Evidence of a healthy volunteer effect in the prostate, lung, colorectal, and ovarian cancer screening trial.

Volunteers for prevention or screening trials are generally healthier and have lower mortality than the general population. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) is an ongoing, multicenter, randomized trial that randomized 155,000 men and women aged 55-74 years to a screening or control arm between 1993 and 2001. The authors compared demographics, mortality rates, and cancer incidence and survival rates of PLCO subjects during the early phase of the trial with those of the US population. Incidence and mortality from PLCO cancers (prostate, lung, colorectal, and ovarian) were excluded because they are the subject of the ongoing trial. Standardized mortality ratios for all-cause mortality were 46 for men, 38 for women, and 43 overall (100 = standard). Cause-specific standardized mortality ratios were 56 for cancer, 37 for cardiovascular disease, and 34 for both respiratory and digestive diseases. Standardized mortality ratios for all-cause mortality increased with time on study from 31 at year 1 to 48 at year 7. Adjusting the PLCO population to a standardized demographic distribution would increase the standardized mortality ratio only modestly to 54 for women and 55 for men. Standardized incidence ratios for all cancer were 84 in women and 73 in men, with a large range of standardized incidence ratios observed for specific cancers.

The Upper Midwest Health Study: a case-control study of primary intracranial gliomas in farm and rural residents.

Since several studies indicated that farmers and agricultural workers had an excess risk of brain cancer, the National Institute for Occupational Safety and Health initiated the Upper Midwest Health Study to examine risk of intracranial glioma in the non-metropolitan population. This population-based, case-control study evaluated associations between gliomas and rural and farm exposures among adults (ages 18 to 80) in four upper midwestern states (Iowa, Michigan, Minnesota, Wisconsin). At diagnosis/selection, participants lived in non-metropolitan counties where the largest population center had fewer than 250,000 residents. Cases were diagnosed 1 January 1995 through 31 January 1997. Over 90% of 873 eligible ascertained cases and over 70% of 1670 eligible controls consented to participate. Participants and nonparticipants, evaluated for "critical questions" on main and refusant questionnaires, differed significantly in farming and occupational experience, ethnicity, education, and lifestyle. The 1,175 controls were more likely than the 798 cases to have reported ever drinking alcohol (77% vs. 73%, adjusted odds ratio (OR) 0. 73, 95% confidence interval (CI) 0.59-0.92) and having had panoramic dental x-rays (34% vs. 29%, OR 0. 75, CI 0.61-0.92). Controls spent a greater percentage of their lives in non-metropolitan counties (78% vs. 75%, OR 0.81, CI 0.67-1.09). Among ever-farmers, controls were more likely to have had exposure to farm insecticides (57% vs. 50%, OR 0.75, CI 0.59-0.95) and farm animals (96% vs. 91%, OR 0.48, CI 0.25-0.90). Moving to a farm as an adolescent (ages 11 to 20) vs. as an adult was associated with a greater risk of glioma. In our study sample, farm or rural residence and summary farm exposures were associated with decreased glioma risk. However, nonparticipation by never-farming eligible controls could have affected results. Comparisons of farm chemical exposures may clarify associations between farming and glioma that others have reported.

Lessons learned: geographic information systems and farmworkers in the Lake States.

Agencies serving the estimated 42,000 to 137,000 migrant and seasonal farmworkers in the Lake States (Wisconsin, Michigan, and Minnesota) face distinct challenges, including inadequate access to farmworker data to address their needs. This project developed and evaluated a geographical information system (GIS) database for compiling and displaying existing farmworker data in the Lake States. A three-step study was conducted in the Lake States: (1) a preliminary resource and needs assessment was conducted among agencies serving farmworkers, (2) a GIS product was created using data available from state agencies, and (3) the GIS product was evaluated by an advisory board of qualified occupational health and safety representatives for appropriateness, applications, and ease of use. Agencies participated by sharing their available farmworker data. The GIS product consisted of a CD-ROM with data displayed in a graphic format and downloadable spreadsheet files consolidated by county demographic, crop, housing, and migrant health clinic information. Evaluators of the GIS product found it to be an accessible, unique clearinghouse for farmworker-related data. The GIS product can become a valuable tool for agencies serving farmworkers and those researching farmworker-related issues. Agencies and health professionals require useful and comprehensive databases to track and serve farmworkers, and a multi-agency partnership using GIS technology could provide this capability. Further research is required with improved definitions and resources to apply the GIS product.

