Significant Independent Predictors Of Time Research Articles

Predictors of time to death after distant recurrence in breast cancer patients.

After experiencing a distant recurrence, breast cancer patients have a poor prognosis; fewer than 5% survive for ten or more years. However, the time to death is highly variable, ranging from a few months to many years. The purpose of this study is to identify, in a large hospital-based series of patients with early-stage breast cancer, factors which predict survival after distant recurrence. We studied a cohort of 2312 women diagnosed with invasive breast cancer at Women's College Hospital between 1987 and 2000 (stages I-III). For each patient, we abstracted information on age at diagnosis, the initial presentation of the cancer (tumour size, lymph node status, tumour grade, ER status, PR status, HER2 status), treatment (surgery, radiotherapy, chemotherapy, hormone therapy), the dates of all tumour recurrences (local, regional, distant) and the dates and causes of death. The Cox proportional hazards model was used to estimate the univariate and multivariate hazard ratios for death from breast cancer following distant recurrence associated with the various tumour features. After a mean follow-up of 12.8years from diagnosis, 523 distant recurrences were recorded among women in the cohort (23% of 2312) and 604 women (26%) died of breast cancer. For the 484 women who had a distant recurrence on record and died of breast cancer, the mean time from distant recurrence to death was 2.0years (range 0-11.9years). In a multivariate analysis, only two factors were significantly associated with time to death after distant recurrence: ER status (positive vs. negative, HR 0.56; 95% CI 0.43-0.71; p < 0.0001) and tumour grade (high vs. low, HR 1.87; 95% CI 1.16-3.01; p = 0.01). Among ER-negative patients (N = 175), high tumour grade and a short time from diagnosis to distant recurrence were associated with a rapid time to death. Among ER-positive patients (N = 336), there was no significant independent predictor of time from recurrence to death. Among ER-negative breast cancer patients, the time to death after distant recurrence was predictable to some extent; women with a short time from diagnosis to recurrence and/or with high-grade tumours were more likely to succumb to breast cancer within 3years. Among ER-positive breast cancer patients who experience a distant recurrence, the time to death varies substantially and between patients could not be predicted by tumour factors or treatment. This suggests that for ER-positive patients, the factors that determine the time from diagnosis to distant recurrence do not predict the course of the cancer post-recurrence.

Achievement of guideline targets in elderly patients on hemodialysis: a multicenter study.

Advanced age is associated with shorter survival on dialysis. The aim of the present study was to compare the adherence with KDOQI guideline targets and the association between mortality and satisfying the guidelines targets between hemodialysis patients aged 65 years and over and those younger than 65 years. Data were collected using a questionnaire sent to all 46 HD centers in Serbia with totally 3868 HD patients. The 24 centers responded and sent the data on all patients aged 18 years or older that were on regular HD for more than 3 months (2153 patients, 1320 males, aged 18-90 years). Data are presented in two groups: a group of patients younger than 65 years (1438, 66.8 %) and a group of patients aged 65 years and over (715, 33.2 %). The percentage of patients whose values failed to meet the targets recommended by KDOQI Clinical Practice Guidelines was calculated for dialysis dose (spKt/V), hemoglobin, serum phosphorus, serum calcium and plasma iPTH (150-300 pg/mL). Patients were followed from enrollment until their death, kidney transplantation, departure from the center or the end of the study. Elderly patients were more likely to have hypertension, significantly lower systolic and diastolic blood pressure and smaller dialysis vintage than younger patients. They were less frequently treated with high-flux membranes and hemodiafiltration and they had significantly lower number of dialysis hours per week and significantly lower interdialytic weight gain. They used ESA and phosphate binders less frequently than younger patients (p < 0.001 and p = 0.002). Older patients had similar Kt/V as younger ones but they had significantly more frequent Hb level outside the target range than younger patients. During the year follow-up period, by using a Cox proportional hazards model it has been confirmed that age, dialysis vintage, weekly dialysis time and target values for Kt/V were significant independent predictors of time to death for younger patients and gender, dialysis vintage and iPTH were independent predictor of time to death for older patients. Despite less favorable dialysis prescription, older patients had similar Kt/V and less frequent deviations from the target values proposed by KDOQI for serum phosphorus and iPTH but more frequent deviation for Hb value as compared with younger patients. Risk factors for mortality differ between older and younger patients; out of five KDOQI targets, only Kt/V proved to be a significant risk factor for mortality for younger and iPTH for older patients.

