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Biomedical subjects

P R Carroll

Publications and source records attributed to P R Carroll.

At least 19 recordsLinked to original sources

Asymptomatic microscopic hematuria in adults: summary of the AUA best practice policy recommendations.

The American Urological Association (AUA) convened the Best Practice Policy Panel on Asymptomatic Microscopic Hematuria to formulate policy statements and recommendations for the evaluation of asymptomatic microhematuria in adults. The recommended definition of microscopic hematuria is three or more red blood cells per high-power microscopic field in urinary sediment from two of three properly collected urinalysis specimens. This definition accounts for some degree of hematuria in normal patients, as well as the intermittent nature of hematuria in patients with urologic malignancies. Asymptomatic microscopic hematuria has causes ranging from minor findings that do not require treatment to highly significant, life-threatening lesions. Therefore, the AUA recommends that an appropriate renal or urologic evaluation be performed in all patients with asymptomatic microscopic hematuria who are at risk for urologic disease or primary renal disease. At this time, there is no consensus on when to test for microscopic hematuria in the primary care setting, and screening is not addressed in this report. However, the AUA report suggests that the patient's history and physical examination should help the physician decide whether testing is appropriate.

Algorithms↗

Time-dependent effects of hormone-deprivation therapy on prostate metabolism as detected by combined magnetic resonance imaging and 3D magnetic resonance spectroscopic imaging.

Combined MRI and 3D spectroscopic imaging (MRI/3D-MRSI) was used to study the metabolic effects of hormone-deprivation therapy in 65 prostate cancer patients, who underwent either short, intermediate, or long-term therapy, compared to 30 untreated control patients. There was a significant time-dependent loss of the prostatic metabolites choline, creatine, citrate, and polyamines during hormone-deprivation therapy, resulting in the complete loss of all observable metabolites (total metabolic atrophy) in 25% of patients on long-term therapy. The amount and time-course of metabolite loss during therapy significantly differed for healthy and malignant tissues. Citrate levels decreased faster than choline and creatine levels during therapy, resulting in an increase in the mean (choline + creatine)/citrate ratio with duration of therapy. Due to a loss of all MRSI detectable citrate, this ratio could not be used to identify cancer in 69% of patients on long-term therapy. In the absence of citrate, however, residual prostate cancer could still be detected by elevated choline levels (choline/creatine ratio > or =1.5), or the presence of only choline in the proton spectrum. The loss of citrate and the presence of total metabolic atrophy correlated roughly with decreasing serum prostatic specific antigen levels with increasing therapy. In summary, MRI/3D-MRSI provided both a measure of residual cancer and a time-course of metabolic response following hormone-deprivation therapy. Magn Reson Med 46:49-57, 2001.

Aged↗

Dietary trial in prostate cancer: Early experience and implications for clinical trial design.

Much epidemiologic and case-controlled evidence suggests that diet may be a modifier of prostate cancer risk. However, the role of dietary modification in men known to have prostate cancer is a matter of some debate. To elucidate the effect of diet and comprehensive lifestyle changes on cancer risk, we are conducting a randomized, prospective clinical trial on men with clinically localized prostate cancer who have selected "watchful waiting" as primary therapy. Since its inception in April 1997, 93 men have been randomized to control (n = 47) or dietary and lifestyle intervention (n = 46). Patients in the intervention group are asked to eat a low-fat, soy-supplemented vegan diet and take part in stress management, psychosocial group support, and exercise programs. After 1 year, adherence to all four interventions was greater than 80%, and no deaths or adverse outcomes have occurred. To date, we have collected prostate-specific antigen and endorectal magnetic resonance imaging and spectroscopy data on 63 patients (34 control and 29 intervention). This study demonstrates that a randomized, prospective dietary trial for men with localized prostate cancer is safe and feasible. The methodologies used provide insights into practical aspects of diet design and compliance assessment that may be useful templates for future dietary trials.

Diet, Vegetarian↗

Relationship of first-year costs of treating localized prostate cancer to initial choice of therapy and stage at diagnosis: results from the CAPSURE database.

