Validation of a Genomic Classifier for Predicting Post-Prostatectomy Recurrence in a Community Based Health Care Setting.

PURPOSE: We determined the value of Decipher®, a genomic classifier, to predict prostate cancer outcomes among patients after prostatectomy in a community health care setting. MATERIALS AND METHODS: We examined the experience of 224 men treated with radical prostatectomy from 1997 to 2009 at Kaiser Permanente Northwest, a large prepaid health plan in Portland, Oregon. Study subjects had aggressive prostate cancer with at least 1 of several criteria such as preoperative prostate specific antigen 20 ng/ml or greater, pathological Gleason score 8 or greater, stage pT3 disease or positive surgical margins at prostatectomy. The primary end point was clinical recurrence or metastasis after surgery evaluated using a time dependent c-index. Secondary end points were biochemical recurrence and salvage treatment failure. We compared the performance of Decipher alone to the widely used CAPRA-S (Cancer of the Prostate Risk Assessment Post-Surgical) score, and assessed the independent contributions of Decipher, CAPRA-S and their combination for the prediction of recurrence and treatment failure. RESULTS: Of the 224 patients treated 12 experienced clinical recurrence, 68 had biochemical recurrence and 34 experienced salvage treatment failure. At 10 years after prostatectomy the recurrence rate was 2.6% among patients with low Decipher scores but 13.6% among those with high Decipher scores (p=0.02). When CAPRA-S and Decipher scores were considered together, the discrimination accuracy of the ROC curve was increased by 0.11 compared to the CAPRA-S score alone (combined c-index 0.84 at 10 years after radical prostatectomy) for clinical recurrence. CONCLUSIONS: Decipher improves our ability to predict clinical recurrence in prostate cancer and adds precision to conventional pathological prognostic measures.

Use of intravenous bisphosphonates in patients with breast, lung, or prostate cancer and metastases to bone: a 15-year study in two large US health systems.

PURPOSE: The purpose of this paper is to document the use of intravenous (IV) bisphosphonates for prevention of skeletal-related events (SREs) in patients with bone metastases (BM) due to breast cancer (BC), lung cancer (LC), or prostate cancer (PC). METHODS: Using data from two large US health systems, we identified all patients aged ≥ 18 years with primary BC, LC, or PC and newly diagnosed BM between 1/1/1995 and 12/31/2009. Starting with the diagnosis of BM, we reviewed medical and administrative records for evidence of receipt of IV bisphosphonates (zoledronic acid or pamidronate) and occurrence of SREs. Initiation of IV bisphosphonates prior to occurrence of an SRE was designated "primary prophylaxis"; use following an SRE was designated "secondary prophylaxis". RESULTS: We identified a total of 1,193 patients with newly diagnosed BM, including 400 with BC, 332 with LC, and 461 with PC. Use of IV bisphosphonates was substantially higher in BC (55.8 % of all patients) than in LC (14.8 %) or PC (20.2 %). Use of IV bisphosphonates was fairly evenly split between primary and secondary prophylaxis in BC (26.3 vs. 29.5 %, respectively) and PC (10.6 vs 9.5 %); in LC, however, primary prophylaxis was much less common than secondary prophylaxis (4.8 vs 9.9 %). CONCLUSIONS: Almost one half of all patients with BM due to BC, and substantially more with LC and PC, do not receive IV bisphosphonates. Among patients receiving such therapy, treatment often is not initiated until after the occurrence of an SRE. Our study suggests that IV bisphosphonates may be substantially underutilized in patients with BM due to these common cancers.

Natural history of skeletal-related events in patients with breast, lung, or prostate cancer and metastases to bone: a 15-year study in two large US health systems.

PURPOSE: To document the risk of skeletal complications in patients with bone metastases from breast cancer (BC), lung cancer (LC), or prostate cancer (PC) in routine clinical practice. METHODS: We used data from two large US health systems to identify patients aged ≥18 years with primary BC, LC, or PC and newly diagnosed bone metastases between January 1, 1995 and December 31, 2009. Beginning with the date of diagnosis of bone metastasis, we estimated the cumulative incidence of skeletal-related events (SREs) (spinal cord compression, pathologic fracture, radiation to bone, bone surgery), based on review of medical records, accounting for death as a competing risk. RESULTS: We identified a total of 621 BC, 477 LC, and 721 PC patients with newly diagnosed bone metastases. SREs were present at diagnosis of bone metastasis in 22.4, 22.4, and 10.0 % of BC, LC, and PC patients, respectively. Relatively few LC or PC patients received intravenous bisphosphonates (14.8 and 20.2 %, respectively); use was higher in patients with BC, however (55.8 %). In BC, cumulative incidence of SREs during follow-up was 38.7 % at 6 months, 45.4 % at 12 months, and 54.2 % at 24 months; in LC, it was 41.0, 45.4, and 47.7 %; and in PC, it was 21.5, 30.4, and 41.9 %. More than one half of patients with bone metastases had evidence of SREs (BC: 62.6 %; LC: 58.7 %; PC: 51.7 %), either at diagnosis of bone metastases or subsequently. CONCLUSIONS: SREs are a frequent complication in patients with solid tumors and bone metastases, and are much more common than previously recognized in women with BC.

Medical history, body size, and cigarette smoking in relation to fatal prostate cancer.

