Prostatic Neoplasms: Albertsen PC

Kramer BS, Hagerty KL, Justman S, Somerfield MR, Albertsen PC, Blot WJ, Ballentine Carter H, Costantino JP, Epstein JI, Godley PA, Harris RP, Wilt TJ, Wittes J, Zon R, Schellhammer P, Anonymous00093, Anonymous00094. · National Institutes of Health, Bethesda, MD, USA. · J Clin Oncol. · Pubmed #19252137 No free full text.

Abstract: PURPOSE To develop an evidence-based guideline on the use of 5-alpha-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention. METHODS The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention. Results The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence. CONCLUSION Asymptomatic men with a prostate-specific antigen (PSA) <or= 3.0 ng/mL who are regularly screened with PSA or are anticipating undergoing annual PSA screening for early detection of prostate cancer may benefit from a discussion of both the benefits of 5-ARIs for 7 years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer). Men who are taking 5-ARIs for benign conditions such as lower urinary tract [obstructive] symptoms (LUTS) may benefit from a similar discussion, understanding that the improvement of LUTS relief should be weighed with the potential risks of high-grade prostate cancer from 5-ARIs (although the majority of the Panel members judged the latter risk to be unlikely). A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI; however, because these changes in PSA may vary across men, and within individual men over time, the Panel cannot recommend a specific cut point to trigger a biopsy for men taking a 5-ARI. No specific cut point or change in PSA has been prospectively validated in men taking a 5-ARI.

Kramer BS, Hagerty KL, Justman S, Somerfield MR, Albertsen PC, Blot WJ, Carter HB, Costantino JP, Epstein JI, Godley PA, Harris RP, Wilt TJ, Wittes J, Zon R, Schellhammer P, Anonymous00066. · National Institutes of Health, Bethesda, MD, USA. · J Urol. · Pubmed #19249063 No free full text.

Abstract: PURPOSE: To develop an evidence-based guideline on the use of 5-alpha-reductase inhibitors (5-ARIs) for prostate cancer chemoprevention. METHODS: The American Society of Clinical Oncology (ASCO) Health Services Committee (HSC), ASCO Cancer Prevention Committee, and the American Urological Association Practice Guidelines Committee jointly convened a Panel of experts, who used the results from a systematic review of the literature to develop evidence-based recommendations on the use of 5-ARIs for prostate cancer chemoprevention. RESULTS: The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period prevalence. CONCLUSION: Asymptomatic men with a prostate-specific antigen (PSA) </=3.0 ng/mL who are regularly screened with PSA or are anticipating undergoing annual PSA screening for early detection of prostate cancer may benefit from a discussion of both the benefits of 5-ARIs for 7 years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer). Men who are taking 5-ARIs for benign conditions such as lower urinary tract [obstructive] symptoms (LUTS) may benefit from a similar discussion, understanding that the improvement of LUTS relief should be weighed with the potential risks of high-grade prostate cancer from 5-ARIs (although the majority of the Panel members judged the latter risk to be unlikely). A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI; however, because these changes in PSA may vary across men, and within individual men over time, the Panel cannot recommend a specific cut point to trigger a biopsy for men taking a 5-ARI. No specific cut point or change in PSA has been prospectively validated in men taking a 5-ARI.

Seidenfeld J, Samson DJ, Albertsen PC. · No affiliation provided · J Natl Cancer Inst. · Pubmed #17925533 links to  free full text

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Albertsen PC. · No affiliation provided · JAMA. · Pubmed #17105802 No free full text.

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Albertsen PC. · No affiliation provided · J Natl Cancer Inst. · Pubmed #12837821 links to  free full text

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Albertsen PC. · Division of Urology, University of Connecticut Health Center, Farmington, CT 06030, USA. · Nat Clin Pract Urol. · Pubmed #18349860 No free full text.