Compliance with guidelines and predictors of mortality in hemodialysis. Learning from Serbia patients

ObjectivesThe aims of the study were to determine the percentage of patients on regular hemodialysis (HD) in Serbia failing to meet KDOQI guidelines targets and find out factors associated with the risk of time to death and the association between guidelines adherence and patient outcome. MethodsA cohort of 2153 patients on regular HD in 24 centers (55.7% of overall HD population) in Serbia were followed from January 2010 to December 2012. The percentage of patients failing to meet KDOQI guidelines targets of dialysis dose (Kt/V>1.2), hemoglobin (>110g/L), serum phosphorus (1.1–1.8mmol/L), calcium (2.1–2.4mmol/L) and iPTH (150–300pg/mL) was determined. Cox proportional hazards analysis was used to select variables significantly associated with the risk of time to death. ResultsThe patients were on regular HD for 5.3±5.3 years, dialyzed 11.8±1.9h/week. Kt/V<1.2 had 42.4% of patients, hemoglobin <110g/L had 66.1%, s-phosphorus <1.1mmol/L had 21.7% and >1.8mmol/L 28.6%, s-calcium <2.1mmol/L had 11.7% and >2.4mmol/L 25.3%, iPTH <150pg/mL had 40% and >300pg/mL 39.7% of patients. Using Cox model (adjustment for patient age, gender, duration of HD treatment) age, duration of HD treatment, hemoglobin, iPTH and diabetic nephropathy were selected as significant independent predictors of time to death. When targets of five examined parameters were included in Cox model, target for KtV, hemoglobin and iPTH were found to be significant independent predictors of time to death. ConclusionSubstantial proportion of patients examined failed to meet KDOQI guidelines targets. The relative risk of time to death was associated with being outside the targets for Kt/V, hemoglobin and iPTH.

Compliance with guidelines and predictors of mortality in hemodialysis. Learning from Serbia patients

ObjectivesThe aims of the study were to determine the percentage of patients on regular hemodialysis (HD) in Serbia failing to meet KDOQI guidelines targets and find out factors associated with the risk of time to death and the association between guidelines adherence and patient outcome. MethodsA cohort of 2153 patients on regular HD in 24 centers (55.7% of overall HD population) in Serbia were followed from January 2010 to December 2012. The percentage of patients failing to meet KDOQI guidelines targets of dialysis dose (Kt/V>1.2), hemoglobin (>110g/L), serum phosphorus (1.1–1.8mmol/L), calcium (2.1–2.4mmol/L) and iPTH (150–300pg/mL) was determined. Cox proportional hazards analysis was used to select variables significantly associated with the risk of time to death. ResultsThe patients were on regular HD for 5.3±5.3 years, dialyzed 11.8±1.9h/week. Kt/V<1.2 had 42.4% of patients, hemoglobin <110g/L had 66.1%, s-phosphorus <1.1mmol/L had 21.7% and >1.8mmol/L 28.6%, s-calcium <2.1mmol/L had 11.7% and >2.4mmol/L 25.3%, iPTH <150pg/mL had 40% and >300pg/mL 39.7% of patients. Using Cox model (adjustment for patient age, gender, duration of HD treatment) age, duration of HD treatment, hemoglobin, iPTH and diabetic nephropathy were selected as significant independent predictors of time to death. When targets of five examined parameters were included in Cox model, target for KtV, hemoglobin and iPTH were found to be significant independent predictors of time to death. ConclusionSubstantial proportion of patients examined failed to meet KDOQI guidelines targets. The relative risk of time to death was associated with being outside the targets for Kt/V, hemoglobin and iPTH.

