Journal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 27, No 15S (May 20 Supplement), 2009: 5008
Background: In men with prostate specific antigen (PSA) recurrence following radical prostatectomy (RP) and no other therapy, the natural history of metastatic progression was previously described in 1999.
We now report data reflecting up to 25 years of follow-up. Methods: We performed a retrospective analysis of 774 men treated with RP between 4/1982 and 7/2008 who developed PSA recurrence (>0.2 ng/ml) and never received adjuvant or salvage therapy.
We investigated factors influencing the development of metastases. Results: Mean follow-up after RP was 8.5 y (median 8 y). Of 774 men with PSA recurrence, 295 (38%) developed metastases, and 433 had data on PSA doubling time (PSADT), forming our cohort. The mean time from RP to PSA recurrence in the entire cohort was 4.2 y (median 3 y). In those who developed metastases, the mean time from PSA recurrence to metastasis was 3.1 y (median 2 y). The mean PSA at the time of metastasis was 90.3 ng/ml (median 31.4 ng/ml). In Cox regression analysis: PSADT, Gleason score, and time to PSA progression were predictive of the development of metastases (Table).
In Kaplan-Meier survival analysis, the median actuarial time from PSA recurrence to metastasis was 10 y (95% CI 9 - 15 y). Median actuarial metastasis-free survival from PSA recurrence for men with PSADT <3 mo, 3 - 8.9 mo, 9 - 14.9 mo, and >15 mo was 1 y (95% CI 0 - 1 y), 4 y (95% CI 2 - 6 y), 9 y (95% CI 7 - 13 y), and 15 y (95% CI 12 - 20 y), respectively.
Conclusions: PSADT, Gleason score, and time to PSA progression are strong independent predictors of metastasis-free survival in men with PSA-recurrent prostate cancer. These data facilitate patient counseling and logical risk-based treatment planning. They also provide the background for appropriate selection of patients, treatments, and endpoints for clinical trials
Tuesday
The natural history of metastatic progression in men with PSA-recurrent prostate cancer after radical prostatectomy: 25-year follow-up
Wednesday
Time Between Treatment And PSA Recurrence Predicts Death From Prostate Cancer
Time Between Treatment And PSA Recurrence Predicts Death From Prostate Cancer
ScienceDaily (Nov. 9, 2009) — Men whose prostate specific antigen (PSA) rise within 18 months of radiotherapy are more likely to develop spread and die of their disease, according to an international study led by Fox Chase Cancer Center radiation oncologist Mark K. Buyyounouski, M.D., M.S. and presented today at the annual meeting of the American Society for Radiation Oncology (ASTRO).
"PSA is the gold standard for following prostate cancer patients after they receive radiation or surgery. But we haven't know if having prostate specific antigen (PSA) rise sooner means a patient has a greater danger of dying of prostate cancer, though it seems logical," Buyyounouski says.
Using a single institution database, Buyyounouski and colleagues showed previously that men who suffered an early biochemical failure, which is defined as their lowest PSA level plus 2 ng/mL, were at greater risk of dying of prostate cancer. The new study confirms those results using a multinational database and shows that the measure is ready for use in the clinic.
"Now we can use the simple criteria from this study, which is widely available for anyone who has PSA testing, to identify men who have a greater than 25% chance of dying from prostate cancer in the next five years. That is huge. There is nothing else that can do that," says Buyyounouski.
A total of 2,132 men with clinically localized prostate cancer who suffered biochemical failure after treatment were studied. The median interval between treatment and biochemical failure was 35.2 months for the entire study group. However, 19% of patients developed biochemical failure at 18 months or less. The five-year cancer-specific survival for these men was 69.5% compared with 89.8% for men who developed biochemical failure after 18 months.
A multivariate analysis showed that the interval to biochemical failure correlated with cancer specific survival, as did Gleason score, tumor stage, age, and PSA doubling time. However, the interval to biochemical failure had the best predictive value for cancer-specific mortality, compared with the other variables.