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Dall'Era MA, Cooperberg MR, Chan JM, Davies BJ, Albertsen PC, Klotz LH, Warlick CA, Holmberg L, Bailey DE, Wallace ME, Kantoff PW, Carroll PR. · Department of Urology, University of California at San Francisco Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94143-1695, USA. · Cancer. · Pubmed #18306379 links to  free full text

Abstract: The natural history of prostate cancer is remarkably heterogeneous and, at this time, not completely understood. The widespread adoption and application of prostate-specific antigen (PSA) screening has led to a dramatic shift toward the diagnosis of low-volume, nonpalpable, early-stage tumors. Autopsy and early observational studies have shown that approximately 1 in 3 men aged >50 years has histologic evidence of prostate cancer, with a significant portion of tumors being small and possibly clinically insignificant. Utilizing the power of improved contemporary risk stratification schema to better identify patients with a low risk of cancer progression, several centers are gaining considerable experience with active surveillance and delayed, selective, and curative therapy. A literature review was performed to evaluate the rationale behind active surveillance for prostate cancer and to describe the early experiences from surveillance protocols. It appears that a limited number of men on active surveillance have required treatment, with the majority of such men having good outcomes after delayed selective intervention for progressive disease. The best candidates for active surveillance are being defined, as are predictors of active treatment. The psychosocial ramifications of surveillance for prostate cancer can be profound and future needs and unmet goals will be discussed.

Albertsen PC. · Department of Surgery, University of Connecticut Health Center, Farmington, 06030-3955, USA. · Acta Oncol. · Pubmed #16076698 No free full text.

Abstract: Screening and treatment for prostate cancer is controversial. In the absence of randomized trials, several prominent medical organizations in the United States and Europe have formulated policies that range from enthusiastic support to significant skepticism concerning the efficacy of screening and subsequent treatment for prostate cancer. Sharp rises in the incidence of prostate cancer have occurred whenever PSA testing has been introduced on a wide scale. Unfortunately, it is unclear whether declines in prostate cancer mortality can be attributed to PSA testing. Other explanations include the early use of anti-androgen therapy or changes in environmental factors such as diet. Repeated testing for serum PSA has produced significant shifts in the types of cases being identified and has raised the possibility of significant over-diagnosis of this disease. The European screening trial and the PLCO trial in the US will hopefully provide some insights into the value of population-based testing.

Albertsen PC. · Department of Surgery (Urology), University of Connecticut Health Center, Farmington, CT 06030-3955, USA. · Cleve Clin J Med. · Pubmed #16018293 links to  free full text

Abstract: There is still no consensus on whether prostate-specific antigen (PSA) measurement should be used as a screening test for prostate cancer, but patients have the right to be informed about its risks and possible benefits. PSA testing is more likely to be beneficial in relatively young men and men at higher risk (ie, African Americans and men with a family history of prostate cancer). A possible schedule is to test at age 40, age 45, and every 2 to 3 years from age 50 until about age 75.

Hsieh K, Albertsen PC. · Division of Urology, Department of Surgery, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3955, USA. · Urol Clin North Am. · Pubmed #14680306 No free full text.

Abstract: Although prostate cancer tends to be a slow-growing neoplasm affecting older men, there is clearly a subset of patients at high risk for developing early and possibly more aggressive disease. This group of high-risk patients includes men with a family history of prostate cancer and various histologic features such as PIN and ASAP identified on an initial biopsy. Black American men have a much higher risk of developing prostate cancer when compared with white men and especially Asian men. This finding may reflect both genetic and environmental factors. Screening men at increased risk of developing prostate cancer appears to be a logical strategy, especially in light of recent reports that suggest a benefit to aggressive treatment.

Samson DJ, Seidenfeld J, Schmitt B, Hasselblad V, Albertsen PC, Bennett CL, Wilt TJ, Aronson N. · Technology Evaluation Center, Blue Cross and Blue Shield Association, Washington, DC 20005, USA. · Cancer. · Pubmed #12124837 links to  free full text

