Prostatic Neoplasms: Hernandez J

Thompson I, Thrasher JB, Aus G, Burnett AL, Canby-Hagino ED, Cookson MS, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus SR, Moul JW, Tangen CM, Anonymous00324. · American Urological Association Education and Research, Inc. · J Urol. · Pubmed #17509297 No free full text.

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Hernandez J, Thompson IM. · No affiliation provided · Cancer. · Pubmed #15742337 links to  free full text

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Hudak SJ, Hernandez J, Thompson IM. · Urology Service, Department of Surgery, Brooke Army Medical Center, Fort Sam Houston,TX 78234-6200, USA. · Clin Interv Aging. · Pubmed #18046919 links to  free full text

Abstract: Prostate cancer is one of the most complex and enigmatic oncologic problems in medicine. It is highly prevalent, particularly in elderly males. Unfortunately, its generally protracted and variable clinical course and high association with treatment-related morbidity raise serious questions about the ideal treatment strategy for the individual patient. 5 alpha-reductase (5AR) inhibitors have a dramatic effect on benign prostatic disease with low toxicity. Thus, there is much interest in the potential role of 5AR inhibitors in the prevention and treatment of prostate cancer. Finasteride is the only agent that has been shown in a randomized clinical trial to decrease the risk of prostate cancer with a reduction of almost 25%. Additionally, a recent analysis of the Prostate Cancer Prevention Trial (PCPT) has found that finasteride improves the performance characteristics of prostate-specific antigen (PSA) blood test as a screening tool for prostate cancer, for both cancer detection as well as for detection of high risk disease. Finally, 5AR inhibitors have been studied as a component of multimodal therapy for all stages of prostate cancer, with the goal of improving oncologic outcomes while avoiding the toxicity of medical and surgical castration.

Burnett AL, Aus G, Canby-Hagino ED, Cookson MS, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus S, Liebert M, Moul JW, Tangen C, Thrasher JB, Thompson I, Anonymous00008. · The Johns Hopkins Hospital, 600 North Wolfe St., Marburg 407, Baltimore, Maryland 21287-2411, USA. · J Urol. · Pubmed #17570435 No free full text.

Abstract: 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.

Lacy GL, Soderdahl DW, Hernandez J. · Urology Service, Department of Surgery, Brooke Army Medical Center, 3851 Roger Brooke Drive, Fort Sam Houston, TX 78234-6200, USA. · Curr Urol Rep. · Pubmed #17459267 No free full text.

Abstract: A new diagnosis of prostate cancer presents to both the patient and physician questions regarding the best approach for further assessing the extent of disease prior to selecting a treatment strategy. In addition to the initial clinical data such as serum prostate-specific antigen level, findings on digital rectal examination, and core biopsy Gleason score, several procedures and imaging modalities are available to further stage newly diagnosed prostate cancer. A substantial percentage of the cost of managing prostate cancer is directly related to staging evaluations. Often, staging evaluations are performed that have limited test performance characteristics, subject the patient to unnecessary morbidity, or simply do not provide additional useful clinical information. It is important that the physician be familiar with the indications for the available staging modalities as well as the test performance characteristics in order to proceed appropriately and in an economically judicious fashion. This paper reviews the literature on this topic and summarizes previous experiences with procedures and imaging modalities for staging newly diagnosed prostate cancer.

Cookson MS, Aus G, Burnett AL, Canby-Hagino ED, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus SR, Moul JW, Tangen C, Thrasher JB, Thompson I. · Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA. · J Urol. · Pubmed #17222629 No free full text.

Abstract: 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.

Canby-Hagino E, Hernandez J, Brand TC, Thompson I. · Department of Urology, University of Texas Health Science Center at San Antonio, TX 78229, USA. · Eur Urol. · Pubmed #17030406 No free full text.

Abstract: 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.

Canby-Hagino ED, Brand TC, Hernandez J, Thompson IM. · Department of Urology, University of Texas Health Science Center, San Antonio, TX 78229, USA. · Expert Opin Pharmacother. · Pubmed #16634712 No free full text.

Abstract: 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.

Brand TC, Hernandez J, Canby-Hagino ED, Basler JW, Thompson IM. · Department of Urology, University of Texas Health Science Center, Mail Code 7845, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. · Curr Urol Rep. · Pubmed #16630521 No free full text.

Abstract: 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.