A longitudinal study of foot ulceration and its risk factors in community-based patients with type 2 diabetes: The Fremantle Diabetes Study

AimsTo determine the prevalence and associates of foot ulcer, and the subsequent incidence and predictors of first-ever hospitalisation for this complication, in well-characterised community-based patients with type 2 diabetes. MethodsBaseline foot ulceration was ascertained in 1296 patients (mean age 64 years, 48.6% male, median diabetes duration 4.0 years) recruited to the longitudinal Fremantle Diabetes Study between 1993 and 1996. Incident hospitalisation for foot ulceration was monitored through validated data linkage until end-December 2010. ResultsAt baseline, 16 participants (1.2%) had a foot ulcer which was independently associated with intermittent claudication, peripheral sensory neuropathy (PSN) and diabetes duration (P≤0.01). The incidence of hospitalisation for this complication in those without prior/prevalent foot ulceration was 5.21 per 1000 patient-years. This rate and other published data suggest that 1 in 7–10 foot ulcers require hospitalisation. In a Cox proportional hazards model, intermittent claudication and PSN were significant independent predictors of time to admission with foot ulceration, in addition to retinopathy, cerebrovascular disease, HbA1c, alcohol consumption, renal impairment, peripheral arterial disease and pulse pressure (P≤0.038). ConclusionsThese data confirm PSN as an important risk factor for foot ulceration but, in contrast to some other studies, peripheral arterial disease was also a major independent contributor. Associations between hospitalisation for foot ulcer and both retinopathy and raised pulse pressure suggest a role for local microvascular dysfunction, while alcohol may have non-neuropathic toxic effects on skin/subcutaneous structures. The multifactorial nature of foot ulceration complicating type 2 diabetes may have implications for its management.

Impulsivity predicts time to reach euthymia in adults with bipolar disorder.

Specific demographic and illness characteristics have been identified as predictors of overall morbidity and treatment course among individuals with bipolar disorder. However, the role of specific cognitive limitations on disease severity and treatment response is unclear. The present study evaluated whether impulsiveness during acute mania was a significant predictor of achieving euthymia within one year following psychiatric hospitalization. Participants were 94 adult inpatients (60 manic) with bipolar I disorder. Baseline symptom severity was assessed using the Young Mania Rating Scale and the Montgomery-Åsberg Depression Rating Scale. Impulsivity was measured with the Stop Signal Task, Degraded Stimulus Continuous Performance Task, Delayed Response Task, and Barratt Impulsiveness Scale-11. Individual predictors of time to reach euthymia included fewer depressive symptoms and better impulse control at baseline, later age at illness onset, shorter illness duration, and the absence of comorbid attention-deficit hyperactivity disorder. Self-reported impulsivity was a significant independent predictor of time to euthymia, even after accounting for relevant clinical variables. Better trait impulse control may be associated with better treatment responsiveness among adults with bipolar disorder.

PC.70 Signs of feed intolerance in the premature infant: is it functional dysmotility or necrotizing enterocolitis (NEC)?

AimTo observe signs of gastrointestinal dysmotility [gastric residual volume (GRV*), bile stained aspirates (BSA), abdominal distension (AD^), first passage of meconium (FPOM), and time to regular bowel habit (RBH)] whilst...

Donor and Recipient Factors Predicting Time to Graft Failure Following Orthotopic Liver Transplantation: A Transplant Risk Index

IntroductionMuch of the success of a transplant depends on appropriate matching of donor to recipient. MethodsWe validated the Donor Risk Index formula (DRI) using Mount Sinai Medical Center's 10-year cohort of over 1000 transplants. ResultsThe DRI was significantly associated to graft failure with a relative risk (RR) of 1.32. Our cohort had an average DRI of 2.6 with survival of 83% at 3 months, 79% at 1 year, and 70% at 3 years. The low rate of graft failure at a high DRI implies that there are other factors important in transplant pairing that are not considered in the DRI model. To determine these variables and quantify their importance, we constructed a Transplant Risk Index by identifying recipient and donor variables not captured in United Network for Organ Sharing (UNOS) that significantly correlated to graft failure. The most significant independent predictors of time to graft failure were donor age, weight, and peak serum sodium; ischemia time; and recipient creatinine, international normalized ratio, and hepatitis C infection. The coefficients for each of these factors were compiled into a Transplant Risk Index formula. A cutoff of 5 resulted in a graft survival rate of 86% at 3 months, 76% at 1 year, and 62% at 3 years using Kaplan-Meier analysis. The predictive ability of the Transplant Risk Index was greater than the DRI or DMELD (the product of donor age and preoperative MELD) as assessed by the area under the receiver operating curve and the positive and negative predictive values. ConclusionThe Transplant Risk Index captures recipient factors and donor factors not captured in UNOS. Including these factors may improve the ability to predict good donor–recipient pairing.