Abstract: BACKGROUND: The current systematic review and meta-analysis compared monotherapy and combined androgen blockade in the treatment of men with advanced prostate carcinoma. Outcomes of interest included overall, cancer specific, and progression-free survival; time to treatment failure; adverse events; and quality of life. METHODS: The literature search identified randomized trials comparing monotherapy (orchiectomy and luteinizing hormone-releasing hormone [LHRH] agonists) with combination therapy using orchiectomy or a LHRH agonist plus a nonsteroidal or steroidal antiandrogen. Dual independent review occurred. The meta-analysis used a random effects model. RESULTS: Twenty-one trials compared survival after monotherapy with survival after combined androgen blockade (n = 6871 patients). The meta-analysis found no statistically significant difference in survival at 2 years between patients treated with combined androgen blockade and those treated with monotherapy (20 trials; hazard ratio [HR] = 0.970; 95% confidence interval [95% CI], 0.866-1.087). The authors determined a statistically significant difference in survival at 5 years that favored combined androgen blockade (10 trials; HR = 0.871; 95% CI, 0.805-0.942). For the subgroup of patients with a good prognosis, there was no statistically significant difference in survival. Adverse effects leading to withdrawal from therapy occurred more often with combined androgen blockade. To the authors' knowledge there is little evidence published to date comparing the effects of combined androgen blockade and monotherapy on quality of life, but the single randomized trial that adequately addressed this outcome reported an advantage for monotherapy over combined androgen blockade. CONCLUSIONS: A thorough examination of the usefulness of combined androgen blockade must balance the modest increase in expected survival observed at 5 years against the increased risk of adverse effects and the potential for adversely affecting the patient's overall quality of life.

Penson DF, Albertsen PC. · University of Washington, Seattle, WA 98106, USA. · Surg Oncol. · Pubmed #12031863 No free full text.

Abstract: Prostate cancer is one of most common solid tumors in men and poses some of the most difficult problems in clinical research. Although many clinical research hypotheses in this condition have been explored using single center cases series and multi-center clinical trials, the results of these studies have often been equivocal, leaving many questions unanswered. Recently, investigators have utilized large, administrative datasets for prostate cancer research. These databases tend to include large numbers of patients from different geographic regions increasing their generalizability and statistical power. The goal of this report is to review lessons learnt about early prostate cancer using these data sources. In particular, we focus on the application of large, population-based datasets to address issues concerning the natural history of prostate cancer, the impact of race on outcomes in prostate cancer and the effectiveness of various treatments for localized disease. Information gathered from large, administrative databases will be helpful when counseling patients regarding their treatments options for localized prostate cancer and in identifying future directions for prostate cancer research.

Albertsen PC, Hanley JA, Murphy-Setzko M. · Division of Urology, University of Connecticut Health Center, Farmington, USA. · J Urol. · Pubmed #10411053 No free full text.

Abstract: PURPOSE: We explore the impact of study designs, biases, outcome variables and statistical techniques when interpreting studies concerning prostate cancer management. MATERIALS AND METHODS: Examples from the current literature and a recently assembled population based sample of patients 55 to 75 years old at diagnosis identified by the Connecticut Tumor Registry as having newly diagnosed localized prostate cancer between 1971 and 1984 are provided to assist the reader to understand the principles discussed. RESULTS: Most reports concerning prostate cancer outcomes suffer from obvious and subtle biases that confound the reader's understanding of the impact of different treatment alternatives. CONCLUSIONS: By remaining vigilant to these confounding issues, clinicians and patients can gain greater insights into the medical literature and can make individual interpretations concerning the potential impact of treatment interventions on men with prostate cancer.

Albertsen PC. · No affiliation provided · J Urol. · Pubmed #16093995 No free full text.

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Barry MJ, Albertsen PC, Bagshaw MA, Blute ML, Cox R, Middleton RG, Gleason DF, Zincke H, Bergstralh EJ, Jacobsen SJ. · General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. · Cancer. · Pubmed #11413519 links to  free full text

