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Biomedical subjects

E D Crawford

Publications and source records attributed to E D Crawford.

At least 19 recordsLinked to original sources
PubMed2005

Testosterone replacement therapy and the risk of prostate cancer. Is there a link?

Substantial evidence supports the value of testosterone replacement therapy (TRT) in improving quality of life in men with proven aging male syndrome (AMS). Benefits of TRT include improved bone mineral density, reduced fracture risk, increased muscle mass, and improved mood, sense of well being, and libido, among others. There is currently a heated debate about the theoretical association between TRT and the initiation, progression, and aggressiveness of prostate cancer; however, this link has not been uniformly studied, and any results have been contradictory and nonconclusive. Although no clear evidence links TRT to prostate cancer, the possibility of increasing the risk of a clinical manifestation of a latent pre-existing malignancy can influence the decision about TRT use. Current recommendations are to exclude prostate cancer before initiating TRT in men over age 40 and to closely monitor men in the first year of testosterone replacement, followed by observation in subsequent years.

Guidelines as Topic↗
PubMed2003

The use of flutamide as a single antiandrogen treatment for hormone-refractory prostate cancer.

OBJECTIVE: To investigate the efficacy of low-dose flutamide (125 mg twice daily) in the treatment of prostate-specific antigen (PSA) recurrence after definitive treatment with radical retropubic prostatectomy (RRP), external-beam radiation therapy (RT), or cryotherapy. PATIENTS AND METHODS: In this phase II prospective trial, patients who had a PSA recurrence after definitive treatment for prostate cancer were treated with flutamide. Endpoints for assessing treatment efficacy were PSA progression, treatment toxicity and clinical symptoms. Results were stratified into complete response (PSA < 0.2 ng/mL on two consecutive assessments), partial response (PSA decrease of half that at baseline on two consecutive assessments) and progressive disease. Seventeen patients were enrolled in who definitive treatment for primary prostate cancer had failed. RESULTS: Low-dose flutamide was clinically effective (i.e. complete or partial response) in 13 patients. Four had a complete response (mean duration 28 months), nine a partial response (mean duration 19 months), and two progressive disease, but were in the study for a mean of 1 year before progression. Two patients discontinued the study at 3 months, secondary to drug-related toxicity; one had grade 3 toxicity and five grade 1 toxicity. CONCLUSIONS: The administration of low-dose flutamide (125 mg) was clinically effective in treating PSA recurrence after definitive treatments for prostate cancer, and was well tolerated. Further investigation in a phase III trial is warranted.

Adult↗
PubMed2003

Prostate cancer update.

Prostate cancer continues to be the most commonly diagnosed malignancy in men of the western world. Its diagnosis, evaluation, and treatment therapies are constantly evolving. This paper summarizes and clarifies the most up-to-date information on prostate cancer prevention and treatment.

Humans↗
PubMed2001

Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer.

BACKGROUND: The value of nephrectomy in metastatic renal-cell cancer has long been debated. Several nonrandomized studies suggest a higher rate of response to systemic therapy and longer survival in patients who have undergone nephrectomy. METHODS: We randomly assigned patients with metastatic renal-cell cancer who were acceptable candidates for nephrectomy to undergo radical nephrectomy followed by therapy with interferon alfa-2b or to receive interferon alfa-2b therapy alone. The primary end point was survival, and the secondary end point was a response of the tumor to treatment. RESULTS: The median survival of 120 eligible patients assigned to surgery followed by interferon was 11.1 months, and among the 121 eligible patients assigned to interferon alone it was 8.1 months (P=0.05). The difference in median survival between the two groups was independent of performance status, metastatic site, and the presence or absence of a measurable metastatic lesion. CONCLUSIONS: Nephrectomy followed by interferon therapy results in longer survival among patients with metastatic renal-cell cancer than does interferon therapy alone.

Actuarial Analysis↗
PubMed2001

Clinical staging of prostate cancer: reproducibility and clarification of issues.

