Objectives
To perform a retrospective analysis to assess the utility of pretreatment serum prostatic acid phosphatase (PAP) as a predictor of cause-specific survival (CSS) in patients with higher risk prostate cancer treated with palladium-103 (103Pd) brachytherapy and supplemental external beam radiotherapy (EBRT).
Methods
From 1992 to 1996, 193 patients with clinically localized prostate adenocarcinoma, a pretreatment PAP level, and Gleason score 7 or more, and/or a prostate-specific antigen (PSA) level of 10 ng/mL or more were treated with 103Pd brachytherapy and supplemental EBRT. The patients underwent EBRT of 41.4 Gy to a limited pelvic field and 103Pd brachytherapy with a prescribed minimum 103Pd dose of 80 Gy. Multivariate analysis was performed to analyze the predictive value of PAP, PSA, and Gleason score on CSS.
Results
The 10-year CSS rate for patients with a PAP level of less than 1.5, 1.5 to 2.4, and 2.5 U/L or more was 93%, 87%, and 75%, respectively (P = 0.013). The 10-year CSS rate for patients with a PSA level of less than 10, 10 to 20, and greater than 20 ng/mL was 92%, 76%, and 83%, respectively (P = 0.393). The 10-year CSS rate for patients with a Gleason score of 6, 7, 8, and 9 was 90%, 89%, 70%, and 68%, respectively (P = 0.002). On Cox multivariate regression analysis, PAP (hazard ratio 1.31, P <0.0001) and Gleason score (hazard ratio 2.37, P = 0.0007) were associated with CSS. PSA was not predictive of CSS (P = 0.393).
Conclusions
The results of this study demonstrated that PAP is a stronger predictor of CSS than PSA or Gleason score in men with higher risk prostate cancer treated with 103Pd brachytherapy and EBRT. Given the findings of this analysis, the use of PAP should be reconsidered in these patients.
Wednesday
Body Mass Index and Prostate-Specific Antigen Failure Following Brachytherapy for Localized Prostate Cancer.
PURPOSE:
Increasing body mass index (BMI) is associated with prostate-specific antigen (PSA) failure after radical prostatectomy and external beam radiation therapy (EBRT). We investigated whether BMI is associated with PSA failure in men treated with brachytherapy for clinically localized prostate cancer.
PATIENTS AND METHODS:
Retrospective analyses were conducted on 374 patients undergoing brachytherapy for stage T1c-T2cNXM0 prostate cancer from 1996-2001. Forty-nine patients (13%) received supplemental EBRT and 131 (35%) received androgen deprivation therapy (ADT). Height and weight data were available for 353 (94%). Cox regression analyses were performed to evaluate the relationship between body mass index (BMI) and PSA failure (nadir + 2 ng/ml definition). Covariates included age, race, preimplantation prostate-specific antigen (PSA), Gleason score, T category, percent of prescription dose to 90% of the prostate, use of supplemental EBRT, and ADT.
RESULTS:
Median age, PSA, and BMI were 66 years (range, 42-80 years), 5.7 ng/ml (range, 0.4-22.6 ng/ml), and 27.1 kg/m(2) (range, 18.2-53.6 kg/m(2)), respectively. After a median follow-up of 6.0 years (range, 3.0-10.2 years), there were 76 PSA recurrences. The BMI was not associated with PSA failure. Six-year PSA failure rates were 30.2% for men with BMI less than 25 kg/m(2), 19.5% for BMI of 25 or greater to less than 30 kg/m(2), and 14.4% for BMI of 30 kg/m(2) or greater (p = 0.19). Results were similar when BMI was analyzed as a continuous variable, using alternative definitions of PSA failure, and excluding patients treated with EBRT and/or ADT. In multivariate analyses, only baseline PSA was significantly associated with shorter time to PSA failure (adjusted hazard ratio, 1.12; 95% confidence interval, 1.05-1.20; p = 0.0006).