Currently, most physicians do not start treatment based on biochemical failure alone, but rather wait until the PSA reaches a high level or there is some other evidence tumor spread. "The potential impact of this finding is that patients can initiate treatment far sooner without waiting for other signs or symptoms of prostate cancer," Buyyounouski says. "If a patient has biochemical failure at 16 months, rather than wait and learn later that the PSA is rising sharply and risk the development of distant metastasis, therapy can be started sooner based on the increased risk of death."
ScienceDaily (Nov. 9, 2009) — Men whose prostate specific antigen (PSA) rise within 18 months of radiotherapy are more likely to develop spread and die of their disease, according to an international study led by Fox Chase Cancer Center radiation oncologist Mark K. Buyyounouski, M.D., M.S. and presented today at the annual meeting of the American Society for Radiation Oncology (ASTRO).
"PSA is the gold standard for following prostate cancer patients after they receive radiation or surgery. But we haven't know if having prostate specific antigen (PSA) rise sooner means a patient has a greater danger of dying of prostate cancer, though it seems logical," Buyyounouski says.
Using a single institution database, Buyyounouski and colleagues showed previously that men who suffered an early biochemical failure, which is defined as their lowest PSA level plus 2 ng/mL, were at greater risk of dying of prostate cancer. The new study confirms those results using a multinational database and shows that the measure is ready for use in the clinic.
"Now we can use the simple criteria from this study, which is widely available for anyone who has PSA testing, to identify men who have a greater than 25% chance of dying from prostate cancer in the next five years. That is huge. There is nothing else that can do that," says Buyyounouski.
A total of 2,132 men with clinically localized prostate cancer who suffered biochemical failure after treatment were studied. The median interval between treatment and biochemical failure was 35.2 months for the entire study group. However, 19% of patients developed biochemical failure at 18 months or less. The five-year cancer-specific survival for these men was 69.5% compared with 89.8% for men who developed biochemical failure after 18 months.
A multivariate analysis showed that the interval to biochemical failure correlated with cancer specific survival, as did Gleason score, tumor stage, age, and PSA doubling time. However, the interval to biochemical failure had the best predictive value for cancer-specific mortality, compared with the other variables.
Currently, most physicians do not start treatment based on biochemical failure alone, but rather wait until the PSA reaches a high level or there is some other evidence tumor spread. "The potential impact of this finding is that patients can initiate treatment far sooner without waiting for other signs or symptoms of prostate cancer," Buyyounouski says. "If a patient has biochemical failure at 16 months, rather than wait and learn later that the PSA is rising sharply and risk the development of distant metastasis, therapy can be started sooner based on the increased risk of death."
Thursday
A review of prostate-specific antigen screening prevalence and risk perceptions for first-degree relatives of men with prostate cancer
McDowell ME, Occhipinti S, Gardiner RA, Baade PD, Steginga SK.
School of Psychology, Griffith University, Brisbane, Australia.
First-degree relatives of men with prostate cancer have a higher risk of being diagnosed with prostate cancer than men without a family history. The present review examines the prevalence and predictors of testing in first-degree relatives, perceptions of risk, prostate cancer knowledge and psychological consequences of screening. Medline, PsycInfo and Cinahl databases were searched for articles examining risk perceptions or screening practices of first-degree relatives of men with prostate cancer for the period of 1990 to August 2007. Eighteen studies were eligible for inclusion. First-degree relatives participated in Prostate Specific Antigen (PSA) testing more and perceived their risk of prostate cancer to be higher than men without a family history. Family history factors (e.g. being an unaffected son rather than an unaffected brother) were consistent predictors of PSA testing. Studies were characterized by sampling biases and a lack of longitudinal assessments. Prospective, longitudinal assessments with well-validated and comprehensive measures are needed to identify factors that cue the uptake of screening and from this develop an evidence base for decision support. Men with a family history may benefit from targeted communication about the risks and benefits of prostate cancer testing that responds to the implications of their heightened risk.
School of Psychology, Griffith University, Brisbane, Australia.