The American Joint Committee on Cancer (AJCC) staging system for prostate cancer adopted in 1992 is based on tumor-node-metastasis (TNM) designations. It has been widely accepted for use in local and advanced disease. The purpose of this study was to assess reproducibility of staging among observers and to help clarify staging issues. Twelve prostate cancer cases were sent to 20 physicians with special expertise in prostate cancer including eight urologists, eight radiation oncologists, and four medical oncologists. Physicians were asked to assign a stage based on the 1992 AJCC clinical staging. The most frequently reported stage assigned to each case was taken to be the consensus. Agreement was the percentage of physicians who reported that particular stage. Seventy-five percent of the physicians responded. The overall agreement for assignment of T stage was 63.9%. Differences were found by specialty for inclusion of available information in designating a T stage. The overall agreement for N stage was 73.8%. The most common designation was Nx regardless of availability of a computed tomography scan. The overall agreement for M stage was 76.6%. Without a bone scan the most common designation was Mx regardless of Gleason grade or prostate-specific antigen (PSA). A frequent comment was that PSA was more indicative of disease extent than current clinical staging. The reproducibility of the 1992 clinical AJCC staging is poor even among experts in the field. This problem arises primarily from disagreement regarding which studies are included in assigning a stage. Some of these difficulties are addressed in the 1997 revision. However, the clinical staging does not address the true biological significance of disease in many instances.

Humans↗
PubMed2001

Impact of different variables on the outcome of patients with clinically confined prostate carcinoma: prediction of pathologic stage and biochemical failure using an artificial neural network.

BACKGROUND: The advent of advanced computing techniques has provided the opportunity to analyze clinical data using artificial intelligence techniques. This study was designed to determine whether a neural network could be developed using preoperative prognostic indicators to predict the pathologic stage and time of biochemical failure for patients who undergo radical prostatectomy. METHODS: The preoperative information included TNM stage, prostate size, prostate specific antigen (PSA) level, biopsy results (Gleason score and percentage of positive biopsy), as well as patient age. All 309 patients underwent radical prostatectomy at the University of Colorado Health Sciences Center. The data from all patients were used to train a multilayer perceptron artificial neural network. The failure rate was defined as a rise in the PSA level > 0.2 ng/mL. The biochemical failure rate in the data base used was 14.2%. Univariate and multivariate analyses were performed to validate the results. RESULTS: The neural network statistics for the validation set showed a sensitivity and specificity of 79% and 81%, respectively, for the prediction of pathologic stage with an overall accuracy of 80% compared with an overall accuracy of 67% using the multivariate regression analysis. The sensitivity and specificity for the prediction of failure were 67% and 85%, respectively, demonstrating a high confidence in predicting failure. The overall accuracy rates for the artificial neural network and the multivariate analysis were similar. CONCLUSIONS: Neural networks can offer a convenient vehicle for clinicians to assess the preoperative risk of disease progression for patients who are about to undergo radical prostatectomy. Continued investigation of this approach with larger data sets seems warranted.

Adult↗
PubMed2001

A phase II trial of estramustine and etoposide in hormone refractory prostate cancer: A Southwest Oncology Group trial (SWOG 9407).

BACKGROUND: The combination of oral estramustine and oral etoposide has generated response rates of 40-50% in patients with hormone refractory prostate cancer in single institution trials. This study tested this regimen in a multi-institutional setting. METHODS: Fifty-five patients were accrued over a period of 4 months between 1 March 1996 and 1 July 1996. Two patients were not analyzable and two patients were ineligible. They were given an oral regimen consisting of estramustine 15 mg/kg/day (capped at 1120 mg per day) and etoposide 50 mg/M(2)/day, days 1-21 every 28 days. Patients received a median of two cycles of therapy. RESULTS: Toxicities included 11 patients (20%) with grades 3 or 4 granulocytopenia, 5 patients (10%) with grades 3 or 4 edema, and 3 patients (6%) with a thrombotic event. There were two treatment-related deaths, one as a result of anemia and the other as a result of a myocardial infarction. Of the 32 men who received at least 2 cycles of therapy, 7 men (22%) demonstrated a partial response to this regimen as measured by prostate-specific antigen (PSA) criteria of a 50% decline from pretreatment values. CONCLUSIONS: This trial demonstrates the toxicity of estramustine delivered in high dose. It also illustrates the difficulty of conducting phase II trials in prostate cancer in the cooperative group setting where the experience and comfort level of oncologists with new agents is less than that of the physicians at the institution where the therapy was developed. As the activity of this regimen with low-dose estramustine is defined, further multi-institutional studies may be warranted.

Administration, Oral↗
PubMed2001

Artificial neural network model for the assessment of lymph node spread in patients with clinically localized prostate cancer.