CONCLUSIONS:
Unlike after surgery or EBRT, body mass index (BMI) is not associated with prostate-specific antigen (PSA) failure in men treated with brachytherapy for prostate cancer. This raises the possibility that brachytherapy may be a preferred treatment strategy in obese patients.
Increasing body mass index (BMI) is associated with prostate-specific antigen (PSA) failure after radical prostatectomy and external beam radiation therapy (EBRT). We investigated whether BMI is associated with PSA failure in men treated with brachytherapy for clinically localized prostate cancer.
PATIENTS AND METHODS:
Retrospective analyses were conducted on 374 patients undergoing brachytherapy for stage T1c-T2cNXM0 prostate cancer from 1996-2001. Forty-nine patients (13%) received supplemental EBRT and 131 (35%) received androgen deprivation therapy (ADT). Height and weight data were available for 353 (94%). Cox regression analyses were performed to evaluate the relationship between body mass index (BMI) and PSA failure (nadir + 2 ng/ml definition). Covariates included age, race, preimplantation prostate-specific antigen (PSA), Gleason score, T category, percent of prescription dose to 90% of the prostate, use of supplemental EBRT, and ADT.
RESULTS:
Median age, PSA, and BMI were 66 years (range, 42-80 years), 5.7 ng/ml (range, 0.4-22.6 ng/ml), and 27.1 kg/m(2) (range, 18.2-53.6 kg/m(2)), respectively. After a median follow-up of 6.0 years (range, 3.0-10.2 years), there were 76 PSA recurrences. The BMI was not associated with PSA failure. Six-year PSA failure rates were 30.2% for men with BMI less than 25 kg/m(2), 19.5% for BMI of 25 or greater to less than 30 kg/m(2), and 14.4% for BMI of 30 kg/m(2) or greater (p = 0.19). Results were similar when BMI was analyzed as a continuous variable, using alternative definitions of PSA failure, and excluding patients treated with EBRT and/or ADT. In multivariate analyses, only baseline PSA was significantly associated with shorter time to PSA failure (adjusted hazard ratio, 1.12; 95% confidence interval, 1.05-1.20; p = 0.0006).
CONCLUSIONS:
Unlike after surgery or EBRT, body mass index (BMI) is not associated with prostate-specific antigen (PSA) failure in men treated with brachytherapy for prostate cancer. This raises the possibility that brachytherapy may be a preferred treatment strategy in obese patients.
Tuesday
Prostate specific antigen versus prostate specific antigen density as a prognosticator of pathological characteristics and biochemical recurrence foll
PURPOSE: The usefulness of prostate specific antigen (PSA) density for predicting pathological stage and biochemical recurrence after radical prostatectomy has not been well defined. We investigated whether prostate specific antigen density yielded an advantage over total prostate specific antigen for predicting adverse pathological characteristics and disease recurrence following radical prostatectomy.
MATERIALS AND METHODS: A total of 13,434 men who underwent radical prostatectomy for clinically localized prostate cancer between 1984 and 2006 were included in this study. The study population was stratified by Gleason score (6 or less, 7, and 8 or greater), and the clinical and pathological characteristics of each group were compared. We constructed ROC curves and determined the ROC AUC and concordance index to specifically investigate the accuracy of prostate specific antigen (PSA) and prostate specific antigen density for predicting pathological stage and biochemical recurrence.
RESULTS: Prostate specific antigen density was better than prostate specific antigen (PSA)for predicting extraprostatic extension and biochemical-free recurrence in patients with a biopsy Gleason score of 6 or less (each p <0.001). In patients with a biopsy Gleason score of 7 prostate specific antigen was more predictive than prostate specific antigen density for seminal vesicle involvement (p <0.001), lymph node involvement (p = 0.017) and biochemical-free recurrence (p <0.001). In men with a biopsy Gleason score of 8 or greater there was no statistical difference between prostate specific antigen and prostate specific antigen density in terms of prognostic value for pathological or clinical outcomes.