First-degree relatives of men with prostate cancer have a higher risk of being diagnosed with prostate cancer than men without a family history. The present review examines the prevalence and predictors of testing in first-degree relatives, perceptions of risk, prostate cancer knowledge and psychological consequences of screening. Medline, PsycInfo and Cinahl databases were searched for articles examining risk perceptions or screening practices of first-degree relatives of men with prostate cancer for the period of 1990 to August 2007. Eighteen studies were eligible for inclusion. First-degree relatives participated in Prostate Specific Antigen (PSA) testing more and perceived their risk of prostate cancer to be higher than men without a family history. Family history factors (e.g. being an unaffected son rather than an unaffected brother) were consistent predictors of PSA testing. Studies were characterized by sampling biases and a lack of longitudinal assessments. Prospective, longitudinal assessments with well-validated and comprehensive measures are needed to identify factors that cue the uptake of screening and from this develop an evidence base for decision support. Men with a family history may benefit from targeted communication about the risks and benefits of prostate cancer testing that responds to the implications of their heightened risk.
Sunday
Transcriptionally regulated, prostate-targeted gene therapy for prostate cancer.
Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in American males today. Novel and effective treatment such as gene therapy is greatly desired. The early viral based gene therapy uses tissue-nonspecific promoters, which causes unintended toxicity to other normal tissues. In this chapter, we will review the transcriptionally regulated gene therapy strategy for prostate cancer treatment. We will describe the development of transcriptionally regulated prostate cancer gene therapy in the following areas: (1) Comparison of different routes for best viral delivery to the prostate; (2) Study of transcriptionally regulated, prostate-targeted viral vectors: specificity and activity of the transgene under several different prostate-specific promoters were compared in vitro and in vivo; (3) Selection of therapeutic transgenes and strategies for prostate cancer gene therapy (4) Oncolytic virotherapy for prostate cancer. In addition, the current challenges and future directions in this field are also discussed.
Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center
Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center
Wednesday
Stage-specific cancer incidence: An artificially mixed multinomial logit model.
Takeda Global Research & Development Center, Inc., Analytical Sciences, 675 North Field Drive, Lake Forest, IL 60045, U.S.A.
Early detection of prostate cancer using the prostate-specific antigen test led to a sharp spike in the incidence of the disease accompanied by an equally sharp improvement in patient prognoses as evaluated at the point of advanced diagnosis. Observed outcomes represent age at diagnosis and stage, a categorical prognostic variable combining the actual stage and the grade of tumor. The picture is summarized by the stage-specific cancer incidence that represents a joint survival-multinomial response regressed on factors affecting the unobserved history of the disease before diagnosis (mixture). Fitting the complex joint mixed model to large population data is a challenge. We develop a stable and structured MLE approach to the problem allowing for the estimates to be obtained iteratively. Factorization of the likelihood achieved by our method allows us to work with only a fraction of the model dimension at a time. The approach is based on generalized self-consistency and the quasi-EM algorithm used to handle the mixed multinomial part of the response through Poisson likelihood. The model provides a causal link between the screening policy in the population and the stage-specific incidence. Copyright (c) 2009 John Wiley & Sons, Ltd
Stat Med. 2009 May 19.
Early detection of prostate cancer using the prostate-specific antigen test led to a sharp spike in the incidence of the disease accompanied by an equally sharp improvement in patient prognoses as evaluated at the point of advanced diagnosis. Observed outcomes represent age at diagnosis and stage, a categorical prognostic variable combining the actual stage and the grade of tumor. The picture is summarized by the stage-specific cancer incidence that represents a joint survival-multinomial response regressed on factors affecting the unobserved history of the disease before diagnosis (mixture). Fitting the complex joint mixed model to large population data is a challenge. We develop a stable and structured MLE approach to the problem allowing for the estimates to be obtained iteratively. Factorization of the likelihood achieved by our method allows us to work with only a fraction of the model dimension at a time. The approach is based on generalized self-consistency and the quasi-EM algorithm used to handle the mixed multinomial part of the response through Poisson likelihood. The model provides a causal link between the screening policy in the population and the stage-specific incidence. Copyright (c) 2009 John Wiley & Sons, Ltd
Stat Med. 2009 May 19.
Prostatic Acid Phosphatase Adversely Affects Cause-Specific Survival in Patients with Intermediate to High-Risk Prostate Cancer Treated with Brachythe
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.
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.
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.
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