Biomedical subjects

Martin G Sanda

Publications and source records attributed to Martin G Sanda.

At least 19 recordsLinked to original sources

PubMed2006

Measuring patients' expectations regarding health-related quality-of-life outcomes associated with prostate cancer surgery or radiotherapy.

OBJECTIVES: Establishing realistic health-related quality-of-life (HRQOL) expectations before the choice of cancer treatment is made is an important goal of patient counseling. We prospectively studied the pretreatment expectations of prostate cancer-specific HRQOL with an adapted Expanded Prostate Cancer Index Composite instrument. METHODS: Baseline pretreatment Expanded Prostate Cancer Index Composite scores, pretreatment expectation scores, and 1-year posttreatment scores were prospectively collected for 50 patients undergoing radical prostatectomy or external beam radiotherapy. The pretreatment expectations and observed HRQOL scores at 1 year after treatment were compared for the urinary incontinence, urinary irritation, bowel, sexual, and hormonal domains. RESULTS: The expectation scores did not differ from the HRQOL scores at 1 year for urinary irritation, bowel function, and the hormonal domain. However, the sexual domain expectations were 22.5% greater than observed sexual domain scores 1 year after treatment (P <0.0001, 99% confidence interval 11 to 34) for both surgery and radiotherapy subjects. Anxiety, depression, education level, and income did not correlate with the expectations for HRQOL outcomes. A modest correlation was found between optimism and greater expectations for the sexual domain (Pearson correlation coefficient 0.38, P <0.001). CONCLUSIONS: Measuring HRQOL expectations before treatment may elucidate discrepancies between patient expectations and observed outcomes. This pilot study found that patients' expectations regarding urinary and bowel outcomes more closely reflected their eventual observed outcome than did their expectations regarding sexual outcome.

Follow-Up Studies↗

PubMed2006

Prognostic factors in lymph node-positive prostate cancer.

OBJECTIVES: To characterize lymph node metastasis of prostate cancer (PCa) and identify the parameters associated with patient outcome. The incidence of clinically localized PCa with concurrent lymph node metastasis has decreased to less than 1% in the United States but is between 10% and 15% in other countries. METHODS: Our study cohort of 1148 patients underwent radical prostatectomy in Ulm, Germany, between 1986 and 2002, and 201 (18%) had lymph node-positive PCa. RESULTS: The metastases showed growth architecture resembling primary PCa. We assigned a Gleason pattern and evaluated for size, extranodal extension, and lymphovascular invasion (LVI). Of 201 patients, 155 had original pathology slides available; 36 of the 155 were excluded because of preoperative hormonal ablation therapy. Of the remaining 119 patients, 22 (19%) were assigned Gleason pattern 3, 93 (78%) Gleason pattern 4, and 4 (3%) Gleason pattern 5. Extranodal extension was present in 66 (55%) of 119 patients and LVI in 29 (25%). An increased risk of prostate-specific antigen (PSA) recurrence was found for Gleason pattern 4/5 (hazard ratio [HR] 2.5, P = 0.038), LVI in the lymph nodes (HR 1.9, P = 0.038), and nuclear grade of the primary tumor (HR 2, P = 0.025). Independent predictors of PSA recurrence included LVI and nuclear grade (HR 1.9, P = 0.03 and HR 2, P = 0.03, respectively). CONCLUSIONS: Lymph node metastases of PCa are heterogeneous and have a close relation to the corresponding primary tumor. Most patients with lymph node-positive PCa remained disease free for up to 13 years after radical prostatectomy. Independent predictors of PSA recurrence among those with lymph node-positive PCa included LVI in the lymph nodes and the nuclear grade of the primary tumor. These parameters may be useful in predicting PSA recurrence in lymph node-positive PCa and could be included in patient follow-up.

Aged↗

PubMed2006

Use of medications or devices for erectile dysfunction among long-term prostate cancer treatment survivors: potential influence of sexual motivation and/or indifference.