CONCLUSIONS: Prostate specific antigen density is highly associated with pathological stage and biochemical-free survival following radical prostatectomy. In lower grade prostate cancers prostate specific antigen density is significantly more accurate for predicting extraprostatic extension and biochemical-free recurrence compared to total prostate specific antigen. It should be considered when counseling patients on outcomes following radical prostatectomy.
MATERIALS AND METHODS: A total of 13,434 men who underwent radical prostatectomy for clinically localized prostate cancer between 1984 and 2006 were included in this study. The study population was stratified by Gleason score (6 or less, 7, and 8 or greater), and the clinical and pathological characteristics of each group were compared. We constructed ROC curves and determined the ROC AUC and concordance index to specifically investigate the accuracy of prostate specific antigen (PSA) and prostate specific antigen density for predicting pathological stage and biochemical recurrence.
RESULTS: Prostate specific antigen density was better than prostate specific antigen (PSA)for predicting extraprostatic extension and biochemical-free recurrence in patients with a biopsy Gleason score of 6 or less (each p <0.001). In patients with a biopsy Gleason score of 7 prostate specific antigen was more predictive than prostate specific antigen density for seminal vesicle involvement (p <0.001), lymph node involvement (p = 0.017) and biochemical-free recurrence (p <0.001). In men with a biopsy Gleason score of 8 or greater there was no statistical difference between prostate specific antigen and prostate specific antigen density in terms of prognostic value for pathological or clinical outcomes.
CONCLUSIONS: Prostate specific antigen density is highly associated with pathological stage and biochemical-free survival following radical prostatectomy. In lower grade prostate cancers prostate specific antigen density is significantly more accurate for predicting extraprostatic extension and biochemical-free recurrence compared to total prostate specific antigen. It should be considered when counseling patients on outcomes following radical prostatectomy.
Hierarchical Changepoint Models for Biochemical Markers Illustratedby Tracking Postradiotherapy Prostate-Specific Antigen Series inMen With Prostate
PURPOSE: Biomarkers provide valuable information when detecting disease onset or monitoring diseaseprogression; 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 beused as prognostic factors of disease progression, such as the postradiotherapy PSA doubling time in mentreated for prostate cancer. The statistical analysis of such data has to incorporate the within and be-tween-series variabilities, the complex patterns of the series over time, the unbalanced format of thedata, and the possibly nonconstant precision of the measurements.
METHODS: We base our analysis on a population-based cohort of 470 men treated with radiotherapy forprostate cancer; after treatment, the log2PSA concentrations follow a piecewise-linear pattern. We illustrate the flexibility of Bayesian hierarchical changepoint models by estimating the individual and popula-tion postradiotherapy log2PSA profiles; parameters such as the PSA nadir and the PSA doubling time wereestimated, 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 alternativemodels were briefly considered.
RESULTS: Precise estimates of all parameters of the PSA trajectory are provided at both the individualand population levels. Estimates suggest greater PSA variability at lower PSA concentrations, as well as anassociation between shorter PSAdts and greater baseline PSA levels, higher Gleason scores, and older age.
CONCLUSIONS: The use of Bayesian hierarchical changepoint models accommodates multiple com-plex features of longitudinal data, permits realistic modeling of the variability as a function of the markerconcentration, and provides precise estimates of all clinically important parameters. This type of modelshould be applicable to the study of marker series in other diseases.
CARINE A. BELLERA,PHD, JAMES A. HANLEY,PHD, LAWRENCE JOSEPH,PHD,AND PETER C. ALBERTSEN,MD
METHODS: We base our analysis on a population-based cohort of 470 men treated with radiotherapy forprostate cancer; after treatment, the log2PSA concentrations follow a piecewise-linear pattern. We illustrate the flexibility of Bayesian hierarchical changepoint models by estimating the individual and popula-tion postradiotherapy log2PSA profiles; parameters such as the PSA nadir and the PSA doubling time wereestimated, 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 alternativemodels were briefly considered.
