Biomedical subjects

M W Kattan

Publications and source records attributed to M W Kattan.

At least 19 recordsLinked to original sources

PubMed1998

A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer.

BACKGROUND: Few published studies have combined clinical prognostic factors into risk profiles that can be used to predict the likelihood of recurrence or metastatic progression in patients following treatment of prostate cancer. We developed a nomogram that allows prediction of disease recurrence through use of preoperative clinical factors for patients with clinically localized prostate cancer who are candidates for treatment with a radical prostatectomy. METHODS: By use of Cox proportional hazards regression analysis, we modeled the clinical data and disease follow-up for 983 men with clinically localized prostate cancer whom we intended to treat with a radical prostatectomy. Clinical data included pretreatment serum prostate-specific antigen levels, biopsy Gleason scores, and clinical stage. Treatment failure was recorded when there was clinical evidence of disease recurrence, a rising serum prostate-specific antigen level (two measurements of 0.4 ng/mL or greater and rising), or initiation of adjuvant therapy. Validation was performed on a separate sample of 168 men, also from our institution. RESULTS: Treatment failure (i.e., cancer recurrence) was noted in 196 of the 983 men, and the patients without failure had a median follow-up of 30 months (range, 1-146 months). The 5-year probability of freedom from failure for the cohort was 73% (95% confidence interval = 69%-76%). The predictions from the nomogram appeared accurate and discriminating, with a validation sample area under the receiver operating characteristic curve (i.e., comparison of the predicted probability with the actual outcome) of 0.79. CONCLUSIONS: A nomogram has been developed that can be used to predict the 5-year probability of treatment failure among men with clinically localized prostate cancer treated with radical prostatectomy.

Adult↗

PubMed1998

Assessment of the biologic markers p53, Ki-67, and apoptotic index as predictive indicators of prostate carcinoma recurrence after surgery.

BACKGROUND: This study was designed to evaluate the potential of the molecular and cellular markers p53, Ki-67, and apoptotic index (AI) as adjuncts to the commonly available variables of tumor grade, clinical stage, and serum prostate specific antigen to predict prostate carcinoma recurrence after radical prostatectomy. METHODS: Representative punch biopsy specimens of prostate carcinoma from whole mount paraffin blocks were evaluated from 47 men who underwent radical prostatectomy. Two groups were defined: those without evidence of prostate carcinoma recurrence after 5 years of follow-up (N = 30) and those with carcinoma recurrence (N = 17). Gleason grade, clustered p53 immunostaining, Ki-67 immunostaining, and AI were determined by standard techniques. RESULTS: All variables tested were associated with disease recurrence by univariate analysis: AI (P = 0.005), clustered p53 immunostaining (P = 0.0070), and Ki-67 immunostaining (P = 0.0390). Using multivariate analyses that included each biomarker with routinely available features, only AI (P = 0.0234) and clustered p53 immunostaining (P = 0.0389) added independent prognostic information (Ki-67 immunostaining, P = 0.1285). In the final logistic regression model that included standard variables with AI and p53, only AI reached statistical significance (P = 0.0332). CONCLUSIONS: The continued assessment of additional biomarkers for prostate carcinoma recurrence is important to identify better those patients who may be candidates for early adjuvant therapy and also to further our understanding of the neoplastic potential of a particular malignancy.

Aged↗

PubMed1998

Quantitative immunohistochemical analysis of insulin-like growth factor binding protein-3 in human prostatic adenocarcinoma: a prognostic study.