OBJECTIVES: To develop an artificial neural network (ANN) model to predict lymph node (LN) spread in men with clinically localized prostate cancer and to describe a clinically useful method for interpreting the ANN's output scores. METHODS: A simple, feed-forward ANN was trained and validated using clinical and pathologic data from two institutions (n = 6135 and n = 319). The clinical stage, biopsy Gleason sum, and prostate-specific antigen level were the input parameters and the presence or absence of LN spread was the output parameter. Patients with similar ANN outputs were grouped and assumed to be part of a cohort. The prevalence of LN spread for each of these patient cohorts was plotted against the range of ANN outputs to create a risk curve. RESULTS: The area under the receiver operating characteristic curve for the first and second validation data sets was 0.81 and 0.77, respectively. At an ANN output cutoff of 0.3, the sensitivity achieved for each validation set was 63.8% and 44.4%; the specificity was 81.5% and 81.3%; the positive predictive value was 13.6% and 6.5%; and the negative predictive value was 98.0% and 98.1%, respectively. The risk curve showed a nearly linear increase (best fit R(2) = 0.972) in the prevalence of LN spread with increases in raw ANN output. CONCLUSIONS: The ANN's performance on the two validation data sets suggests a role for ANNs in the accurate clinical staging of patients with prostate cancer. The risk curve provides a clinically useful tool that can be used to give patients a realistic assessment of their risk of LN spread.

False Negative Reactions↗
PubMed2001

Combined androgen blockade with nonsteroidal antiandrogens for advanced prostate cancer: a systematic review.

OBJECTIVES: Combined androgen blockade with medical or surgical castration plus a nonsteroidal antiandrogen for metastatic prostate cancer has been the subject of 20 randomized trials. The findings range from no expected increase in survival in 17 studies to an estimated 3.7 to 7 months' survival improvement noted in 3 studies. Most recently, a 1999 evidence report from the Agency for Healthcare Research and Quality and a 2000 overview from the Prostate Cancer Trialists Collaborative Group indicated that combined androgen blockade was associated with an approximately 3% to 5% increase in 5-year survival. We report herein a systematic review on combined androgen blockade performed by the Cochrane Collaborative Review Group on Prostate Diseases. METHODS: Controlled trials that included a randomization of immediate nonsteroidal antiandrogens with castration versus castration alone for metastatic prostate cancer and provided information on survival were reviewed. Information on overall survival, toxicity, progression-free survival, cancer-specific survival, and type of nonsteroidal antiandrogen and castration therapies was abstracted by two independent reviewers. RESULTS: Twenty trials (n = 6320 patients) were included. The pooled odds ratio (OR) for overall survival with combined androgen blockade was 1.03 (95% confidence interval [CI] 0.85 to 1.25; n = 4970 from 13 trials), 1.16 (95% CI 1.00 to 1.33; n = 5286 from 14 trials), and 1.29 (95% CI 1.11 to 1.50; n = 3550 from 7 trials) at 1, 2, and 5 years, respectively. Progression-free survival was improved at 1 year (OR = 1.38; 95% CI 1.15 to 1.67; n = 2278 from 7 trials). Cancer-specific survival was improved at 5 years (OR = 1.58; 95% CI 1.05 to 2.37; n = 781 from 2 trials). When analysis was limited to studies identified as being of high quality, the pooled OR for overall survival progressively increased but was not significant at any follow-up interval. CONCLUSIONS: We find that there is a 5% improvement in the percentage of men surviving at 5 years (30% vs. 25%) with combined androgen blockade with nonsteroidal antiandrogens as well as improvements in progression-free survival at 1 year. Appropriate patients with metastatic prostate cancer should be informed of the potential benefits, toxicities, and out-of-pocket expenditures.

Androgen Antagonists↗
PubMed2001

Phase II trial of bicalutamide in patients with advanced prostate cancer in whom conventional hormonal therapy failed: a Southwest Oncology Group study (SWOG 9235).

OBJECTIVES: To determine the efficacy and tolerability of bicalutamide in patients with advanced prostate cancer with progression after conventional hormonal therapy. METHODS: Fifty-two patients received bicalutamide, 150 mg once daily, as second-line therapy after progressing following treatment with orchiectomy or luteinizing hormone-releasing hormone analogue or diethylstilbestrol, alone or in combination. Patients had measurable (n = 8) or assessable (n = 44) disease, a Southwest Oncology Group performance status of 0 to 2, and no prior antiandrogen therapy or chemotherapy. The objective response to treatment was assessed every 12 weeks; symptoms and pain were assessed monthly with questionnaires for 6 months. RESULTS: There was evidence of palliation with three measures of pain and, to a lesser extent, with a measure of overall symptom status after 3 months of taking bicalutamide. No complete or partial responses occurred. However, 9 (20%) of 44 subjects with adequate prostate-specific antigen data had a 50% or higher decrease in their prostate-specific antigen levels, which did not correlate with symptom improvement. The median survival time was 15 months. The most common side effects were hot flashes (23%) and nausea (21%). CONCLUSIONS: These data suggest that bicalutamide decreases pain and improves symptom status in patients with prostate cancer in whom first-line hormonal therapy failed.