RESULTS: Precise estimates of all parameters of the PSA trajectory are provided at both the individualand population levels. Estimates suggest greater PSA variability at lower PSA concentrations, as well as anassociation between shorter PSAdts and greater baseline PSA levels, higher Gleason scores, and older age.
CONCLUSIONS: The use of Bayesian hierarchical changepoint models accommodates multiple com-plex features of longitudinal data, permits realistic modeling of the variability as a function of the markerconcentration, and provides precise estimates of all clinically important parameters. This type of modelshould be applicable to the study of marker series in other diseases.
CARINE A. BELLERA,PHD, JAMES A. HANLEY,PHD, LAWRENCE JOSEPH,PHD,AND PETER C. ALBERTSEN,MD
PSA velocity does not aid long-term prediction of prostate cancer incidence
Elevated serum prostate-specific antigen (PSA) levels can indicate the presence of prostate cancer, although PSA levels are also elevated in some nonmalignant conditions, which affects the reliability of prostate cancer prediction. PSA levels rise sharply in patients with aggressive prostate cancer, and a recent study suggested that the rate of increase (PSA velocity) could predict life-threatening prostate cancer 10–15 years before diagnosis. Ulmert and colleagues evaluated data from the Malmö Preventative Medicine population-based study to compare the accuracy of a single PSA measurement versus PSA velocity in the long-term prediction of prostate cancer diagnosis.
Nature Clinical Practice Oncology (2008) 5, 302
Nature Clinical Practice Oncology (2008) 5, 302
Racial Differences in Prostate Cancer Screening by Family History
Purpose
Prostate cancer (CaP) is disproportionately prevalent among black, compared to white, men. Additionally, men with a family history of CaP have 75% to 80% higher risk of CaP. Therefore we examined racial variation in the association of family history of CaP and self-reported prostate-specific antigen (PSA) testing in the nationally-representative National Health Interview Survey (NHIS).
Methods
Data were obtained from the 2005 NHIS, including the Cancer Control Module supplement. We restricted the study sample to men over the age of 40 who reported having “ever heard of a PSA test” (N = 1,744). Men were considered to have a positive family history if either their biological father or at least one biological brother had been diagnosed with CaP. SUDAAN 9.0 was used to perform descriptive and multivariable logistic regression analyses.
Results
Men with a family history of CaP were more likely to have a PSA test than those who never had a PSA test (odds ratio [OR] = 1.8; 95% confidence interval [CI]: 1.3–2.5). Among blacks, men with a family history were not significantly more likely to have a PSA test.
Conclusions
Despite having the highest risk of cancer, black men with a family history are not screened more than black men without a family history.
Bettina F. Drake MPH, PhDa, Christopher S. Lathan MD, MPHb, Cassandra A. Okechukwu MSN, MPHc and Gary G. Bennett PhD
ARTICLE
Prostate cancer (CaP) is disproportionately prevalent among black, compared to white, men. Additionally, men with a family history of CaP have 75% to 80% higher risk of CaP. Therefore we examined racial variation in the association of family history of CaP and self-reported prostate-specific antigen (PSA) testing in the nationally-representative National Health Interview Survey (NHIS).
Methods
Data were obtained from the 2005 NHIS, including the Cancer Control Module supplement. We restricted the study sample to men over the age of 40 who reported having “ever heard of a PSA test” (N = 1,744). Men were considered to have a positive family history if either their biological father or at least one biological brother had been diagnosed with CaP. SUDAAN 9.0 was used to perform descriptive and multivariable logistic regression analyses.
Results
Men with a family history of CaP were more likely to have a PSA test than those who never had a PSA test (odds ratio [OR] = 1.8; 95% confidence interval [CI]: 1.3–2.5). Among blacks, men with a family history were not significantly more likely to have a PSA test.
Conclusions
Despite having the highest risk of cancer, black men with a family history are not screened more than black men without a family history.