OBJECTIVES: Prostate cancer has few known risk factors. As part of a population-based case-control study conducted in four health maintenance organizations, the authors examined the associations between fatal prostate cancer and several medical and behavioral characteristics. METHODS: Cases were 768 health plan members who died of prostate adenocarcinoma during the period 1997-2001. We randomly selected controls (929) from the health plan membership and matched them to cases on health plan, age, race, and pattern of health plan membership. We examined medical records to obtain information on potential risk factors during the 10 years before the date on which prostate cancer was first suspected; the same reference date was used for the matched controls. RESULTS: Anthropometric characteristics, as well as personal histories of benign prostatic hypertrophy, transurethral prostatectomy, cancer, diabetes, prostatitis, hypertension, and vasectomy were largely similar for cases and controls. Men who died from prostate cancer were more likely than controls to have been cigarette smokers according to the most recent smoking notation before the reference date (odds ratio 1.5, 95% confidence interval 1.1-2.0). CONCLUSIONS: The observed increase in risk associated with recent cigarette smoking is consistent with the findings of several other studies. However, in contrast with some reports, we observed no connection between fatal prostate cancer and some prior health conditions or measures of body size.

Racial differences in treatment of early-stage prostate cancer.

OBJECTIVES: To determine whether differences existed in prostate cancer treatment received by white and African American men at a health maintenance organization where access to medical care is theoretically equal for all members and, if so, to determine the reasons for these differences. METHODS: We used information from the Kaiser Permanente Northwest Tumor Registry to identify all men diagnosed with local- or regional-stage prostate cancer between 1980 and 2000. We compared the likelihood of treatment with curative intent (TCI) between the two races, adjusting for age, tumor grade, stage, and the presence of comorbid conditions. We reviewed medical records of all 79 African American men and a sample of 158 white men (matched for age, stage, grade, and year of diagnosis) to determine the reasons that men did or did not receive TCI. RESULTS: Seventy-one percent of African American men and 82% of white men were treated with curative intent (P = 0.01). African American men were not more likely than white men to refuse TCI when it was offered (10.6% versus 8.1%, respectively; P = 0.6). However, urologists offered TCI less often to African American men than to white men (85% versus 91%, respectively; P = 0.02), and this difference could not be explained by differences in age, tumor grade, stage, or presence of comorbid conditions. CONCLUSIONS: African American men were less likely to receive TCI than white men. Because all of the men were insured, economic factors did not cause this difference. Furthermore, the cause did not seem to be differences in age, tumor grade, stage, or comorbid conditions.

Screening by prostate-specific antigen and digital rectal examination in relation to prostate cancer mortality: a case-control study.

BACKGROUND: The potential role of prostate cancer screening in reducing mortality is uncertain. To examine whether screening with the prostate-specific antigen (PSA) test or digital rectal examination is associated with reduced prostate cancer mortality, we conducted a population-based case-control study in 4 health maintenance organizations. METHODS: Cases were 769 health plan members who died because of prostate adenocarcinoma during the years 1997-2001. We randomly selected 929 controls from the health plan membership and matched them to cases on health plan, age, race, and membership history. Medical records were used to document all screening tests in the 10 years before and including the date on which prostate cancer was first suspected. RESULTS: Among white participants, 62% of cases and 69% of controls had a least 1 screening PSA test or digital rectal examination (odds ratio = 0.73; 95% confidence interval = 0.55-0.97). The corresponding proportions for blacks were 59% and 61% (1.0; 0.59-1.4). Most screening tests were digital rectal examinations; therefore, in the subgroup with no history of PSA screening, the association between digital rectal screening and prostate cancer mortality was similar to the overall association (0.65 [0.48-0.88] among whites; 0.86 [0.53-1.4] among blacks). Very few men received screening PSA without screening digital rectal examination (6% of cases and 7% of controls among whites). CONCLUSIONS: Digital rectal screening was associated with a reduced risk of death due to prostate cancer in our population. Because of several data limitations, this study could not accurately estimate the effect of PSA screening separate from digital rectal examination.

The incidence of colorectal cancer following a negative screening sigmoidoscopy: implications for screening interval.

BACKGROUND & AIMS: Current guidelines recommend a 5-year interval for colorectal cancer (CRC) screening by sigmoidoscopy. However, the optimal screening interval is uncertain. We estimated the annual incidence of distal and proximal CRC in the first 5 years following a negative sigmoidoscopy examination to gauge the potential benefit of rescreening in <5 years. METHODS: A cohort of 72,483 participants in the Colon Cancer Prevention program of Kaiser Permanente of Northern California (KP) was defined using computerized databases. Men and women aged 50 years and older who had a negative screening flexible sigmoidoscopy examination between 1994 and 1996 and were considered not to be at high risk for developing CRC were included. Subjects were censored at the time of diagnosis (for cases), death, termination of KP membership, or subsequent colon examination. RESULTS: Thirty cases of distal and 80 cases of proximal CRC occurred. Age-adjusted incidence rates of distal CRC ranged from a low of 2.8 per 100,000 person-years in the first year of follow-up to a high of 13.0 per 100,000 in the fourth year (rate difference, 10.2; 95% confidence interval, 1.1-19.3). However, for the entire follow-up period, incidence of distal CRC remained much lower than age-adjusted rates of 70.6 in the general population (Surveillance, Epidemiology, and End Results registry). The incidence of proximal CRC was also decreased modestly over population rates of disease. CONCLUSIONS: Screening by sigmoidoscopy more frequently than every 5 years would likely lead, at best, to only modest improvements as compared with a 5-year screening interval.