Gerald Andriole - Academia.edu (original) (raw)

Papers by Gerald Andriole

JNCI Journal of the National Cancer Institute, 2013

Background Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to ... more Background Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality by the European Randomized Study of Screening for Prostate Cancer (ERSPC). We evaluated mortality results in the Finnish Prostate Cancer Screening Trial, the largest component of ERSPC. The primary endpoint was PC-specific mortality. Methods A total of 80 144 men were identified from the population registry and randomized to either a screening arm (SA) or a control arm (CA). Men in the SA were invited to serum PSA determination up to three times with a 4-year interval between each scan and referred to biopsy if the PSA concentration was greater than or equal to 4.0 ng/ mL or 3.0 to 3.99 ng/mL with a free/total PSA ratio less than or equal to 16%. Men in the CA received usual care. The analysis covers follow-up to 12 years from randomization for all men. Hazard ratios (HRs) were estimated for incidence and mortality using Cox proportional hazard model. All statistical tests were two-sided.

The New England Journal of Medicine, Mar 26, 2009

BACKGROUND-The effect of screening with prostate-specific-antigen (PSA) testing and digital recta... more BACKGROUND-The effect of screening with prostate-specific-antigen (PSA) testing and digital rectal examination on the rate of death from prostate cancer is unknown. This is the first report from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality. METHODS-From 1993 through 2001, we randomly assigned 76,693 men at 10 U.S. study centers to receive either annual screening (38,343 subjects) or usual care as the control (38,350 subjects). Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years. The subjects and health care providers received the results and decided on the type of follow-up evaluation. Usual care sometimes included screening, as some organizations have recommended. The numbers of all cancers and deaths and causes of death were ascertained. RESULTS-In the screening group, rates of compliance were 85% for PSA testing and 86% for digital rectal examination. Rates of screening in the control group increased from 40% in the first year to 52% in the sixth year for PSA testing and ranged from 41 to 46% for digital rectal examination. After 7 years of follow-up, the incidence of prostate cancer per 10,000 person-years was 116 (2820 cancers) in the screening group and 95 (2322 cancers) in the control group (rate ratio, 1.22; 95% confidence interval [CI], 1.16 to 1.29). The incidence of death per 10,000 person-years was 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the control group (rate ratio, 1.13;95% CI,0.75 to 1.70). The data at 10 years were 67% complete and consistent with these overall findings. CONCLUSIONS-After 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups. The benefit of screening for prostate cancer with serum prostate-specific-antigen (PSA) testing, digital rectal examination, or any other screening test is unknown. There has been no comprehensive assessment of the trade-offs between benefits and risks. Despite these uncertainties, PSA screening has been adopted by many patients and physicians in the United

BJU International, 2018

ObjectiveTo examine prostate cancer (PCa) incidence and mortality by arm in the randomized Prosta... more ObjectiveTo examine prostate cancer (PCa) incidence and mortality by arm in the randomized Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial.Patients and MethodsPatients aged 55–74 years at 10 screening centres were randomized between 1993 and 2001 to an intervention or usual care arm. Patients in the intervention arm received six annual prostate‐specific antigen (PSA) tests and four annual digital rectal examinations. The patients were followed for PCa incidence and for mortality via active follow‐up processes and by linkage to state cancer registries and the National Death Index. For cancers identified through active follow‐up, trial abstractors recorded the mode of diagnosis (screen‐detected, symptomatic, other).ResultsA total of 38 340 patients were randomized to the intervention arm and 38 343 to a usual care arm. The median follow‐up for mortality was 16.9 (intervention) and 16.7 years (usual care). There were 333 (intervention) and 352 (usual care) PCa canc...