OBJECTIVES: To evaluate the potential association between sexual motivation and patterns of erectile dysfunction (ED) therapy among a large cohort of localized prostate cancer treatment survivors. METHODS: The use of medications and devices to improve erections and sexual health-related quality of life (HRQOL) were evaluated using a mailed Expanded Prostate Cancer Index Composite survey administered to 896 men 4 to 8 years after brachytherapy, three-dimensional conformal external beam radiotherapy (3D-CRT), or radical prostatectomy and 112 control men. The responding participants (73% of those surveyed) were classified by prostate cancer treatment, sexual motivation, and ED therapy use. Bivariate and multivariate analyses were used to identify the factors associated with ED therapy use and sexual HRQOL outcome. RESULTS: The quality of erections unassisted by medications or devices was not different among the treatment groups. Prostate cancer survivors used medications or devices for ED more commonly than did the control men (30% versus 13%; P <0.01). One half of the prostate cancer survivors with ED reported indifference regarding their ED (small to no sexual bother despite absent or poor unassisted erections). Conversely, among men who were bothered by poor erections, 48% of the brachytherapy, 61% of the 3D-CRT, and 23% of radical prostatectomy subjects had never tried commonly available medications or devices to improve their erections (P <0.01). The current use of at least one erection aid was an independent determinant of more favorable sexual HRQOL (P <0.01). CONCLUSIONS: Many men who are bothered by posttreatment ED reported never having tried medications or devices to improve their erections. The lack of ED therapy was more prevalent among patients with erectile concerns after brachytherapy or 3D-CRT than after radical prostatectomy, suggesting possible opportunities for improving sexual HRQOL among long-term survivors.

Aged↗

PubMed2006

Obesity adversely affects health related quality of life before and after radical retropubic prostatectomy.

PURPOSE: Obesity adversely affects surgical procedures and outcomes. We used a validated health related quality of life measure to examine the effects of obesity on disease specific health related quality of life before and following radical retropubic prostatectomy. MATERIALS AND METHODS: From June 2000 to April 2003, 575 consecutive patients with prostate cancer were approached to participate in a prospective, health related quality of life study. Health related quality of life was assessed before surgery, and 1, 4, 12, 24 and 36 months postoperatively. Repeated measures mixed models were constructed to determine the independent effects of body mass index on health related quality of life. RESULTS: Of 472 consenting subjects 376 (80%) completed a baseline and at least 1 followup survey. Higher body mass index was associated with worse preoperative hormonal/vitality function (p = 0.0009) and bother (p = 0.02), and delayed recovery of bowel function (p = 0.01) and bother (p = 0.01) health related quality of life. There were no measurable differences postoperatively in hormonal/vitality, urinary or sexual health related quality of life associated with higher body mass index. Increased body mass index was associated with prostate specific antigen recurrence (p = 0.05) and adjuvant treatment (p = 0.02). Adjuvant treatment was independently associated with worse bowel function (p = 0.01) and bother (p = 0.01) health related quality of life in obese patients. At 24 months bowel health related quality of life in obese patients no longer significantly differed from that in nonobese patients. CONCLUSIONS: Obesity is associated with worse preoperative hormonal/vitality health related quality of life, slower recovery of bowel function and bother health related quality of life after radical retropubic prostatectomy, and prostate specific antigen recurrence. Impaired health related quality of life recovery in obese patients is influenced by disease recurrence and resultant adjuvant therapies. Despite these findings obese patients should not be dissuaded from considering prostatectomy as definitive treatment for localized prostate cancer.

Body Mass Index↗

PubMed2005

Autoantibody signatures in prostate cancer.

BACKGROUND: New biomarkers, such as autoantibody signatures, may improve the early detection of prostate cancer. METHODS: With a phage-display library derived from prostate-cancer tissue, we developed and used phage protein microarrays to analyze serum samples from 119 patients with prostate cancer and 138 controls, with the samples equally divided into training and validation sets. A phage-peptide detector that was constructed from the training set was evaluated on an independent validation set of 128 serum samples (60 from patients with prostate cancer and 68 from controls). RESULTS: A 22-phage-peptide detector had 88.2 percent specificity (95 percent confidence interval, 0.78 to 0.95) and 81.6 percent sensitivity (95 percent confidence interval, 0.70 to 0.90) in discriminating between the group with prostate cancer and the control group. This panel of peptides performed better than did prostate-specific antigen (PSA) in distinguishing between the group with prostate cancer and the control group (area under the curve for the autoantibody signature, 0.93; 95 percent confidence interval, 0.88 to 0.97; area under the curve for PSA, 0.80; 95 percent confidence interval, 0.71 to 0.88). Logistic-regression analysis revealed that the phage-peptide panel provided additional discriminative power over PSA (P<0.001). Among the 22 phage peptides used as a detector, 4 were derived from in-frame, named coding sequences. The remaining phage peptides were generated from untranslated sequences. CONCLUSIONS: Autoantibodies against peptides derived from prostate-cancer tissue could be used as the basis for a screening test for prostate cancer.

