School of Social and Community Medicine, University of Bristol, Bristol, Oncology Centre, Addenbrooke's Hospital, Cambridge, andNuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Abstract
Study Type - Aetiology (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Evidence for seasonal or climatic effects on PSA levels is mixed and inconclusive. In this large, long-term study, no seasonal or climatic patterns in PSA levels were identified.
OBJECTIVE: To assess whether a seasonal change in prostate specific antigen (PSA) levels can be detected in men recruited to a large clinical trial.
PATIENTS AND METHODS: A total of 66 969 men aged 50-69 years were drawn from a large study conducted at general practices across the UK between 2002 and 2007. Trigonometric algorithms and regression methods were used to assess the relationship between the time of year and serum PSA and blood pressure measurements. We obtained local daily mean temperatures and hours of sunlight per day to assess whether these factors were potential mechanisms for seasonal variation in PSA levels or blood pressure. The proportion of participants who would be considered clinically at risk according to their PSA or blood pressure measurement, by month, was also assessed. The strength of associations between time of year and blood pressure were used to reinforce conclusions from the PSA models.
RESULTS: There was no relationship between time of year and PSA levels (P= 0.11) or between climate and PSA levels (P= 0.42). No difference was found in the prevalence of clinically raised PSA content by month (P= 0.50). This lack of an association with PSA content was despite our data being sufficient to provide clear evidence of an association between blood pressure and time of year (systolic P < 0.001; diastolic P < 0.001), and to show that this association was largely explained by climatic factors (temperature and sunlight).
CONCLUSIONS: There was no pattern in PSA levels by time of year, air temperature or levels of sunlight in this cohort, so there is no need to take these factors into account when reviewing PSA results
Risk Profiles and Treatment Patterns Among Men Diagnosed as Having Prostate Cancer and a Prostate-Specific Antigen Level Below 4.0 ng/mL
Background Despite controversy over the benefit of prostate-specific antigen (PSA) screening, little is known about risk profiles and treatment patterns in men diagnosed as having prostate cancer who have a PSA value less than or equal to 4.0 ng/mL.
Methods We used data from the Surveillance, Epidemiology, and End Results system to describe patient characteristics and treatment patterns in the cases of 123 934 men with newly diagnosed prostate cancer from 2004 to 2006. Age-standardized treatment rates were calculated in 5-year age strata. Logistic regression was used to quantify the odds ratios (ORs) of men with low- and high-risk disease and the use of radical prostatectomy (RP) or radiation therapy (RT).
Results Men with a PSA level of 4.0 ng/mL or lower represent 14% of incident prostate cancer cases. Fifty-four percent of men diagnosed as having prostate cancer and PSA levels lower than 4.0 ng/mL harbor low-risk disease (stage, T2a, PSA level, 10 ng/mL, and Gleason score, 6), but over 75% of them received RP or RT. Men with screen-detected prostate cancer and PSA values lower than 4 ng/mL were 1.49 (95% confidence interval [CI], 1.38-1.62) and 1.39 (95% CI, 1.30-1.49) times more likely to receive RP and RT, respectively, and were less likely to have high-grade disease than men who had non–screen-detected prostate cancer (OR, 0.67; 95% CI, 0.60-0.76).
Conclusions Most men diagnosed as having prostate cancer with a PSA threshold below 4.0 ng/mL had low-risk disease but underwent aggressive local therapy. Lowering the biopsy threshold but retaining our inability to distinguish indolent from aggressive cancers might increase the risk of overdiagnosis and overtreatment.
Yu-Hsuan Shao, PhD; Peter C. Albertsen, MD; Calpurnyia B. Roberts, PhD; Yong Lin, PhD; Amit R. Mehta, MD; Mark N. Stein, MD; Robert S. DiPaola, MD; Grace L. Lu-Yao, PhD
Arch Intern Med. 2010;170(14):1256-1261. doi:10.1001/archinternmed.2010.221
Methods We used data from the Surveillance, Epidemiology, and End Results system to describe patient characteristics and treatment patterns in the cases of 123 934 men with newly diagnosed prostate cancer from 2004 to 2006. Age-standardized treatment rates were calculated in 5-year age strata. Logistic regression was used to quantify the odds ratios (ORs) of men with low- and high-risk disease and the use of radical prostatectomy (RP) or radiation therapy (RT).
