the Surveillance, Epidemiology and End Results population. While most cases are characterized as low risk, aggressive management is elected.

Semaphorin 3B and 3F single nucleotide polymorphisms are associated with prostate cancer risk and poor prognosis.

PURPOSE: SEMA3B and SEMA3F are 2 closely related genes lying 80 kb apart on chromosome 3 that have been shown to suppress tumor formation in vivo and in vitro. Each gene has a single nucleotide polymorphism that results in a nonsynonymous coding change, rs2071203 (SEMA3B) and rs1046956 (SEMA3F), as well as noncoding single nucleotide polymorphisms. MATERIALS AND METHODS: We performed a case-control study of 789 prostate cancer cases and 907 controls from 3 races/ethnicities to determine possible associations of 10 variants with prostate cancer risk or prognosis. RESULTS: The risk of prostate cancer increased more than 2-fold in Hispanic men with TT alleles at rs2071203 in SEMA3B and with CC alleles for rs2072054 at the 5' end of SEMA3F (OR 2.13, 95% CI 1.12-4.04, p = 0.02 and OR 2.55, 95% CI 1.34-4.84, p = 0.0045, respectively). These 2 single nucleotide polymorphisms were also associated with a poor prognosis in Hispanic men (2.71 and 3.48-fold increased risk). A frequent G-C-G-G-A-T-C-C-T-G haplotype encompassing 10 SNPs was associated with an increased risk of prostate cancer and poor prognosis in Hispanic samples (OR 2.72, 95% CI 1.20-6.12, p = 0.016 and OR 3.32, 95% CI 1.21-9.10, p = 0.02). In nonHispanic white men the T-C-G-A-A-T-C-C haplotype was associated with a high Gleason score (OR 1.44, 95% CI 1.06-1.96, p = 0.021). CONCLUSIONS: These data indicate that polymorphisms in SEMA3B and SEMA3F are associated with prostate cancer risk and poor prognosis in Hispanic and nonHispanic white men.

Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial.

PURPOSE: Extraprostatic disease will be manifest in a third of men after radical prostatectomy. We present the long-term followup of a randomized clinical trial of radiotherapy to reduce the risk of subsequent metastatic disease and death. MATERIALS AND METHODS: A total of 431 men with pT3N0M0 prostate cancer were randomized to 60 to 64 Gy adjuvant radiotherapy or observation. The primary study end point was metastasis-free survival. RESULTS: Of 425 eligible men 211 were randomized to observation and 214 to adjuvant radiation. Of those men under observation 70 ultimately received radiotherapy. Metastasis-free survival was significantly greater with radiotherapy (93 of 214 events on the radiotherapy arm vs 114 of 211 events on observation; HR 0.71; 95% CI 0.54, 0.94; p = 0.016). Survival improved significantly with adjuvant radiation (88 deaths of 214 on the radiotherapy arm vs 110 deaths of 211 on observation; HR 0.72; 95% CI 0.55, 0.96; p = 0.023). CONCLUSIONS: Adjuvant radiotherapy after radical prostatectomy for a man with pT3N0M0 prostate cancer significantly reduces the risk of metastasis and increases survival.

Association of polymorphisms in TGFB1 and prostate cancer prognosis.

PURPOSE: Because of the role of TGFB1 in prostate cancer and progression, we hypothesized that polymorphisms of TGFB1 at C-509T may be associated with prostate cancer risk and/or more aggressive tumors. MATERIALS AND METHODS: This is a case-control study. Controls consisted of male volunteers 40 years old or older with a normal digital rectal examination and prostate specific antigen 2.5 ng/ml or less. Cases consisted of men with biopsy proven prostate cancer. High grade prostate cancer included all cancers of Gleason sum 7 or greater. Poor prognosis in cases was defined as any stage with Gleason sum 8-10, pT3A (if Gleason sum was greater than 7), pT3B or higher (all Gleason sums), any N1 or higher, any M1 or higher, or any documented PSA recurrence (biochemical failure). Single nucleotide polymorphisms were genotyped using allelic discrimination assays. Logistic regression models were used to estimate the OR with the corresponding 95% CI for individual racial/ethnic groups. Allelic frequency across ethnic/racial groups was compared using Pearson's chi-square test. RESULTS: A total of 653 cases and 1,476 controls were genotyped at C-509T. The TT genotype showed a significant protective effect against high grade prostate cancer (OR 0.482, 95% CI 0.274-0.849). In addition, the TT genotype was associated with a decreased risk of poor prognosis prostate cancer (OR 0.488, 95% CI 0.236-1.009). Limiting analysis to nonHispanic white men showed that the TT genotype had an even more pronounced protective effect for poor prognosis prostate cancer (OR 0.297, 95% CI 0.100-0.887). Finally, there was a significant difference in the distribution of allelic frequency across racial/ethnic groups (p <0.0001). CONCLUSIONS: We observed an association between single nucleotide polymorphisms of TGFB1 at C-509T and a decreased risk of aggressive prostate cancer. The TT genotype of TGFB1 at C-509T demonstrates a protective effect against high grade prostate cancer and cases with poor prognosis.