ARTICLE BY NYLEN AND COLLEAGUES

To the Editor: Nylen and colleagues reported that physical fitness, as represented by exercise capacity, reduces the risk of mortality in people with diabetes mellitus regardless of age.1 I compliment the authors on their excellent study. I would also like to mention that data were reported from a study of 609 people with diabetes mellitus with a mean age of 70 with no history of coronary artery disease who were referred for an exercise treadmill sestamibi stress test because of chest pain or dyspnea.2 At 47-month follow-up, stepwise Cox regression analysis showed that a predicted exercise capacity of greater than 85% was a significant independent predictor of time to development of myocardial infarction, stroke, or death (hazard ratio=0.52, 95% confidence interval=0.34–0.78; P=.002). Older persons with diabetes mellitus with a predicted exercise capacity of greater than 85% had a 48% lower chance of myocardial infarction, stroke, or death than those with a predicted exercise capacity of 85% or less. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the author and has determined that the author has no financial or any other kind of personal conflicts with this paper. Author Contributions: WSA wrote the letter to the editor. Sponsor's Role: There is no sponsor.

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Severe Hypoglycemia Complicating Type 2 Diabetes: The Fremantle Diabetes Study

The aim of this study was to determine whether the angiotensin-converting enzyme (ACE) gene I/D polymorphisms independently predict severe hypoglycemia in community-dwelling type 2 patients. Six hundred and two patients who were ACE genotyped at baseline and assessed in 1998 were followed up to the end of June 2006. Severe hypoglycemia was defined as that requiring documented health service use as the primary diagnosis. Cox proportional hazards modeling was used to determine the predictors of first episode and zero-inflated negative binomial regression modeling identified predictors of frequency. Forty-nine patients (8.1%) experienced 63 episodes of severe hypoglycemia. After adjusting for previously identified significant independent predictors of time to first episode, both ACE DD genotype and ACE inhibitor therapy, but not their interaction, added to the model [hazard ratio (95% confidence interval): 2.34 (1.29-4.26), P = 0.006, and 1.77 (0.99-3.13), P = 0.052, respectively]. Similarly, after adjusting for previously identified risk factors for multiple episodes of severe hypoglycemia, ACE DD genotype was independently associated with increased risk [incidence relative risk (95% confidence interval): 1.80 (1.00-3.24), P = 0.050]. ACE DD genotype was associated with an approximately 2-fold increased risk of the first episode of severe hypoglycemia and its subsequent frequency in well-characterized patients with type 2 diabetes. Consistent with previous case-control studies, ACE inhibitor therapy was a weak predictor of severe hypoglycemia. ACE I/D genotyping might provide useful adjunctive prognostic information when intensive glycemic control measures are contemplated.

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Severe Hypoglycemia Complicating Type 2 Diabetes: The Fremantle Diabetes Study

Abstract Aims/Hypotheses: The aims of this study were to determine whether the angiotensin-converting enzyme (ACE) gene I/D polymorphisms independently predict severe hypoglycemia in community-dwelling type 2 patients. Methods: Six hundred two patients who were ACE genotyped at baseline and assessed in 1998 were followed up to the end of June 2006. Severe hypoglycemia was defined as that requiring documented health service use as the primary diagnosis. Cox proportional hazards modeling was used to determine the predictors of first episode and zero-inflated negative binomial regression modeling identified predictors of frequency. Results: Forty-nine patients (8.1%) experienced 63 episodes of severe hypoglycemia. After adjusting for previously identified significant independent predictors of time to first episode, both ACE DD genotype and ACE inhibitor therapy, but not their interaction, added to the model [hazard ratio (95% confidence interval): 2.34 (1.29–4.26), P = 0.006, and 1.77 (0.99–3.13), P = 0.052, respectively]. Similarly, after adjusting for previously identified risk factors for multiple episodes of severe hypoglycemia, ACE DD genotype was independently associated with increased risk [incidence relative risk (95% confidence interval): 1.80 (1.00–3.24), P = 0.050]. Conclusions/Interpretation: ACE DD genotype is associated with an increased the risk of the first episode of severe hypoglycemia and its subsequent frequency approximately 2-fold in well-characterized patients with type 2 diabetes. Consistent with previous case-control studies, ACE inhibitor therapy was a weak predictor of severe hypoglycemia. ACE I/D genotyping might provide useful adjunctive prognostic information when intensive glycemic control measures are contemplated.

