Kathryn Richert-Boe

Screening Colonoscopy and Risk for Incident Late-Stage Colorectal Cancer Diagnosis in Average-Risk Adults: A Nested Case–Control Study

BACKGROUND The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancer. OBJECTIVE To examine the association between screening colonoscopy and risk for incident late-stage colorectal cancer (CRC). DESIGN Nested case-control study. SETTING Four U.S. health plans. PATIENTS 1039 average-risk adults enrolled for at least 5 years in one of the health plans. Case patients were aged 55 to 85 years on their diagnosis date (reference date) of stage IIB or higher (late-stage) CRC during 2006 to 2008. One or 2 control patients were selected for each case patient, matched on birth year, sex, health plan, and prior enrollment duration. MEASUREMENTS Receipt of CRC screening 3 months to 10 years before the reference date, ascertained through medical record audits. Case patients and control patients were compared on receipt of screening colonoscopy or sigmoidoscopy by using conditional logistic regression that accounted for health history, socioeconomic status, and other screening exposures. RESULTS In analyses restricted to 471 eligible case patients and their 509 matched control patients, 13 case patients (2.8%) and 46 control patients (9.0%) had undergone screening colonoscopy, which corresponded to an adjusted odds ratio (AOR) of 0.29 (95% CI, 0.15 to 0.58) for any late-stage CRC, 0.36 (CI, 0.16 to 0.80) for right colon cancer, and 0.26 (CI, 0.06 to 1.11; P = 0.069) for left colon/rectum cancer. Ninety-two case patients (19.5%) and 173 control patients (34.0%) had screening sigmoidoscopy, corresponding to an AOR of 0.50 (CI, 0.36 to 0.70) overall, 0.79 (CI, 0.51 to 1.23) for right colon late-stage cancer, and 0.26 (CI, 0.14 to 0.48) for left colon cancer. LIMITATION The small number of screening colonoscopies affected the precision of the estimates. CONCLUSION Screening with colonoscopy in average-risk persons was associated with reduced risk for diagnosis of incident late-stage CRC, including right-sided colon cancer. For sigmoidoscopy, this association was seen for left CRC, but the association for right colon late-stage cancer was not statistically significant.

Prostate cancer screening and mortality: A case-control study (United States)

Objective: We performed a case–control study at Kaiser Permanente Northwest to assess the association between digital rectal examination (DRE) and prostate-specific antigen (PSA) testing, separately and together, and prostate cancer mortality. Methods: We identified 171 KPNW members who died as a result of prostate cancer from 1992 to 1999 and 342 randomly-selected KPNW members matched to the cases on age, sex, and length of plan membership. History of screening was determined from medical records and laboratory databases for cases and controls. Results: DRE and/or PSA screening at any time up to and including the case diagnosis date had taken place among 69.0% of cases and 74.6% of controls. After using logistic regression analysis to adjust for matching variables and a provider diagnosis of benign prostatic hypertrophy (BPH), we found an inverse association between receipt of a prostate cancer screening test and prostate cancer mortality (odds ratio (OR): 0.70, 95% confidence interval (CI): 0.46 – 1.1). Most of the screening tests were DREs, and it was not possible to assess the separate influence of PSA screening. Conclusions: The results of this study suggest that men who have been screened for prostate cancer have a reduced risk of dying as a result of this disease.

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.