The prognostic impact of seminal vesicle involvement found at prostatectomy and the effects of adjuvant radiation: data from Southwest Oncology Group 8794.

PURPOSE: From the randomized study Southwest Oncology Group 8794 we evaluated the effect of seminal vesicle involvement on outcomes and whether those patients benefited from post-prostatectomy adjuvant radiation therapy. MATERIALS AND METHODS: Southwest Oncology Group study 8794 randomized high risk patients (with seminal vesicle positive disease and/or capsular penetration and/or positive margins) to radiation vs observation after prostatectomy. A total of 431 subjects with pathologically advanced prostate cancer were randomized. RESULTS: Median followup was 12.2 years. Of the patients 139 had seminal vesicle involvement with or without capsular penetration and/or positive margins. Compared to the 286 patients with seminal vesicle negative disease there was poorer 10-year biochemical failure-free survival (33% for seminal vesicle negative and 22% for seminal vesicle positive, p = 0.04), metastasis-free survival (70% and 56%, respectively, p = 0.005) and overall survival (10-year overall survival 74% and 61%, respectively, p = 0.02) for those with seminal vesicle positive disease. Patients with seminal vesicle positive disease who received adjuvant radiation compared to observation realized an improvement in 10-year biochemical failure-free survival from 12% to 36% (p = 0.001), in 10-year overall survival from 51% to 71% (p = 0.08) and in metastasis-free survival from 47% to 66% (p = 0.09), respectively. CONCLUSIONS: Although seminal vesicle involvement is a negative prognostic factor, long-term control is possible especially if patients are given adjuvant radiation therapy. This therapy appears to be effective in patients with seminal vesicle involvement.

Testosterone replacement therapy and prostate cancer: a word of caution.

The number of men for whom testosterone is prescribed is rapidly increasing. The aging man normally demonstrates a gradual decline in testosterone. Symptoms of hypogonadism include erectile dysfunction, diminished libido, sarcopenia, increased adiposity, osteopenia and osteoporosis, impaired cognition, and depression. There is a paucity of data regarding both efficacy and safety of testosterone replacement therapy. Testosterone levels have been shown to modulate prostate cancer risk and progression. A prospective evaluation of prostate cancer risk with testosterone replacement therapy has not been conducted. We outline concerns and recommendations for the use of testosterone replacement therapy in the aging man.

Chemoprevention of prostate cancer.

Prostate cancer is a common malignancy with multiple potential opportunities for cancer prevention. As the genetic basis of this malignancy is further understood, prevention strategies will be developed for individual patients based on specific risk factors and pathways of carcinogenesis. The PCPT has conclusively proven that prostate cancer prevention is possible. The results of the SELECT should be available within several years. An enormous challenge for the medical community will be the development of an efficient strategy to evaluate the substantial number of dietary, behavioral, and pharmacologic prevention opportunities. Ultimately, the goal of prostate can-cer prevention is to (1) identify men who are destined to develop clinically significant prostate cancer, and (2) provide individualized agents to prevent disease development.

Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial.