Aged↗

PubMed2005

Serum antibodies to huntingtin interacting protein-1: a new blood test for prostate cancer.

Huntingtin-interacting protein 1 (HIP1) is frequently overexpressed in prostate cancer. HIP1 is a clathrin-binding protein involved in growth factor receptor trafficking that transforms fibroblasts by prolonging the half-life of growth factor receptors. In addition to human cancers, HIP1 is also overexpressed in prostate tumors from the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model. Here we provide evidence that HIP1 plays an important role in mouse tumor development, as tumor formation in the TRAMP mice was impaired in the Hip1null/null background. In addition, we report that autoantibodies to HIP1 developed in the sera of TRAMP mice with prostate cancer as well as in the sera from human prostate cancer patients. This led to the development of an anti-HIP1 serum test in humans that had a similar sensitivity and specificity to the anti-alpha-methylacyl CoA racemase (AMACR) and prostate-specific antigen tests for prostate cancer and when combined with the anti-AMACR test yielded a specificity of 97%. These data suggest that HIP1 plays a functional role in tumorigenesis and that a positive HIP1 autoantibody test may be an important serum marker of prostate cancer.

Adenocarcinoma↗

PubMed2005

Long-term outcomes among localized prostate cancer survivors: health-related quality-of-life changes after radical prostatectomy, external radiation, and brachytherapy.

PURPOSE: We sought to elucidate long-term changes in health-related quality-of-life (HRQOL) outcomes by prospectively re-evaluating a well-characterized cohort of prostate cancer (PC) survivors 4 to 8 years after primary treatment. PATIENTS AND METHODS: Patients who had been evaluated previously at a median of 2.6 years after radical prostatectomy (RP), external radiation (three-dimensional conformal radiation therapy [3-D CRT]), or brachytherapy (BT) were recontacted at a median of 6.2 years after treatment. The clinical relevance of long-term HRQOL impairment among survivors was established by comparison with controls of similar age. Factors associated with HRQOL changes during this interval were evaluated. RESULTS: Of the 964 eligible men, 709 (73.5%) completed measurable questionnaires. In four domains (urinary irritative-obstructive, urinary incontinence, bowel, and sexual), significant HRQOL differences were detected for at least one of the therapy groups, compared with controls (all P < .05). During the 4-year interval, significant improvement was observed for the urinary irritative-obstructive (P < .0001) and bowel (P < .0001) domains among BT patients, whereas urinary incontinence HRQOL worsened for both the BT (P = .0017) and 3-D CRT (P = .0008) treatment groups. Overall sexual HRQOL deteriorated for the 3-D CRT cohort (P = .0017), as well as for controls (P = .0136). Among RP patients, significant HRQOL changes were not observed. CONCLUSION: During a 4-year interval from earlier to longer-term phases of PC treatment survivorship, sexual, urinary, and bowel dysfunction remain significant concerns among early-stage PC treatment survivors, compared with control men. Although postprostatectomy HRQOL remains relatively stable during this interval, disease-specific HRQOL continues to evolve among men treated with BT and 3-D CRT.

Aged↗

PubMed2005

[The Japanese translation and cultural adaptation of Expanded Prostate Cancer Index Composite (EPIC)].

