OBJECTIVE: To determine the association between concentration of prostate specific antigen (PSA) at age 40-55 and subsequent risk of prostate cancer metastasis and mortality in an unscreened population to evaluate when to start screening for prostate cancer and whether rescreening could be risk stratified.
DESIGN: Case-control study with 1:3 matching nested within a highly representative population based cohort study.
SETTING: Malmö Preventive Project, Sweden.
PARTICIPANTS: 21,277 Swedish men aged 27-52 (74% of the eligible population) who provided blood at baseline in 1974-84, and 4922 men invited to provide a second sample six years later. Rates of PSA testing remained extremely low during median follow-up of 27 years.
MAIN OUTCOME MEASURES: Metastasis or death from prostate cancer ascertained by review of case notes.
RESULTS: Risk of death from prostate cancer was associated with baseline PSA: 44% (95% confidence interval 34% to 53%) of deaths occurred in men with a PSA concentration in the highest 10th of the distribution of concentrations at age 45-49 (≥ 1.6 µg/L), with a similar proportion for the highest 10th at age 51-55 (≥ 2.4 µg/L: 44%, 32% to 56%). Although a 25-30 year risk of prostate cancer metastasis could not be ruled out by concentrations below the median at age 45-49 (0.68 µg/L) or 51-55 (0.85 µg/L), the 15 year risk remained low at 0.09% (0.03% to 0.23%) at age 45-49 and 0.28% (0.11% to 0.66%) at age 51-55, suggesting that longer intervals between screening would be appropriate in this group.
CONCLUSION: Measurement of PSA concentration in early midlife can identify a small group of men at increased risk of prostate cancer metastasis several decades later. Careful surveillance is warranted in these men. Given existing data on the risk of death by PSA concentration at age 60, these results suggest that three lifetime PSA tests (mid to late 40s, early 50s, and 60) are probably sufficient for at least half of men.
INTRODUCTION: Prostate Cancer Gene 3 (PCA3) is a recently described and highly specific urinary marker for prostate cancer (CaP). Its introduction in clinical practice to supplement low specificity of prostate specific antigen (PSA) can improve CaP diagnosis and follow-up. However, before its introduction, it is necessary to validate the method of PCA3 detection in distinct geographic populations.
OBJECTIVES: Our aim was to describe for the first time in Latin America, the application of the PROGENSA PCA3 assay for PCA3 detection in urine in Chilean men and its utility for CaP diagnosis in men with an indication of prostate biopsy.
MATERIALS AND METHODS: Sixty-four Chilean patients (mean age, 64 years) with indication of prostate biopsy because of elevated PSA and/or suspicious digital rectal examination (DRE) were prospectively recruited. PCA3 scores were assessed from urine samples obtained after DRE, before biopsy, and compared with PSA levels and biopsy outcome.
RESULTS: The median PSA value and mean PCA3 score were 5.8 ng/ml and 31.7, respectively. Using a cutoff PCA3 score of 35, the sensitivity and specificity for detecting CaP were 52% and 87%, respectively. The receiver operating characteristic (ROC) curve analysis showed an area under the curve of 0.77 for PCA3 and 0.57 for PSA, for the same group of patients. In patients with previous negative biopsy, PCA3 specificity increased by 2.2%.
CONCLUSIONS: This is the first report in Latin America on the use of PCA3 in diagnosing CaP. Our results are comparable to those reported in other populations in the literature, demonstrating the reproducibility of the test. PCA3 score was highly specific and we specially recommend its use in patients with persistent elevated PSA and prior negative biopsies.
PURPOSE: Contemporary patients with localized prostate cancer (PCa) are more frequently treated with radiotherapy. However, there are limited data on the effect of this treatment on cancer-specific mortality (CSM). Our objective was to test the relationship between radiotherapy and survival in men with localized PCa and compare it with those treated with observation.
METHODS: A population-based cohort identified 68,797 men with cT1-T2 PCa treated with radiotherapy or observation between the years 1992 and 2005. Propensity-score matching was used to minimize potential bias related to treatment assignment. Competing-risks analyses tested the effect of treatment type (radiotherapy vs. observation) on CSM, after accounting to other-cause mortality. All analyses were carried out within PCa risk, baseline comorbidity status, and age groups.
RESULTS: Radiotherapy was associated with more favorable 10-year CSM rates than observation in patients with high-risk PCa (8.8 vs. 14.4%, hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.50-0.68). Conversely, the beneficial effect of radiotherapy on CSM was not evident in patients with low-intermediate risk PCa (3.7 vs. 4.1%, HR: 0.91, 95% CI: 0.80-1.04). Radiotherapy was beneficial in elderly patients (5.6 vs. 7.3%, HR: 0.70, 95% CI: 0.59-0.80). Moreover, it was associated with improved CSM rates among patients with no comorbidities (5.7 vs. 6.5%, HR: 0.81, 95% CI: 0.67-0.98), one comorbidity (4.6 vs. 6.0%, HR: 0.87, 95% CI: 0.75-0.99), and more than two comorbidities (4.2 vs. 5.0%, HR: 0.79, 95% CI: 0.65-0.96).