CONTEXT: Despite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer, pathologically advanced disease is detected at radical prostatectomy in 38% to 52% of patients. However, the optimal management of these patients after radical prostatectomy is unknown. OBJECTIVE: To determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 N0 M0 prostate cancer. DESIGN, SETTING, AND PATIENTS: Randomized, prospective, multi-institutional, US clinical trial with enrollment between August 15, 1988, and January 1, 1997 (with database frozen for statistical analysis on September 21, 2005). Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy. INTERVENTION: Men were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211). MAIN OUTCOME MEASURES: Primary outcome was metastasis-free survival, defined as time to first occurrence of metastatic disease or death due to any cause. Secondary outcomes included prostate-specific antigen (PSA) relapse, recurrence-free survival, overall survival, freedom from hormonal therapy, and postoperative complications. RESULTS: Among the 425 men, median follow-up was 10.6 years (interquartile range, 9.2-12.7 years). For metastasis-free survival, 76 (35.5%) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died (median metastasis-free estimate, 14.7 years), compared with 91 (43.1%) of 211 (median metastasis-free estimate, 13.2 years) of those in the observation group (hazard ratio [HR], 0.75; 95% CI, 0.55-1.02; P = .06). There were no significant between-group differences for overall survival (71 deaths, median survival of 14.7 years for radiotherapy vs 83 deaths, median survival of 13.8 years for observation; HR, 0.80; 95% CI, 0.58-1.09; P = .16). PSA relapse (median PSA relapse-free survival, 10.3 years for radiotherapy vs 3.1 years for observation; HR, 0.43; 95% CI, 0.31-0.58; P<.001) and disease recurrence (median recurrence-free survival, 13.8 years for radiotherapy vs 9.9 years for observation; HR, 0.62; 95% CI, 0.46-0.82; P = .001) were both significantly reduced with radiotherapy. Adverse effects were more common with radiotherapy vs observation (23.8% vs 11.9%), including rectal complications (3.3% vs 0%), urethral strictures (17.8% vs 9.5%), and total urinary incontinence (6.5% vs 2.8%). CONCLUSIONS: In men who had undergone radical prostatectomy for pathologically advanced prostate cancer, adjuvant radiotherapy resulted in significantly reduced risk of PSA relapse and disease recurrence, although the improvements in metastasis-free survival and overall survival were not statistically significant. Trial Registration clinicaltrials.gov Identifier: NCT00394511.

Screening for prostate cancer: opportunities and challenges.

Prostate cancer screening with PSA and with digital rectal examination isa reality in the United States. Regardless of recent observations regarding the complexities of PSA interpretation, millions of U.S. men expect an annual PSA test and physicians have come to rely on the test, in combination with digital rectal examination, to assess for prostate cancer risk. What has become evident is that PSA can no longer be interpreted dichotomously as a simple yes or no. The test reflects a range of risk and PSA value must be merged with other risk factors of an individual man including ethnicity, family history, as well as the individual's risk aversion to complications from prostate cancer. The future of prostate cancer screening will be built upon incorporation of new biomarkers to the prediction of risk of disease. As these markers move forward in testing, it will no longer be acceptable to move these into clinical usage without formal validation studies and, because of the high frequency of prostate cancer in the general male population, these validation studies will almost certainly have to include measures of prognosis. It is the holy grail of cancer biomarker development to acquire a test that is positive in the man with clinically-aggressive prostate cancer but is negative in both the patient without disease and in the man with disease that will be of no clinical consequence over his lifetime.

Ten-year follow-up of neoadjuvant therapy with goserelin acetate and flutamide before radical prostatectomy for clinical T3 and T4 prostate cancer: update on Southwest Oncology Group Study 9109.

OBJECTIVE: To update the results with 10-year data of a phase II prospective trial of neoadjuvant hormonal therapy with goserelin acetate and flutamide followed by radical prostatectomy for locally advanced prostate cancer (SWOG 9109). The optimal management for clinical stage T3 and T4 N0,M0 prostate cancer is uncertain. MATERIALS AND METHODS: Sixty-two patients with clinical stage T3 and T4 N0,M0 prostate cancer were enrolled. Cases were classified by stage T3 vs T4 and by volume of disease (bulky >4 cm and nonbulky ≤ 4 cm). RESULTS: Fifty-five of 61 eligible patients completed the trial with radical prostatectomy after neoadjuvant androgen deprivation therapy (ADT). The median preoperative prostate-specific antigen value was 19.8 ng/mL, and 67% of patients had a Gleason score of ≥ 7. Among 41 patients last known to be alive, median follow-up is 10.6 years (range 5.1-12.6). In all, 38 patients have had disease progression (30/55, 55%) or died without progression (8/55, 15%) for a 10-year progression-free survival (PFS) estimate of 40% (95% CI 27-53). Median PFS was 7.5 years, and median survival has not been reached. The 10-year overall survival (OS) estimate is 68% (95% CI 56-80). CONCLUSIONS: In this small, prospective phase II study, neoadjuvant hormonal therapy with goserelin acetate and flutamide followed by radical prostatectomy achieves long-term PFS and OS comparable with alternative treatments. This approach is feasible and may be an alternative to a strategy of combined radiation and ADT.