Expression and initial promoter characterization of PCAN1 in retinal tissue and prostate cell lines.

Prostate cancer is the most frequently diagnosed neoplasia in men and one of the leading causes of cancer-related deaths in men over 60. In an effort to understand the molecular events leading to prostate cancer, we have identified PCAN1 (prostate cancer gene 1) (also known as GDEP), a gene that is highly expressed in prostate epithelial tissue and frequently mutated in prostate tumors. Here we demonstrate its expression in neural retina, and retinoblastoma cell culture but not retinal pigment epithelial cell culture. We further characterize PCAN1 expression in the prostate cell lines RWPE1, RWPE2, and LnCAP FGC. We demonstrate an increase in expression when the cells are grown in the presence of Matrigel, an artificial extracellular basement membrane. Expression was time dependent, with expression observed on d 6 and little or no expression on d 12. Testosterone was not found to increase PCAN1 expression in this culture system. In addition, normal prostate epithelial cells co-cultured with normal prostate stromal cells did not exhibit PCAN1 expression at any time. To definitively locate the transcription initiation sites, we performed restriction-ligase-mediated 5' RACE, to selectively amplify only mRNA with a 5' cap. An initial characterization of the sequence upstream of the initiation sites determined six possible binding sites for the prostate specific regulatory protein NKX3.1 and four potential binding sites for the PPAR/RXR heterodimer that is involved in the control of cell differentiation and apoptosis.

Risk behaviours and benign prostatic hyperplasia.

OBJECTIVE: To identify risk factors for benign prostatic hyperplasia (BPH). SUBJECTS AND METHODS: Medical history data, including reported urological conditions and treatments, and risk factor data were collected from 34 694 participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial designed to evaluate methods for the early detection of cancer. RESULTS: Asian men had the lowest risks (odds ratio, 95% confidence interval) for nocturia (0.7, 0.5-0.9), physician-diagnosed BPH (0.3, 0.2-0.5) and transurethral prostatectomy (TURP, 0.2, 0.1-0.6), while risks for Whites and Blacks were similar for most measures of BPH. Greater alcohol intake was associated with decreased nocturia (P trend = 0.002), BPH (P trend < 0.001) and TURP (P trend < 0.001). Current tobacco use was associated with decreased nocturia (0.8, 0.7-0.9), BPH (0.7, 0.6-0.8) and TURP (0.6, 0.4-0.8) but dose-response patterns were weak. CONCLUSION: Asian-Americans have the lowest risk of clinical BPH. Alcohol and possibly cigarettes are related to a lower risk for BPH.

Genetics of prostate cancer.

Prostate cancer is the most frequently diagnosed visceral cancer of men, responsible for approximately 40,000 deaths in adult males per year. To identify the genetic causes of prostate cancer, we performed a whole genome scan of affected sib pairs, using DNA markers spaced evenly across the human genome. We demonstrated that regions on chromosomes 1, 4, 5, 7, 8, 11, 16 and 19 might harbor genes that predispose individuals to prostate cancer and may affect tumor growth rate and tumor aggressiveness. Here we present DNA sequence analysis of KIAA 0872 and 17-beta hydroxysteroid dehydrogenase that are located on chromosome 16 within the mapped region, and we demonstrate that neither of these genes carries mutations in the protein coding region or their splice junction sites. These results suggest that these genes are less likely to be associated with the cause of familial prostate cancer.

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

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

Is shorter always better? Relative importance of questionnaire length and cognitive ease on response rates and data quality for two dietary questionnaires.

In this study, the authors sought to determine the effects of length and clarity on response rates and data quality for two food frequency questionnaires (FFQs): the newly developed 36-page Diet History Questionnaire (DHQ), designed to be cognitively easier for respondents, and a 16-page FFQ developed earlier for the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The PLCO Trial is a 23-year randomized controlled clinical trial begun in 1992. The sample for this substudy, which was conducted from January to April of 1998, consisted of 900 control and 450 screened PLCO participants aged 55-74 years. Controls received either the DHQ or the PLCO FFQ by mail. Screenees, who had previously completed the PLCO FFQ at baseline, were administered the DHQ. Among controls, the response rate for both FFQs was 82%. Average amounts of time needed by controls to complete the DHQ and the PLCO FFQ were 68 minutes and 39 minutes, respectively. Percentages of missing or uninterpretable responses were similar between instruments for questions on frequency of intake but were approximately 3 and 9 percentage points lower (p < or = 0.001) in the DHQ for questions on portion size and use of vitamin/mineral supplements, respectively. Among screenees, response rates for the DHQ and the PLCO FFQ were 84% and 89%, respectively, and analyses of questions on portion size and supplement use showed few differences. These data indicated that the shorter FFQ was not better from the perspective of response rate and data quality, and that clarity and ease of administration may compensate for questionnaire length.