Bettina F. Drake MPH, PhDa, Christopher S. Lathan MD, MPHb, Cassandra A. Okechukwu MSN, MPHc and Gary G. Bennett PhD
ARTICLE
Monday
Using spectral moments of spiral networks based on PSA/mass spectra outcomes to derive quantitative proteome–disease relationships (QPDRs) and predict
In prostate cancer (PCa), prognostic (predictive) factors are particularly important given the marked heterogeneity of this disease at clinical, morphologic, and biomolecular levels. Blood contains a treasure of previously unstudied biomarkers that could reflect the ongoing physiological state of all tissue. The serum prostate-specific antigen (PSA) measurement is a very good biomarker for PCa, but the percentage of bad classification is somewhat high. The blood proteome mass spectra (MS) represent a potential tool for detection of diseases; however the identification of a single biomarker from the complex output from MS is often difficult. In this paper, we propose a general strategy, based on computational chemistry techniques, which should improve the predictive power of PSA. Our group adapted the square–spiral graph to represent human serum-plasma–proteome MS for healthy and PCa patients. These graphs were previously applied to DNA and/or protein sequences. In this work, we calculated different classes of connectivity indices (CIs), and created various models based on the spectral moments. The best QPDRs model found showed accuracy values ranging from 71.7% to 97.2%, and 70.4% to 99.2% of specificity. This methodology might be useful for several applications in computational chemistry.
Giulio Ferinoa, Humberto González-Díaza b, Giovanna Delogua, Gianni Poddaa, and Eugenio Uriarteb
ARTICLE
Giulio Ferinoa, Humberto González-Díaza b, Giovanna Delogua, Gianni Poddaa, and Eugenio Uriarteb
ARTICLE
Wednesday
Gene Linked to Deadly Prostate Cancer
Prostate cancer is common. It's also deadly. About 220,000 men in the United States will learn that they have prostate cancer this year. Despite tests to detect it early and several effective treatments, the disease kills about 27,000 men in the United States each year.
On the other hand, many men with prostate cancer have tiny tumors that pose no significant threat to their health. For these men, early detection and treatment provides no benefit. So, it's a big challenge to learn how to detect the dangerous tumors while leaving the others alone. That's not easy.
To make matters worse, non-cancerous enlargement of the prostate, a nearly universal part of aging for men, may mimic prostate cancer . For example, the prostate-specific antigen (PSA) blood test may be high. This can raise concern about prostate cancer even when no cancer is present.
Clearly, we need better ways to identify men who have early prostate cancer requiring treatment. That's why the results of a new research study from Iceland are notable. The study links a gene mutation to an increased risk of aggressive prostate cancer. Interestingly, the mutation is located on a gene – called BRCA2 – known to increase the risk of cancers of the breast and ovary among women.
In this new research, scientists reviewed cases of prostate cancer in Iceland from the last 50 years. They selected study subjects with prostate cancer who also had female relatives with breast cancer. Researchers discovered that men who carried a particular BRCA2 gene mutation tended to have the worst forms of prostate cancer.
For example, men with the BRCA2 mutation had:
· Onset of prostate cancer at a younger age
· More advanced prostate cancer
· Shorter survival
The effect on survival was particularly striking. On average, those with the mutation lived just 2 years from the time of diagnosis. Non-carriers of the mutation survived more than 12 years.
It's hard to know whether these results will have a big impact on prostate cancer detection or treatment. The mutation was found in less than 6% of study subjects with prostate cancer. The rate might have been lower if these men did not have relatives with breast cancer. This mutation might be even rarer outside Iceland.
Still, the findings suggest that looking for mutations in genes with known links to cancer could provide valuable information. It's easy to imagine that genetic testing could someday be a routine part of screening for prostate cancer (and other cancers). Perhaps the results could be used to predict the need for aggressive treatment.
by Harvard Publications
On the other hand, many men with prostate cancer have tiny tumors that pose no significant threat to their health. For these men, early detection and treatment provides no benefit. So, it's a big challenge to learn how to detect the dangerous tumors while leaving the others alone. That's not easy.