Adenocarcinoma↗
PubMed2001

Terazosin, doxazosin, and prazosin: current clinical experience.

Lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction are common in aging men. Nearly 25% of men >40 years of age have LUTS. Medical therapy with alpha-blockade is the most common method of medical therapy for benign prostatic obstruction. Multiple methods of minimally invasive surgical therapies have been introduced in the last decade. These methods include balloon dilatation, temporary and permanent urethral stents, various laser techniques, microwave thermotherapy, transurethral needle ablation, electrovaporization, and high-intensity focused ultrasound. alpha-Receptor blockers to reduce the sympathetic tone of the prostate are considered as first-line therapy to relieve the symptoms of benign prostatic hyperplasia. Selective alpha(1)-receptor blockers relax prostatic smooth muscle, relieve bladder outlet obstruction, and enhance urine flow with fewer side effects. In addition, it was determined that treating patients with alpha-blockers increases prostatic apoptosis. Pharmacokinetic activity, mode of action, clinical efficacy, and side effects of the selective alpha(1)-receptor blockers terazosin, doxazosin, and prazosin are reviewed.

Adrenergic alpha-Antagonists↗
PubMed2001

Relationship of demographic and clinical factors to free and total prostate-specific antigen.

OBJECTIVES: To characterize the role of demographic and clinical parameters in the measurements of prostate-specific antigen (PSA), free PSA (fPSA), and percent free PSA (%fPSA). METHODS: This was a cohort study of volunteers to a randomized screening trial. A central laboratory determined PSA and fPSA for the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. A baseline evaluation of free and total PSA was done for 7183 white, black, Asian, Hispanic, and other male volunteers, aged 55 to 74 years. Comparisons were made across racial and ethnic groups and across a set of clinical parameters from a baseline questionnaire. RESULTS: The median levels of serum PSA were less than 2.1 ng/mL in each age-race grouping of the study participants. The levels of free and total PSA were higher in black (n = 868, 12%) participants than in white (n = 4995, 70%) and Asian (n = 849, 11.8%) participants. Individuals who identified themselves as ethnically Hispanic (n = 339, 4.7%) had median PSA levels higher than whites who were not Hispanic. The free and total PSA levels increased with age, particularly among men 70 to 74 years old. However, the %fPSA levels showed less variation among the four racial groups or by age. The free and total PSA levels were higher among those who had a history of benign prostatic disease. CONCLUSIONS: Demographic (age and race/ethnicity) and clinical (history of benign prostatic disease) variables had a moderate effect on the measures of PSA and fPSA and very little effect on %fPSA.

Aged↗
PubMed2001

Predictive modeling techniques in prostate cancer.

A number of new predictive modeling techniques have emerged in the past several years. These methods can be used independently or in combination with traditional modeling techniques to produce useful tools for the management of prostate cancer. Investigators should be aware of these techniques and avail themselves of their potentially useful properties. This review outlines selected predictive methods that can be used to develop models that may be useful to patients and clinicians for prostate cancer management.

Humans↗
PubMed2001

Use of artificial neural networks in prostate cancer.

Artificial neural networks (ANNs) are a type of artificial intelligence software inspired by biological neuronal systems that can be used for nonlinear statistical modeling. In recent years, these applications have played an increasing role in predictive and classification modeling in medical research. We review the basic concepts behind ANNs and examine the role of this technology in selected applications in prostate cancer research.

Humans↗
PubMed2001

Artificial neural network model to predict biochemical failure after radical prostatectomy.

