Deborah P. Lubeck

The Changing Face of Low-Risk Prostate Cancer: Trends in Clinical Presentation and Primary Management

PURPOSE Early intervention for prostate cancer is associated with excellent long-term survival, but many affected men, especially those with low-risk disease characteristics, might not experience adverse impact to survival or quality of life were treatment deferred. We sought to characterize temporal trends in clinical presentation and primary disease management among patients with low-risk prostate cancer. METHODS Data were abstracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a disease registry of 8,685 men with various stages of prostate cancer. Included were 2,078 men who were diagnosed between 1989 and 2001 and had a serum prostate specific antigen </= 10 ng/mL, Gleason sum </= 6, and clinical T stage </= 2a. Trends in risk distribution, tumor characteristics, and primary treatment were evaluated. RESULTS The proportion of patients with low-risk tumor characteristics rose from 29.8% in 1989 to 1992, to 45.3% in 1999 to 2001 (P <.0001). There have been sharp increases in the use of brachytherapy and androgen deprivation monotherapy, from 3.1% and 3.1%, to 12.0% and 21.7%, respectively. Utilization rates for prostatectomy, external-beam radiotherapy, and observation have fallen accordingly, from 63.8%, 16.1%, and 13.8%, to 51.6%, 6.8%, and 7.9% (P <.0001 for all except prostatectomy [P =.0019]). Age and socioeconomic status were significantly associated with treatment selection, but overall, the treatment trends were echoed on subgroup analysis of patients 75 years or older. CONCLUSION Low-risk features characterize a growing proportion of prostate cancer patients, and there have been significant shifts in the management of low-risk disease. Overtreatment may be a growing problem, especially among older patients.

Cancer-Specific Mortality After Surgery or Radiation for Patients With Clinically Localized Prostate Cancer Managed During the Prostate-Specific Antigen Era

PURPOSE To determine whether pretreatment risk groups shown to predict time to prostate cancer-specific mortality (PCSM) after treatment at a single institution retained that ability in a multi-institutional setting. PATIENTS AND METHODS From 1988 to 2002, 7,316 patients treated in the United States at 44 institutions with either surgery (n = 4,946) or radiation (n = 2,370) for clinical stage T1c-2, N0 or NX, M0 prostate cancer made up the study cohort. A Cox regression analysis was performed to determine the ability of pretreatment risk groups to predict time to PCSM after treatment. The relative risk (RR) of PCSM and 95% confidence intervals (CIs) were calculated for the intermediate- and high-risk groups relative to the low-risk group. RESULTS Estimates of non-PCSM 8 years after prostate-specific antigen (PSA) failure were 4% v 15% (surgery versus radiation; Plog rank =.002) compared with 13% v 18% (surgery versus radiation; Plog rank =.35) for patients whose age at the time of PSA failure was less than 70 as compared with >or= 70 years, respectively. The RR of PCSM after treatment for surgery-managed patients with high- or intermediate-risk disease was 14.2 (95% CI, 5.0 to 23.4; PCox <.0001) and 4.9 (95% CI, 1.7 to 8.1; PCox =.0037), respectively. These values were 14.3 (95% CI, 5.2 to 24.0; PCox <.0001) and 5.6 (95% CI, 2.0 to 9.3; PCox =.0012) for radiation-managed patients. CONCLUSION This study provided evidence to support the prediction of time to PCSM after surgery or radiation on the basis of pretreatment risk groups for patients with clinically localized prostate cancer managed during the PSA era.

DIFFERENCES IN UROLOGIST AND PATIENT ASSESSMENTS OF HEALTH RELATED QUALITY OF LIFE IN MEN WITH PROSTATE CANCER: RESULTS OF THE CAPSURE DATABASE

PURPOSE We determine whether urologists caring for men with prostate cancer accurately captured the nuances of quality of life, as disclosed by patients in validated, self-administered health related quality of life instruments. MATERIALS AND METHODS We analyzed information on 2,252 patients 42 to 95 years old enrolled in CaPSURE, a large, observational cancer of the prostate strategic urological research endeavor database, in which men with all stages of prostate cancer are followed quarterly with standardized validated written surveys to assess clinical parameters, symptoms and health related quality of life. At each visit urologists recorded Karnofsky performance status rating and the presence or absence of various symptoms, such as fatigue, pain and dysfunction in the sexual, urinary and bowel domains. Within 30 days of the visit patients independently completed self-administered health related quality of life instruments, including the RAND 36-Item Health Survey and University of California, Los Angeles Prostate Cancer Index, in which scores of 80 to 100 and 0 to 79 were interpreted as absence of impairment and moderate to severe impairment, respectively. Using chi-square analysis we compared symptoms, as recorded by the urologist, with health related quality of life impairment in relevant domains, as reported by the patient. RESULTS Significant differences (p < or = 0.002) were noted between physician and patient assessment of clinical domains, such as physical, sexual, urinary and bowel function, fatigue and bone pain. In all domains urologists underestimated patient symptoms, causing health related quality of life impairment. CONCLUSIONS In men with early stage and advanced prostate cancer physician ratings of patient symptoms do not correlate well with patient self-assessments of health related quality of life. Hence, urologists should attempt to elucidate more completely the components of patient quality of life after the diagnosis and treatment of prostate cancer.