Health-related quality of life results in pathologic stage C prostate cancer from a Southwest Oncology Group trial comparing radical prostatectomy alone with radical prostatectomy plus radiation therapy.

PURPOSE: To compare short- and long-term effects of adjuvant treatment versus observation after surgery on health-related quality of life (HRQL) of prostate cancer patients. PATIENTS AND METHODS: The Southwest Oncology Group (SWOG) intergroup trial compared radical prostatectomy (RP) plus observation versus RP plus adjuvant radiation therapy (RT). Two-hundred seventeen of 425 therapeutic trial patients were eligible and registered to the HRQL study. Patients completed the SWOG Quality of Life Questionnaire (emotional, physical, social, and role function; general symptom status; treatment/disease-specific symptoms; and global HRQL [GHRQL]) at baseline, 6 weeks, 6 months, and annually for 5 years. Prespecified outcomes were three genitourinary symptoms (bowel function tenderness, frequent urination, and erectile dysfunction [ED]) and measures of physical and emotional function. Adjustments were made for the baseline score. RESULTS: Patients receiving adjuvant RT reported worse bowel function (through approximately 2 years) and worse urinary function. There were no statistically significant differences for ED. GHRQL was initially worse for the RP+RT arm but improved over time and was better at the end of the period than the GHRQL reported for RP alone (treatment arm x time interaction, P = .0004). Symptom distress was significantly worse for the RP+RT arm compared with the RP alone arm, but the treatment arms did not differ with respect to other general measures of HRQL. CONCLUSION: The addition of RT to surgery resulted in more frequent urination, as well as early report of more bowel dysfunction, although bowel function differences disappeared over the 5-year period. The addition of RT did not negatively impact ED.

Looking back at PCPT: looking forward to new paradigms in prostate cancer screening and prevention.

OBJECTIVES: Provide a critical summary of the latest interpretation of findings from the Prostate Cancer Prevention Trial (PCPT). METHODS: Findings from PCPT and recently published post-hoc analyses are reviewed. RESULTS: PCPT demonstrated that finasteride can reduce the prevalence of prostate cancer, permitted the first large-scale assessment of the performance characteristics of prostate-specific antigen for prostate cancer screening, and identified new-onset erectile dysfunction as an early predictor of cardiovascular events. CONCLUSIONS: PCPT has and will continue to yield valuable information regarding future strategies for prostate cancer prevention and detection, benign prostatic hyperplasia, and other matters of public health importance.

Prostate cancer risk with positive family history, normal prostate examination findings, and PSA less than 4.0 ng/mL.

OBJECTIVES: Family history has been identified as a risk factor for prostate cancer. We assessed the risk of prostate cancer in men with a positive family history (at least one first-degree or second-degree relative), normal digital rectal examination (DRE) and a serum prostate-specific antigen (PSA) level of 4.0 ng/mL. METHODS: A total of 87 volunteers from the San Antonio Center of biomarkers of risk for prostate cancer study enrolled in a prospective study to assess the prevalence of prostate cancer in men with a family history of prostate cancer, normal DRE findings, and a serum PSA level of 4.0 ng/mL or less. All subjects underwent transrectal ultrasound-guided prostate biopsy. RESULTS: Prostate cancer was diagnosed in 22 (25.3%) of the 87 participants. The PSA values were significantly greater statistically in the men with prostate cancer (median 2.1 ng/mL) than in the men without prostate cancer (median 1.2 ng/mL, P = 0.01), and the odds of prostate cancer nearly doubled for a doubling of the PSA level within this interval (odds ratio 1.97, P = 0.02). No statistically significant difference was found in age, race, or number and type of affected relatives in men with and without prostate cancer. CONCLUSIONS: The results of our study have demonstrated a high frequency of prostate cancer in men with a positive family history but normal DRE findings and a PSA level of 4.0 ng/mL or less. These prospectively collected data raise an important consideration regarding lowering the PSA cutoff values for offering biopsy in patients with a positive family history and normal DRE findings.

Predominant treatment failure in postprostatectomy patients is local: analysis of patterns of treatment failure in SWOG 8794.