Identification of a gene frequently mutated in prostate tumors.

Although prostate cancer is the second leading cause of cancer death for men in the United States, the genetics of tumor development are poorly understood. Several expressed sequence tagged genes (ESTs) that are expressed predominantly in the prostate have recently been identified, although their role in the development and maintenance of the prostate is unknown. Here, we demonstrate that the gene identified as UNIGENE cluster Hs. 104215, which codes for a message found predominantly in the prostate, may be important in tumor development. We name this gene PCan1 for Prostate Cancer gene 1. Northern blot experiments were performed using RNA isolated from tumor-derived cell lines and human prostate to determine the expression pattern of the gene. DNA sequencing was used to identify mutations that occurred in tumor tissue. By Northern blot analysis, this gene product was not detectable in LNCaP, DU 145, or PC-3 prostate cancer cell lines, although it was readily observed in RNA isolated from total prostate and from dissected central and peripheral regions of prostate. Sequence analysis of genomic DNA from LNCaP, DU 145, or PC-3 cells demonstrated a G/A polymorphism at position 193. Analysis of matched tumor-derived DNA and blood-derived DNA samples from 11 of 13 patients who had undergone a radical prostatectomy and who were homozygous for A in blood-derived DNA demonstrated mutation of position 193 in matched tumor samples resulting in G/A polymorphism. Sixteen additional patient samples were G/A polymorphic in both blood-derived DNA and tumor-derived DNA and two samples were GG in both blood-derived and tumor-derived DNA. Our results suggest that this gene may be a hot spot for mutation in prostate cancer, especially because our radiation hybrid mapping located this gene within a region identified in linkage mapping studies of affected families with prostate cancer. Loss of heterozygosity in prostate tumors has also been reported at the location of PCan1. Further studies to determine the functional role of this candidate tumor suppressor gene are warranted.

Complex ovarian cysts in postmenopausal women are not associated with ovarian cancer risk factors: preliminary data from the prostate, lung, colon, and ovarian cancer screening trial.

OBJECTIVE: We assessed whether asymptomatic ovarian abnormalities detected on ultrasonography in postmenopausal women are precursors to ovarian cancer. STUDY DESIGN: We compared the transvaginal ultrasonographic findings from the initial examination of 20,000 postmenopausal women enrolled to date in an ongoing randomized trial of cancer screening with data on the established risk factors for ovarian cancer obtained from self-administered questionnaires. We distinguished cysts with the suggestive characteristic(s) of a septum, a solid component, or an irregular or thick wall ("complex cysts") from simple sonolucent cysts with none of those features. RESULTS: High parity, a strong ovarian cancer protective factor, was negatively associated with complex cysts (odds ratio for > or =5 births vs no births, 0.72; 95% confidence interval, 0.53-0.97), but long-term oral contraceptive use, another strong ovarian cancer protective factor, was not associated with complex cysts (odds ratio, 0.96; 95% confidence interval, 0.76-1.20). A family history of ovarian cancer or multiple breast cancers, a strong risk factor for cancer, was not associated with complex cysts (odds ratio, 0.99; 95% confidence interval, 0.68-1.44). Other abnormalities found on ultrasonography (including simple cysts, bilateral cysts, or all abnormalities combined) also did not share the established risk factors for ovarian malignancy. We did not identify any combination of features of abnormalities (septum, echogenicity, size, or papillary projections) that manifested the cancer risk factor profile. CONCLUSIONS: Although a very small proportion of the clinically silent ovarian abnormalities found on ultrasonography are determined to be ovarian cancers, the remaining complex cysts and other clinically suspicious abnormalities do not appear to be the immediate precursors of ovarian cancer. The eventual identification of such precursors will yield opportunities for earlier diagnosis, screening of high-risk groups, and better understanding of the cause of this often lethal malignancy.