Journal of the National Comprehensive Cancer Network, 2014

JAMA oncology, Jan 31, 2016

Overdiagnosis and overtreatment of indolent prostate cancer (PCA) is a serious health issue in mo... more Overdiagnosis and overtreatment of indolent prostate cancer (PCA) is a serious health issue in most developed countries. There is an unmet clinical need for noninvasive, easy to administer, diagnostic assays to help assess whether a prostate biopsy is warranted. To determine the performance of a novel urine exosome gene expression assay (the ExoDx Prostate IntelliScore urine exosome assay) plus standard of care (SOC) (ie, prostate-specific antigen [PSA] level, age, race, and family history) vs SOC alone for discriminating between Gleason score (GS)7 and GS6 and benign disease on initial biopsy. In training, using reverse-transcriptase polymerase chain reaction (PCR), we compared the urine exosome gene expression assay with biopsy outcomes in 499 patients with prostate-specific antigen (PSA) levels of 2 to20 ng/mL. The derived prognostic score was then validated in 1064 patients from 22 community practice and academic urology clinic sites in the United States. Eligible participants i...

Cancer prevention research (Philadelphia, Pa.), Jan 9, 2015

The role of metformin in prostate cancer chemoprevention remains unclear. REDUCE, which followed ... more The role of metformin in prostate cancer chemoprevention remains unclear. REDUCE, which followed biopsy-negative men with protocol-dictated PSA-independent biopsies at 2- and 4-years, provides an opportunity to evaluate the link between metformin use and prostate cancer diagnosis with minimal confounding from screening biases. In diabetic men from REDUCE, we tested the association between metformin use, use of other anti-diabetic medications, vs. no anti-diabetic medication use and prostate cancer diagnosis as well as prostate cancer grade (low-grade Gleason 4-6, high-grade Gleason 7-10) using logistic regression. Of the 540 diabetic men with complete data, 205 (38%) did not report use of any anti-diabetic medications, 141 (26%) reported use of at least one anti-diabetic medication other than metformin, and 194 (36%) reported use of metformin. During the 4-year study, 122 men (23%) were diagnosed with prostate cancer. After adjusting for various clinical and demographic characterist...

European Urology Focus, 2015

Context: Cigarette smoking is the leading cause of death from cancer, although the relationship b... more Context: Cigarette smoking is the leading cause of death from cancer, although the relationship between smoking and prostate cancer (PCa) is controversial. Objective: To evaluate the available evidence of the role of cigarette smoking and PCa development and progression and to discuss possible clinical implications for PCa management. Evidence acquisition: A PubMed search for relevant articles published between 2004 and September 2014 was performed by combining the following PICO (patient population, intervention, comparison, outcome) terms: male, smoking, prostate, prostate cancer, prevention, diagnosis, treatment, and prognosis. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed. Evidence synthesis: The association between cigarette smoking and PCa incidence is controversial, particularly in recent series. Current cigarette smoking is associated with an increased risk of PCa death, and the number of cigarettes smoked per day had a doseresponse association with PCa mortality. Smokers present a higher risk of biochemical or distant failure after PCa treatment. Several biological mechanisms behind these associations have been proposed, although the molecular mechanisms remain unclear. Further research is required to better understand the role of smoking on PCa development and progression and, particularly, to evaluate the possible effect of smoking cessation on PCa management. Conclusions: Data from the peer-reviewed literature suggested an association of smoking and aggressive PCa. Although the pathophysiology underlying this association remains unclear, smokers presented higher PCa mortality and worse outcome after treatment. Smoking-cessation counseling should be implemented for patients with PCa, although its effect on PCa progression should be investigated. Patient summary: We looked at the association between smoking and prostate cancer (PCa). Smokers have a higher risk of PCa mortality and worse outcomes after treatment. Smoking cessation should be encouraged in men with or at risk of having PCa.

The American journal of clinical nutrition, 2007

Selenium is a potential chemopreventive agent against prostate cancer, whose chemoprotective effe... more Selenium is a potential chemopreventive agent against prostate cancer, whose chemoprotective effects are possibly mediated through the antioxidative properties of selenoenzymes. Interrelations with other antioxidative agents and oxidative stressors, such as smoking, are poorly understood. The aims were to investigate the association between serum selenium and prostate cancer risk and to examine interactions with other antioxidants and tobacco use. A nested case-control study was performed within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Serum selenium in prospectively collected samples was compared between 724 incident prostate cancer case subjects and 879 control subjects, frequency-matched for age, time since initial screen, and year of blood draw. The men were followed for up to 8 y. Overall, serum selenium was not associated with prostate cancer risk (P for trend = 0.70); however, higher serum selenium was associated with lower risk...

Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 15, 2014

Although the relationship between smoking and prostate cancer risk is inconsistent, some studies ... more Although the relationship between smoking and prostate cancer risk is inconsistent, some studies show that smoking is associated with prostate cancer mortality. Whether this reflects delayed diagnosis or direct smoking-related effects is unknown. REDUCE, which followed biopsy-negative men with protocol-dictated prostate-specific antigen (PSA)-independent biopsies at 2 and 4 years, provides an opportunity to evaluate smoking and prostate cancer diagnosis with minimal confounding from screening biases. Logistic regression was conducted to test the association between smoking and cancer on the first on-study biopsy (no cancer, low-grade Gleason 4-6, high-grade Gleason 7-10) in REDUCE. Of 6,240 men with complete data and ≥1 on-study biopsy, 2,937 (45.8%) never smoked, 929 (14.5%) were current smokers, and 2,554 (39.8%) were former smokers. Among men with negative first on-study biopsies, smokers were 36% less likely to receive a second on-study biopsy (P < 0.001). At first on-study b...

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2014

Studies suggest that obesity is associated with lower risk of prostate cancer but more aggressive... more Studies suggest that obesity is associated with lower risk of prostate cancer but more aggressive cancers. As obesity lowers PSA levels, these observations may be influenced by detection bias. We examined the association between obesity and risk of low- and high-grade prostate cancer in REDUCE, in which biopsies were largely independent of PSA. The REDUCE study tested dutasteride for prostate cancer risk reduction in men with a PSA of 2.5 to 10.0 ng/mL and a negative biopsy. Study participants included 6,729 men who underwent at least one on-study biopsy. The association between baseline body mass index (BMI <25 kg/m(2) normal weight; 25-29.9 kg/m(2) overweight; and ≥30 kg/m(2) obese) and risk of high-grade (Gleason ≥7) or low-grade prostate cancer (Gleason <7) versus no prostate cancer was examined using multinomial logistic regression. Overall, 1,739 men (27%) were normal weight, 3,384 (53%) overweight, and 1,304 (20%) were obese. Obesity was associated with lower risk of lo...

American Journal of Cancer Prevention, 2014

Purpose: In REDUCE, dutasteride was associated with a ~5% absolute reduction in the risk of biops... more Purpose: In REDUCE, dutasteride was associated with a ~5% absolute reduction in the risk of biopsydetected prostate cancer (PCa). Material and methods: We tested the influence of family history on the association between dutasteride and PCa diagnosis and calculated the number needed to treat (NNT) with dutasteride to avoid one PCa diagnosis. The REDUCE trial tested dutasteride 0.5mg/day for PCa risk reduction in men aged 50-75 with a serum PSA of 2.5-10.0ng/mL and a negative biopsy. Among men who underwent >1 on-study biopsy with complete data (n=6,415; 78.1%), the association between dutasteride and PCa risk as a function of PCa and/or breast cancer (BCa) family history was examined using multivariable logistic regression. Absolute risk reduction (ARR) and NNT were calculated. Results: On multivariate analysis, dutasteride was significantly associated with lower PCa risk in men without family history (25% lower; p<0.001), PCa family history only (37% lower; p=0.009), or BCa family history only (38% lower; p=0.04). While dutasteride lowered PCa risk in men with both PCa and BCa family history by 15%, this was not significant (p=0.69), though the number of men was small (n=115). ARRs were 6-9% for men with a PCa and/or BCa family history vs. 5% in men with no family history which translated into NNTs of 11-16 in men with PCa and/or BCa family history vs. 21 for men without family history. Conclusion: Using dutasteride as a model of chemoprevention, therapies targeting individuals with specific family histories may improve the risk-benefit profile. However, future studies are warranted to confirm our findings.