PURPOSE: To develop a Japanese version of the Expanded Prostate Cancer Index Composite (EPIC): originally designed to measure the Quality of Life of localized prostate cancer patients, after careful assessments of cross-cultural equivalence, face validity and practically. METHODS: We translated the original version that consisted of 50 items into a preliminary Japanese version. This multi-stage procedure included a forward-translation, back-translation and discussion with the original developer. Additionally, we tested the preliminary Japanese version on 11 localized prostate cancer patients and identified problems with its cross-cultural equivalence, practicality. Based on the findings of this pretest, we revised the Japanese version. Consensus by discussion among all researchers was obtained through out this process. RESULTS: The original developer reviewed the back-translation of the preliminary Japanese version: some wording was revised. In the pretest, the average age of patients was 68.8 years old. Four of the sexual subscale showed over 10 percent missing data. In five items, all patients chose identical answers. We conducted an in-depth qualitative investigation of these items. The average response time was 11.7 minutes. We revised the Japanese to reflect patients' opinions as much as possible. Items which were showed problems in terms of cross-cultural adaptation included questions measuring 'bother' and two items of the sexual subscale. The wordings of these items were revised so that Japanese patients could easier understand them. We ensured that the original developer's intentions remained the same. The original developed approved all revisions. CONCLUSION: We translated and adapted the original EPIC to the Japanese culture. The Japanese version of EPIC was found to be functional in the pretest.

Asian People↗

PubMed2004

Humoral immune response to alpha-methylacyl-CoA racemase and prostate cancer.

BACKGROUND: Although prostate-specific antigen (PSA) is a prototypic biomarker for prostate cancer, it has poor specificity. Expression of alpha-methylacyl-CoA racemase (AMACR), which is involved in the conversion of R-stereoisomers of branched-chain fatty acids to S-stereoisomers, has been shown to be specifically increased in prostate cancer epithelia. However, attempts to detect AMACR in circulation have not been successful. Hence, we determined whether an immune response to AMACR could be used as a serum biomarker for prostate cancer. METHODS: Sera from patients with biopsy-proven prostate cancer and from control subjects were screened for a humoral immune response to selected tumor antigens, including AMACR, by using protein microarrays (46 patients, 28 control subjects). Humoral immune response to AMACR was then validated using high-throughput immunoblot analysis (151 patients, 259 control subjects) and enzyme-linked immunosorbent assay (ELISA) (54 patients, 55 control subjects). Receiver operating characteristic curves were used to determine the sensitivity and specificity of the immune response to AMACR to detect prostate cancer. RESULTS: Immunoreactivity against AMACR was statistically significantly higher in sera from patients with prostate cancer than in control subjects by all three techniques (P(protein microarray) =.009, P(immunoblot)<.001, P(ELISA) =.011). High-throughput immunoblot analysis revealed that, in subjects with intermediate PSA levels (4-10 ng/mL), the immune response against AMACR was more sensitive and specific than was PSA in distinguishing sera from prostate cancer patients relative to control subjects (sensitivity and specificity of 77.8% and 80.6% versus 45.6% and 50%, respectively; area under the curve of 0.789 versus 0.492; P<.001). CONCLUSION: Assays to detect a humoral immune response against AMACR may have the potential to supplement PSA screening in identifying patients with clinically significant prostate cancer, especially those with intermediate PSA levels.

Adult↗

PubMed2004

The role of metastasis-associated protein 1 in prostate cancer progression.

Distinguishing aggressive prostate cancer from indolent disease represents an important clinical challenge, as current therapy requires over treating men with prostate cancer to prevent the progression of a few cases. Expression of the metastasis-associated protein 1 (MTA1) has previously been found to be associated with progression to the metastatic state in various cancers. Analyzing DNA microarray data, we found MTA1 to be selectively overexpressed in metastatic prostate cancer compared with clinically localized prostate cancer and benign prostate tissue. These results were validated by demonstrating overexpression of MTA1 in metastatic prostate cancer by immunoblot analysis. MTA1 protein expression was evaluated by immunohistochemistry in a broad spectrum of prostate tumors with tissue microarrays containing 1940 tissue cores from 300 cases. Metastatic prostate cancer demonstrated significantly higher mean MTA1 protein expression intensity (score = 3.4/4) and percentage of tissue cores staining positive for MTA1 (83%) compared with clinically localized prostate cancer (score = 2.8/4, 63% positive cores) or benign prostate tissue (score = 1.5/4, 25% positive cores) with a mean difference of 0.54 and 1.84, respectively (P < 0.00001 for both). Paradoxically, for localized disease, higher MTA1 protein expression was associated with lower rates of prostate specific antigen recurrence after radical prostatectomy for localized disease. In summary, this study identified an association of MTA1 expression and prostate cancer progression.