To make matters worse, non-cancerous enlargement of the prostate, a nearly universal part of aging for men, may mimic prostate cancer . For example, the prostate-specific antigen (PSA) blood test may be high. This can raise concern about prostate cancer even when no cancer is present.
Clearly, we need better ways to identify men who have early prostate cancer requiring treatment. That's why the results of a new research study from Iceland are notable. The study links a gene mutation to an increased risk of aggressive prostate cancer. Interestingly, the mutation is located on a gene – called BRCA2 – known to increase the risk of cancers of the breast and ovary among women.
In this new research, scientists reviewed cases of prostate cancer in Iceland from the last 50 years. They selected study subjects with prostate cancer who also had female relatives with breast cancer. Researchers discovered that men who carried a particular BRCA2 gene mutation tended to have the worst forms of prostate cancer.
For example, men with the BRCA2 mutation had:
· Onset of prostate cancer at a younger age
· More advanced prostate cancer
· Shorter survival
The effect on survival was particularly striking. On average, those with the mutation lived just 2 years from the time of diagnosis. Non-carriers of the mutation survived more than 12 years.
It's hard to know whether these results will have a big impact on prostate cancer detection or treatment. The mutation was found in less than 6% of study subjects with prostate cancer. The rate might have been lower if these men did not have relatives with breast cancer. This mutation might be even rarer outside Iceland.
Still, the findings suggest that looking for mutations in genes with known links to cancer could provide valuable information. It's easy to imagine that genetic testing could someday be a routine part of screening for prostate cancer (and other cancers). Perhaps the results could be used to predict the need for aggressive treatment.
by Harvard Publications
Tuesday
Link Between Severe Acne and Prostate Cancer
(Ivanhoe Newswire) A higher risk of prostate cancer may be linked to severe acne.
New research from Johns Hopkins Bloomberg School of Public Health in Baltimore finds men who took tetracycline -- an antibiotic used to treat severe acne -- for four years or longer were 70 percent more likely to develop prostate cancer over a 10-year period than men who had taken the drug, or had taken it for a shorter time.
But the studys authors urge caution in interpreting their findings. They note the small number of participants who had used tetracycline for at least four years -- 0.5-percent of the 34,629 men in the study -- the indirect assessment of severe acne, and the fact that acne can have several causes.
The research looked at the link between severe acne and prostate cancer because recent studies found the acne-related bacterium Propionibacterium acnes in one third of prostate samples taken from men with prostate cancer. The tissue containing P. acnes was more likely to be inflamed. Inflammation is believed to be an important part of the development of prostate cancer.
Researchers say it is unlikely tetracycline itself would raise the risk of prostate cancer . They believe one possible explanation for the acne-prostate cancer link is that men who develop severe acne may be more likely to have stronger inflammatory immune responses when P. acnes goes into the prostate.
SOURCE: International Journal of Cancer, 2007;121:2688-2692
New research from Johns Hopkins Bloomberg School of Public Health in Baltimore finds men who took tetracycline -- an antibiotic used to treat severe acne -- for four years or longer were 70 percent more likely to develop prostate cancer over a 10-year period than men who had taken the drug, or had taken it for a shorter time.
But the studys authors urge caution in interpreting their findings. They note the small number of participants who had used tetracycline for at least four years -- 0.5-percent of the 34,629 men in the study -- the indirect assessment of severe acne, and the fact that acne can have several causes.
The research looked at the link between severe acne and prostate cancer because recent studies found the acne-related bacterium Propionibacterium acnes in one third of prostate samples taken from men with prostate cancer. The tissue containing P. acnes was more likely to be inflamed. Inflammation is believed to be an important part of the development of prostate cancer.
Researchers say it is unlikely tetracycline itself would raise the risk of prostate cancer . They believe one possible explanation for the acne-prostate cancer link is that men who develop severe acne may be more likely to have stronger inflammatory immune responses when P. acnes goes into the prostate.
SOURCE: International Journal of Cancer, 2007;121:2688-2692
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