Determinants of Severe Hypoglycemia Complicating Type 2 Diabetes: The Fremantle Diabetes Study

There are limited published data characterizing severe hypoglycemia complicating type 2 diabetes. The objective of the study was to determine the incidence and predictors of severe hypoglycemia in community-dwelling type 2 patients. This was a longitudinal observational cohort study. This was a community-based study. There were 616 patients (mean age 67.0 yr, 52.3% males, median diabetes duration 7.7 yr) assessed in 1998 and followed up to the end of June 2006. Severe hypoglycemia defined as that requiring ambulance attendance, emergency department services, and/or hospitalization. Cox proportional hazards modeling was used to determine predictors of first episode, and Poisson, negative binomial, zero-inflated Poisson, and zero-inflated negative binomial regression models identified predictors of frequency. Fifty-two (8.4%) experienced 66 episodes during 3953 patient-years (incidence 1.7 per 100 patient-years). Those experiencing severe hypoglycemia had one to four episodes. Significant independent predictors of time to first episode were duration of insulin treatment, estimated glomerular filtration rate less than 60 ml/min per 1.73 m(2), peripheral neuropathy, education beyond primary level, and past severe hypoglycemia. The zero-inflated negative binomial provided the best model of severe hypoglycemia frequency. Lower fasting serum glucose and higher glycosylated hemoglobin were significantly associated with frequency, whereas patients at minimal risk of repeated severe hypoglycemia were unlikely to use insulin or to have short-duration insulin treatment, to have renal impairment or peripheral neuropathy, or to be educated beyond primary level. Duration of insulin treatment was confirmed as an independent risk factor for severe hypoglycemia. The novel association with educational attainment suggests knowledge-driven intensive glycemic self-management. The positive relationship between frequency and glycosylated hemoglobin may identify patients with unstable glycemic control.

Brain mu-opioid receptor binding: relationship to relapse to cocaine use after monitored abstinence

Cocaine users have increased regional brain mu-opioid receptor (mOR) binding which correlates with cocaine craving. The relationship of mOR binding to relapse is unknown. To evaluate regional brain mOR binding as a predictor of relapse to cocaine use is the objective of the study. Fifteen nontreatment-seeking, adult cocaine users were housed on a closed research ward for 12 weeks of monitored abstinence and then followed for up to 1 year after discharge. Regional brain mOR binding was measured after 1 and 12 weeks using positron emission tomography (PET) with [11C]carfentanil (a selective mOR agonist). Time to first cocaine use (lapse) and to first two consecutive days of cocaine use (relapse) after discharge was based on self-report and urine toxicology. A shorter interval before relapse was associated with increased mOR binding in frontal and temporal cortical regions at 1 and 12 weeks of abstinence (Ps < 0.001) and with a lesser decrease in binding between 1 and 12 weeks (Ps < 0.0008). There were significant positive correlations between mOR binding at 12 weeks and percent days of cocaine use during first month after relapse (Ps < 0.002). In multiple linear regression analysis, mOR binding contributed significantly to the prediction of time to relapse (R2= 0.79, P < 0.001), even after accounting for clinical variables. Increased brain mOR binding in frontal and temporal cortical regions is a significant independent predictor of time to relapse to cocaine use, suggesting an important role for the brain endogenous opioid system in cocaine addiction.