Results Men with a PSA level of 4.0 ng/mL or lower represent 14% of incident prostate cancer cases. Fifty-four percent of men diagnosed as having prostate cancer and PSA levels lower than 4.0 ng/mL harbor low-risk disease (stage, T2a, PSA level, 10 ng/mL, and Gleason score, 6), but over 75% of them received RP or RT. Men with screen-detected prostate cancer and PSA values lower than 4 ng/mL were 1.49 (95% confidence interval [CI], 1.38-1.62) and 1.39 (95% CI, 1.30-1.49) times more likely to receive RP and RT, respectively, and were less likely to have high-grade disease than men who had non–screen-detected prostate cancer (OR, 0.67; 95% CI, 0.60-0.76).
Conclusions Most men diagnosed as having prostate cancer with a PSA threshold below 4.0 ng/mL had low-risk disease but underwent aggressive local therapy. Lowering the biopsy threshold but retaining our inability to distinguish indolent from aggressive cancers might increase the risk of overdiagnosis and overtreatment.
Yu-Hsuan Shao, PhD; Peter C. Albertsen, MD; Calpurnyia B. Roberts, PhD; Yong Lin, PhD; Amit R. Mehta, MD; Mark N. Stein, MD; Robert S. DiPaola, MD; Grace L. Lu-Yao, PhD
Arch Intern Med. 2010;170(14):1256-1261. doi:10.1001/archinternmed.2010.221
Symptoms and Risk Factors for Prostate Cancer
SYMPTOMS
Different people have different symptoms for prostate cancer. Some men do not have symptoms at all.
Some symptoms of prostate cancer are—
•Difficulty starting urination.
•Weak, or interrupted flow of urine.
•Frequent urination, especially at night.
•Difficulty emptying the bladder completely.
•Pain or burning during urination.
•Blood in the urine or semen.
•Pain in the back, hips, or pelvis that doesn't go away.
•Painful ejaculation.
If you have any symptoms that worry you, be sure to see your doctor right away. Keep in mind that these symptoms may be caused by conditions other than prostate cancer.
RISK FACTORS
Research has found risk factors that increase your chances of getting prostate cancer. These risk factors include—
•Age: The older a man is, the greater his risk for getting prostate cancer.1
•Family history: Certain genes (the functional and physical units of heredity passed from parent to offspring) that you inherited from your parents may affect your prostate cancer risk. Currently, no single gene is sure to raise or lower your risk of getting prostate cancer. However, a man with a father, brother, or son who has had prostate cancer is two to three times more likely to develop the disease himself.1
•Race: Prostate cancer is more common in some racial and ethnic groups than in others, but medical experts do not know why.
Researchers are trying to determine the causes of prostate cancer and whether it can be prevented. They do not yet agree on the factors that can influence a man's risk of developing the disease, either positively or negatively. Some of the factors under study include—1 2 3 4
•Vitamins, minerals, and herbal supplements.
•Diets high in animal fat, especially polyunsaturated fat.
•Men's hormone levels.
•Environmental agents (pesticide residues on foods, and industrial and occupational exposures).
References
1Bostwick DG, Burke HB, Djakiew D, Euling S, Ho SM, Landolph J, Morrison H, Sonawane B, Shifflett T, Waters DJ, Timms B. Human prostate cancer risk factors. Cancer 2004;101(10 Suppl):2371–2490.
2Vainio H, Bianchini F, eds. IARC Handbooks of Cancer Prevention, Vol 6: Weight Control and Physical Activity. Lyon, France: IARC Press; 2002.
3Curry S, Byers T, Hewitt M, eds. Fulfilling the Potential of Cancer Prevention and Early Detection.