BJU International, 2014

To evaluate the relationship between number of metabolic syndrome (MetS)-like components and pros... more To evaluate the relationship between number of metabolic syndrome (MetS)-like components and prostate cancer diagnosis in a group of men where nearly all biopsies were taken independent of prostate-specific antigen (PSA) level, thus minimising any confounding from how the various MetS-like components may influence PSA levels. Subjects/Patients and Methods We analysed data from 6426 men in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study with at least one on-study biopsy. REDUCE compared dutasteride vs placebo on prostate cancer risk among men with an elevated PSA level and negative pre-study biopsy and included two on-study biopsies regardless of PSA level at 2 and 4 years. Available data for MetS-like components included data on diabetes, hypertension, hypercholesterolaemia, and body mass index. The association between number of these MetS-like components and prostate cancer risk and low-grade (Gleason sum <7) or high-grade (Gleason sum >7) vs no prostate cancer was evaluated using logistic regression. Results In all, 2171 men (34%) had one MetS-like component, 724 (11%) had two, and 163 (3%) had three or four. Men with more MetS-like components had lower PSA levels (P = 0.029). One vs no MetS-like components was protective for overall prostate cancer (P = 0.041) and low-grade prostate cancer (P = 0.010). Two (P = 0.69) or three to four (P = 0.15) MetS-like components were not significantly related to prostate cancer. While one MetS-like component was unrelated to high-grade prostate cancer (P = 0.97), two (P = 0.059) or three to four MetS-like components (P = 0.02) were associated with increased high-grade prostate cancer risk, although only the latter was significant. Conclusion When biopsies are largely PSA level independent, men with an initial elevated PSA level and a previous negative biopsy, and multiple MetS-like components were at an increased risk of high-grade prostate cancer, suggesting the link between MetS-like components and high-grade prostate cancer is unrelated to a lowered PSA level.

Value in Health, 2013

To compare Computed Tomographic (CT) utilization and potentially related cancer risks in the Unit... more To compare Computed Tomographic (CT) utilization and potentially related cancer risks in the United States and in Canada. METHODS: While CT scans can provide great medical benefits, there is growing concern about potential cancer risks because they deliver much higher radiation doses than do conventional diagnostic x-rays. Using epidemiological databases, we developed a risk projection model to assess radiation exposure from CT use, to estimate the number of CT related incident cancers, according to age, gender, and CT scan type in Canada. 95% uncertainty limits (UL) using Monte Carlo simulations were estimated. These results were compared to projected cancer risks from CT scans performed in the United States. RESULTS: In 2007, there were 240,000 and 114,000 CT examinations per million population in the United States and Canada, respectively. Scans of the abdomen/pelvis, brain, and thorax accounted for 88% and 78% of all CT scans in Canada and the United States. We estimated 46 (95% UL 24-89) potential CT-related incident cancers per million in Canada, compared to 98 (51-152) in the United States. In the United States, 48% of potential cancers might be attributed to abdomen/pelvis CT scans, while in Canada the estimate is 66%. In Canada, 36 (18-71) and 56 (29-106) potential cancers per million were estimated for males and females, respectively. In the United States, the estimates were 76 (41-110) and 119 (60-185) per million for males and females, respectively. CONCLUSIONS: Given the different patterns of care in the United States and in Canada, our findings might have important health policy implications. Strategies to monitor the appropriate use of CT scans, especially CT abdomen/pelvis, should be followed. Efforts to reduce cancer risk might include decreasing the number of decisionally marginal CT scans, as well as the dose per scan.