Adult↗

PubMed2004

Sexual health recovery after prostatectomy, external radiation, or brachytherapy for early stage prostate cancer.

Each of the three most common contemporary treatments for localized prostate cancer, radical prostatectomy, external beam radiotherapy, and brachytherapy, can have adverse effects on sexual health. Sexual health outcome can be improved by treatment-specific factors, such as the use of nerve-sparing technique during radical prostatectomy, or worsened by the use of androgen deprivation before external beam radiotherapy or brachytherapy. Contemporary studies that have used validated questionnaires to evaluate multiple components of patient-reported sexuality following prostate cancer treatments provide benchmarks of sexual outcome expectations that are of interest to patients selecting their prostate cancer treatment.

Brachytherapy↗

PubMed2004

Neoadjuvant hormonal therapy impairs sexual outcome among younger men who undergo external beam radiotherapy for localized prostate cancer.

OBJECTIVES: To evaluate the effects of treatment factors and other covariates on sexual health-related quality of life (HRQOL) after radiotherapy (RT) for prostate cancer. The effects of clinical and treatment factors on sexual health after external beam RT have not been fully characterized by patient-reported, validated questionnaires. METHODS: A total of 259 subjects (147 patients who had undergone RT for prostate cancer and 112 age-matched controls) participated in a cross-sectional assessment of HRQOL using the validated expanded prostate cancer index to measure patient-reported sexual function and bother. Multivariable models were used to determine the association of 13 prospectively measured clinical and treatment factors with post-RT sexual HRQOL. RESULTS: Increasing age, time since RT, and use of neoadjuvant hormonal therapy (NHT) were independently associated with sexual function (P <0.01) after RT. The effects of NHT on sexual HRQOL were most notable among the youngest (younger than 67 years) patients and among those closest to treatment. These effects may be conceptualized by examining the distribution of responses to individual Expanded Prostate Cancer Index Composite questions. For example, among the youngest patients, those treated with NHT were less than half as likely to report a fair ability to have erections compared with hormone-naive men. CONCLUSIONS: These patient-reported data, elicited using a validated HRQOL instrument, indicate that older age and NHT significantly and independently hinder post-RT sexual HRQOL outcome among men with localized prostate cancer and provide a framework for counseling patients regarding long-term sexual outcome on the basis of treatment plan and age.

Age Factors↗

PubMed2004

Patient, surgeon, and treatment characteristics associated with homologous blood transfusion requirement during radical retropubic prostatectomy: multivariate nomogram to assist patient counseling.

OBJECTIVES: To identify the preoperative patient, treatment, and surgeon factors associated with the administration of homologous blood transfusion during or after radical retropubic prostatectomy (RRP) to be able to better inform patients regarding the probability of transfusion. Homologous blood transfusion is sometimes required during or after RRP, but predictive models for estimating transfusion probability using patient and surgical characteristics are lacking. METHODS: Data were prospectively collected regarding patient characteristics, cancer severity, surgeon experience, anesthetic used, operative blood loss, and transfusion among 1123 consecutive RRP cases. Multivariate regression analysis identified baseline factors associated with a homologous transfusion requirement and generated a model for predicting the likelihood of perioperative homologous transfusion. RESULTS: Homologous transfusion was administered in 3.8% of subjects; the mean estimated blood loss was 953 mL. Multivariable regression analysis identified prostate size (P <0.0001, odds ratio [OR] 1.74), use of general anesthesia (P = 0.01, OR 2.22), use of neoadjuvant hormonal therapy (P = 0.006, OR 3.35), and surgeon expertise (P <0.0001, OR 8.63) as independent risk factors associated with a need for perioperative homologous transfusion. The most influential factor, surgical expertise, clustered among surgeons who performed more than 15 RRPs annually, because these surgeons had lower transfusion rates and lower estimated blood loss more consistently than did surgeons who performed fewer RRPs annually. CONCLUSIONS: Larger prostate size, use of general anesthesia, use of neoadjuvant hormonal therapy, and annual surgeon case volume were independently associated with an increased probability that an individual patient would receive homologous transfusion during or after RRP. A nomogram indicating the probability of homologous transfusion based on these factors provides a benchmark of expected homologous transfusion rates according to individual patient and treatment parameters.