Predicting prostate cancer specific mortality following biochemical recurrence after radical prostatectomy

4546 Background: The natural history of biochemical recurrence (BCR) after radical prostatectomy (RP) can be long, but variable. Better predictive models are needed to identify men early who are at high-risk for CaP death for aggressive salvage treatment as well as to identify men who are at low-risk for CaP death and can be safely observed. We sought to define risk factors for CaP specific mortality following RP and develop tables to risk stratify for CaP specific survival. Methods: We retrospectively studied 5,096 patients treated with RP between 1982 and 2000 of which 379 experienced a BCR and had at least 2 PSA values available after BCR separated by at least 3 months in order to calculate a PSA doubling time (PSADT). Multivariable Cox proportional hazards analysis was used to determine the significant predictors of CaP specific mortality. Results: With a median follow-up of 10.3 yrs after BCR (range 1–16 yrs) the CaP specific survival was 55%. On multivariable analysis, pathological Gleason sum (p=0.002), time from RP to BCR (p=0.02), and PSADT as a continuous variable (p<0.001) were all significant independent predictors of time to CaP death. Using these three variables, the 5-, 10-, and 15-year risk of CaP specific survival can be estimated. The 15-year risk of CaP specific survival is shown in the table. Conclusions: Clinical parameters (PSADT, pathological Gleason sum, and time from RP to BCR) can help risk stratify patients for CaP death following BCR after RP. No significant financial relationships to disclose.

Lipoprotein levels are associated with incident hypertension in older adults.

To determine the relationship between baseline measures of serum lipoproteins and incident hypertension in older adults. Prospective cohort study. Pittsburgh, Pennsylvania, site of Systolic Hypertension in the Elderly Program (SHEP). One hundred eighty-seven men and women (mean age 71.3), normotensive (systolic blood pressure (SBP) <160 mmHg, diastolic blood pressure (DBP) <90 mmHg) at baseline, were followed annually over 8 years as an ancillary study to the SHEP. Hypertension development, defined as initiation of antihypertensive therapy or SBP greater than 160 mmHg or DBP greater than 90 mmHg. Lipoprotein measures included total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), HDL(2)-C, HDL(3)-C, triglycerides, and apolipoproteins 1, 2, and B. Over 8 years, 44 participants developed hypertension, for a Kaplan-Meier cumulative incidence rate of 31% (95% confidence interval (CI)=23-39%). Cumulative incidence rates were highly associated with baseline SBP, ranging from 8% in those with baseline SBP less than 120 mmHg to 70% in those with SBP of 140 to 159 mmHg. Other univariate associations included higher DBP, pulse pressure (P <.01 for both), triglycerides (P=.03), apolipoprotein B (P=.03), and lower HDL-C (P=.04) and HDL(3)-C (P=.02). In multivariate Cox regression analysis, higher baseline SBP (relative risk (RR)=1.8 per 10 mmHg, 95% CI=1.5-2.3) and lower HDL(3)-C (RR=0.8 per 5 mg/dL, 95% CI=0.42-1.0) remained significant independent predictors of time to hypertension. Older adults with abnormal serum lipoproteins are at increased risk of developing hypertension. Clinical trials exploring the effects of the modification of lipoprotein levels on hypertension incidence rates are needed.

Role of cardiac troponin T in the long-term risk stratification of patients undergoing percutaneous coronary intervention.

To investigate the long-term prognostic significance of pre- and post-procedure troponin T (TnT) elevations in patients undergoing percutaneous coronary intervention (PCI). TnT and CK-MB were measured pre- and post-procedure in 212 patients undergoing PCI. Major adverse events (composite of death, myocardial infarction and revascularization) were ascertained 6 years later. Pre-procedural TnT was a significant independent predictor of time to major events (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.16-2.64) and death or myocardial infarction. Post-procedural TnT elevation above normal was the only independent predictor of the primary end-point at 1 year (HR 2.39, 95% CI 1.09-5.26) but was not significantly related to event-free survival throughout follow-up. Post-PCI elevation of TnT 5x above normal, however, did significantly predict time to events during the entirety of follow-up. By contrast, CK-MB was not an independent predictor in any of the analyses. Our study confirms the long-term prognostic value of pre-procedural TnT elevation in patients undergoing PCI, and demonstrates the superior predictive ability of a post-procedural increase in TnT 5x normal for long-term adverse events. Whether the prognostic significance of smaller post-procedural TnT elevations extends beyond the intermediate-term awaits further investigation.