Sexual function and bother after radical prostatectomy or radiation for prostate cancer : multivariate quality-of-life analysis from CaPSURE

OBJECTIVES To measure the effect of treatment choice (pelvic irradiation [XRT] versus radical prostatectomy [RP] with or without nerve sparing) on sexual function and sexual bother during the first 2 years after treatment. METHODS We studied sexual function and sexual bother in 438 men recently diagnosed with early-stage prostate cancer and treated with XRT or RP with or without nerve sparing. Outcomes were assessed with the University of California, Los Angeles Prostate Cancer Index, a validated health-related quality-of-life instrument that includes these two domains. To minimize the influence of other factors, we adjusted for age, comorbidity, general health, and previous treatment for erectile dysfunction. All subjects were drawn from CaPSURE, a national, longitudinal data base. RESULTS Sexual function improved over time during the first year in all treatment groups; however, during the second year, sexual function began to decline in the XRT group. Older patients who received XRT showed substantial declines in sexual function throughout the 2 years, and older patients who underwent RP experienced a return of very low baseline sexual function. Sexual function was improved by the use of nerve-sparing procedures or erectile aids. Alterations in sexual bother were ameliorated by many factors, including age, general health perceptions, and sexual function. CONCLUSIONS Patients undergoing XRT or RP with or without nerve sparing all showed comparable rates of improvement in sexual function during the first year after treatment for early-stage prostate cancer. However, in the second year after treatment, patients treated with XRT began to show declining sexual function; patients treated with RP did not.

Sleep problems and their correlates in a working population

AbstractOBJECTIVE: To measure the prevalence of sleep problems in a working population and examine their association with health problems, health-related quality-of-life measures, work-related problems, and medical expenditures. Also, to explore the usefulness of a sleep-problems screen for mental health conditions and underlying sleep disorders. DESIGN: Cross-sectional survey administered via voice mail and telephone interview. SETTING: A San Francisco Bay Area telecommunications firm. PARTICIPANTS: Volunteer sample of 588 employees who worked for a minimum of six months at the company and were enrolled in its fee-for-service health plan. MEASUREMENTS AND MAIN RESULTS: Thirty percent of respondents reported currently experiencing sleep problems and were found to have worse functioning and well-being (general health, cognitive functioning, energy), more work-related problems (decreased job performance and lower satisfaction, increased absenteeism), and a greater likelihood of comorbid physical and mental health conditions than were the respondents who did not have sleep problems. They also demonstrated a trend toward higher medical expenditures. CONCLUSIONS: Self-perceived sleep problems were common among the respondents and were associated with poorer health and health-related quality of life. A single question about sleep problems may serve as an effective screen for identifying primary care patients with mental health problems, as well as underlying sleep disorders.

The capsure database: a methodology for clinical practice and research in prostate cancer*

OBJECTIVES Implicit in the modern concept of patient outcome assessment is a shift from primary reliance on clinical indicators to a broader definition that includes physical, psychological, and social well-being. This is especially true of prostate cancer, where treatment can profoundly alter patient well-being. We have initiated a longitudinal observational database, CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) to document the impact of prostate cancer on resource utilization, clinical outcomes, health-related quality of life and survival in typical practice settings. METHODS Observational databases have been used in the treatment of other conditions. We have incorporated many well-tested elements in our study. Data are collected from two sources: the physician and the patient. The urologist enrolls eligible patients into the study, completes a medical history, and records current status, treatment, and laboratory results at each office visit. Patients complete quarterly questionnaires on health-related quality of life, resource utilization, work loss, and satisfaction with care. RESULTS Currently 21 sites participate in CaPSURE with 1419 patients enrolled by April 1996. Twenty percent of patients are newly diagnosed with prostate cancer. Time since diagnosis averages 3.0 years (SD = 3.1); mean age at diagnosis is 68.9 years (SD = 7.9, range = 39.6 to 90.7). The majority of patients (72%) are diagnosed with Stage B cancer. Patients receive a variety of treatments including surgery, irradiation, hormonal therapy, and watchful waiting. CONCLUSIONS Information available from CaPSURE will assist practicing urologists who must make clinical decisions on the basis of data such as the results of treatment in typical care settings, the effect of prostate cancer and its treatment methods on patient quality of life, and the effect on health care costs of the early detection of prostate cancer.