Association of body mass index and prostate cancer mortality

OBJECTIVES Inconsistent evidence exists on whether obesity is associated with an increased risk of prostate cancer death post-radical prostatectomy. We examined data from three large health plans to evaluate if an increased body mass index (BMI) at prostate cancer diagnosis is related to prostate cancer mortality SUBJECTS AND METHODS This population-based case-control study included 751 men with prostate cancer who underwent radical prostatectomy. Cases were men who died due to prostate cancer (N=323) and matched controls (N=428). We used multivariable logistic regression models to assess the association between BMI at diagnosis and prostate cancer mortality, adjusted for Gleason score, PSA, tumour characteristics, and matching factors. RESULTS Study subjects were classified into the following BMI (kg/m2) categories: healthy (18.5-24.9), overweight (25-29.9) and obese (≥30). Nearly 43% of the participants had a BMI ≥25 at diagnosis. A higher fraction of cases (30%) were obese compared to controls (22%). Overall, obese men had more than a 50% increase in prostate cancer mortality (adjusted odds ratio=1.50 [95% CI, 1.03-2.19]) when compared to men with healthy BMI. After stratifying by Gleason score, the odds of mortality generally rose with increasing BMI. The strongest effect was observed in the Gleason score 8+ category (2.37, 95% CI: 1.11-5.09). These associations persisted after adjusting for PSA at diagnosis and other tumour characteristics. CONCLUSIONS These results suggest that BMI at diagnosis is strongly correlated with prostate cancer mortality, and that men with aggressive disease have a markedly greater odds of death if they are overweight or obese.

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.

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.

HER2 Evaluation and Its Impact on Breast Cancer Treatment Decisions

Background: Eighteen to twenty percent of breast cancer tumors show abnormal amplification of the Human Epidermal growth factor Receptor 2 (HER2) gene and increased expression of the associated protein. HER2 amplification is associated with rapid tumor proliferation and shorter disease-free and overall survival. Because women with HER2 amplification are more likely to benefit from treatment with the drug trastuzumab, testing for HER2 is recommended to guide therapy. However, little is known about use of HER2 testing in real-world settings. This study examined uptake, use, appropriateness of HER2 testing, and the relationship between HER2 test results and treatment decisions. Methods: We assessed electronic data from 3,634 patients with invasive breast cancer diagnosed from 1998 to 2007 in a large integrated health system. We collected data on patient and tumor characteristics, HER2 testing status, test results, and trastuzumab treatment. Results:From 1998 to 2000, the percent of patients who underwent HER2 evaluation increased from 12 to 94%; <3% of women with ductal carcinoma in situ, for whom HER2 testing is not recommended, were tested. Trastuzumab use increased 5-fold after 2004, when guidelines expanded to include recommending adjuvant treatment for early-stage breast cancer in addition to metastatic treatment. Ninety-five percent of women receiving trastuzumab had a positive HER2 result. After 2004, 55% of women with invasive breast cancer and overexpression of HER2 received trastuzumab treatment; this ranged from 44% of women with localized breast cancer to 80% of women with distant metastatic disease. Conclusions:These findings illustrate appropriate and effective implementation of a HER2 testing strategy in a managed care setting.

5-Alpha Reductase Inhibitors and the Risk of Prostate Cancer Mortality in Men Treated for Benign Prostatic Hyperplasia

OBJECTIVE To compare the risk of prostate cancer mortality among men treated with 5- alpha reductase inhibitors (5-ARIs) with those treated with alpha-adrenergic blockers (ABs) in community practice settings. PATIENTS AND METHODS A retrospective matched cohort (N=174,895) and nested case-control study (N=18,311) were conducted in 4 regions of an integrated health care system. Men 50 years and older who initiated pharmaceutical treatment for benign prostatic hyperplasia between January 1, 1992, and December 31, 2007, and had at least 3 consecutive prescriptions were followed through December 31, 2010. Adjusted subdistribution hazard ratios, accounting for competing risks of death, and matched odds ratios were used to estimate prostate cancer mortality associated with 5-ARI use (with or without concomitant ABs) as compared with AB use. RESULTS In the cohort study, 1,053 men died of prostate cancer (mean follow-up, 3 years), 15% among 5-ARI users (N= 25,388) and 85% among AB users (N=149,507) (unadjusted mortality rate ratio, 0.80). After accounting for competing risks, it was found that 5-ARI use was not associated with prostate cancer mortality when compared with AB use (adjusted subdistribution hazard ratio, 0.85; 95% CI, 0.72-1.01). Similar results were observed in the case-control study (adjusted matched odds ratio, 0.95; 95% CI, 0.78-1.17). CONCLUSION Among men being pharmaceutically treated for benign prostatic hyperplasia, 5-ARI use was not associated with an increased risk of prostate cancer-specific mortality when compared with AB use. The increased prevalence of high-grade lesions at the time of diagnosis noted in our study and the chemoprevention trials may not result in increased prostate cancer mortality.