OBJECTIVES: To determine the relationship among the initial choice of therapy, stage at presentation, and first-year treatment costs in men with newly diagnosed localized prostate cancer. METHODS: First-year resource use and clinical data were collected for 235 subjects with newly diagnosed localized prostate cancer. The costs were estimated from the standard Medicare payment schedules. The relationship among the initial therapy, stage at presentation, and overall cost was examined for the entire cohort and in the subgroup of patients who underwent radical prostatectomy. In addition, the inpatient, outpatient, and medication cost components were evaluated separately to determine what influenced the changes in cost by stage. RESULTS: The mean first-year cost of treating localized prostate cancer in CaPSURE was $6375. When broken down by stage, the mean first-year cost for patients with Stage T1c was $5731, with T2a/b was $6426, and with Stage T2c was $6810 (P = 0.059). The initial treatment choice was significantly associated with the total first-year costs (P <0.001). The mean cost specifically for radical prostatectomy patients with Stage T1c disease was $6881, with T2a/b was $7216, and with T2c was $8027 (P = 0.004). The increases in the first-year cost with higher stage appeared to primarily be associated with increased inpatient resource use and the greater use of adjuvant hormonal therapy. CONCLUSIONS: The first-year costs of treating localized prostate cancer in CaPSURE are associated with the choice of primary and adjuvant therapy. This supports the notion that cost savings may be possible with earlier detection of disease or by minimizing the use of hormonal adjuvant therapy.

Aged↗

Intermittent androgen deprivation: update of cycling characteristics in patients without clinically apparent metastatic prostate cancer.

OBJECTIVES: To update the cycling characteristics and patterns of treatment in patients receiving intermittent androgen deprivation (IAD) for clinically localized and recurrent prostate cancer. METHODS: We report our experience with 61 patients treated with IAD. Thirty-four patients had received no prior treatment, and 27 had developed recurrent disease after previous local therapy. No patient had clinically apparent metastatic disease before the initiation of therapy. The mean and median serum prostate-specific antigen (PSA) level before treatment was 25.3 ng/mL and 16.0 ng/mL, respectively (range 0.5 to 190 ng/mL). For each cycle, androgen deprivation was continued until PSA became undetectable or a nadir level was reached. Patients were then observed without treatment, and therapy was reinstituted after the serum PSA value reached a predetermined level. Patients were no longer eligible to cycle off treatment when their serum PSA increased despite ongoing androgen deprivation or if any objective evidence of disease progression was present on imaging studies. RESULTS: Follow-up ranged from 7 to 60 months (mean 30) from the start of treatment. Patients received from one to five treatment cycles (median two), with a median cycle length of 14 months. The median nadir serum PSA level during androgen deprivation was 0.01 ng/mL and was reached within an average of 6 months (range 4 to 9) after beginning treatment. Patients spent an average of 45% of the time not receiving therapy, but the time off therapy decreased as the number of treatment cycles increased. Five patients (8.1%) demonstrated progressive disease, with a median time to progression of 48 months. When examining the cycling characteristics of these patients, no consistent pattern of failure emerged. CONCLUSIONS: IAD appears to be a viable treatment option in select patients with localized prostate cancer. With each consecutive cycle, the amount of time the patient was not receiving therapy decreased, despite achieving a low nadir PSA. Longer follow-up with more patients failing IAD will be required before clear patterns of failure emerge in these patients.

Aged↗

Androgen deprivation therapy for patients with clinically localized (stages T1 to T3) prostate cancer and for patients with biochemical recurrence after radical prostatectomy.

Recently published studies suggest a benefit for androgen deprivation therapy (ADT) delivered early in the course of prostate cancer. However, the use of ADT specifically in patients with clinically localized disease or biochemical-disease recurrence after local therapy is not well defined. Potential candidates for primary ADT include patients who are poor candidates for definitive local therapy because of advanced age or comorbid conditions, as well as patients with significant local disease who refuse standard therapy. Treatment strategies designed to minimize the side effects of prolonged therapy, such as intermittent ADT or antiandrogen monotherapy, show promise as alternatives to continuous ADT in some patients. The role of ADT in patients with clinically localized and recurrent prostate cancer, whether it is delivered in a continuous or intermittent fashion, must be determined in randomized, prospective trials.

Androgen Antagonists↗

The effect of androgen deprivation therapy on health-related quality of life in men with prostate cancer.