Abstract: BACKGROUND: With a lack of data from randomized trials, the optimal management of men with nonmetastatic prostate carcinoma is controversial. The authors sought to define the outcomes of three common strategies for managing patients with nonmetastatic prostate carcinoma: expectant management, radiotherapy, and radical prostatectomy. METHODS: The authors conducted a retrospective cohort study with standardized collection of key prognostic data, including centralized assignment of Gleason grades from original biopsy specimens. Participants included all Connecticut hospitals (the expectant management cohort) and three academic medical centers in other states (the radiotherapy and surgery cohorts). Two thousand three hundred eleven consecutive men ages 55-74 years who were diagnosed during 1971-1984 with nonmetastatic prostate carcinoma and were treated at the participating sites were included. RESULTS: Kaplan-Meier estimates with 95% confidence intervals (95% CI) of overall survival at 10 years for each cohort were as follows: expectant management cohort, 42% of patients (95% CI, 38-46%); radiotherapy cohort, 52% of patients (95% CI, 46-58%); and radical prostatectomy cohort, 69% of patients (95% CI, 67-71%); for disease specific mortality, the estimates were as follows: expectant management cohort, 75% of patients (95% CI, 71-79%); radiotherapy cohort, 67% of patients (95% CI, 61-73%); and radical prostatectomy cohort, 86% of patients (95% CI, 84-88%). There were large differences in distributions of important prognostic factors among men in the different treatment groups. CONCLUSIONS: These data provide precise estimates of the outcomes of patients who have been treated with different modalities for nonmetastatic prostate carcinoma in the recent past. Direct comparisons of outcomes between treatment groups are inadvisable because of the different characteristics of patients who select these alternative management strategies.

Albertsen PC, Hanley JA, Harlan LC, Gilliland FD, Hamilton A, Liff JM, Stanford JL, Stephenson RA. · Division of Urology, University of Connecticut Health Center, Farmington, USA. · J Urol. · Pubmed #10737483 No free full text.

Abstract: PURPOSE: We determine the positive yield of imaging studies performed on men with newly diagnosed prostate cancer. MATERIALS AND METHODS: A prospective, population based survey was conducted on 3,690 men with prostate cancer diagnosed between October 1, 1994 and October 31, 1995. Cases were identified by the rapid case ascertainment systems used in 6 geographic regions participating in the Surveillance, Epidemiology and End Results Program. Based on information captured in primary medical record reviews we estimated the positive yield of bone scans, computerized tomography (CT) and magnetic resonance imaging. RESULTS: The positive yield of bone scan and CT was less than 5% and 12%, respectively, for all men with prostate specific antigen (PSA) 4 to 20 ng./ml., and less than 2% and 9%, respectively, for those who also had a Gleason score of 6 or less. Only men with PSA greater than 50 ng./ml. and those with Gleason scores 8 to 10 and PSA greater than 20 ng./ml. had positive yields greater than 10% and 20% for bone scan and CT, respectively. CONCLUSIONS: Imaging studies designed to identify metastases and/or extracapsular extension in men with newly diagnosed prostate cancer frequently have a low positive yield. Wide variations exist in the use of imaging studies and are associated with tumor factors, such as Gleason score and serum PSA, and nontumor factors, such as state of residence. More extensive cost-effectiveness analyses are needed to define appropriate guidelines for ordering imaging studies to optimize the positive yield among men with newly diagnosed prostate cancer.

Lu-Yao G, Albertsen PC, Stanford JL, Stukel TA, Walker-Corkery E, Barry MJ. · The Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ, USA. · J Gen Intern Med. · Pubmed #18795372 No free full text.

Abstract: BACKGROUND: Prior to introduction of the prostate-specific antigen (PSA) test, the Seattle-Puget Sound and Connecticut Surveillance, Epidemiology and End Results (SEER) areas had similar prostate cancer mortality rates. Early in the PSA era (1987-1990), men in the Seattle area were screened and treated more intensively for prostate cancer than men in Connecticut. OBJECTIVE: We previously reported more intensive screening and treatment early in the PSA era did not lower prostate cancer mortality through 11 years and now extend follow-up to 15 years. DESIGN: Natural experiment comparing two fixed population-based cohorts. SUBJECTS: Male Medicare beneficiaries ages 65-79 from the Seattle (N = 94,900) and Connecticut (N = 120,621) SEER areas, followed from 1987-2001. MEASUREMENTS: Rates of prostate cancer screening; treatment with radical prostatectomy, external beam radiotherapy, and androgen deprivation therapy; and prostate cancer-specific mortality. MAIN RESULTS: The 15-year cumulative incidences of radical prostatectomy and radiotherapy through 2001 were 2.84% and 6.02%, respectively, for Seattle cohort members, compared to 0.56% and 5.07% for Connecticut cohort members (odds ratio 5.20, 95% confidence interval 3.22 to 8.42 for surgery and odds ratio 1.24, 95% confidence interval 0.98 to 1.58 for radiation). The cumulative incidence of androgen deprivation therapy from 1991-2001 was 4.78% for Seattle compared to 6.13% for Connecticut (odds ratio 0.77, 95% confidence interval 0.67 to 0.87). The adjusted rate ratio of prostate cancer mortality through 2001 was 1.02 (95% C.I. 0.96 to 1.09) in Seattle versus Connecticut. CONCLUSION: Among men aged 65 or older, more intensive prostate cancer screening early in the PSA era and more intensive treatment particularly with radical prostatectomy over 15 years of follow-up were not associated with lower prostate cancer-specific mortality.