Canby-Hagino ED, Swanson GP, Crawford ED, Basler JW, Hernandez J, Thompson IM. · Department of Urology, University of Texas Health Sciences Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. · Curr Urol Rep. · Pubmed #15869722 No free full text.

Abstract: Data from well-designed, prospective clinical trials are lacking to support treatment of primary tumor in men diagnosed with metastatic prostate cancer. However, a growing body of evidence suggests that treatment of the primary tumor may enhance cancer control and survival in some men. This evidence is examined and recommendations are made for identifying patients with metastatic prostate cancer who may benefit from definitive treatment of the prostate tumor.

Mahal K, Hernandez J, Basler JW, Thompson IM. · Division of Urology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. · Curr Urol Rep. · Pubmed #15869721 No free full text.

Abstract: Chemoprevention trials for several malignancies are completed, planned, or underway. Prostate cancer is one of the most common forms of cancer and understandably has received considerable recent attention as a potential target for chemoprevention. This article examines chemoprevention trials for prostate cancer, including the Prostate Cancer Prevention Trial, Selenium and Vitamin E Cancer Prevention Trial, and cyclooxygenase inhibitors in the prevention of prostate cancer.

Hernandez J, Canby-Hagino E, Thompson IM. · Department of Urology, University of Texas Health Sciences Center, A7703, Floyd Curl Drive, San Antonio, TX 78229, USA. · Curr Urol Rep. · Pubmed #15869720 No free full text.

Abstract: Recent studies have cast doubt on the reliability of serum total prostate-specific antigen as a biomarker for the detection and prognosis of prostate cancer. Biomarkers that can identify those men at risk for clinically significant prostate cancer are desperately needed. The search for biomarkers that may improve the detection of biologically consequential prostate cancer is one of the most active areas under current investigation. In this review, we highlight some of these ongoing efforts. Proper validation of newly discovered biomarkers is of paramount importance.

Williams MB, Hernandez J, Thompson I. · Eastern Virginia Medical School (MBW), Norfolk, USA. · J Urol. · Pubmed #15758703 No free full text.

Abstract: PURPOSE: Since the discovery of Huggins in 1941 demonstrating the androgen dependence of prostate cancer cells, the use of pharmacological therapies to decrease systemic androgen concentrations has been one of the main treatment options for prostate cancer. Despite their efficacy luteinizing hormone releasing hormone agonists (LHRHas) have a number of side effects, of which many have not been fully investigated in humans. This review focuses on the effects of LHRHas on skeletal muscle in 3 main areas, namely effects at the androgen receptor, at the neuromuscular junction and on skeletal muscle myofibers. Since prostate cancer is predominantly a disease of elderly individuals, the aging effects of LHRHa therapy on skeletal muscle are magnified and of clinical importance. MATERIALS AND METHODS: A comprehensive MEDLINE search was performed of pertinent studies in the literature relating to the use of LHRHa and skeletal muscle. RESULTS: LHRHas affect 3 primary sites within the skeletal muscle system, namely androgen receptor, the neuromuscular junction and second messenger systems, including insulin-like growth factor-1. All sites have been demonstrated to lead to a decrease in isokinetic exercise strength in large muscle groups. CONCLUSIONS: The musculoskeletal effects of LHRHas for the treatment of prostate cancer should be counteracted via a program of exercise strength training to decrease the morbidity associated with skeletal muscle weakness.

Soderdahl DW, Hernandez J. · Urology Service, Dwight David Eisenhower Army Medical Center, Fort Gordon, Georgia 30905-5650, USA. · Prostate Cancer Prostatic Dis. · Pubmed #15195128 links to  free full text

Abstract: INTRODUCTION AND OBJECTIVES: Dwight D. Eisenhower Army Medical Center has been involved in Prostate Cancer Awareness Week (PCAW) screening during the period 1995-2000. The purpose of this study is to review the results of screening in a self-selected population of military beneficiaries at our institution. MATERIALS AND METHODS: Screening involving a brief urologic history, digital rectal examination (DRE) and serum prostatic specific antigen (PSA) measurement was offered to our screening population. Patients with an elevated PSA (>4.0 ng/ml) and/or a suspicious DRE were considered for transrectal ultrasonography with prostate needle biopsy (TRUS/PNB). Patient health records were reviewed retrospectively and analyzed to determine patient demographic characteristics, PSA distribution, DRE results and cancer detection rates. RESULTS: A total of 455 screening visits were performed from 1995 to 2000, of which 426 visits were included for analysis. Mean age of the study population was 57.4 y (40-83). Seventy-one percent of the patients reported prior PSA screening visits. Forty-four patients met indications for biopsy. A total of 30 TRUS/PNB were performed demonstrating presence of cancer in three patients for an overall cancer detection rate of 0.7%. CONCLUSIONS: Our study shows that the overall prostate cancer detection rate at our institution is lower than detection rates previously reported in the literature. Potential reasons for this finding may include that the subjects participating in PCAW screening tended to be younger than in other series and that a majority of them had already undergone prior screening. These findings suggest the need to modify prostate cancer screening recommendations and to improve prostate cancer screening efficacy.