Treatment for prostate cancer has a significant impact on health-related quality of life (HRQOL). We examined HRQOL in a cohort of men receiving androgen deprivation therapy (ADT) and a cohort who opted for surveillance. The cohort consisted of 1178 newly diagnosed patients from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database (a national longitudinal registry of patients with prostate cancer). General and disease-specific HRQOL outcomes were measured with validated instruments (the SF-36 and University of California at Los Angeles [UCLA] Prostate Cancer Index) at study entry and quarterly thereafter. Individuals were grouped by initial treatment: ADT, surveillance, radical prostatectomy, or radiation therapy. There were 106 men who selected surveillance, 167 men receiving ADT, 351 men treated by radical prostatectomy, and 75 men receiving radiation therapy in the first year after diagnosis. Mean age at diagnosis was 73 years of age, with surveillance patients the oldest and radical prostatectomy patients the youngest. Men receiving ADT reported poorer urinary and sexual function and a higher rate of urinary and sexual bother than patients selecting surveillance. ADT and surveillance HRQOL scores remained low (ie, poorer function) in the year after treatment, whereas men undergoing radical prostatectomy showed improvement in these scales. Patients who received ADT had reduced energy, poorer sexual and urinary function, and were more bothered by their urine and sexual function than patients undergoing other treatments, except surveillance. Longer follow-up time after start of ADT and surveillance is needed to discern the impact of comorbidities on HRQOL.

Age Factors↗

Localized prostate cancer: effect of hormone deprivation therapy measured by using combined three-dimensional 1H MR spectroscopy and MR imaging: clinicopathologic case-controlled study.

PURPOSE: To determine the accuracy of combined magnetic resonance (MR) imaging and three-dimensional (3D) proton MR spectroscopic imaging in localizing prostate cancer to a sextant of the gland in patients receiving hormone deprivation therapy. MATERIALS AND METHODS: Combined MR imaging/3D MR spectroscopic imaging examinations were performed in 16 hormone-treated patients and 48 nontreated matched control patients before radical prostatectomy and step-section histopathologic analysis. At MR imaging, cancer presence within the peripheral zone was assessed on a per sextant basis by two readers. At 3D MR spectroscopic imaging, cancer was identified by using (choline plus creatine)-to-citrate ratios at cutoff values of 2 and 3 SDs above mean normal peripheral zone values. Data were compared by using receiver operating characteristic analysis. RESULTS: There was no significant difference in the ability of combined MR imaging/3D MR spectroscopic imaging to localize prostate cancer in treated versus control patients. For MR imaging alone, the sensitivity and specificity were 91% and 48% (reader 1) and 75% and 60% (reader 2) in treated patients versus 79% and 60% (reader 1) and 84% and 43% (reader 2) in control patients. For 3D MR spectroscopic imaging alone (>3 SDs cutoff), higher specificity (treated, 80%; controls, 73%) but lower sensitivity (treated, 56%; controls, 53%) was attained. In treated patients, high sensitivity or specificity (up to 92%) was achieved when either or both modalities indicated cancer. CONCLUSION: When performed within 4 months after initiating hormone deprivation therapy, combined MR imaging/3D MR spectroscopic imaging had the same accuracy in localizing prostate cancer as in nontreated patients.

Antineoplastic Agents, Hormonal↗

Under staging and under grading in a contemporary series of patients undergoing radical prostatectomy: results from the Cancer of the Prostate Strategic Urologic Research Endeavor database.

PURPOSE: We determined the prevalence of under staging and under grading in contemporary patients undergoing radical prostatectomy in academic and community based urology practices, and defined important predictors of under staging in this population. MATERIALS AND METHODS: We compared clinical T stage and biopsy Gleason score with pathological T stage and prostatectomy Gleason score in 1,313 patients enrolled in the Cancer of the Prostate Strategic Urologic Research Endeavor database, a longitudinal registry of patients with prostate cancer, who underwent radical prostatectomy, including 53% since 1995. Under grading was determined for the primary and secondary Gleason patterns and defined as a biopsy Gleason pattern of 1 to 3 that became pathological Gleason pattern 4 or 5. Under staging was defined as a clinically organ confined tumor that was extraprostatic stages pT3 to 4 or N+ at radical prostatectomy. Univariate and multivariate analysis was performed to determine important risk factors for under staging and significant risk factors were used to identify the likelihood of under staging in clinically relevant patient subgroups. The importance of the percent of positive biopsies in regard to the likelihood of under staging was determined by assigning patients to previously described risk groups based on serum prostate specific antigen (PSA) at diagnosis and biopsy Gleason score. RESULTS: Under grading of primary and secondary Gleason patterns occurred in 13% and 29% of patients, respectively, while under staging occurred in 24%. Univariate and multivariate analysis revealed that PSA at diagnosis, biopsy Gleason score and the percent of positive biopsies were significant predictors of under staging. The percent of positive biopsies appeared to be most important for predicting the likelihood of extraprostatic disease extension in intermediate or high risk disease based on serum PSA at diagnosis and biopsy Gleason grade. CONCLUSIONS: The prevalence of under grading and under staging in contemporary patients undergoing radical prostatectomy may be lower than previously reported. PSA at diagnosis, biopsy Gleason score and the percent of positive biopsies are important predictors of under staging. The percent of positive biopsies should be incorporated into risk assessment models of newly diagnosed prostate cancer.