4Platz EA, Giovannucci E. Prostate Cancer. In: Schottenfeld D, Fraumeni JF, eds. Cancer Epidemiology and Prevention, 3rd ed. New York, NY: Oxford University Press, 2006.
Different people have different symptoms for prostate cancer. Some men do not have symptoms at all.
Some symptoms of prostate cancer are—
•Difficulty starting urination.
•Weak, or interrupted flow of urine.
•Frequent urination, especially at night.
•Difficulty emptying the bladder completely.
•Pain or burning during urination.
•Blood in the urine or semen.
•Pain in the back, hips, or pelvis that doesn't go away.
•Painful ejaculation.
If you have any symptoms that worry you, be sure to see your doctor right away. Keep in mind that these symptoms may be caused by conditions other than prostate cancer.
RISK FACTORS
Research has found risk factors that increase your chances of getting prostate cancer. These risk factors include—
•Age: The older a man is, the greater his risk for getting prostate cancer.1
•Family history: Certain genes (the functional and physical units of heredity passed from parent to offspring) that you inherited from your parents may affect your prostate cancer risk. Currently, no single gene is sure to raise or lower your risk of getting prostate cancer. However, a man with a father, brother, or son who has had prostate cancer is two to three times more likely to develop the disease himself.1
•Race: Prostate cancer is more common in some racial and ethnic groups than in others, but medical experts do not know why.
Researchers are trying to determine the causes of prostate cancer and whether it can be prevented. They do not yet agree on the factors that can influence a man's risk of developing the disease, either positively or negatively. Some of the factors under study include—1 2 3 4
•Vitamins, minerals, and herbal supplements.
•Diets high in animal fat, especially polyunsaturated fat.
•Men's hormone levels.
•Environmental agents (pesticide residues on foods, and industrial and occupational exposures).
References
1Bostwick DG, Burke HB, Djakiew D, Euling S, Ho SM, Landolph J, Morrison H, Sonawane B, Shifflett T, Waters DJ, Timms B. Human prostate cancer risk factors. Cancer 2004;101(10 Suppl):2371–2490.
2Vainio H, Bianchini F, eds. IARC Handbooks of Cancer Prevention, Vol 6: Weight Control and Physical Activity. Lyon, France: IARC Press; 2002.
3Curry S, Byers T, Hewitt M, eds. Fulfilling the Potential of Cancer Prevention and Early Detection.
4Platz EA, Giovannucci E. Prostate Cancer. In: Schottenfeld D, Fraumeni JF, eds. Cancer Epidemiology and Prevention, 3rd ed. New York, NY: Oxford University Press, 2006.
Prostate-specific antigen: An evolving role in diagnosis, monitoring, and treatment evaluation in prostate cancer.
Prostate specific antigen (PSA) was introduced as a prostate cancer screening tool more than 20 years ago. However, there is continuing debate regarding its utility in screening for prostate cancer. Mass screening is costly, may result in the diagnosis and treatment of prostate cancers that never become clinically significant, and the evidence of a subsequent reduction in mortality is inconclusive. In addition to its role in screening, PSA is also used to monitor the progression of the disease, both localized and metastatic.
Although the evidence is contradictory, PSA is still an important tool for monitoring patient progression following treatment of definitive localized prostate cancer. However, its use in monitoring castrate-resistant prostate cancer (CRPC) is more controversial, particularly in the context of novel targeted treatments, which may have little impact on PSA levels. These issues highlight the urgent need to identify prostate cancer biomarkers that will improve early disease detection, increase accuracy of diagnosis, determine the aggressiveness of disease, and monitor treatment efficacy, particularly in late-stage disease.
This review discusses the key issues associated with the use of PSA as an early screening tool for prostate cancer, as a prognostic marker to measure disease progression in both early- and late-stage prostate cancer, and as a surrogate endpoint in clinical trials with new agents. Copyright © 2009 Elsevier Inc. All rights reserved.
Payne H, Cornford P.
Department of Oncology, UCLH NHS Foundation Trust, London, United Kingdom.