Hernandez J, Basler JW, Thompson IM. · Division of Urology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. · Urol Clin North Am. · Pubmed #15123401 No free full text.

Abstract: Prevention of urologic cancer is a new field for urology. It focuses attention on men and women who may not be under the regular care of physicians and are without symptoms of disease. Although risk factors (eg, smoking in bladder cancer, family history or African-American ethnicity in prostate cancer, cryptorchid testes in testis cancer, Von Hippel-Lindau disease in renal cell carcinoma) can identify individuals at a greater risk for genitourinary malignancies, most patients have no risk factors except gender and age. Thus, developing public health recommendations that will have a major impact on these diseases will be challenging. Prevention strategies will be held to a higher standard of safety than traditional cancer treatment unless populations at a high risk for disease can be identified. It will be necessary for urologists to monitor the field of disease prevention because of the high frequency of urologic malignancies and the growing elderly population in the United States. Urologists are frequently providers for and confidants of this patient population and must be able to counsel these men and women about the benefits and risks of such prevention strategies.

Mahal K, Hernandez J, Basler JW, Thompson IM. · Division of Urology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. · Curr Oncol Rep. · Pubmed #15066236 No free full text.

Abstract: Chemoprevention trials for several malignancies are completed, planned, or underway. Prostate cancer is one of the most common forms of cancer and understandably has received considerable recent attention as a potential target for chemoprevention. This article examines chemoprevention trials for prostate cancer, including the Prostate Cancer Prevention Trial, Selenium and Vitamin E Cancer Prevention Trial, and cyclooxygenase inhibitors in the prevention of prostate cancer.

Hernandez J, Thompson IM. · Urology Service, Department of Surgery, Brooke Army Medical Center, 3851 Roger Brooke Drive, Fort Sam Houston, TX 78234, USA. · Med Clin North Am. · Pubmed #15049578 No free full text.

Abstract: Many controversies surround the management of prostate cancer to include screening practices, diagnosis, and treatment options. The lack of randomized prospective studies comparing the various definitive treatment modalities currently available occasionally can make the decision process challenging for patients and their providers. In this setting of controversy, the cost of treating clinically localized prostate cancer is significant. In the face of these unanswered questions, this article summarizes some important principles regarding the diagnosis and treatment of prostate cancer. This review is limited to the diagnosis and management of clinically localized disease.

Canby-Hagino E, Hernandez J, Brand TC, Troyer DA, Higgins B, Ankerst DP, Thompson IM, Leach RJ, Parekh DJ. · Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. · Urology. · Pubmed #17991549 No free full text.

Abstract: 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.

Parekh DJ, Ankerst DP, Baillargeon J, Higgins B, Platz EA, Troyer D, Hernandez J, Leach RJ, Lokshin A, Thompson IM. · Department of Urology, University of Texas Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284-7802, USA. · Cancer Epidemiol Biomarkers Prev. · Pubmed #17932343 links to  free full text