Obstetrical & Gynecological Survey, 2009

To test whether annual screening with transvaginal ultrasonography and CA 125 reduces ovarian can... more To test whether annual screening with transvaginal ultrasonography and CA 125 reduces ovarian cancer mortality. METHODS: Data from the first four annual screens, denoted T0-T3, are reported. A CA 125 value at or above 35 units/mL or an abnormality on transvaginal ultrasonography was considered a positive screen. Diagnostic follow-up of positive screens was performed at the discretion of participants' physicians. Diagnostic procedures and cancers were tracked and verified through medical records. RESULTS: Among 34,261 screening arm women without prior oophorectomy, compliance with screening ranged from 83.1% (T0) to 77.6% (T3). Screen positivity rates declined slightly with transvaginal ultrasonography, from 4.6 at T0 to 2.9-3.4 at T1-T3; CA 125 positivity rates (range 1.4-1.8%) showed no time trend. Eighty-nine invasive ovarian or peritoneal cancers were diagnosed; 60 were screen detected. The positive predictive value (PPV) and cancer yield per 10,000 women screened on the combination of tests were similar across screening rounds (range 1.0-1.3% for PPV and 4.7-6.2 for yield); however, the biopsy (surgery) rate among screen positives decreased from 34% at T0 to 15-20% at T1-T3. The overall ratio of surgeries to screen-detected cancers was 19.5:1. Seventy-two percent of screen-detected cases were late stage (III/IV). CONCLUSION: Through four screening rounds, the ratio of surgeries to screen-detected cancers was high, and most cases were late stage. However, the effect of screening on mortality is as yet unknown.

JNCI Journal of the National Cancer Institute, 2014

Background The chance that a prostate cancer detected by screening is overdiagnosed (ie, it would... more Background The chance that a prostate cancer detected by screening is overdiagnosed (ie, it would not have been detected in the absence of screening) can vary widely depending on the patient's age and tumor characteristics. The purpose of this study is to use age, Gleason score, and prostate-specific antigen (PSA) level to help inform patients with screen-detected prostate cancers about the chances their cancers were overdiagnosed. Methods A computer microsimulation model of prostate cancer natural history was used to generate virtual life histories in the presence and absence of PSA screening, including an indicator of whether screen-detected cancers are overdiagnosed. A logistic regression model was fit to nonmetastatic patients diagnosed by screening with PSA less than 10 ng/mL, and a nomogram was created to predict the individualized risk of overdiagnosis given age, Gleason score, and PSA at diagnosis. Results The calibrated microsimulation model closely reproduces observed incidence trends in the Surveillance, Epidemiology, and End Results registries by age, stage, and Gleason score. The fitted logistic regression predicts risks of overdiagnosis among PSA-detected patients with an area under the curve of 0.75. Chances of overdiagnosis range from 2.9% to 88.1%. Conclusions The chances of overdiagnosis vary considerably by age, Gleason score, and PSA at diagnosis. The overdiagnosis nomogram presents tailored estimates of these risks based on patient and tumor information known at diagnosis and can be used to inform decisions about treating PSA-detected prostate cancers.

Journal of Internal Medicine, 2012

Background-To what degree the associations between PCa risk and family history of prostate cancer... more Background-To what degree the associations between PCa risk and family history of prostate cancer (PCa) and/or breast cancer (BCa) are attributable to screening biases is unclear. We examined these questions within the REDUCE study, where biopsies were largely independent of prostate specific antigen (PSA) minimizing screening biases. Methods-Data were from REDUCE, which tested dutasteride 0.5 mg daily for PCa risk reduction in men with PSA 2.5-10.0 ng mL −1 and a negative pre-study biopsy. Among men undergoing at least one on-study biopsy with complete data (n = 6415; 78.1%), the association

European Urology, 2014

Background-Although most studies found no association between alcohol intake and prostate cancer ... more Background-Although most studies found no association between alcohol intake and prostate cancer (PCa) risk, an analysis of the Prostate Cancer Prevention Trial found that high alcohol intake significantly increased PCa risk among men randomized to the 5a-reductase inhibitor (5-ARI) finasteride. Objective-Determine whether alcohol affects PCa risk among men taking the 5-ARI dutasteride. Design, settings, and participants-Reduction by Dutasteride of Prostate Cancer Events was a 4-yr, multicenter, randomized, double-blind, placebo-controlled trial to compare PCa after dutasteride administration (0.5 mg/d) with placebo. Participants had a baseline prostate-specific