The functioning and well-being of patients with unrecognized anxiety disorders and major depressive disorder

This study examines the degree to which untreated anxiety disorders and major depressive disorder, occurring either singly or in combination, reduce functioning and well-being among primary care patients. Adult patients were screened using the SCL-52 to identify those with clinically significant anxiety symptoms. They also completed the Rand Short-Form (SF-36) to measure self-reported patient functioning and well-being. Patients with untreated disorders were identified using the Q-DIS-III-R to diagnose six DIS-anxiety disorders (generalized anxiety disorder, post-traumatic stress disorder (PTSD), simple phobia, social phobia, panic/agoraphobia, obsessive/compulsive disorder) and major depression. Of 319 patients identified, 137 (43%) had a single disorder and 182 (57%) had multiple disorders. Regression models estimated the relative effects of these disorders on health status (SF-36) by comparing patients with the disorders to patients screened as being not-anxious. Estimates of these effects were consistent with available national norms. The estimated effect of each single disorder on all subscales for physical, social and emotional functioning was negative, often as much as a 20-30 point reduction on this 100-point scale. Major depression had the greatest negative impact, followed by PTSD and panic/ agoraphobia. For patients with multiple disorders, the presence of major depression was associated with the greatest reduction in functioning status. The impact of untreated anxiety disorders and major depressive disorder on functioning was comparable to, or greater than, the effects of medical conditions such as low back pain, arthritis, diabetes and heart disease.

Changes in health-related quality of life in the first year after treatment for prostate cancer: results from CaPSURE

OBJECTIVES Treatment for prostate cancer has a significant impact on health-related quality of life (HRQOL). We examined HRQOL immediately after diagnosis and treatment and 1 and 2 years after treatment for a cohort of men with early and late-stage prostate cancer. METHODS We studied 692 men enrolled in CaPSURE, a large national observational data base of patients with prostate cancer. General and disease-specific HRQOL were measured with validated instruments at study entry and quarterly thereafter. Individuals were grouped by initial treatment: radical prostatectomy, radiotherapy, hormonal therapy, and observation (ie, no treatment in first year). Trends in HRQOL scores were evaluated immediately after treatment through 2 years, adjusting for age and length of follow-up. RESULTS Patients who underwent radical prostatectomy demonstrated statistically significant increases in functioning in general and in disease-specific components during the year after treatment when compared with scores immediately after treatment. Patients receiving radiotherapy and hormonal therapy had significant improvements in patient reports of health change during the year. CONCLUSIONS Patients undergoing radical prostatectomy have low HRQOL scores just after treatment in almost all general and disease-specific areas, but at 1 year there is a sharp improvement. Patients undergoing observation, radiotherapy, or hormonal therapy remain stable over time. All treatment groups continue to have decrements in sexual function.

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.

The association between socioeconomic status, health insurance coverage, and quality of life in men with prostate cancer

The objective of this study was to examine the effect of socioeconomic status and insurance status on health-related quality of life (HRQOL) outcomes in men with prostate cancer. The design was a retrospective cohort study using multiple sites, including both academic and private practice settings. A cohort of 860 men with newly diagnosed, biopsy-proven prostate cancer of any stage was identified within CaPSURE, a longitudinal disease registry of prostate cancer patients. HRQOL was assessed with validated instruments, including the RAND 36-item Health Survey (SF-36) and the UCLA Prostate Cancer Index. Covariates included insurance status, education level, annual income, age, stage, comorbidity, Gleason grade, baseline PSA, marital status, ethnicity and primary treatment. HRQOL measurements were taken at 3-6-month intervals. Analysis of covariance was used to determine the effect of SES and insurance status on the HRQOL domains at baseline and over time. Patients with lower annual income had significantly lower baseline HRQOL scores in the all of the domains of the SF-36 and four of eight disease-specific HRQOL domains. No relationship was seen between annual income and HRQOL outcomes over time. Conversely, health insurance status was associated with HRQOL over time, but not at baseline. Health insurance status appears to have a unique effect on general HRQOL outcomes in men after treatment for prostate cancer. This study confirms the commonly held belief that patients of lower SES tend to have worse quality of life at baseline and following treatment for their disease. These findings have important ramifications for clinicians, researchers and policy makers.