PURPOSE: We sought to characterize and quantitate the expression of IGFBP-3 in adenocarcinoma of the prostate and to test whether it correlated with tumor differentiation determined by Gleason grade. We also investigated the potential of using IGFBP-3 as a prognostic indicator of clinically localized prostate cancer. MATERIALS AND METHODS: Initially we evaluated the expression of IGFBP-3 in six normal and twenty neoplastic prostates using standard immunohistochemical techniques (study 1). We then obtained radical prostatectomy specimens from twenty-four patients with a preoperative diagnosis of clinically localized prostate adenocarcinoma and five year follow up information, and nine normal prostates from organ donors or from patients undergoing cystoprostatectomy (study 2). All specimens were immunostained with a polyclonal anti-human IGFBP-3 antibody. A single pathologist reviewed all sections and assigned a Gleason grade to each cancer focus. Using computer-assisted video image analysis, we quantified the intensity of IGFBP-3 immunostaining of each cancer focus and of normal controls. RESULTS: Normal prostatic epithelium showed intense cytoplasmic IGFBP-3 staining. The stromal compartment showed less intense staining, although there were occasional areas with strong immunoreactivity. The cellular distribution of IGFBP-3 staining in prostatic adenocarcinoma was comparable to normal tissue; however, the intensity of detectable staining in neoplastic epithelial cells was significantly decreased. Two foci of prostatic intraepithelial neoplasia (PIN) demonstrated IGFBP-3 immunoreactivity decreased in comparison to normal epithelium, but greater than prostatic adenocarcinoma. Histologically normal epithelium surrounding cancer foci also showed decreased immunostaining for IGFBP-3 compared with normal prostate. The marked decrease in immunostaining intensity of IGFBP-3 in prostate adenocarcinoma was not associated with Gleason grade or with clinical outcome. CONCLUSION: Malignant transformation of prostatic epithelium was associated with a significant decrease in the amount of immunoreactive IGFBP-3 (p <0.0001); however, this parameter did not correlate with Gleason grade of the tumor or with patient outcome. The decrease in immunostaining intensity of IGFBP-3 in all Gleason grades and in PIN suggests that lower expression of IGFBP-3 is an early event in prostatic carcinogenesis. The finding that decreased IGFBP-3 immunostaining did not correlate with clinical outcome suggests that this parameter is not a therapy-guiding prognostic indicator for clinically localized prostate cancer.

Adenocarcinoma↗

PubMed1998

Prostate-specific antigen doubling times are similar in patients with recurrence after radical prostatectomy or radiotherapy: a novel analysis.

PURPOSE: Some investigators have analyzed the rate of growth of prostate cancer that has recurred after definitive radiotherapy or radical prostatectomy using serum prostate-specific antigen (PSA) doubling times (DT). We examined all PSA values in recurrent patients to determine the pattern and rate of increase in PSA after radiation therapy and radical prostatectomy. PATIENTS AND METHODS: Charts of 96 recurrent radical prostatectomy patients (mean age, 62.8 years; range, 47 to 76) and 42 recurrent radiation therapy patients (mean age, 67.2 years; range, 52 to 83) were reviewed. All available PSA values between the date of operation/radiation treatment and last follow-up evaluation or the initiation of second-line therapy are included. Rate of PSA DT was not assumed to be constant over time; it was instead allowed to vary. We use a piecewise linear random-coefficients model in time for log (PSA), which allowed different mean models for both treatments. RESULTS: The PSA DT in the first year after radiation therapy was--1.17 years, which reflects the continuous decline in PSA in the average patients during the first year after radiotherapy despite eventual biochemical progression. In contrast, the PSA DT in the radical prostatectomy group was 0.66 in the first year. In year 2, after radiation therapy, the PSA DT was lengthy at 1.82 years, significantly longer (P = .0025) than in the radical prostatectomy group (0.76 years). After year 2, there were no significant differences between the two groups (P > .05). CONCLUSION: A piecewise linear random-coefficients model enables interval analysis of PSA DT. While the PSA DT after radiation therapy and radical prostatectomy are different in the first 2 years, the rate of increase in PSA appears to be similar in the two groups after year 2, which suggests the rate of growth of cancers that recur after radiation therapy and radical prostatectomy is similar.

Aged↗

PubMed1998

The correlation of urodynamic findings with cranial magnetic resonance imaging findings in multiple sclerosis.