European Urology, 2011

Background: A 23% relative risk reduction (RRR) in prostate cancer (PCa) was shown in men receivi... more Background: A 23% relative risk reduction (RRR) in prostate cancer (PCa) was shown in men receiving dutasteride in the 4-yr Reduction by Dutasteride of Prostate Cancer Events study, in whom biopsies were protocol dependent. Objective: Our aim was to explore PCa risk reduction in men with benign prostatic hyperplasia (BPH) from the Combination of Avodart and Tamsulosin (CombAT) study, in which biopsies were undertaken for cause. Design, setting, and participants: CombAT was a 4-yr randomized double-blind parallel group study in 4844 men !50 yr of age with clinically diagnosed moderate to severe BPH, International Prostate Symptom Score !12, prostate volume !30 ml, and serum prostatespecific antigen (PSA) 1.5-10 ng/ml. Men underwent annual PSA measurement and digital rectal examination (DRE), and prostate biopsies were performed for cause. Intervention: All patients took tamsulosin 0.4 mg/d, dutasteride 0.5 mg/d, or a combination of both. Measurements: The primary end point was incidence of PCa. Secondary end points included postbaseline prostate biopsy rates and Gleason score of cancers. Results and limitations: Dutasteride (alone or in combination with tamsulosin) was associated with a 40% RRR of PCa diagnosis compared with tamsulosin monotherapy (95% confidence interval, 16-57%; p = 0.002) and a 40% reduction in the likelihood of biopsy. There were similar reductions in low-and high-grade Gleason score cancers. The biopsy rate in the groups receiving dutasteride trended toward a higher diagnostic yield (combination: 29%, dutasteride: 28%, tamsulosin: 24%). One limitation was the lack of a standardized approach to PCa diagnosis and grading. Conclusions: Dutasteride, alone or in combination with tamsulosin, significantly reduced the relative risk of PCa diagnosis in men with BPH undergoing annual DRE and PSA screening. Consistent with the increased usefulness of PSA for PCa detection, men receiving dutasteride had a numerically lower biopsy rate and higher yield of PCa on biopsy. Trial registration: Clinicaltrials.gov identifier: NCT00090103 (http://www.clinicaltrials.gov/ ct2/show/NCT00090103).

Cancer Research, 2005

High-temperature cooked meat contains heterocyclic amines, including 2-amino-1-methyl-6-phenylimi... more High-temperature cooked meat contains heterocyclic amines, including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP). In rodents, a high intake of PhIP induces prostate tumors. We prospectively investigated the association between meat and meat mutagens, specifically PhIP, and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Diet was assessed using a 137-item food frequency questionnaire and a detailed meat-cooking questionnaire linked to a database for BaP and the heterocyclic amines 2-amino-3,8-dimethylimidazo[4,5-b]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and PhIP. During follow-up, we ascertained a total of 1,338 prostate cancer cases among 29,361 men; of these, 868 were incident cases (diagnosed after the first year of follow-up) and 520 were advanced cases (stage III or IV or a Gleason score of ≥7). Total, red, or white m...

Cancer Epidemiology, Biomarkers & Prevention, 2012

Background: Coronary artery disease (CAD) and prostate cancer (PCa) are not only common diseases,... more Background: Coronary artery disease (CAD) and prostate cancer (PCa) are not only common diseases, but share many risk factors. To date, only a few studies have explored the relationship between CAD and PCa risk, with conflicting results. Methods: The four-year REDUCE study tested dutasteride 0.5 mg daily for PCa risk reduction in men with prostate specific antigen (PSA) of 2.5 to 10.0 ng/mL and a negative biopsy. Among men who underwent at least one on-study biopsy (n = 6,729; 82.8%), the association between CAD and overall PCa risk and disease grade was examined with logistic and multinomial logistic regression adjusting for clinicopathologic features, respectively. Results: Overall, 547 men (8.6%) had a history of CAD. Men with CAD were significantly older and had higher body mass index, PSA, and larger prostate volumes and were more likely to have diabetes, hypertension, and hypercholesterolemia and take aspirin and statins. On multivariate analysis, CAD was associated with a 35%...