Immunohistochemical expression of ERG in the molecular epidemiology of fatal prostate cancer study

Gene fusions between the ERG transcription factor and the androgen‐regulated gene TMPRSS2 occur in a subset of prostate cancers and contribute to transformation of prostatic epithelial cells. Prior reports have used fluorescence in situ hybridization (FISH) or quantitative PCR (QPCR) to determine the presence of TMPRSS2‐ERG fusions or ERG expression, respectively. Recently, several groups have reported on immunohistochemistry (IHC) to measure ERG expression, which is much more readily performed in clinical practice. However, the prior studies examining ERG expression by IHC had small sample sizes or they failed to clarify the association of ERG protein expression with important clinico‐pathological features or prostate cancer‐specific mortality. Methods: To address these deficits, we evaluated ERG expression by IHC in 208 radical prostatectomy samples from the Kaiser Permanente Molecular Epidemiology of Fatal Prostate Cancer (MEFPC) study, a case–control study of prostate cancer‐specific mortality.

Abstract P3-12-12: HER2 Evaluation in Relation to Breast Cancer Treatment Decisions in a Managed Care Plan

Background: In 18-20% of breast cancer tumors, the human epidermal growth factor receptor 2 (HER2) gene is abnormally amplified with increased expression of the associated protein. HER2 amplification is associated with rapid tumor proliferation, shorter disease-free survival, and poorer overall survival. Because women with HER2 amplification are more likely to benefit from treatment with the drug trastuzumab, testing for HER2 is recommended to guide therapy. However, little is known about HER2 testing practices and associated treatment in real-world settings. This study examined uptake, use, and appropriateness of HER2 testing, and the relationship between HER2 test results and treatment decisions in a large integrated health system. Methods: We identified 3,634 patients with primary breast cancer diagnosed from 1998-2007 who were members of the Kaiser Permanente Northwest health plan. We collected data on patient and tumor characteristics, HER2 testing status, test results, and trastuzumab treatment from tumor registry and pharmacy datasets. We defined women as evaluated for HER2 if they received HER2 testing by immunohistochemistry (IHC) and/or fluorescent in-situ hybridization (FISH). We manually abstracted medical charts for a subset of patients to verify findings and investigate anomalies. We compared testing and treatment results to professional guidelines. Results: From 1998-2000, the percentage of patients with invasive breast cancer who underwent HER2 evaluation increased from 12% to 94%; from 2000-2007, 94% (2304/2461) received HER2 testing over all years combined. In most cases, an equivocal or positive IHC test was followed by FISH. Only 2.4% of women with ductal carcinoma in situ (13/538), for whom HER2 testing is not recommended, were tested, and the proportion remained consistently low over the entire study period. Trastuzumab use increased five-fold after 2004, when guidelines expanded to include recommending adjuvant treatment for early-stage breast cancer in addition to metastatic treatment. Ninety-five percent of women receiving trastuzumab had a positive HER2 result, while the remainder had equivocal HER2 results or received treatment outside thedelivery system. After 2004, 55% of women with invasive breast cancer and overexpression of HER2 received trastuzumab treatment; this ranged from 44% of women with localized breast cancer to 80% of women with distant metastatic disease. We estimate that, after correcting for errors in the datasets, professional guidelines were followed for over 97% of patients diagnosed since 2000. Conclusions: Kaiser Permanente Northwest is systematically performing HER2 evaluation on patients with invasive breast cancer, and the information is used to make appropriate treatment decisions. This information should be gathered in other health care settings for comparison. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-12.