Improved Clinical Staging System Combining Biopsy Laterality and TNM Stage for Men With T1c and T2 Prostate Cancer: Results From the SEARCH Database

A number of studies have failed to show significant differences in outcome following radical prostatectomy between men with palpable, clinically localized prostate cancer (cT2) and those whose tumors are not palpable (cT1c). We determined whether we could improve the prognostic value of the TNM staging system in men with cT1c and cT2 cancers by including information on whether prostate needle biopsy was unilaterally or bilaterally positive. A retrospective survey of 992 patients from the SEARCH (Shared Equal Access Regional Cancer Hospital) Database treated with radical prostatectomy at 4 equal access medical centers between 1988 and 2002 was done. TNM 1992 clinical stage was T1c in 421 patients, T2a in 287, T2b in 202 and T2c in 82. Multivariate analysis was used to examine whether biopsy laterality and clinical stage were significant predictors of surgical margin status, nonorgan confined disease, seminal vesicle invasion, and time to prostate specific antigen (PSA) recurrence following radical prostatectomy. Patients with clinical stages T2b and T2c cancers had similar rates of PSA recurrence, which were significantly higher than in patients with T1c and T2a disease, who also had similar rates of PSA recurrence. Bilateral positive biopsy further stratified patients with T1c and T2a disease (p = 0.01) but not those with T2b and T2c cancers (p = 0.207). Grouping these 1992 clinical stages with biopsy laterality resulted in a new clinical staging system, which was a significant predictor of PSA recurrence following radical prostatectomy (p <0.001). On multivariate analysis whether TNM clinical stage was evaluated as a categorical or continuous variable only PSA, biopsy Gleason score and the new clinical staging system (1992 TNM stage groupings combined with biopsy laterality) were significant independent predictors of time to biochemical recurrence following radical prostatectomy. Combining low (T1c and T2a) and high (T2b and T2c) risk 1992 clinical stages with biopsy laterality (unilateral versus bilateral positive) resulted in a new clinical staging system that was a stronger predictor of PSA recurrence following radical prostatectomy than the 1992 or 1997 TNM clinical staging system. If confirmed at other centers and in men who undergo with other treatment modalities, consideration should be given to revising the current TNM staging system to reflect these findings.

Percent of Prostate Needle Biopsy Cores With Cancer is Significant Independent Predictor of Prostate Specific Antigen Recurrence Following Radical Prostatectomy: Results From SEARCH Database

Recent studies have suggested that the percent of positive cores in the prostate needle biopsy is a significant predictor of outcome among men undergoing radical prostatectomy or radiation therapy for prostate cancer. We evaluate whether either percent of cores with cancer or percent of cores positive from the most and least involved side of the prostate needle biopsy was associated with a worse outcome among men treated with radical prostatectomy. A retrospective survey of 1,094 patients from the SEARCH Database treated with radical prostatectomy at 4 different equal access medical centers in California between 1988 and 2002 was undertaken. We used multivariate analysis to examine whether total percent of prostate needle biopsy cores with cancer, percent of cores positive from each side of the prostate and other clinical variables were significant predictors of adverse pathology and time to prostate specific antigen (PSA) recurrence following radical prostatectomy. On multivariate analysis serum PSA and percent of positive cores were significant predictors of positive surgical margins, nonorgan confined disease and seminal vesicle invasion. Percent of positive cores (p <0.001), serum PSA (p = 0.008) and biopsy Gleason score (p = 0.014) were significant independent predictors of time to biochemical recurrence. On a separate multivariate analysis that included the variables of total percent of positive cores, percent of positive cores from the most involved side of the biopsy, percent of positive cores from the least involved side of the biopsy and whether the biopsy was positive unilaterally or bilaterally, only the percent of positive cores from the most involved side of the biopsy was a significant independent predictor of PSA failure following radical prostatectomy. Percent of positive cores was used to separate patients into a low risk (less than 34%), intermediate risk (34% to 50%) and high risk (greater than 50%) groups, which provided significant preoperative risk stratification for PSA recurrence following radical prostatectomy (p <0.001). Percent of positive cores cut points were able to further risk stratify men who were at low (p = 0.001) or intermediate (p = 0.036) but not high (p = 0.674) risk for biochemical failure based on serum PSA and biopsy Gleason score. Percent of positive cores in the prostate needle biopsy was a significant predictor of adverse pathology and biochemical failure following radical prostatectomy, and the cut points of less than 34%, 34% to 50% and greater than 50% can be used to risk stratify patients preoperatively. The finding that percent of positive cores from the most involved side of the biopsy was a stronger predictor of PSA failure than the total percent of cores involved suggests that multiple positive biopsies from a single side might be a better predictor of a larger total cancer volume and thus correlate with clinical outcome.