Ercole B, Marietti SR, Fine J, Albertsen PC. · Division of Urology, University of Connecticut Health Center, Farmington, Connecticut 06030-3955, USA. · J Urol. · Pubmed #18707696 No free full text.

Abstract: PURPOSE: We gained insights concerning outcomes associated with men who elect active surveillance for the management of localized prostate cancer. MATERIALS AND METHODS: This is a retrospective case series analysis of 40 patients diagnosed with localized prostate cancer since 1990 who elected active surveillance. RESULTS: A total of 31 patients remained on active surveillance for a median of 48 months (range 12 to 168). The 5-year probability of remaining on active surveillance was 74%. Most patients who abandoned this strategy did so within 33 months of diagnosis (range 12 to 84). An increasing prostate specific antigen and anxiety were the 2 most common reasons. A delay in treatment did not appear to compromise subsequent outcomes. CONCLUSIONS: Men with low grade prostate cancer can elect active surveillance and have excellent long-term results.

Lu-Yao GL, Albertsen PC, Moore DF, Shih W, Lin Y, DiPaola RS, Yao SL. · Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA. · JAMA. · Pubmed #18612114 links to  free full text

Abstract: CONTEXT: Despite a lack of data, increasing numbers of patients are receiving primary androgen deprivation therapy (PADT) as an alternative to surgery, radiation, or conservative management for the treatment of localized prostate cancer. OBJECTIVE: To evaluate the association between PADT and survival in elderly men with localized prostate cancer. DESIGN, SETTING, AND PATIENTS: A population-based cohort study of 19,271 men aged 66 years or older receiving Medicare who did not receive definitive local therapy for clinical stage T1-T2 prostate cancer. These patients were diagnosed in 1992-2002 within predefined US geographical areas, with follow-up through December 31, 2006, for all-cause mortality and through December 31, 2004, for prostate cancer-specific mortality. Instrumental variable analysis was used to address potential biases associated with unmeasured confounding variables. MAIN OUTCOME MEASURES: Prostate cancer-specific survival and overall survival. RESULTS: Among patients with localized prostate cancer (median age, 77 years), 7867 (41%) received PADT, and 11,404 were treated with conservative management, not including PADT. During the follow-up period, there were 1560 prostate cancer deaths and 11,045 deaths from all causes. Primary androgen deprivation therapy was associated with lower 10-year prostate cancer-specific survival (80.1% vs 82.6%; hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.03-1.33) and no increase in 10-year overall survival (30.2% vs 30.3%; HR, 1.00; 95% CI, 0.96-1.05) compared with conservative management. However, in a prespecified subset analysis, PADT use in men with poorly differentiated cancer was associated with improved prostate cancer-specific survival (59.8% vs 54.3%; HR, 0.84; 95% CI, 0.70-1.00; P = .049) but not overall survival (17.3% vs 15.3%; HR, 0.92; 95% CI, 0.84-1.01). CONCLUSION: Primary androgen deprivation therapy is not associated with improved survival among the majority of elderly men with localized prostate cancer when compared with conservative management.

Collin SM, Martin RM, Metcalfe C, Gunnell D, Albertsen PC, Neal D, Hamdy F, Stephens P, Lane JA, Moore R, Donovan J. · Department of Social Medicine, University of Bristol, Canynge Hall, Bristol, UK. · Lancet Oncol. · Pubmed #18424233 No free full text.