Although the evidence is contradictory, PSA is still an important tool for monitoring patient progression following treatment of definitive localized prostate cancer. However, its use in monitoring castrate-resistant prostate cancer (CRPC) is more controversial, particularly in the context of novel targeted treatments, which may have little impact on PSA levels. These issues highlight the urgent need to identify prostate cancer biomarkers that will improve early disease detection, increase accuracy of diagnosis, determine the aggressiveness of disease, and monitor treatment efficacy, particularly in late-stage disease.
This review discusses the key issues associated with the use of PSA as an early screening tool for prostate cancer, as a prognostic marker to measure disease progression in both early- and late-stage prostate cancer, and as a surrogate endpoint in clinical trials with new agents. Copyright © 2009 Elsevier Inc. All rights reserved.
Payne H, Cornford P.
Department of Oncology, UCLH NHS Foundation Trust, London, United Kingdom.
Serum Prostate-Specific Antigen Hemodilution Among Obese Men Undergoing Screening in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Tria
(Cancer Epidemiol Biomarkers Prev 2009;18(3):748–51)
Background: Previous studies have shown an inverse relationship between prostate-specific antigen (PSA) concentration and body mass index (BMI). It has been recently proposed that this relationship may be explained by the larger plasma volume of obese men diluting a fixed amount of PSA (hemodilution effect). We examined this hypothesis in a cohort of men enrolled in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.
Methods: Of 38,349 men ages 55 to 74 years randomized in PLCO to receive annual PSA and digital rectal examination screening, 28,380 had a baseline PSA, complete demographic information, and no prostate cancer diagnosis within 6 years from baseline. Self-reported height and weight were used to calculate BMI and to estimate plasma volume. PSA mass was estimated as PSA concentration times plasma volume. Multivariable linear regression models were used to investigate the relationship between PSA concentration, plasma volume, PSA mass, and BMI.
Results: PSA concentration significantly decreased with increasing BMI (P < 0.001); mean PSA values were 1.27, 1.25, 1.18, and 1.07 ng/mL among normal (BMI, 18.5-25), overweight (BMI, 25-30), obese (BMI, 30-35), and morbidly obese (BMI, >35) men, respectively. However, plasma volume also increased with increasing BMI and PSA mass showed no association with BMI, with mean values of 3.78, 3.95, 3.97, and 3.82 μg across the four BMI categories (P = 0.10).
Conclusions: This study confirms earlier findings that the inverse relationship between PSA concentration and BMI may be explained by a hemodilution effect. These findings could have implications for prostate cancer screening in large men.
Background: Previous studies have shown an inverse relationship between prostate-specific antigen (PSA) concentration and body mass index (BMI). It has been recently proposed that this relationship may be explained by the larger plasma volume of obese men diluting a fixed amount of PSA (hemodilution effect). We examined this hypothesis in a cohort of men enrolled in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.
Methods: Of 38,349 men ages 55 to 74 years randomized in PLCO to receive annual PSA and digital rectal examination screening, 28,380 had a baseline PSA, complete demographic information, and no prostate cancer diagnosis within 6 years from baseline. Self-reported height and weight were used to calculate BMI and to estimate plasma volume. PSA mass was estimated as PSA concentration times plasma volume. Multivariable linear regression models were used to investigate the relationship between PSA concentration, plasma volume, PSA mass, and BMI.
Results: PSA concentration significantly decreased with increasing BMI (P < 0.001); mean PSA values were 1.27, 1.25, 1.18, and 1.07 ng/mL among normal (BMI, 18.5-25), overweight (BMI, 25-30), obese (BMI, 30-35), and morbidly obese (BMI, >35) men, respectively. However, plasma volume also increased with increasing BMI and PSA mass showed no association with BMI, with mean values of 3.78, 3.95, 3.97, and 3.82 μg across the four BMI categories (P = 0.10).
Conclusions: This study confirms earlier findings that the inverse relationship between PSA concentration and BMI may be explained by a hemodilution effect. These findings could have implications for prostate cancer screening in large men.
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