PURPOSE: To our knowledge there are no studies of the correlation between urinary complaints or urodynamic findings in multiple sclerosis and magnetic resonance imaging (MRI) findings. We investigated the correlation of urodynamic results in multiple sclerosis patients with voiding complaints to the cranial MRI findings. We also sought to correlate urodynamic results in these patients with International Prostate Symptom Scores (IPSS). MATERIALS AND METHODS: We retrospectively reviewed urodynamic results and cranial MRI findings in 90 multiple sclerosis patients (64 women, 26 men, mean age 44.5 years) with voiding complaints. The most recent urodynamic study and cranial MRI for each patient were reviewed. The interval between the 2 studies and MRI was no more than 6 months. Detrusor contractions were categorized as areflexic, hyporeflexic, hyperreflexic or hyperreflexic with impaired contractility. The presence of impaired compliance or detrusor-external sphincter dyssynergia was recorded. The cranial MRI findings were categorized on the basis of the presence of atrophy or enhancing lesions, total number of lesions and size of largest lesion. The urodynamic and MRI findings were correlated. Of the patients 40 who had urodynamic studies done within the last 6 months completed the IPSS, and severity of cranial MRI findings in these patients was correlated with the IPSS results. In addition, the presence of irritative findings of detrusor hyperreflexia or detrusor hyperreflexia with impaired contractility was correlated with the irritative score (sum of questions 1, 2, 4, 7), and the presence of detrusor-external sphincter dyssynergia was correlated with the obstructive score (sum of questions 3, 5, 6). RESULTS: There was no correlation between urodynamic category, presence of impaired compliance or presence of detrusor-external sphincter dyssynergia and any of the MRI findings of atrophy or enhancing lesions, total number of lesions or size of the largest lesions. In the patients who completed the IPSS there was no correlation between total number of lesions and IPSS score. There was no correlation between the presence of detrusor-external sphincter dyssynergia and obstructive score on the IPSS or between the presence of detrusor hyperreflexia and irritative score. CONCLUSIONS: Although patients with multiple sclerosis often are followed closely with urodynamic studies and cranial MRI, there appears to be no correlation between these 2 studies. Symptom scores also do not appear to correlate with urodynamic findings. Therefore, urodynamic studies appear to be warranted and irreplaceable in the evaluation of voiding dysfunction in multiple sclerosis patients.

Adolescent↗

PubMed1997

Androgen-independent prostate cancer progression in the TRAMP model.

We previously established the autochthonous transgenic adenocarcinoma mouse prostate (TRAMP) model to facilitate characterization of molecular mechanisms involved in the initiation and progression of prostate cancer. TRAMP mice display high grade prostatic intraepithelial neoplasia or well-differentiated prostate cancer by 10-12 weeks of age. To test the hypothesis that molecular events leading to androgen independence and metastasis can occur early in the natural history of prostate cancer yet remain silent until selective pressures such as androgen deprivation are applied, we have examined the consequences of castration on the initiation and progression to metastatic prostate cancer in TRAMP mice. Cohorts were castrated at 12 weeks of age and sacrificed at 18 (T12/18) or 24 (T12/24) weeks of age, and the development of primary cancer and metastatic disease was compared to noncastrated (T18 and T24) controls. Median T12/18 and T12/24 genitourinary (GU) weight was significantly less than T18 and T24, respectively. In addition, T12/24 GU weight was significantly greater than T12/18. Histological prostate tumors developed in 3 of 7 T12/18 and 8 of 10 T12/24 mice. All tumors that developed in castrated mice were poorly differentiated in contrast to 27% in noncastrated controls. Although castration significantly decreased GU tumor burden, overall progression to poorly differentiated and metastatic disease was not ultimately delayed. These results demonstrate that prostate cancer in the TRAMP model is heterogeneous with respect to androgen dependence as early as 12 weeks of age; therefore, early androgen ablation may have a variable impact on progression in an individual mouse. Further analysis of this prostate cancer model to identify specific molecular mechanisms that determine androgen sensitivity may facilitate future initiation of appropriate individualized hormonal therapy for the management of human prostate cancer.

Adenocarcinoma↗

PubMed1997

Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update.