CONCLUSIONS: Radiotherapy substantially improves CSM in patients with high-risk PCa, with little or no benefit in patients with low-/intermediate-risk PCa relative to observation. These findings must be interpreted within the context of the limitations of observational data.
OBJECTIVE: To validate the hypothesis that men displaying serum prostate-specific antigen (PSA) slopes ≤ 2.0 pg/mL/mo after prostatectomy, measured using a new immuno-polymerase chain reaction diagnostic test (NADiA ProsVue), have a reduced risk of clinical recurrence as determined by positive biopsy, imaging findings, or death from prostate cancer.
MATERIALS AND METHODS: From 4 clinical sites, we selected a cohort of 304 men who had been followed up for 17.6 years after prostatectomy for clinical recurrence. We assessed the prognostic value of a PSA slope cutpoint of 2.0 pg/mL/mo against established risk factors to identify men at low risk of clinical recurrence using uni- and multivariate Cox proportional hazards regression and Kaplan-Meier analyses.
RESULTS: The univariate hazard ratio of a PSA slope >2.0 pg/mL/mo was 18.3 (95% confidence interval 10.6-31.8) compared with a slope ≤ 2.0 pg/mL/mo (P <.0001). The median disease-free survival interval was 4.8 years vs >10 years in the 2 groups (P <.0001). The multivariate hazard ratio for PSA slope with the covariates of preprostatectomy PSA, pathologic stage, and Gleason score was 9.8 (95% confidence interval 5.4-17.8), an 89.8% risk reduction for men with PSA slopes ≤ 2.0 pg/mL/mo (P <.0001). The Gleason score (<7 vs ≥ 7) was the only other significant predictor (hazard ratio 5.4, 95% confidence interval 2.1-13.8, P = .0004).
CONCLUSION: Clinical recurrence after radical prostatectomy is difficult to predict using established risk factors. We have demonstrated that a NADiA ProsVue PSA slope of ≤ 2.0 pg/mL/mo after prostatectomy is prognostic for a reduced risk of prostate cancer recurrence and adds predictive power to the established risk factors.
CONTEXT: Wide variation exists internationally for prostate cancer (PCa) rates due to differences in detection practices, treatment, and lifestyle and genetic factors.
OBJECTIVE: We present contemporary variations in PCa incidence and mortality patterns across five continents using the most recent data from the International Agency for Research on Cancer.
EVIDENCE ACQUISITION: PCa incidence and mortality estimates for 2008 from GLOBOCAN are presented. We also examine recent trends in PCa incidence rates for 40 countries and mortality rates for 53 countries from 1985 and onward via join-point analyses using an augmented version of Cancer Incidence in Five Continents and the World Health Organization mortality database.
EVIDENCE SYNTHESIS: Estimated PCa incidence rates remain most elevated in the highest resource counties worldwide including North America, Oceania, and western and northern Europe. Mortality rates tend to be higher in less developed regions of the world including parts of South America, the Caribbean, and sub-Saharan Africa. Increasing PCa incidence rates during the most recent decade were observed in 32 of the 40 countries examined, whereas trends tended to stabilize in 8 countries. In contrast, PCa mortality rates decreased in 27 of the 53 countries under study, whereas rates increased in 16 and remained stable in 10 countries.
CONCLUSIONS: PCa incidence rates increased in nearly all countries considered in this analysis except in a few high-income countries. In contrast, the increase in PCa mortality rates mainly occurred in lower resource settings, with declines largely confined to high-resource countries.
BACKGROUND: We previously reported that a single prostate-specific antigen (PSA) measured at ages 44-50 was highly predictive of subsequent prostate cancer diagnosis in an unscreened population. Here we report an additional 7 years of follow-up. This provides replication using an independent data set and allows estimates of the association between early PSA and subsequent advanced cancer (clinical stage ≥T3 or metastases at diagnosis).
METHODS: Blood was collected from 21,277 men in a Swedish city (74% participation rate) during 1974-1986 at ages 33-50. Through 2006, prostate cancer was diagnosed in 1408 participants; we measured PSA in archived plasma for 1312 of these cases (93%) and for 3728 controls.
RESULTS: At a median follow-up of 23 years, baseline PSA was strongly associated with subsequent prostate cancer (area under the curve, 0.72; 95% CI, 0.70-0.74; for advanced cancer, 0.75; 95% CI, 0.72-0.78). Associations between PSA and prostate cancer were virtually identical for the initial and replication data sets, with 81% of advanced cases (95% CI, 77%-86%) found in men with PSA above the median (0.63 ng/mL at ages 44-50).
CONCLUSIONS: A single PSA at or before age 50 predicts advanced prostate cancer diagnosed up to 30 years later. Use of early PSA to stratify risk would allow a large group of low-risk men to be screened less often but increase frequency of testing on a more limited number of high-risk men. This is likely to improve the ratio of benefit to harm for screening.