Adenocarcinoma↗

PubMed2004

Elevated alpha-methylacyl-CoA racemase enzymatic activity in prostate cancer.

Alpha-methylacyl-CoA racemase (AMACR) is a peroxisomal and mitochondrial enzyme involved in the beta-oxidation of branched fatty acids, shown to be elevated in prostate cancer by several recent studies. Sequence variants of AMACR have been linked to prostate cancer risk. Although mRNA transcript, protein, and sequence variants of AMACR have been studied in the context of prostate cancer, AMACR enzymatic activity has not been addressed. Here we present evidence that AMACR activity is consistently elevated in prostate cancer tissue specimens. This activity can be immunodepleted from prostate cancer tissue extracts. Furthermore, mock needle biopsy cores containing foci of prostate cancer exhibited increased AMACR enzymatic activity, correlating with both protein levels and histopathology. Taken together, our studies suggest that AMACR activity is increased in prostate cancer relative to benign epithelia and suggests that monitoring AMACR activity levels in prostate needle biopsies may have clinical applications.

Biomarkers, Tumor↗

PubMed2004

Racial/ethnic disparities in the treatment of localized/regional prostate cancer.

PURPOSE: Racial/ethnic disparities in the utilization of definitive therapy for prostate cancer are well recognized in the United States. The effect of race on the use of contemporary definitive therapies, including brachytherapy, and the assessment of Hispanic men with regard to racial/ethnic disparity has not been fully characterized. MATERIALS AND METHODS: We evaluated treatment patterns using Surveillance, Epidemiology and End Results registry data on 142340 localized/regional stage cases between 1992 and 1999 in white, black and Hispanic American men. Definitive therapy was defined as radical prostatectomy, external beam radiation, brachytherapy or combinations thereof. Logistic regression models were constructed to determine the odds of receiving definitive treatment, adjusting for age, marital status, tumor grade, and Surveillance, Epidemiology and End Results site. RESULTS: Black and Hispanic men were less likely to receive definitive therapy than white men (p <0.001). Higher tumor grade was associated with decreasing odds of definitive therapy for black and Hispanic men (p <0.001) compared to white men. The racial/ethnic disparities in the use of definitive therapy decreased between 1992 and 1999 with the greatest decrease in Hispanic men. CONCLUSIONS: Hispanic and black men were less likely than white men to receive definitive therapy. The disparity in the use of definitive therapy between 1992 and 1999 decreased significantly in Hispanic men, although a significant disparity in the use of definitive therapy persisted in black men. Our observation of an association between tumor grade and the racial/ethnic disparity in definitive therapy ties together relevant biological and social factors that may contribute to the observed racial/ethnic disparity in mortality.

Aged↗

PubMed2003

The role of an 80 kDa fragment of E-cadherin in the metastatic progression of prostate cancer.

PURPOSE: The purpose of this study was to evaluate an 80 kDa proteolytic fragment of E-cadherin as a potential biomarker for prostate cancer progression and to identify putative proteases that are responsible for the cleavage of E-cadherin. EXPERIMENTAL DESIGN: A wide spectrum of prostate cancer tissue and serum specimens representing different stages of prostate cancer was examined for the accumulation of the 80 kDa fragment of E-cadherin. Additionally, an expression array analysis was used to identify putative proteases that may have been involved in the cleavage of E-cadherin. RESULTS: A reproducible E-cadherin fragment was detected as a strong 80 kDa band in tissue samples. This fragment was detectable almost exclusively in metastatic sites. It was not visible in normal prostate tissue and was weak in 1 of 16 localized prostate cancers. The fragment is shed into the extracellular space and was detectable in patient serum in which the expression of the fragment showed a strong association with advanced prostate cancer. On the basis of cDNA expression analysis, several members of the metalloproteinase family could be identified as potentially responsible for the cleavage of the fragment from full-length E-cadherin. CONCLUSIONS: In this study, we present the first report of serum levels of the 80 kDa fragment of E-cadherin in prostate cancer patients. This fragment is exclusively seen in neoplastic prostate tissue and may represent a useful biomarker of prostate cancer disease progression. This study also demonstrates an association of increased levels of several metalloproteinases with metastatic prostate cancer and could provide a useful correlation between metalloproteinase expression/activity and E-cadherin cleavage and the metastatic progression of prostate cancer.