OBJECTIVE: To combine the clinical data from 3 academic institutions that serve as centers of excellence for the surgical treatment of clinically localized prostate cancer and develop a multi-institutional model combining serum prostate-specific antigen (PSA) level, clinical stage, and Gleason score to predict pathological stage for men with clinically localized prostate cancer. DESIGN: In this update, we have combined clinical and pathological data for a group of 4133 men treated by several surgeons from 3 major academic urologic centers within the United States. Multinomial log-linear regression was performed for the simultaneous prediction of organ-confined disease, isolated capsular penetration, seminal vesicle involvement, or pelvic lymph node involvement. Bootstrap estimates of the predicted probabilities were used to develop nomograms to predict pathological stage. Additional bootstrap analyses were then obtained to validate the performance of the nomograms. PATIENTS AND SETTINGS: A total of 4133 men who had undergone radical retropubic prostatectomy for clinically localized prostate cancer at The Johns Hopkins Hospital (n=3116), Baylor College of Medicine (n=782), and the University of Michigan School of Medicine (n=235) were enrolled into this study. None of the patients had received preoperative hormonal or radiation therapy. OUTCOME MEASURES: Simultaneous prediction of organ-confined disease, isolated capsular penetration, seminal vesicle involvement, or pelvic lymph node involvement using updated nomograms. RESULTS: Prostate-specific antigen level, TNM clinical stage, and Gleason score contributed significantly to the prediction of pathological stage (P<.001). Bootstrap estimates of the median and 95% confidence interval of the predicted probabilities are presented in the nomograms. For most cells in the nomograms, there is a greater than 25% probability of qualifying for more than one of the pathological stages. In the validation analyses, 72.4% of the time the nomograms correctly predicted the probability of a pathological stage to within 10% (organ-confined disease, 67.3%; isolated capsular penetration, 59.6%; seminal vesicle involvement, 79.6%; pelvic lymph node involvement, 82.9%). CONCLUSIONS: The data represent a multi-institutional modeling and validation of the clinical utility of combining PSA level measurement, clinical stage, and Gleason score to predict pathological stage for a group of men with localized prostate cancer. Clinicians can use these nomograms when counseling individual patients regarding the probability of their tumor being a specific pathological stage; this will enable patients and physicians to make more informed treatment decisions based on the probability of a pathological stage, as well as risk tolerance and the values they place on various potential outcomes.

Decision Support Techniques↗

PubMed1997

Evaluation of a nomogram used to predict the pathologic stage of clinically localized prostate carcinoma.

BACKGROUND: A Nomogram based on pretreatment prostate specific antigen (PSA) level, tumor grade, and clinical stage has recently been developed and distributed to physicians. It was distributed to aid physicians in making treatment recommendations by predicting the probability of the final pathologic stage of clinically localized prostate carcinoma. The Nomogram was based on data for one patient population, and the validity of its application in general urologic practices had not yet been evaluated. METHODS: In the current study, the authors tested the performance of the Nomogram against data from their series of 697 men who underwent radical prostatectomy during the PSA era. Predictions made with the Nomogram were applied to the authors' data set, and the predictions were compared with actual outcomes of the authors' patients. A localized least-squares regression smoothing technique was used to determine whether the Nomogram was calibrated accurately for the authors' data and whether it discriminated across a full spectrum of patient characteristics. RESULTS: Many of the predicted probabilities of the Nomogram were accurate, but some were suboptimal when applied to the authors' data set. Although the Nomogram did discriminate quite well between organ-confined and nonconfined cancer, it had difficulty predicting high probabilities of seminal vesicle invasion and lymph node metastasis, which are the pathologic features with the most profound impact on prognosis. CONCLUSIONS: The Nomogram predicted organ-confined disease accurately. However, because not all of its predictions were completely calibrated when applied to the authors' data set, the authors conclude that the Nomogram may not be totally applicable to general urologic practice until further validation and possible modifications are performed.

Data Interpretation, Statistical↗

PubMed1997

Prostate-specific antigen (PSA) and PSA density: racial differences in men without prostate cancer.

