Prostatic Neoplasms: Burnett AL

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.

This publication has no abstract.

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.

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.

Burnett AL. · Department of Urology, James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, 600 North Wolfe Street, Marburg 407, Baltimore, Maryland 21287-2411, USA. · World J Urol. · Pubmed #12811492 No free full text.

Abstract: While the application of penile autonomic nerve-sparing techniques during radical prostatectomy for clinically localized prostate cancer has improved erection recovery rates after surgery, many men still experience delayed or incomplete recovery of erectile function. In recognition of neuropathy as a likely basis for erectile dysfunction after radical prostatectomy, investigators have begun exploring new strategies to promote the functional recovery of nerves responsible for penile erection in the course of this management. Primary efforts continue for preserving the integrity of the penile nerves, while the next frontier in clinical management has encompassed strategies directed toward maximally restoring their function. Such strategies include cavernous nerve interposition grafting and neurotrophic treatments that meet nerve reconstructive and nerve regenerative objectives, respectively. Early successes with both innovations preclinically and clinically suggest their feasibility and potential roles to reduce the incidence of erectile dysfunction after radical prostatectomy. The purpose of this report is to review strategies under development to promote post-prostatectomy erectile function, particularly with respect to preserving penile innervation involved in this function.

Burnett AL. · Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD 21287-2411, USA. · Urology. · Pubmed #12639630 No free full text.

This publication has no abstract.

Burnett AL, Teloken PE, Briganti A, Whitehurst T, Montorsi F. · Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD 21287-2411, USA. <> · J Sex Med. · Pubmed #18466264 No free full text.

Abstract: INTRODUCTION: Erectile dysfunction remains a major functional complication of radical prostatectomy in the modern era despite surgical techniques to preserve the penile autonomic nerve supply. AIM: To develop and evaluate a neurostimulation system for cavernous nerve electrical stimulation for future use as a chronic implantation device that neurotrophically promotes erectile function recovery following radical prostatectomy. METHOD: After radical retropubic prostatectomy, the neurovascular bundle was stimulated using a temporarily placed electrode array of an implantable neurostimulation system (20 Hz frequency, 260 micro seconds pulse width, 5 mA-60 mA amplitude up to 10 minutes), and penile circumference increases were measured. MAIN OUTCOME MEASURE: Increase in penile circumference. Results. Among 12 men (mean age 60.3 years) enrolled in this study, 6 (50%) demonstrated measurable increases in penile circumference in response to cavernous nerve stimulation. Among these six men, the mean increase was 5.0 mm (range 1.6 mm to 7.0 mm). Temporary surgical placement of the device was done with relative ease, and there was no evidence of injury to the neurovascular bundle. Conclusions. A chronic implantable nerve stimulation system for cavernous nerve stimulation having possible neuromodulatory effects on the recovery of penile erections after radical prostatectomy is feasible.

Liu T, Allaf ME, Lagoda G, Burnett AL. · James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. · BJU Int. · Pubmed #17868418 No free full text.

Abstract: OBJECTIVE: To investigate whether the erythropoietin (EPO) receptor is expressed in human periprostatic (including the neurovascular bundles) and penile tissues, and define its distribution in these tissues, as the administration of exogenous EPO in cavernous nerve injury promoted the recovery of erectile function in a rat model. MATERIALS AND METHODS: Human prostate (six samples) and penile (two) tissue were collected and paraffin-embedded. Tissue was sectioned and processed for immunohistochemical studies using an antibody for the EPO receptor; immunolocalization was assessed using light microscopy. RESULTS: There was prominent staining for the EPO receptor in neuronal cell bodies of the periprostatic neurovascular bundles, and in the axons emanating from these ganglia. The glandular epithelium of the prostate also had weak staining. There was EPO receptor immunoreactivity in the penile specimens in the penile dorsal nerves, sinusoidal endothelium of the corpus cavernosum, and endothelial cells lining the dorsal veins and arteries. All slides processed with no primary antibody or blocking peptide showed no staining. CONCLUSIONS: EPO receptor expression was identified and localized in human penile tissues and in the periprostatic neurovascular bundles responsible for erectile function. This suggests a likely role for endogenous EPO within these tissues, and provides the rationale for its clinical use as a protective agent locally.

Burnett AL, Kramer MF, Dalrymple S, Isaacs JT. · Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-2411, USA. · Urology. · Pubmed #15882753 No free full text.

Abstract: OBJECTIVES: Nonimmunosuppressant immunophilin ligands such as GPI-1046 have gained interest recently for their clinical potential to reduce the extent of injury sustained by penile innervation during radical prostatectomy for prostate cancer treatment and thereby improve erectile function recovery postoperatively. Preclinical studies in rat animal models of cavernous nerve injury have demonstrated that immunophilin ligands exert both neuroprotective and neuroregenerative effects on physiologic erection and on the morphology of erectile tissue and penile innervation. Before establishing their clinical roles, however, it would be useful to evaluate whether they exert mitogenic effects on malignant prostate cells. METHODS: Human prostate cancer cell lines (LAPC-4, CWR22Rv1, LNCaP, and PC-3) were treated in vitro with 0 to 10 microM of the prototypical nonimmunosuppressant ligand GPI-1046 in 1% fetal bovine serum (FBS)-containing (ie, low growth) media, and their growth was assayed during a 7-day period using spectrophotometric cell counting. The results were normalized for comparison to the maximal growth produced in 10% FBS-containing media. RESULTS: All four prostate cancer cell lines grew maximally in 10% FBS-containing media, and this growth was reduced by more than twofold (P <0.05) when the cells were maintained in 1% FBS-containing media. The addition of 10 microM or less GPI-1046 to the cells in 1% FBS-containing media did not exert statistically significant mitogenic effects on human prostate cancer cells in vitro. CONCLUSIONS: These data contribute toward allaying concerns that the use of nonimmunosuppressant immunophilin ligand therapy for the improvement of erectile function recovery after radical prostatectomy will promote recurrent prostate cancer.