Aged↗

Prostate cancer detection in men with prior high grade prostatic intraepithelial neoplasia or atypical prostate biopsy.

PURPOSE: We used clinical variables to predict prostate cancer detection on re-biopsy among patients diagnosed with high grade prostatic intraepithelial neoplasia (PIN) or atypia on initial prostate biopsy. MATERIALS AND METHODS: A total of 45 men with atypia and 43 with high grade PIN were eligible for our study. Clinical variables were tested with univariate and multivariate logistic regression to predict who would have cancer on re-biopsy. We also calculated the odds of detecting cancer with various repeat sampling strategies and determined whether the location of initial atypia or high grade PIN is correlated to that of cancer on re-biopsy. RESULTS: Of the patients in the atypia and high grade PIN groups 51% had cancer on re-biopsy. Cancer was diagnosed significantly earlier in the high grade PIN than in the atypia cohort (average 7.5 versus 22.9 months, respectively, p = 0.005). Multivariate logistic modeling showed that digital rectal examination and patient age were independent predictors of cancer in atypia, whereas no variables were significantly predictive for high grade PIN. Of cancers in the atypia and high grade PIN 65% and 74%, respectively, would have been detected if re-biopsy was focused only at the initial site of disease. CONCLUSIONS: Men with atypia or high grade PIN merit close followup because 50% will have cancer on re-biopsy as will those who are older with an abnormal digital rectal examination. Although re-biopsy should focus primarily on the original site of atypia or high grade PIN, cancer detection significantly increases with the sampling of adjacent sites.

Aged↗

Is anastomotic biopsy necessary before radiotherapy after radical prostatectomy?

PURPOSE: External beam radiotherapy may be given after radical prostatectomy as adjuvant (immediate) or therapeutic (delayed) treatment, the latter in response to evidence of disease recurrence. In patients receiving delayed radiotherapy the necessity of a positive anastomotic biopsy before treatment remains unclear. We determined whether a positive anastomotic biopsy predicted the response to radiation in this setting. MATERIALS AND METHODS: We reviewed the records of 67 patients who received radiotherapy for biochemical or biopsy proved recurrent prostate cancer after radical prostatectomy. Patients underwent surgery at our institution or its affiliated hospitals, or were referred to our institution for radiotherapy. All patients had a negative metastatic evaluation before receiving radiotherapy. Biochemical failure after radiotherapy was defined as serum prostate specific antigen (PSA) 0.2 ng./dl. or greater on 2 or more consecutive occasions. Biochemical recurrence-free survival was calculated using the Kaplan-Meier method. Independent predictors of PSA failure after radiotherapy were identified using the multivariate Cox proportional hazards model. RESULTS: Of the 67 patients evaluated 33 and 34 received radiotherapy for biochemical failure and biopsy proved local recurrence, respectively. The 3-year recurrence-free survival rate was 49% in patients treated for biochemical failure and 39% in those with biopsy proved local recurrence. There was no significant difference in PSA-free survival in these 2 groups. Only pre-radiotherapy PSA 1 ng./dl. or greater (p = 0.02) and seminal vesicle invasion (p = 0.02) were significant independent predictors of biochemical failure. CONCLUSIONS: A positive anastomotic biopsy did not predict an improved outcome after radiotherapy following radical prostatectomy. Anastomotic biopsy was associated with a longer time to salvage radiotherapy. However, this delay did not translate into worse disease-free outcomes in patients who underwent anastomotic biopsy. High pre-radiotherapy PSA greater than 1 ng./ml. was the most significant predictor of biochemical failure after therapeutic radiotherapy. Decisions regarding local radiation therapy after radical prostatectomy may be made without documenting recurrent local disease.