BACKGROUND: Many physicians now use serum prostate-specific antigen (PSA) to screen for prostate cancer in asymptomatic men. Whether or not a prostate biopsy should also be performed depends on an accurate definition of what constitutes a normal PSA value. Until recently, studies conducted to establish normal serum PSA values have involved study populations that have included few African-American men. PURPOSE: We sought to compare serum PSA levels and PSA density (i.e., serum PSA level/prostate volume ratio) in African-American and white men without histologic evidence of prostate cancer. METHODS: We reviewed the medical records of 826 consecutive men who underwent one or more prostate biopsies at the Veterans Affairs Medical Center in Shreveport, LA, from January 1993 through December 1995. In this retrospective review, we recorded patient's age, race, serum PSA level, digital rectal examination result, ultrasound-determined prostate volume, indications for biopsy, and biopsy results. Data from a total of 752 consecutive men who were either white or African-American and whose indication for biopsy included a serum PSA of greater than 4.0 ng/mL and/or an abnormal digital rectal examination were analyzed. To examine possible differences in serum PSA level, PSA density, prostate volume, and patient age, the two-sided Student's t test was employed. Multivariate linear regression analysis was used to determine if serum PSA levels were associated with the patient's age, race, or prostate volume in men without prostate cancer. RESULTS: Of the 752 men included in this analysis, 254 had histologic evidence of prostate cancer and 498 did not. Of the 498 men without prostate cancer, 367 (74%) men were white and 131 (26%) were black. There were no racial differences in age or calculated prostate volume. Serum PSA levels and calculated PSA density, however, were significantly (both P < .0001) higher in African-American men that in white men. A multivariate linear regression analysis indicated that race and prostate volume were independent variables associated with serum PSA level. For African-American and white men, serum PSA values of greater than 4 ng/mL were associated with prostate cancer with sensitivities of 89.5% and 81.9%, respectively, and specificities of 38.2% and 52.3%, respectively. CONCLUSION: Among biopsied men without histologic evidence of prostate cancer, African-Americans have a significantly higher PSA level and PSA density than similarly aged white men. IMPLICATIONS: Published criteria for normal PSA level and density have been derived primarily from white men and may not be directly applicable to other populations. Race-specific data are needed to fully optimize PSA as a tumor marker in racial populations that are at high risk for prostate cancer death.

Adult↗

PubMed1997

Adenovirus-mediated suicide gene therapy for experimental bladder cancer.

OBJECTIVES: To determine the feasibility, safety, and efficacy of suicide gene therapy using adenoviral-mediated herpes simplex virus thymidine kinase gene (HSV-tk) and the prodrug ganciclovir (GCV) in a murine model of human transitional cell carcinoma. METHODS: We used a replication-defective adenoviral construct containing the beta-galactosidase gene (ADV/Rous sarcoma virus [RSV]-beta-gal) as a control or ADV/RSV-tk as the therapeutic vector under the transcriptional control of the RSV long-terminal repeat promoter. Transduction efficiency was assessed in vitro by infection of MBT-2 cells with ADV/RSV-beta-gal at various multiplicities of infection (MOI) utilizing 5-bromo-4-chlor-3-indolyl-beta-D-galactoside (X-gal) staining. Sensitivity of MBT-2 cells to the therapeutic vector was determined after infection with ADV/RSV-tk with or without GCV. Subcutaneous tumors were established in syngeneic C3H/He female mice with 5 x 10(5) MBT-2 cells. Optimal dosing of ADV/RSV-tk was determined by direct percutaneous tumor injection with increasing viral doses and treatment with GCV. Treatment efficacy, long-term survival, and toxicity were determined in separate, similar, controlled experiments. RESULTS: In vitro studies indicated greater than 95% transduction 96 hours after inoculation at an MOI of 3000 and a greater than 95% cell death rate with RSV-tk + GCV at an MOI of 61 or greater. In vivo experiments demonstrated an optimal viral dose of 3 x 10(8) plaque-forming units (pfu) and a greater than fourfold reduction in tumor growth for the animals treated with ADV/RSV-tk compared with control animals (P = 0.0013). Toxicity was limited to histologic evidence of hepatitis with ADV/RSV-tk doses greater than 3 x 10(8) pfu + GCV. Long-term survival of treatment animals was significantly increased over that of control animals (59%, P = 0.0001). CONCLUSIONS: ADV/RSV-tk with GCV treatment results in efficient gene transfer in vitro and provides effective therapy in experimental murine bladder cancer by significantly inhibiting tumor growth and improving host survival.

Adenoviridae↗

PubMed1997

Hazard rates for progression after radical prostatectomy for clinically localized prostate cancer.