Generalists and oncologists show similar care practices and outcomes for hospitalized late-stage cancer patients. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks for Treatment.

OBJECTIVE: The objective of this work was to identify similarities and differences in primary attending physicians' (generalists' versus oncologists') care practices and outcomes for seriously ill hospitalized patients with malignancy. DESIGN: This was a prospective cohort study (SUPPORT project). SETTING: Subjects were recruited from 5 US teaching hospitals; data were gathered from 1989 to 1994. SUBJECTS: Included in the study was a matched sample of 642 hospitalized patients receiving care for non-small-cell lung cancer, colon cancer metastasized to the liver, or multiorgan system failure associated with malignancy with either a generalist or an oncologist as the primary attending physician. MEASUREMENTS: Care practices and patient outcomes were determined from hospital records. Length of survival was identified with the National Death Index. Physicians' perceptions of patient's prognosis, preference for cardiopulmonary resuscitation (CPR), and length of relationship were assessed by interview. A propensity score for receiving care from an oncologist was constructed. After propensity-based matching of patients, practices and outcomes of oncologists' and generalists' patients were assessed through group comparison techniques. RESULTS: Generalist and oncologist attendings showed comparable care practices, including the number of therapeutic interventions, eg, "rescue care" and chemotherapy, and the number of care topics discussed with patients/ families. Length of stay, discharge to supportive care, readmission, total hospital costs, and survival rates were similar. For both physician groups, perception of patients' wish for CPR was associated with rescue care (P < 0.03), and such care was related to higher hospital costs (P < 0.000). Poorer prognostic estimates predicted aggressiveness-of-care discussions by both types of physicians. Length of the patient-doctor relationship was associated with oncologists' care practices. More documented discussion about aggressiveness of care was related to higher hospital costs and shorter survival for patients in both physician groups (P < 0.001). CONCLUSIONS: Generalists and oncologists showed similar care practices and outcomes for comparable hospitalized late-stage cancer patients. Physicians' perceptions about patients' preferences for CPR and prognosis influenced decision making and outcomes for patients in both physician groups. Length of relationship with patients was associated only with oncologists' care practices. Rescue care increased hospital costs but had no effect on patient survival. Future studies should compare physicians' palliative care as well as acute-care practices in both inpatient and ambulatory care settings. Patients' end-of-life quality and interchange between physician groups should also be documented and compared.

Complex ovarian cysts in postmenopausal women are not associated with ovarian cancer risk factors. Preliminary data from the plco cancer screening trial.

PURPOSE: We assessed whether ovarian abnormalities detected on ultrasound in postmenopausal women are precursors to ovarian cancer.METHODS: We compared the transvaginal ultrasound findings from the initial examination of twenty thousand postmenopausal women enrolled to date in an ongoing randomized trial of cancer screening to data on the established risk factors for ovarian cancer obtained from self-administered questionnaires. We distinguished cysts with the suspicious characteristics of a septum, solid component, irregular or thick wall ("complex cysts") from simple sonolucent cysts with none of those features.RESULTS: High parity, protective for cancer, was negatively associated with complex cysts (Odds Ratio ["OR"] for five or more births versus no births = 0.72, 95% CI = 0.53-0.97), but long-term oral contraceptive use was not (OR = 0.96, 95% CI = 0.76-1.20). A family history of ovarian cancer or multiple breast cancers, a strong risk factor for cancer, was not associated with complex cysts (OR = 0.99, 95% CI = 0.68-1.44). Other abnormalities found on ultrasound (including simple cysts, bilateral cysts, or all abnormalities combined) also did not share the established risk factors for ovarian malignancy. We formed no combination of features of abnormalities (septum, echogenicity, size, or papillary projection) with the cancer risk factor profile.CONCLUSIONS: Although a very small proportion of the clinically silent ovarian abnormalities found on ultrasound are found to be ovarian cancers, the remaining complex cysts and other clinically suspicious abnormalities do not appear to be the immediate precursors of ovarian cancer.