BACKGROUND: Biochemical failure, defined here as a rise in the serum prostate specific antigen (PSA) concentration to >0.3 ng/mL or the initiation of adjuvant therapy, is thought to be an adverse prognostic factor for men who undergo radical prostatectomy (RP) as definitive treatment for clinically localized cancer of the prostate (CAP). We have developed an artificial neural network (ANN) to predict biochemical failure that may benefit clinicians and patients choosing among the definitive treatment options for CAP. MATERIALS AND METHODS: Clinical and pathologic data from 196 patients who had undergone RP at one institution between 1988 and 1999 were utilized. Twenty-one records were deleted because of missing outcome, Gleason sum, PSA, or clinical stage data. The variables from the 175 remaining records were analyzed for input variable selection using principal component analysis, decision tree analysis, and stepped logistic regression. The selected variables were age, PSA, primary and secondary Gleason grade, and Gleason sum. The records were randomized and split into three bootstrap training and validation sets of 140 records (80%) and 35 records (20%), respectively. RESULTS: Forty-four percent of the patients suffered biochemical failure. The average duration of follow up was 2.5 years (range 0-11.5 years). Forty-two percent of the patients had pathologic evidence of non-organ-confined disease. The average area under the receiver operator characteristic (ROC) curve for the validation sets was 0.75 +/- 0.07. The ANN with the highest area under the ROC curve (0.80) was used for prediction and had a sensitivity of 0.74, a specificity of 0.78, a positive predictive value of 0.71, and a negative predictive value of 0.81. CONCLUSION: These results suggest that ANN models can predict PSA failure using readily available preoperative variables. Such predictive models may offer assistance to patients and physicians deciding on definitive therapy for CaP.

Adjuvants, Pharmaceutic↗
PubMed2001

Genetic adaptive neural network to predict biochemical failure after radical prostatectomy: a multi-institutional study.

BACKGROUND AND PURPOSE: Despite many new procedures, radical prostatectomy remains one of the commonest methods of treating clinically localized prostate cancer. Both from the physician's and the patient's point of view, it is important to have objective estimation of the likelihood of recurrence, which forms the foundation for treatment selection for an individual patient. Currently, it is difficult to predict the probability of biochemical recurrence (rising serum prostate specific antigen [PSA] concentration) in an individual patient, and approximately 30% of the patients do experience recurrence. Tools predicting the recurrence will be of immense practical utility in the treatment selection and planning follow up. We have utilized preoperative parameters through a computer based genetic adaptive neural network model to predict recurrence in such patients, which can help primary care physicians and urologists in making management recommendations. PATIENTS AND METHODS: Fourteen hundred patients who underwent radical prostatectomy at participating institutions form the subjects of this study. Demographic data such as age, race, preoperative PSA, systemic biopsy based staging and Gleason scores were used to construct a neural network model. This model simulated the functioning of a trained human mind and learned from the database. Once trained, it was used to predict the outcomes in new patients. RESULTS: The patients in this comprehensive database were representative of the average prostate cancer patients as seen in USA. Their mean age was 68.4 years, the mean PSA concentration before surgery was 11.6 ng/mL, and 67% patients had a Gleason sum of 5 to 7. The mean length of follow-up was 41.5 months. Eighty percent of the cancers were clinical stage T2 and 5% T3. In our series, 64% of patients had pathologically organ-confined cancer, 33% positive margins, and 14% had seminal vesicle invasion. Lymph node positive patients were not included in this series. Progression as judged by serum PSA was noted in 30.6%. With entry of a few routinely used parameters, the model could correctly predict recurrence in 76% of the patients in the validation set. The area under the curve was 0.831. The sensitivity was 85%, the specificity 74%, the positive predictive value 77%, and the negative predictive value of 83%. CONCLUSION: It was possible to predict PSA recurrence with a high accuracy (76%). Physicians desiring objective treatment counseling can use this model, and significant cost savings are anticipated because of appropriate treatment selection and patient-specific follow-up protocols. This technology can be extended to other treatments such as watchful waiting, external-beam radiation, and brachytherapy.

Aged↗
PubMed2001

Advancing perspectives on prostate cancer: multihormonal influences in pathogenesis.

Nonandrogenic hormones are implicated in the growth and function of the prostate, which is itself an endocrine gland that synthesizes and secretes hormones and growth factors, including follicle-stimulating hormone (FSH) and prostatic inhibin peptide (PIP). Findings of increased FSH concentrations and receptor expression in diseased prostate tissue suggest a role for FSH in prostate cancer growth. Not only does PIP suppress circulating levels of FSH, but it responds to and modulates prostatic FSH, suggesting a close interlinkage of these compounds in controlling both healthy and diseased prostate cells. Other focuses of endocrinologic research include androgen receptors, vitamin D, growth factors (including insulin-like growth factors I and II), and retinoids. Issues such as optimal therapy timing, intermittent administration, and the adoption of a multihormonal approach to the management of prostate cancer remain to be resolved.

Follicle Stimulating Hormone↗