Aged↗

Predicting risk of prostate specific antigen recurrence after radical prostatectomy with the Center for Prostate Disease Research and Cancer of the Prostate Strategic Urologic Research Endeavor databases.

PURPOSE: Biostatistical models to predict stage or outcome in patients with clinically localized prostate cancer with pretreatment prostate specific antigen (PSA), Gleason sum on biopsy or prostatectomy specimen, clinical or pathological stage and other variables, including ethnicity, have been developed. However, to date models have relied on small subsets from academic centers or military populations that may not be representative. Our study validates and updates a model published previously with the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE, UCSF, Urology Outcomes Research Group and TAP Pharmaceutical Products, Inc.), a large multicenter, community based prostate cancer database and Center for Prostate Disease Research (CPDR), a large military database. MATERIALS AND METHODS: We validated a biostatistical model that includes pretreatment PSA, highest Gleason sum on prostatectomy specimen, prostatectomy organ confinement status and ethnicity, including white and black patients. We then revised it with the Cox regression analysis of the combined 503 PSA era surgical cases from the CPDR prospective cancer database and 1,012 from the CaPSURE prostate cancer outcomes database. RESULTS: The original equation with 3 risk groups stratified CaPSURE cases into distinct categories with 7-year disease-free survival rates of 72%, 42.1% and 27.6% for low, intermediate and high risk men, respectively. Parameter estimates obtained from a Cox regression analysis provided a revised model equation that calculated the relative risk of recurrence as: exponent (exp)[(0.54 x Race) + (0.05 x sigmoidal transformation of PSA [PSA(ST)]) + (0.23 x Postop Gleason) + (0.69 x Pathologic stage). The relative risk of recurrence, as calculated by the aforementioned equation, was used to stratify the cases into 4 risk groups. Very low-4.7 or less, low-4.7 to 7.1, high-7.1 to 16.7 and very high-greater than 16.7, and patients at risk had 7-year disease-free survival rates of 85.4%, 66.0%, 50.6% and 21.3%, respectively. CONCLUSIONS: With a broad cohort of community based, academic and military cases, we developed an equation that stratifies men into 4 discrete risk groups of recurrence after radical prostatectomy and confirmed use of a prior 3 risk group model. Although the variables of ethnicity, pretreatment PSA, highest Gleason sum on prostatectomy specimen and organ confinement status on surgical pathology upon which the model is based are easily obtained, more refined modeling with additional variables are needed to improve prediction of intermediate risk in individuals.

Databases, Factual↗

Minichromosome maintenance protein 2 expression in prostate: characterization and association with outcome after therapy for cancer.

The minichromosome maintenance (MCM) proteins are highly conserved proteins essential for initiating and regulating eukaryotic DNA replication. Recent studies have demonstrated the potential use of MCM proteins as markers of proliferation. We characterized the pattern of Mcm 2 staining in benign and malignant prostate tissues and examined the role of Mcm 2 expression in disease-free survival after surgery in men with localized prostate cancer. Tumors from 92 patients who underwent radical prostatectomy for prostate cancer (median follow-up of 54 months) were examined for Mcm 2 expression by immunohistochemistry using a monoclonal antibody. Prostate tissue from five men without histopathological evidence of prostate cancer was also stained for Mcm 2. Mcm 2 expression was quantified by calculating a labeling index, and patients were grouped according to degree of staining. An analysis of the association between Mcm 2 expression with traditional clinicopathological characteristics of prostate cancer was carried out. A Cox proportional hazards analysis was performed to determine whether Mcm 2 staining was a significant independent predictor of disease-free survival. Mcm 2 expression is low (<2%) and limited to the basal cell layer in nonmalignant prostate glands. Mcm 2 expression is consistently increased in malignant glands and is significantly associated with disease-free survival in univariate (P = 0.002) and multivariate (P = 0.01) analyses. Patients with high Mcm 2 expression exhibited shorter disease-free survival. Mcm 2 expression was not associated with any traditional clinical or pathological factors and therefore is an independent predictor of survival in these patients with prostate cancer. These data support evidence that Mcm 2 may serve as a novel proliferation marker in the prostate. Mcm 2 expression is an independent predictor of disease-free survival after definitive local therapy and has potential as a molecular marker for clinical outcome in prostate cancer.

Adenocarcinoma↗