Design of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

The objectives of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial are to determine in screenees ages 55-74 at entry whether screening with flexible sigmoidoscopy (60-cm sigmoidoscope) can reduce mortality from colorectal cancer, whether screening with chest X-ray can reduce mortality from lung cancer, whether screening men with digital rectal examination (DRE) plus serum prostate-specific antigen (PSA) can reduce mortality from prostate cancer, and whether screening women with CA125 and transvaginal ultrasound (TVU) can reduce mortality from ovarian cancer. Secondary objectives are to assess screening variables other than mortality for each of the interventions including sensitivity, specificity, and positive predictive value; to assess incidence, stage, and survival of cancer cases; and to investigate biologic and/or prognostic characterizations of tumor tissue and biochemical products as intermediate endpoints. The design is a multicenter, two-armed, randomized trial with 37,000 females and 37,000 males in each of the two arms. In the intervention arm, the PSA and CA125 tests are performed at entry, then annually for 5 years. The DRE, TVU, and chest X-ray exams are performed at entry and then annually for 3 years. Sigmoidoscopy is performed at entry and then at the 5-year point. Participants in the control arm follow their usual medical care practices. Participants will be followed for at least 13 years from randomization to ascertain all cancers of the prostate, lung, colorectum, and ovary, as well as deaths from all causes. A pilot phase was undertaken to assess the randomization, screening, and data collection procedures of the trial and to estimate design parameters such as compliance and contamination levels. This paper describes eligibility, consent, and other design features of the trial, randomization and screening procedures, and an outline of the follow-up procedures. Sample-size calculations are reported, and a data analysis plan is presented.

Etiologic and early marker studies in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial.

The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which is randomizing 74,000 screening arm participants (37,000 men, 37,000 women; ages 55-74) and an equal number of nonscreened controls, is a unique setting for the investigation of the etiology of cancer and other diseases and for the evaluation of potential molecular markers of early disease. At entry, baseline information is collected by questionnaire on dietary intake, tobacco and alcohol use, reproductive history (for women), family history of cancer, use of selected drugs, and other selected risk factors. Blood samples collected at the baseline screening exam are aliquoted to serum, plasma, red blood cell, and buffy coat fractions. At the next two annual screening visits, serum samples are collected. At the third annual reexamination, cryopreserved whole blood is obtained, in addition to serum, plasma, red blood cell, and buffy coat fractions. At the fourth and fifth years, serum, plasma, and buffy coat are collected. All blood samples are shipped to a central repository for long-term storage at -70 degrees C. Dietary questionnaires and buccal cells for DNA analysis are obtained from nonscreened controls. Cancer cases are identified through annual follow-up questionnaires, and all deaths are identified through vital status tracing mechanisms. Procedures are being developed to obtain archival pathologic material for selected cases of cancer and related diseases. Initial investigations are focusing on the etiology of colorectal cancer and on the operative characteristics of tests for the early detection of colorectal and prostate cancer.

Influence of patient preferences and local health system characteristics on the place of death. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Risks and Outcomes of Treatment.

OBJECTIVE: To examine the degree to which variation in place of death is explained by differences in the characteristics of patients, including preferences for dying at home, and by differences in the characteristics of local health systems. DESIGN: We drew on a clinically rich database to carry out a prospective study using data from the observational phase of the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT component). We used administrative databases for the Medicare program to carry out a national cross-sectional analysis of Medicare enrollees place of death (Medicare component). SETTING: Five teaching hospitals (SUPPORT); All U.S. Hospital Referral Regions (Medicare). STUDY POPULATIONS: Patients dying after the enrollment hospitalization in the observational phase of SUPPORT for whom place of death and preferences were known. Medicare beneficiaries who died in 1992 or 1993. MAIN OUTCOME MEASURES: Place of death (hospital vs non-hospital). RESULTS: In SUPPORT, most patients expressed a preference for dying at home, yet most died in the hospital. The percent of SUPPORT patients dying in-hospital varied by greater than 2-fold across the five SUPPORT sites (29 to 66%). For Medicare beneficiaries, the percent dying in-hospital varied from 23 to 54% across U.S. Hospital Referral Regions (HRRs). In SUPPORT, variations in place of death across site were not explained by sociodemographic or clinical characteristics or patient preferences. Patient level (SUPPORT) and national cross-sectional (Medicare) multivariate models gave consistent results. The risk of in-hospital death was increased for residents of regions with greater hospital bed availability and use; the risk of in-hospital death was decreased in regions with greater nursing home and hospice availability and use. Measures of hospital bed availability and use were the most powerful predictors of place of death across HRRs. CONCLUSIONS: Whether people die in the hospital or not is powerfully influenced by characteristics of the local health system but not by patient preferences or other patient characteristics. These findings may explain the failure of the SUPPORT intervention to alter care patterns for seriously ill and dying patients. Reforming the care of dying patients may require modification of local resource availability and provider routines.