Abstract: OBJECTIVE: We analyzed the association of 54 biomarkers from seven classes including adipokines, immune response metalloproteinases, adhesion molecules, and growth factors with prostate cancer risk adjusting for the Prostate Cancer Prevention Trial (PCPT) risk score. METHODS: A total of 123 incident prostate cancer cases and 127 age-matched controls were selected from subjects in the San Antonio Center for Biomarkers of Risk of Prostate Cancer cohort study. Prediagnostic serum concentrations were measured in the sample collected at baseline using LabMAP technology. The odds ratios (OR) of prostate cancer risk associated with serum concentrations of 54 markers were estimated using univariate conditional logistic regression before and after adjustment for the PCPT risk score. Two-way hierarchical unsupervised clustering techniques were used to evaluate whether the 54-marker panel distinguished cases from controls. RESULTS: Vascular endothelial growth factor, resistin, interleukin 1Ra (IL-1Ra), granulocyte colony-stimulating factor, matrix metalloproteinase-3, plasminogen activator inhibitor, and kallikrein-8 were statistically significantly (P < 0.05) underexpressed in prostate cancer cases, and alpha-fetoprotein was statistically significantly overexpressed in prostate cancer cases, but all had area underneath the receiver-operating characteristic curve <60%; none were statistically significant adjusting for multiple comparisons (P < 0.0008) or after adjustment for the PCPT risk score. Statistical clustering of patients by the marker panel did not distinguish a separate group of cases from controls. CONCLUSIONS: This age-matched case-control study did not support findings of increased diagnostic potential from a 54-marker panel when compared with the conventional risk factors incorporated in the PCPT risk calculator. Future discovery of new biomarkers should always be tested and compared against conventional risk factors before applying them in clinical practice.

Parekh DJ, Ankerst DP, Higgins BA, Hernandez J, Canby-Hagino E, Brand T, Troyer DA, Leach RJ, Thompson IM. · Department of Urology, University of Texas Health Science Center, San Antonio, Texas 78229, USA. · Urology. · Pubmed #17169636 No free full text.

Abstract: 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.

Baillargeon J, Platz EA, Rose DP, Pollock BH, Ankerst DP, Haffner S, Higgins B, Lokshin A, Troyer D, Hernandez J, Lynch S, Leach RJ, Thompson IM. · Center for Epidemiology and Biostatistics, University of Texas Health Sciences Center at San Antonio, 78284-7802, USA. · Cancer Epidemiol Biomarkers Prev. · Pubmed #16835332 links to  free full text

Abstract: BACKGROUND: The purpose of this investigation was to examine the association of obesity and the adipokines leptin, adiponectin, and interleukin-6 (IL-6) with prostate cancer risk and aggressiveness. METHODS: One hundred twenty-five incident prostate cancer cases and 125 age-matched controls were sampled from among participants in the original San Antonio Center for Biomarkers of Risk of Prostate Cancer cohort study. The odds ratios (OR) of prostate cancer and high-grade disease (Gleason sum >7) associated with the WHO categories of body mass index (kg/m(2)) and with tertiles of serum concentrations of adiponectin, leptin, and IL-6 were estimated using multivariable conditional logistic regression models. RESULTS: Body mass index was not associated with either incident prostate cancer [obese versus normal; OR, 0.75; 95% confidence interval (95% CI), 0.38-1.48; P(trend) = 0.27] or high-grade versus low-grade disease (OR, 1.17; 95% CI, 0.39-3.52; P(trend) = 0.62). Moreover, none of the three adipokines was statistically significant associated with prostate cancer risk or high-grade disease, respectively: leptin (highest versus lowest tertile; OR, 0.77; 95% CI, 0.28-1.37; P(trend) = 0.57; OR, 1.20; 95% CI, 0.48-3.01; P(trend) = 0.85); adiponectin (OR, 0.87; 95% CI, 0.46-1.65; P(trend) = 0.24; OR, 1.93; 95% CI, 0.74-5.10; P(trend) = 0.85); IL-6 (OR, 0.84; 95% CI, 0.46-1.53; P(trend) = 0.98; OR, 0.84; 95% CI, 0.30-2.33; P(trend) = 0.17). CONCLUSIONS: Findings from this nested case-control study of men routinely screened for prostate cancer and who had a high prevalence of overweight and obesity do not provide evidence to support that prediagnostic obesity or factors elaborated by fat cells strongly influence prostate cancer risk or aggressiveness. However, due to the small sample population, a small or modest effect of obesity and adipokines on these outcomes cannot be excluded.

