PSA Velocity and Doubling Time in Diagnosis and Prognosis of Prostate Cancer

Cancer is a growth process and it is natural that we should be concerned with how the routinely used marker of prostate cancer tumour burden - PSA - changes over time. Such change is measured by PSA velocity or PSA doubling time, described in general as "PSA kinetics". However, it turns out that calculation of PSA velocity and doubling time is far from straightforward. More than 20 different methods have been proposed, and many of these give quite divergent results. There is clear evidence that PSA kinetics are critical for understanding prognosis in advanced or relapsed prostate cancer. However, PSA kinetics have no value for men with an untreated prostate: neither PSA velocity nor doubling time have any role in diagnosing prostate cancer or providing a prognosis for men before treatment.     

hK2 and free PSA, a prognostic combination in predicting minimal prostate cancer in screen-detected men within the PSA range 4-10 ng/ml

OBJECTIVES: The purpose of screening for prostate cancer is to decrease the disease-specific mortality. However not every screen-detected prostate cancer is a threat to the patient's life. The risk of overdetection and subsequent overtreatment in prostate cancer has been recognised. The purpose of this investigation was to evaluate the role of tumour markers total PSA, free PSA, and hK2, and their combinations in predicting minimal prostate cancer. METHODS: Within the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam, The Netherlands, prebiopsy serum samples were analysed for 100 selected men who underwent a radical prostatectomy for their screen-detected prostate cancer. All had a PSA value between 4 and 10 ng/ml prior to diagnosis. Minimal prostate cancer is defined as organ confined, Gleason score 相似文献   

Circulating biomarkers for prostate cancer

Due to its significant applicability for early detection, risk prediction and follow-up evaluation, prostate specific antigen (PSA) has revolutionized our ability to treat prostate cancer patients. With the prevalent use of PSA for early detection during the last two decades, disease characteristics have been altered towards early detected, localized tumors with a high chance of cure following local therapy. This advantage faces the risk of overdetection and overtreatment. In addition, PSA lacks both, sensitivity and specificity to accurately detect patients at risk of prostate cancer. Therefore, novel biomarkers are urgently needed to improve identification of men at risk of having the disease and to predict the natural behaviour of the tumor. Recent advances in the evaluation of high-throughput technologies have led to the discovery of novel candidate markers for prostate cancer. This article will briefly discuss current PSA-based strategies and review several novel biomarkers for prostate cancer, detectable in blood.     

年龄≤50岁非前列腺癌男性初始PSA及PSA速度的分布特点分析

目的 探讨年龄≤50岁非前列腺癌男性初始PSA及PSA速度的分布特点.方法回顾性分析2001年1月至2009年11月初始PSA检测年龄≤50岁的非前列腺癌患者的PSA值,计算PSA检测≥2次者的PSA速度.研究不同年龄段初始PSA及PSA速度的分布范围,分析初始PSA、初始PSA年龄及PSA速度之间的相关性.用生存分析和log-rank检验比较初始PSA高于和低于中位数2组患者将来PSA≥2.5 ng/ml风险的差异.结果 4206例非前列腺癌者,初始PSA中位数为0.6 ng/ml,其中≥1.0、≥2.5和≥4.0 ng/ml者分别1026例(24.4%)、177例(4.2%)和90例(2.1%).417例PSA检测≥2次者PSA速度的中位数为0.03 ng·ml-1·y-1,其中≥0.35、≥0.75和≥2.00 ng·ml-1·y-1者分别为25例(6.0%)、13例(3.1%)和8例(1.9%).年龄与PSA、年龄与PSA速度、PSA与PSA速度之间均无明显相关性(r值分别为0.019、-0.015和-0.006,P值分别为0.218、0.754和0.897).395例PSA检测≥2次且初始PSA＜2.5 ng/ml者随访3个月～7.1年,中位时间2.0年,初始PSA高于和低于中位数2组患者将来PSA超过2.5 ng/ml的风险差异有统计学意义(P＜0.01).结论年龄≤50岁非前列腺癌男性的中位初始PSA和PSA速度分别为0.6 ng/ml 和0.03 ng·ml-1·y-1.初始PSA高于中位数的患者将来PSA超过2.5 ng/ml的风险明显增高.