Outcomes, preferences for resuscitation, and physician-patient communication among patients with metastatic colorectal cancer. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

PURPOSE: To describe characteristics, outcomes, and decision making in patients with colorectal cancer metastatic to the liver, and to examine the relationship of doctor-patient communication with patient understanding of prognosis and physician understanding of patients' treatment preferences. PATIENTS AND METHODS: The Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) was a prospective cohort study conducted at five teaching hospitals in the United States between 1989 and 1994. Participants in this study were hospitalized patients 18 years of age or older with known liver metastases who had been diagnosed with colorectal cancer at least 1 month earlier. Data were collected by patient interview and chart review at study entry; patients were interviewed again at 2 and 6 months. Data collected by physician interview included estimates of survival and impressions of patients' preferences for cardiopulmonary resuscitation (CPR). Patients and physicians were also asked about discussions about prognosis and resuscitation preferences. RESULTS: We studied 520 patients with metastatic colorectal cancer (median age 64, 56% male, 80% white, 2-month survival 78%, 6-month survival 56%). Quality of life (62% "good" to "excellent") and functional status (median number of disabilities = 0) were high at study entry and remained so among interviewed survivors at 2 and 6 months. Of 339 patients with available information, 212 (63%) of 339 wanted CPR in the event of a cardiopulmonary arrest. Factors independently associated with preference for resuscitation included younger age, better quality of life, absence of lung metastases, and greater patient estimate of 2-month prognosis. Of the patients who preferred not to receive CPR, less than half had a do-not-resuscitate note or order written. Patients' self-assessed prognoses were less accurate than those of their physicians. Physicians incorrectly identified patient CPR preferences in 30% of cases. Neither patient prognostication nor physician understanding of preferences were significantly better when discussions were reported between doctors and patients. CONCLUSIONS: A majority of patients with colorectal cancer have preferences regarding end of life care. The substantial misunderstanding between patients and their physicians about prognosis and treatment preferences appears not to be improved by direct communication. Future research focused on enhancing the effectiveness of communication between patients and physicians about end of life issues is needed.

Relationship between cancer patients' predictions of prognosis and their treatment preferences.

CONTEXT: Previous studies have documented that cancer patients tend to overestimate the probability of long-term survival. If patient preferences about the trade-offs between the risks and benefits associated with alternative treatment strategies are based on inaccurate perceptions of prognosis, then treatment choices may not reflect each patient's true values. OBJECTIVE: To test the hypothesis that among terminally ill cancer patients an accurate understanding of prognosis is associated with a preference for therapy that focuses on comfort over attempts at life extension. DESIGN: Prospective cohort study. SETTING: Five teaching hospitals in the United States. PATIENTS: A total of 917 adults hospitalized with stage III or IV non-small cell lung cancer or colon cancer metastatic to liver in phases 1 and 2 of the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). MAIN OUTCOME MEASURES: Proportion of patients favoring life-extending therapy over therapy focusing on relief of pain and discomfort, patient and physician estimates of the probability of 6-month survival, and actual 6-month survival. RESULTS: Patients who thought they were going to live for at least 6 months were more likely (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.8-3.7) to favor life-extending therapy over comfort care compared with patients who thought there was at least a 10% chance that they would not live 6 months. This OR was highest (8.5; 95% CI, 3.0-24.0) among patients who estimated their 6-month survival probability at greater than 90% but whose physicians estimated it at 10% or less. Patients overestimated their chances of surviving 6 months, while physicians estimated prognosis quite accurately. Patients who preferred life-extending therapy were more likely to undergo aggressive treatment, but controlling for known prognostic factors, their 6-month survival was no better. CONCLUSIONS: Patients with metastatic colon and lung cancer overestimate their survival probabilities and these estimates may influence their preferences about medical therapies.

Cancer screening and prevention in rural Wisconsin: the Greater Marshfield Experience.