OBJECTIVES: We calculated the annual hazard rate (HR) for prostate cancer recurrence after radical prostatectomy (RP) to elucidate the pattern of treatment failure over time and to assess the efficacy of definitive therapy. METHODS: We calculated the progression-free probabilities (PFP) and HRs after RP for a cohort of 611 consecutive men with clinically localized (cT1-2, NX, M0) prostate cancer and no other treatment before documented progression. RESULTS: PFP for the entire study population was 78% at 5 and 76% at 10 years. The highest HR (0.09) was observed in the year immediately after surgery and dropped to 0 by year 7 (no patient recurred after year 6). Average annual HRs calculated for 3-year intervals resulted in steadily declining HRs over time for the entire study population and for all subsets, except those with a cancer pathologically confined to the prostate. Overall, the more ominous the prognostic factor, the higher the initial HR. For poorly differentiated cancers (biopsy Gleason sum 8 to 10), the HR was high in years 1 and 2 and dropped rapidly to 0 thereafter. CONCLUSIONS: Prostate-specific antigen (PSA) progression after RP usually occurred early (77% within the first 2 years) and was largely due to understaging. Late recurrences were rare in patients who were regularly evaluated with PSA. However, because the confidence intervals in our study were broad, larger patient populations with longer follow-up are needed for a definitive establishment of the time, course, and pattern of recurrence after surgery.

Adenocarcinoma↗

PubMed1997

Correlation of urodynamic results and urethral coaptation with success after transurethral collagen injection.

OBJECTIVES: We correlated preoperative urodynamic and intraoperative endoscopic findings with initial improvement, single collagen injection effectiveness for intrinsic sphincter deficiency (ISD), and long-term improvement following transurethral collagen injection for stress urinary incontinence (SUI). METHODS: Since 1993, 79 patients have been treated with transurethral collagen injection by the same urologist. Of these patients, intraoperative photographs of urothelial coaptation immediately after injection were available in 67 patients: 35 women with ISD, 24 men with incontinence, primarily following prostatectomy, and 8 children with neurogenic bladder. Urothelial coaptation was described as snug, fair, or poor. Preoperative Valsalva leak point pressure (VLPP), detrusor instability, impaired bladder compliance, bladder neck appearance, urothelial scarring, and degree of coaptation were correlated with both initial and long-term improvement. Initial improvement was compared with long-term improvement. RESULTS: Initial improvement was experienced by 85% of all the subjects (86%) of the women, 80% of the men, and 100% of the children with a neurogenic bladder condition). Overall, 31% of patients had long-term improvement after a mean follow-up of 2.2 years, including 43% of the women, 13% of the men, and 33% of the children. The patients underwent a mean of 1.5 (1 to 4) collagen injections. There was a significant correlation between degree of coaptation and initial improvement (P = 0.003), but not with long-term improvement. There was no correlation between VLPP detrusor instability, impaired compliance, bladder neck appearance, or urethral scarring and initial improvement. There was no correlation between any parameter and long-term improvement or between initial and long-term improvement. CONCLUSIONS: Initial endoscopic appearance following collagen injection predicted initial, but not long-term, improvement after one collagen injection. Initial improvement was high in both men and women but decreased considerably over time, more so in men, and was not significantly correlated with long-term success. Urodynamic and endoscopic findings do not predict long-term success following collagen injection.

Adaptation, Physiological↗

PubMed1997

A decision analysis for treatment of clinically localized prostate cancer.

OBJECTIVE: To determine the preferred treatment of clinically localized prostate cancer. DESIGN: Cancer grade, patient age, and comorbidities are considered in a Markov model with Monte Carlo sensitivity analyses. Large and recent pooled analyses and patient-derived utilities are included. RESULTS: Principal findings suggest benefit for radical prostatectomy relative to watchful waiting for men under 70 years of age with low to moderate comorbidity. Men older than 70 with high comorbidity and disease of low to moderate grade do better with watchful waiting. CONCLUSIONS: Cohort-level sensitivity analyses suggest a quality-based treatment benefit for radical prostatectomy for younger men and treatment harm for older men. Tailored patient and clinician decisions remain necessary, especially for men older than 70 in good health but with aggressive cancers.

Adenocarcinoma↗

PubMed1997

Fifteen-year survival and recurrence rates after radiotherapy for localized prostate cancer.