PURPOSE: Southwest Oncology Group (SWOG) trial 8794 demonstrated that adjuvant radiation reduces the risk of biochemical (prostate-specific antigen [PSA]) treatment failure by 50% over radical prostatectomy alone. In this analysis, we stratified patients as to their preradiation PSA levels and correlated it with outcomes such as PSA treatment failure, local recurrence, and distant failure, to serve as guidelines for future research. PATIENTS AND METHODS: Four hundred thirty-one subjects with pathologically advanced prostate cancer (extraprostatic extension, positive surgical margins, or seminal vesicle invasion) were randomly assigned to adjuvant radiotherapy or observation. RESULTS: Three hundred seventy-four eligible patients had immediate postprostatectomy and follow-up PSA data. Median follow-up was 10.2 years. For patients with a postsurgical PSA of 0.2 ng/mL, radiation was associated with reductions in the 10-year risk of biochemical treatment failure (72% to 42%), local failures (20% to 7%), and distant failures (12% to 4%). For patients with a postsurgical PSA between higher than 0.2 and

Erectile function outcome reporting after clinically localized prostate cancer treatment.

PURPOSE: In conjunction with the assignment to update the Guidelines for Management of Clinically Localized Prostate Cancer, the American Urological Association Prostate Cancer Guideline Update Panel performed a side analysis of the reporting of erectile function outcomes in this clinical context as published in the medical literature. MATERIALS AND METHODS: Four National Library of Medicine PubMed(R) Services literature searches targeting articles published from 1991 through early 2004 were done to derive outcome reporting (efficacy or side effects) for the treatment of clinical stage T1 or T2 N0M0 prostate cancer. A database was constructed containing descriptions relating to erectile function as well as numerical frequency rates of complete erectile dysfunction, and partial and intact erectile function for various treatments. A literature review was also done, consisting of a PubMed Services search of current measures and protocols used for assessing erectile function outcomes and a survey of consensus opinion sources on the management of male sexual dysfunctions. RESULTS: Based on inclusion criteria 436 articles were selected. Of these articles database extraction from 100 pertaining to radical prostatectomy garnered various characterizations of erectile function, including qualitative descriptions, generic terminology and rating systems. Database extraction from 31 articles, in which results for at least 50 patients were reported, yielded ranges of rates for complete erectile dysfunction, partial erectile function and intact erectile function that were 26% to 100%, 16% to 48% and 9% to 86% for radical prostatectomy, 8% to 85%, 21% to 47% and 36% to 63% for external beam radiation, and 14% to 61%, 21% and 18% for interstitial radiation, respectively. The literature review showed an evolution in standards for studying and reporting erectile function outcomes. CONCLUSIONS: Clinical studies reporting erectile function outcomes after localized prostate cancer treatment often demonstrate poorly interpretable and inconsistent manners of assessment as well as widely disparate rates of erectile dysfunction and erectile function. Future studies must apply scientifically rigorous methodology and standard outcomes measures to advance this field of study.

Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes.

PURPOSE: The American Urological Association Prostate Guideline Update Panel was charged with updating the Guidelines for Clinically Localized Prostate Cancer. In assessing outcomes with treatment, it became apparent that a highly variable number of definitions exist with respect to biochemical recurrence. Herein, we review the variability in published definitions of biochemical recurrence and make recommendations directed toward improving this terminology by recommending a standard definition in patients treated with radical prostatectomy. MATERIALS AND METHODS: Four PubMed literature searches were performed between May 2001 and April, 2004 and covered articles published from 1991 through early 2004. The search terms included the MeSH major headings of prostate cancer and prostatic neoplasm. All potentially relevant articles were retrieved and a more detailed screen for relevance was performed. An article was considered relevant if it reported treatment outcomes of patients with clinical T1 or T2N0M0 prostate cancer. Data extractors recorded the definition of biochemical recurrence and definitions were then collapsed into categories representing the same criteria. The results of biochemical failure were subcategorized by initial treatment. RESULTS: Of 13,800 citations, a total of 436 articles were selected. Among these, a total of 145 articles contained 53 different definitions of biochemical recurrence for those treated with radical prostatectomy. Of these, the most common definition (35) was a prostate specific antigen of >0.2 ng/mL or a slight variation thereof. In addition, a total of 208 articles reported 99 different definitions of biochemical failure among those treated with radiation therapy. Of these, the American Society for Therapeutic Radiology and Oncology definition (70) and/or a variation thereof was the most commonly reported. In total, 166 different definitions of biochemical failure were identified. Following radical prostatectomy, the Panel recommends defining biochemical recurrence as an initial serum prostate specific antigen of > or =0.2 ng/mL, with a second confirmatory level of prostate specific antigen of >0.2 ng/mL. The Panel recommends the use of the American Society for Therapeutic Radiology and Oncology criteria for patients treated with radiation therapy and acknowledges that these criteria will soon be updated although not yet published. CONCLUSIONS: A high degree of variability in the definition of biochemical recurrence exists following treatment for localized prostate cancer. Strict definitions for biochemical recurrence are necessary to identify men at risk for disease progression and to allow meaningful comparisons among patients treated similarly. The Panel acknowledges the American Society for Therapeutic Radiology and Oncology criteria and future modifications thereof for those receiving radiation therapy and recommends the newly developed American Urological Association criteria for those treated with radical prostatectomy. The purpose for the establishment of this standard is for data reporting purposes and for comparison of similarly treated patients. It is not intended to represent a threshold value for which to initiate treatment. The Panel acknowledges that the clinical decision to initiate treatment will be dependent on multiple factors including patient and physician interaction rather than a specific prostate specific antigen threshold value.