BACKGROUND: Providing medical services to rural residents results in unique challenges to providers and patients. Cancer screening (CS) and early detection services (EDS) are frequently underutilized with rural residents often presenting with advanced cancer at diagnosis. A comprehensive approach to determine barriers and overcome them constitutes "The Greater Marshfield Experience." METHODS: Focus groups with rural residents determined the greatest barriers to receipt of CS and EDS were distance, cost, time from work and self-reliant behavior. Directives to address these concerns were to keep information simple and provide services at the workplace. In response, Marshfield Clinic and its research division developed a collaborative research partnership with public health agencies (PHA), federally funded government programs and volunteer agencies. RESULTS: In-house activities to remove barriers for providing CS and EDS included the development of a separate screening unit for these activities. Reminder systems were employed to notify patients of the need and availability of preventative services. Co-payments for health screening services were eliminated from the clinic owned health plan. Area residents near poverty level were encouraged to enroll in federally subsidized health plans that promoted and paid for CS and EDS. Federally funded cancer screening studies were implemented that funded breast and cervical cancer screening and evaluated the benefits of screening for prostate, lung, colorectal and ovarian cancers (PLCO). Outreach activities included developing partnerships with local PHA and minority groups and providing mobile screening services to remote areas. CONCLUSION: Concentrated, collaborative efforts to develop in-house systems and outreach activities resulted in delivery of CS and EDS in remote areas.

Seriously ill hospitalized adults: do we spend less on older patients? Support Investigators. Study to Understand Prognoses and Preference for Outcomes and Risks of Treatments.

OBJECTIVE: To determine the effect of age on hospital resource use for seriously ill adults, and to explore whether age-related differences in resource use are explained by patients' severity of illness and preferences for life-extending care. STUDY DESIGN: Prospective cohort study. SETTING: Five geographically diverse academic acute care medical centers participating in the SUPPORT Project. PATIENTS: A total of 4301 hospitalized adults with at least one of nine serious illnesses associated with an average 6-month mortality of 50%. MEASUREMENTS: Resource utilization was measured using a modified version of the Therapeutic Intervention Scoring System (TISS); the performance of three invasive procedures (major surgery, dialysis, and right heart catheter placement); and estimated hospital costs. RESULTS: The median patient age was 65; 43% were female, and 48% died within 6 months. After adjustment for severity of illness, prior functional status, and study site, when compared with patients younger than 50, patients 80 years or older were less likely to undergo major surgery (adjusted odds ratio .46), dialysis (.19), and right heart catheter placement (.59) and had median TISS scores and estimated hospital costs that were 3.4 points and $ 71.61 lower, respectively. These differences persisted after further adjustment for patients' preferences for life-extending care. CONCLUSIONS: Compared with similar younger patients, seriously ill older patients receive fewer invasive procedures and hospital care that is less resource-intensive and less costly. This preferential allocation of hospital services to younger patients is not based on differences in patients' severity of illness or general preferences for life-extending care.

Is economic hardship on the families of the seriously ill associated with patient and surrogate care preferences? SUPPORT Investigators.

BACKGROUND: Serious illness often causes economic hardship for patients' families. However, it is not known whether this hardship is associated with a preference for the goal of care to focus on maximizing comfort instead of maximizing life expectancy or whether economic hardship might give rise to disagreement between patients and surrogates over the goal of care. METHODS: We performed a cross-sectional study of 3158 seriously ill patients (median age, 63 years; 44% women) at 5 tertiary medical centers with 1 of 9 diagnoses associated with a high risk of mortality. Two months after their index hospitalization, patients and surrogates were surveyed about patients' preferences for the primary goal of care: either care focused on extending life or care focused on maximizing comfort. Patients and surrogates were also surveyed about the financial impact of the illness on the patient's family. RESULTS: A report of economic hardship on the family as a result of the illness was associated with a preference for comfort care over life-extending care (odds ratio, 1.26; 95% confidence interval, 1.07-1.48) in an age-stratified bivariate analysis. Similarly, in a multivariable analysis controlling for patient demographics, illness severity, functional dependency, depression, anxiety, and pain, economic hardship on the family remained associated with a preference for comfort care over life-extending care (odds ratio, 1.31; 95% confidence interval, 1.10-1.57). Economic hardship on the family did not affect either the frequency or direction of patient-surrogate disagreements about the goal of care. CONCLUSIONS: In patients with serious illness, economic hardship on the family is associated with preferences for comfort care over life-extending care. However, economic hardship on the family does not appear to be a factor in patient-surrogate disagreements about the goal of care.