Race as an outcome predictor after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database

Objectives Whether race is an independent predictor of prostate-specific antigen (PSA) recurrence after RP is controversial. To compare racial differences in clinical and pathologic features and biochemical recurrence in men undergoing radical prostatectomy (RP), we used a newly established multicenter database of patients from four equal-access healthcare centers in California, the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Methods A retrospective survey of 1547 patients treated with RP at four different equal-access medical centers in California between 1988 and 2001 was undertaken. Race was categorized as white (n = 1014), black (n = 338), or nonwhite-nonblack (n = 195). Patients were analyzed for racial differences in preoperative variables (age at surgery, clinical stage, PSA, and biopsy Gleason score) and surgical variables (pathologic stage, surgical Gleason score, incidence of seminal vesicle invasion, positive surgical margins, capsular penetration, and pelvic lymph node involvement). Patients were followed up for PSA recurrence. Multivariate analysis was used to determine whether race was an independent predictor of biochemical failure. Results Significant differences were found among the races in the preoperative factors of clinical stage, age, serum PSA, and biopsy Gleason score, although the absolute differences were small. No differences were found among the races in the pathologic features of the RP specimens, including Gleason score, pathologic stage, and incidence of positive surgical margins, capsular penetration, seminal vesicle invasion, or lymph node involvement. In both univariate and multivariate analyses, only serum PSA ( P <0.001) and biopsy Gleason score ( P <0.001) were significant independent predictors of time to biochemical recurrence. Conclusions In a large multicenter cohort of patients from four equal-access medical care facilities in California, although racial differences were found in clinical stage, age, biopsy Gleason score, and serum PSA level at diagnosis, we found race was not an independent predictor of biochemical recurrence after RP. Race should not be used in models or nomograms predicting PSA failure after RP. The current study represents the largest series of black patients and the first large series of nonwhite-nonblack patients treated with RP reported to date. The Shared Equal Access Regional Cancer Hospital database is a valuable resource for studying patients treated with RP.

Prediction of atherosclerotic cardiovascular death in men using a prognostic score

Treadmill and clinical data were gathered prospectively on consecutive patients who underwent exercise testing for evaluation for coronary artery disease in a 1,200 bed Veterans Affairs Medical Center. From 3,609 men referred for exercise testing from 1984 to 1990, 3,134 patients remained after excluding those with significant valvular heart disease and those with prior coronary artery bypass surgery. Of these, 588 were selected for clinical reasons to undergo cardiac catheterization within 3 months of evaluation leaving 2,546 who were not selected. Over 3 years, there were 158 cardiovascular deaths, 99 nonfatal myocardial infarcts and 183 patients who underwent coronary artery bypass surgery. In the total population, the Cox proportional-hazards model demonstrated the following characteristics to be statistically significant independent predictors of time until cardiovascular death: a history of congestive heart failure and/or taking digoxin, exercise-induced ST depression, the change in systolic blood pressure during exercise, and exercise capacity in METs. Using the Cox model coefficients to weight the variables, a simple score (the Veterans Affairs Prognostic Score) was constructed based on these items. Average annual cardiovascular mortality was plotted against the score enabling its estimation for any given patient. In the subgroup selected for cardiac catheterization (n = 588), the mean score was greater, consistent with a poorer prognosis, compared with the total population; 53% (n = 312) had a score <−2 associated with an annual mortality <2%. Thus, in over half of the patients selected for catheterization, the catheterization was unnecessary if performed to lessen their chance of cardiovascular death, since no intervention could improve their prognosis. Similarly, in patients selected for bypass surgery, the mean score was −0.5, which is associated with an estimated annual cardiovascular mortality of 5%. Thirty-five percent of these patients had a score <−2. Thus, variables available from the usual noninvasive workup of patients with known or suspected coronary artery disease can be used to estimate cardiovascular mortality. Exercise-induced ST depression can be falsely excluded from predictive models because of workup bias. This score can estimate cardiovascular mortality in male veterans being evaluated for stable coronary artery disease, obviating the need for cardiac catheterization in many of them.