PURPOSE: To determine 15-year survival and recurrence rates after radiotherapy for localized prostate cancer. METHODS: One hundred thirty-six patients with clinically localized prostate cancer treated from 1966 to 1974 with interstitial gold seed and external-beam irradiation were evaluated to determine the probability of recurrence and survival > or = 15 years after therapy. All patients were surgically staged with pelvic lymphadenectomy and none received hormonal therapy before relapse. RESULTS: Overall, 60 patients (44%) have never recurred, although 57% (34 of 60) of these same patients have died of causes other than prostate cancer. Local progression developed in 39% of patients and distant metastases in 42%. At 15 years, the probability of dying of prostate cancer was 33%+/-8% (% +/- 2SE) and of all causes was 72%+/-8%. In clinical stage A2 and B, 29%+/-9% of patients died of their cancer within 15 years, compared with 57%+/-21% in stage C1, while only 18%+/-8% with clinical stage A2 and B and negative lymph nodes died of cancer within this period. In contrast, the prostate cancer mortality rate at 15 years was high for patients with positive nodes regardless of the stage of the primary tumor (73% for A2 and B; 71% for C1). Patients with nodal metastases, poorly differentiated tumors, and advanced local disease all had a significantly (P < .0001) increased risk of cancer death. CONCLUSION: The cancer-specific mortality rate for patients with stage A2 and B tumors and negative nodes compares favorably with other series of patients treated with radiation therapy and > or = 15 years' follow-up evaluation. While local progression rates are high and associated with a substantial risk of prostate cancer death, many patients live with the disease and ultimately die of causes other than prostate cancer.

Adult↗

PubMed1997

Risk factors for complications and morbidity after radical retropubic prostatectomy.

PURPOSE: With recognition of the efficacy of surgical therapy for prostate cancer, there has been a marked increase in the number of radical prostatectomies performed, and substantial changes in surgical technique and perioperative management have decreased the morbidity of this procedure. We assessed the rate of perioperative complications with time and the risk factors for these complications, particularly age, operative time and co-morbidity. MATERIALS AND METHODS: A detailed review of all medical records of a consecutive series of 472 patients treated with radical retropubic prostatectomy by 1 surgeon between 1990 and 1994 was performed to document any complication within 30 days postoperatively. American Society of Anesthesiologists (ASA) physical status classification recorded by the staff anesthesiologist was used as a standard index of co-morbidity. RESULTS: Major complications were identified in 46 patients (9.8%), minor complications in 101 (21.4%) and none in 341 (72.2%). There were 2 deaths (0.42%). Major complications were not associated with age, operative time or year of operation but were significantly associated with ASA class (p = 0.006) and operative blood loss (p = 0.015) in a logistic regression analysis. Only 16% of patients were assigned to ASA class 3, yet this group included both deaths, a 3-fold increase in major complications, prolonged hospital stay, greater need for intensive care unit admission and more frequent blood transfusions. Major complications were almost 3 times more frequent in class 3 (21.3%) than in class 1 or 2 (7.6%) cases (p <0.005). Minor complications significantly increased hospital stay by a mean of 26% and major complications by 47% (p <0.0001). CONCLUSIONS: Radical retropubic prostatectomy was performed with no perioperative complication in 72% of patients. Major complications resulted in more intensive use of medical resources and were related to co-morbidity rather than age.

Adult↗

PubMed1997

Has there been a recent shift in the pathological features and prognosis of patients treated with radical prostatectomy?

PURPOSE: We determined if there has been a significant change in pathological stage or prognosis of patients with clinically localized prostate cancer treated with radical prostatectomy between 1983 and 1995. During this period the methods of detection of prostate cancer changed to include, in recent years, a large proportion of nonpalpable cancers detected by prostate specific antigen (PSA). MATERIALS AND METHODS: The method of diagnosis, pathological features and prognosis (PSA detected progression-free probability) of 754 consecutive patients treated by 1 surgeon for clinical stages T1 to 3NXMO prostate cancer from 1983 to 1995 were analyzed by year of diagnosis. RESULTS: There was a marked increase in the annual number of radical prostatectomies performed with time. The proportion of cancers initially detected by transurethral resection decreased markedly after 1989. Beginning in 1990 nonpalpable cancers detected by PSA increased substantially to 52% by 1995. However, there was no significant change in preoperative serum PSA, tumor volume or pathological stage during the study period. The proportion of patients with well differentiated cancer decreased somewhat, while those with moderate to poorly differentiated (Gleason sum 7) cancers increased significantly after 1991. There was no increase with time in the proportion of patients with a small (less than 0.5 cm.3), well or moderately differentiated (Gleason grades 1 to 3) cancer confined to the prostate (an indolent or clinically unimportant cancer) but fewer patients in recent years had an advanced cancer (established extraprostatic extension with a positive surgical margin, seminal vesicle invasion or lymph node metastases). The actuarial probability of progression after surgery was similar for patients treated from 1983 to 1987, 1988 to 1991 and 1992 to 1995. CONCLUSIONS: Despite marked changes in the number of patients treated each year and the method by which cancers were first detected, we found no change in pathological stage or prognosis (progression rate) for patients treated with radical prostatectomy between 1983 and 1995. Despite concerns that the increased detection of prostate cancer could lead to many more patients being treated unnecessarily for small, indolent cancers, we found no increase in the proportion of such cancers with time.