Prostate cancer detection strategies.

Prostate cancer is the most common malignancy in men and, as a result, there has been a nationwide emphasis on screening and detection. With the widespread use of the prostate-specific antigen (PSA), prostate cancer screening effectively detects localized prostate cancer. However, recent reports have identified a significant proportion of prostate cancer in men with low PSA levels. Many of these cancers are higher-grade malignancies. Consequently, PSA may function more effectively as a screening tool when applied over a continuum that is associated with degree of risk, rather than a binary measure. Other markers are currently being investigated. Ideally, a marker will identify the malignancy that is a clinical threat, thereby avoiding intervention for indolent disease. Prevention strategies may be employed for higher-risk patients, and these strategies eventually may be tailored to genetic or other risks.

Chemoprevention of prostate cancer with finasteride.

Prostate cancer is a significant cause of disease and death, making it an attractive target for chemoprevention. The association between lifetime exposure to dihydrotestosterone and risk of developing prostate cancer suggests that chemoprevention is possible with 5alpha-reductase inhibition. The recently completed Prostate Cancer Prevention Trial indicates that chemoprevention is possible with the 5alpha-reductase inhibitor finasteride. Development of a cost-effective chemoprevention strategy for prostate cancer is evolving, and is expected to have significant positive economic and public health benefits.

External validation of the Prostate Cancer Prevention Trial risk calculator in a screened population.

OBJECTIVES: To evaluate the recently developed Prostate Cancer Prevention Trial (PCPT) prostate cancer risk calculator in the San Antonio Center of Biomarkers of Risk for Prostate Cancer (SABOR) cohort of the Early Detection Research Network, a younger and more ethnically diverse population than that in the PCPT. METHODS: From 3488 SABOR participants, we identified 446 who had undergone prostate biopsy and had undergone prostate-specific antigen measurement and digital rectal examination before biopsy. Most biopsies were performed for abnormal digital rectal examination findings, a prostate-specific antigen level of more than 2.5 ng/mL, or elevated risk because of a first-degree relative with prostate cancer. We evaluated the operating characteristics of the PCPT calculator for detecting prostate cancer in this cohort of SABOR participants. Of the 446 men in this cohort, 24% were younger than 55 years of age. RESULTS: Of the 446 men who had undergone biopsy, 148 (33.2%) had prostate cancer. The observed SABOR prostate cancer rates increased with increasing PCPT risk: 15.7%, 39.0%, 48.8%, and 100.0% for a PCPT risk calculator value of less than 25%, 25% to 50%, 50% to 75%, and greater than 75%, respectively. The PCPT risk calculator had an area under the receiver operating characteristic curve of 65.5% (95% confidence interval 60.2% to 70.8%, P < 0.0001), was greater in African-American men (area under curve of 80.0%, 95% confidence interval 67.8% to 92.2%) than in other races (P = 0.02), and was not different in Hispanic men (P > 0.05). CONCLUSIONS: The results of our study have shown that the PCPT risk calculator, available from the Internet and incorporating the current best panel of risk factors, is valid in other, more diverse, populations.