Baillargeon J, Pollock BH, Kristal AR, Bradshaw P, Hernandez J, Basler J, Higgins B, Lynch S, Rozanski T, Troyer D, Thompson I. · Center for Epidemiology and Biostatistics, University of Texas Health Science Center, San Antonio, Texas 78284-7802, USA. · Cancer. · Pubmed #15668913 links to  free full text

Abstract: BACKGROUND: Recent studies of men with prostate carcinoma suggest that obesity may be associated with more advanced-stage disease and lower overall survival rates. One possible link between body mass index (BMI) and prostate carcinoma prognosis may be disease ascertainment. Prostate-specific antigen (PSA) is widely used to screen for prostate carcinoma. METHODS: The authors examined the association between BMI and PSA in a population-based study of 2779 men without prostate carcinoma. Between 2001 and 2004, these men were enrolled in a study sponsored by the San Antonio Center of Biomarkers of Risk, a clinical and epidemiologic center of the Early Detection Research Network of the National Cancer Institute. RESULTS: The mean PSA value decreased in a linear fashion with an increase in BMI category, from 1.01 ng/mL in normal weight men to 0.69 ng/mL in obese (Class III) men, after adjusting for race/ethnicity and age. CONCLUSIONS: Lower levels of PSA in obese and overweight men could mask biologically consequential prostate carcinoma.

Moul JW, Wu H, Sun L, McLeod DG, Amling C, Donahue T, Kusuda L, Sexton W, O'Reilly K, Hernandez J, Chung A, Soderdahl D. · Department of Surgery, Uniformed Services University of the Health Sciences, National Naval Medical Center, Bethesda 20852, USA. · J Urol. · Pubmed #14767288 No free full text.

Abstract: PURPOSE: Hormonal therapy (HT) is the current mainstay of systemic treatment for prostate specific antigen (PSA) only recurrence (PSAR), however, there is virtually no published literature comparing HT to observation in the clinical setting. The goal of this study was to examine the Department of Defense Center for Prostate Disease Research observational database to compare clinical outcomes in men who experienced PSAR after radical prostatectomy by early versus delayed use of HT and by a risk stratified approach. MATERIALS AND METHODS: Of 5382 men in the database who underwent primary radical prostatectomy (RP), 4967 patients were treated in the PSA-era between 1988 and December 2002. Of those patients 1352 men who had PSAR (PSA after surgery greater than 0.2 ng/ml) and had postoperative followup greater than 6 months were used as the study cohort. These patients were further divided into an early HT group in which patients (355) received HT after PSA only recurrence but before clinical metastasis and a late HT group for patients (997) who received no HT before clinical metastasis or by current followup. The primary end point was the development of clinical metastases. Of the 1352 patients with PSAR clinical metastases developed in 103 (7.6%). Patients were also stratified by surgical Gleason sum, PSA doubling time and timing of recurrence. Univariate and multivariate Cox proportional hazard models were used to evaluate the effect of early and late HT on clinical outcome. RESULTS: Early HT was associated with delayed clinical metastasis in patients with a pathological Gleason sum greater than 7 or PSA doubling time of 12 months or less (Hazards ratio = 2.12, p = 0.01). However, in the overall cohort early HT did not impact clinical metastases. Race, age at RP and PSA at diagnosis had no effect on metastasis-free survival (p >0.05). CONCLUSIONS: The retrospective observational multicenter database analysis demonstrated that early HT administered for PSAR after prior RP was an independent predictor of delayed clinical metastases only for high-risk cases at the current followup. Further study with longer followup and randomized trials are needed to address this important issue.

Hernandez J, Garcia-Pons F, Lone YC, Firat H, Schmidt JD, Langlade-Demoyen P, Zanetti M. · Department of Medicine and Cancer Center, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0837, USA. · Proc Natl Acad Sci U S A. · Pubmed #12218171 links to  free full text

Abstract: Telomerase reverse transcriptase (TRT) is a tumor-associated antigen expressed in the vast majority of human tumors and is presently one of the most promising target candidates for a therapeutic cancer vaccine. TRT is also expressed at low level in selected tissues and should be considered a self antigen. In the present study we sought to develop cytotoxic T lymphocytes (CTL) responses directed against human (h)TRT peptides with low relative affinity for which the available repertoire is to be preferentially spared from tolerance. This was accomplished by using analogue peptides of hTRT whose relative affinity for the MHC was increased by a targeted (-->Tyr) substitution in position one. By immunizing HLA A2.1 transgenic mice with these analogue peptides, we identified one such low relative affinity peptide (p572) that is endogenously processed and presented by HLA A2.1 in tumor cells, and is recognized by specific CTL. We used the highly immunogenic analogue peptide to successfully induce TRT-specific CTL in cancer patients and normal donors. CTL against p572-lysed human and mouse tumor cells but not activated autologous B cells. This peptide represents, therefore, an important candidate component of a cancer vaccine based on a TRT substrate and validates the strategy of targeting peptides with low affinity for the MHC for cancer immunotherapy.