Actuarial Analysis↗

PubMed1996

A national survey of attitudes regarding participation in prostate carcinoma testing.

BACKGROUND: The prevalence of prostate carcinoma testing is rapidly changing. Little is known about the frequency of testing in the non-Medicare population in the United States. The current study was conducted for a better understanding of who is being tested and some of the reasons why. METHODS: A randomized national telephone survey was administered to 800 men by the George H. Gallup International Institute. Questions in the survey were evaluated for their association with participation in prostate carcinoma testing reported by the men interviewed. RESULTS: Participation in prostate carcinoma testing approximated the frequency of colon carcinoma testing Eighty-six percent of the men surveyed believed that prostate carcinoma is a serious malignancy, and 78% believed that it could be cured often if detected early. Multivariate logistic regression models identified six factors that increased the likelihood of men in the survey being tested: white race, willingness to be tested, previous conversation with a physician or health professional, having had serum cholesterol tested, having been tested for colon carcinoma, and belonging to successively advanced age groups. CONCLUSIONS: Prostate carcinoma testing is commonly performed in men older than 40 years. Physician counsel and patient prevention consciousness appear to be the major influences when a patient decides to be tested. If early detection is considered beneficial, special efforts would be needed to reach the nonwhite population.

Adult↗

PubMed1996

Cost-effectiveness of interferon-alpha and conventional chemotherapy in chronic myelogenous leukemia.

OBJECTIVE: To compare the cost-effectiveness of interferon-alpha with that of hydroxyurea as initial therapy for patients with chronic myelogenous leukemia (CML) in the chronic phase. DESIGN: A decision analysis and Markov model that described the natural history of the therapeutic process. The Markov model contained two treatment arms (interferon-alpha and hydroxyurea) and eight states of health (complete hematologic remission with cytogenetic response, complete hematologic remission without cytogenetic response, partial hematologic remission, chronic phase without hematologic remission, accelerated phase, blast crisis, bone marrow transplantation, and death). Probabilities, costs, and utilities were obtained from published clinical studies and clinical investigators. MEASUREMENT: Quality-adjusted years of life saved and costs and qualities discounted at 5% per year. SETTING: University medical centers in North America and Europe. PATIENTS: Meta-analysis of results from patients studied in clinical trials. RESULTS: The model's predictions of median survival (69 months with interferon-alpha therapy and 58 months with hydroxyurea therapy) were derived from data in the recent literature. In patients 50 years of age, interferon-alpha improved life expectancy over hydroxyurea by approximately 18 months. The marginal cost-effectiveness of interferon-alpha (incremental discounted cost of interferon-alpha compared with that of conventional therapy) was $34800 per quality-adjusted year of life saved. The model was sensitive to the monthly cost of interferon-alpha therapy (if the cost of interferon-alpha is reduced by one third, the cost-effectiveness becomes $19300 per quality-adjusted year of life saved) but was not particularly sensitive to the costs associated with blast crisis or bone marrow transplantation. The other significant variable was quality of life during therapy with interferon-alpha; when this measure was varied from 70% to 100% of the quality of life during hydroxyurea therapy, cost-effectiveness changed from $123200 to $25620 per quality-adjusted year of life saved. When the quality of life associated with interferon-alpha was less than 62% of the quality of life associated with hydroxyurea, the discounted quality-adjusted life expectancy with interferon-alpha was less than that with hydroxyurea. CONCLUSION: Compared with hydroxyurea, interferon-alpha is, in most clinical scenarios, a cost-effective initial therapy for patients with chronic-phase CML who can tolerate the drug.

Antineoplastic Agents↗