Abstract: BACKGROUND: There is no conclusive evidence that screening based on serum prostate-specific antigen (PSA) tests decreases prostate-cancer mortality. Since its introduction in the USA around 1990, uptake of PSA testing has been rapid in the USA, but much less common in the UK. Our aim was to study trends over time in prostate-cancer mortality and incidence in the USA and UK in 1975-2004, and compare these patterns with trends in screening and treatment. METHODS: Joinpoint regression analysis of cancer-mortality statistics from Cancer Research UK (London, UK) and from the US National Cancer Institute Surveillance, Epidemiology and End Results (SEER) programme from 1975 to 2004 was used to estimate the annual percentage change in prostate-cancer mortality in both countries and the points in time when trends changed. The ratio of USA to UK age-adjusted prostate-cancer incidence was also assessed. FINDINGS: Age-specific and age-adjusted prostate-cancer mortality peaked in the early 1990s at almost identical rates in both countries, but age-adjusted mortality in the USA subsequently declined after 1994 by -4.17% (95% CI -4.34 to -3.99) each year, four-times the rate of decline in the UK after 1992 (-1.14% [-1.44 to -0.84]). The mortality decline in the USA was greatest and most sustained in patients aged 75 years or older (-5.32% [-8.23 to -2.32]), whereas death rates had plateaued in this age group in the UK by 2000. The mean ratio of USA to UK age-adjusted prostate-cancer incidence rates in 1975-2003 was 2.5, with a pronounced peak around the time that PSA testing was introduced in the USA. Numbers needed to treat to prevent one death from prostate cancer were 33 000 in the 55-64-year age group. INTERPRETATION: The striking decline in prostate-cancer mortality in the USA compared with the UK in 1994-2004 coincided with much higher uptake of PSA screening in the USA. Explanations for the different trends in mortality include the possibility of an early effect of initial screening rounds on men with more aggressive asymptomatic disease in the USA, different approaches to treatment in the two countries, and bias related to the misattribution of cause of death. Speculation over the role of screening will continue until evidence from randomised controlled trials is published.

Albertsen PC. · Division of Urology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3955, USA. · World J Urol. · Pubmed #18401585 No free full text.

Abstract: OBJECTIVES: To define high risk prostate cancer using prostate cancer specific mortality as the key outcome metric. METHODS: Data from two population based cohorts of men from Connecticut who were diagnosed with localized prostate cancer were analyzed to determine the natural history of prostate cancer and the impact of treatment on long term survival. RESULTS: Men with Gleason 7-10 prostate cancer and a potential survival of 10 years have a high risk of dying from their disease if they elect active surveillance. Surgery appears to offer an improved survival for these men when compared to radiation therapy or observation. Men diagnosed with Gleason 6 tumors in the contemporary era are more likely to harbor low risk prostate cancer when compared to historical series. CONCLUSIONS: Our studies confirm that high risk prostate cancer is best identified by Gleason score 7-10, but challenge the concept that men with high-grade disease are less likely to benefit from radical surgery. Men who have rising PSA values following treatment with either surgery or radiation have residual prostate cancer and are at very high risk of dying from prostate cancer within 10 years.

Bellera CA, Hanley JA, Joseph L, Albertsen PC. · Department of Clinical Epidemiology and Clinical Research, Institut Bergonié, Regional Comprehensive Cancer Center, Bordeaux, France. · Ann Epidemiol. · Pubmed #18374279 No free full text.

Abstract: PURPOSE: Biomarkers provide valuable information when detecting disease onset or monitoring disease progression; examples include bone mineral density (for osteoporosis), cholesterol (for coronary artery diseases), or prostate-specific antigens (PSA, for prostate cancer). Characteristics of markers series can then be used as prognostic factors of disease progression, such as the postradiotherapy PSA doubling time in men treated for prostate cancer. The statistical analysis of such data has to incorporate the within and between-series variabilities, the complex patterns of the series over time, the unbalanced format of the data, and the possibly nonconstant precision of the measurements. METHODS: We base our analysis on a population-based cohort of 470 men treated with radiotherapy for prostate cancer; after treatment, the log(2)PSA concentrations follow a piecewise-linear pattern. We illustrate the flexibility of Bayesian hierarchical changepoint models by estimating the individual and population postradiotherapy log(2)PSA profiles; parameters such as the PSA nadir and the PSA doubling time were estimated, and their associations with baseline patient characteristics were investigated. The residual PSA variability was modeled as a function of the PSA concentration. For comparison purposes, two alternative models were briefly considered. RESULTS: Precise estimates of all parameters of the PSA trajectory are provided at both the individual and population levels. Estimates suggest greater PSA variability at lower PSA concentrations, as well as an association between shorter PSAdts and greater baseline PSA levels, higher Gleason scores, and older age. CONCLUSIONS: The use of Bayesian hierarchical changepoint models accommodates multiple complex features of longitudinal data, permits realistic modeling of the variability as a function of the marker concentration, and provides precise estimates of all clinically important parameters. This type of model should be applicable to the study of marker series in other diseases.