Blotting, Western↗

PubMed2003

Multiplex biomarker approach for determining risk of prostate-specific antigen-defined recurrence of prostate cancer.

BACKGROUND: Molecular signatures in cancer tissue may be useful for diagnosis and are associated with survival. We used results from high-density tissue microarrays (TMAs) to define combinations of candidate biomarkers associated with the rate of prostate cancer progression after radical prostatectomy that could identify patients at high risk for recurrence. METHODS: Fourteen candidate biomarkers for prostate cancer for which antibodies are available included hepsin, pim-1 kinase, E-cadherin (ECAD; cell adhesion molecule), alpha-methylacyl-coenzyme A racemase, and EZH2 (enhancer of zeste homolog 2, a transcriptional repressor). TMAs containing more than 2000 tumor samples from 259 patients who underwent radical prostatectomy for localized prostate cancer were studied with these antibodies. Immunohistochemistry results were evaluated in conjunction with clinical parameters associated with prostate cancer progression, including tumor stage, Gleason score, and prostate-specific antigen (PSA) level. Recurrence was defined as a postsurgery PSA level of more than 0.2 ng/mL. All statistical tests were two-sided. RESULTS: Moderate or strong expression of EZH2 coupled with at most moderate expression of ECAD (i.e., a positive EZH2:ECAD status) was the biomarker combination that was most strongly associated with the recurrence of prostate cancer. EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence in a training set of 103 patients (relative risk [RR] = 2.52, 95% confidence interval [CI] = 1.09 to 5.81; P =.021), in a validation set of 80 patients (RR = 3.72, 95% CI = 1.27 to 10.91; P =.009), and in the combined set of 183 patients (RR = 2.96, 95% CI = 1.56 to 5.61; P<.001). EZH2:ECAD status was statistically significantly associated with disease recurrence even after adjusting for clinical parameters, such as tumor stage, Gleason score, and PSA level (hazard ratio = 3.19, 95% CI = 1.50 to 6.77; P =.003). CONCLUSION: EZH2:ECAD status was statistically significantly associated with prostate cancer recurrence after radical prostatectomy and may be useful in defining a cohort of high-risk patients.

Adult↗

PubMed2003

Use of quality indicators to evaluate the care of patients with localized prostate carcinoma.

BACKGROUND: The goal of quality assurance in health care is to preserve and improve patient care. Recently, RAND developed a set of evidence-based candidate indicators for evaluating the quality of care for patients with localized prostate carcinoma; however, the feasibility and sensitivity of these indicators have not been tested in a clinical setting. The objectives of this study were to evaluate the feasibility of measuring these quality indicators and to determine their sensitivity to change in practice patterns over time. METHODS: One hundred sixty-eight men who presented in either 1995 or in 2000 and were treated for localized prostate carcinoma were selected randomly from the University of Michigan tumor registry. A combination of electronic data base review and explicit chart review was used to assess the feasibility of measuring compliance for each indicator. For each indicator in which assessment was feasible, compliance with the RAND indicators was determined for patients in both years. Multivariate regression analysis was used to adjust for potential confounding effects of disease stage, tumor grade, prostate specific antigen (PSA) level, patient age, and therapy. RESULTS: Based on review of available clinical data, measurement of compliance was feasible for 19 of 22 RAND candidate quality indicators (86%). For five indicators, significant differences in documentation (compliance) were detected between 1995 and 2000 (P < 0.05). Treatment received and higher PSA levels were associated independently with documentation of compliance for several indicators (P < 0.05). CONCLUSIONS: Measurement of the majority of the RAND quality indicators for the treatment of patients with localized prostate carcinoma was feasible, and improvements in several indicators were observed between 1995 and 2000. Demonstration of such variation, even within a single institution, suggests that the indicators are sufficiently sensitive to detect differences in practice patterns.

Aged↗