Bellera CA, Hanley JA, Joseph L, Albertsen PC. · Department of Clinical Epidemiology and Clinical Research, Institut Bergonié, Regional Comprehensive Cancer Center, Bordeaux, France. · Am J Epidemiol. · Pubmed #18303004 links to  free full text

Abstract: It is common to define a change in health status or in a disease state on the basis of a sustained rise (or decline) in a biomarker over time. However, such observations are often subject to important variability unrelated to the underlying biologic process. The authors propose a method to evaluate rules that define an event on the basis of consecutive increases (or decreases) in the observations, given the presence of random variation. They examine how well these rules correctly identify a truly rising biomarker trajectory and, conversely, how often they can recognize a truly stable series or a slowly rising series. The method relies on simulation of realistic, sophisticated data sets that accurately reflect the systematic and random variations observed in marker series. These flexible, empirically based simulations enable estimation of the sensitivity and specificity of rules of consecutive rises as a function of the underlying trend, amount of random variation, and schedule of measurements (frequency and duration of follow-up). The authors illustrate the approach with postradiotherapy series of prostate-specific antigen, where three consecutive rises in prostate-specific antigen indicate treatment failure; the data are described by using a Bayesian hierarchical changepoint model. The method is particularly flexible and could be applied to evaluate other rules that purport to accurately detect upturns (downturns) in other noisy data series, including other medical data or other application areas.

Judge A, Evans S, Gunnell DJ, Albertsen PC, Verne J, Martin RM. · MRC Health Services Research Collaboration, Department of Social Medicine, University of Bristol, Bristol, UK. · BJU Int. · Pubmed #17784890 No free full text.

Abstract: OBJECTIVE: To investigate the morbidity and mortality after radical prostatectomy (RP) in relation to the numbers of RPs carried out at individual hospitals, as recent studies of complex surgery report worse outcomes in low-volume hospitals, and there has been a large increase in RPs for localized prostate cancer. METHODS: We analysed hospital episode statistics data for all 18 027 RPs in English National Health Service hospitals between 1997 and 2004. RESULTS: In multivariate analysis, there was a U-shaped association of hospital volume with mortality (P for nonlinear trend, 0.004), but this finding was based on only 59 (0.3%) deaths. The mean length of stay was 6 days and decreased by 2.96% (95% confidence interval, CI, 1.98-3.92; P < 0.001) per quintile increase in hospital volume. In all, 16.1% of men had 30-day in-hospital complications; 20.3% were readmitted with complications within a year. The odds of 30-day in-hospital wound/bleeding complications decreased by 6% (95% CI 1-11; P = 0.02), and miscellaneous medical complications decreased by 10% (0-19; P = 0.04) per increase in hospital volume quintile. For re-admissions within a year, the hazard of vascular complications decreased by 15% (6-22; P = 0.001), wound/bleeding complications decreased by 8% (2-13; P = 0.01) and genitourinary complications decreased by 5% (2-8; P = 0.002), per increase in hospital volume quintile. CONCLUSION: In men undergoing RP the length of hospital stay and rates of some short- and long-term postoperative complications afterward are lower in high-volume hospitals. The magnitudes of these effects on the outcomes studied may be too small and inconsistent to indicate a policy of selective referral to high-volume hospitals. Quality of life and oncological outcomes, however, could not be investigated in this dataset.

Albertsen PC. · University of Connecticut Health Center, Division of Urology, Urology Office, Farmington, CT 06030-2817, USA. · Int J Epidemiol. · Pubmed #17567643 links to  free full text

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