Abstract：

Objective To explore the distribution and characteristics of initial PSA and PSA velocity in men younger than years without prostate cancer. Methods PSA in men younger than 50 years without prostate cancer from January 2001 to November 2009 were retrieved retrospectively from our computer center. PSA velocity was calculated if their PSA was measured twice or more. The distributions of initial PSA and PSA velocity were analyzed. The correlations between initial PSA, initial PSA age, and PSA velo-city were also analyzed. Kaplan-meier and log-rank tests were used to estimate the significant difference at the risk of PSA≥ 2.5 ng/ml after initial PSA measurement, stratified by median initial PSA (0.6 ng/ml). Results A total of 4206 men without prostate cancer were included. The median initial PSA value in these men was 0.6 ng/ml. Of these men, 1026 (24.4%), 177 (4.2%), and 90 (2.1%) had an initial PSA≥1.0, ≥2.5, and ≥4.0 ng/ml, respectively. A total of 417 men had their PSA measured these men, 25 (6.0%), 13 (3.1%), and 8 (1.9%) had a PSA velocity≥0.35, ≥0.75, initial PSA age and initial PSA, initial PSA age and PSA velocity, and initial PSA and PSA velocity (correlation coefficient r=0.019, -0.015, and -0.006, respectively; P=0.218, 0.754, and 0.897, respectively). After a follow-up of up to 7.1 years from baseline PSA measurement, the risk of PSA≥2.5 ng/ml, stratified by median initial PSA (0.6 ng/ml) was significantly different (log-rank test, P＜0.001). Conclusions The median baseline PSA and PSA velocity in men younger than 50 years old without prostate cancer are 0.6 ng/ml and 0.03 cancer with an initial PSA higher than median (0.6 ng/ml) have a subsequently higher risk of PSA value ≥2.5 ng/ml.     

Do We Need PSA and Early Detection of Prostate Cancer?

The limitations of PSA as a screening marker for diagnosis and prostate cancer treatment are well known. The low specificity of PSA results in many unnecessary prostate biopsies, furthermore high rates of overdetection and overtreatment affect patients’ quality of life. New assays measuring different molecular forms of PSA have resulted only in a moderate improvement of specificity especially beyond the PSA range of 2 to 10 ng/ml. Novel biomarkers for prostate cancer detection are emerging and they might enable clinicians to differentiate indolent from aggressive cancers in order to minimize overtreatment in future.     

PSA doubling time versus PSA velocity to predict high-risk prostate cancer: data from the Baltimore Longitudinal Study of Aging

Background

Our group has previously shown that prostate-specific antigen (PSA) velocity (PSAV) is associated with the presence of life-threatening prostate cancer. Less is known about the relative utility of pretreatment PSA doubling time (PSA DT) to predict tumor aggressiveness.

Objective

To compare the utility of PSAV and PSA DT for the prediction of life-threatening prostate cancer.

Design, setting, and participants

From the Baltimore Longitudinal Study of Aging, we identified 681 men with serial PSA measurements.

Measurements

Receiver operating characteristic analysis was used to evaluate the relationship between PSAV, PSA DT, and the presence of high-risk disease.

Results and limitations

Within the period of 5 yr prior to diagnosis, PSAV was significantly higher among men with high-risk or fatal prostate cancer than men without it. By contrast, PSA DT was not significantly associated with high-risk or fatal disease. On multivariate analysis, including age, date of diagnosis, and PSA, the addition of PSAV significantly improved the concordance index from 0.85 to 0.88 (p < 0.001), whereas PSA DT did not.

Conclusions

These data suggest that PSAV is more useful than PSA DT in the pretreatment setting to help identify those men with life-threatening disease.     

Prostate cancer detection in men with a 'normal' total prostate-specific antigen (PSA) level using percentage free PSA: a prospective screening study

OBJECTIVE: To assess the utility of percentage free/total prostate-specific antigen (f/tPSA) levels for detecting prostate cancer in a prospectively screened population of men with a 'normal' total PSA level. PATIENTS AND METHODS: Men aged 50-65 years were contacted via their general practitioner and invited for prostate cancer screening. All had their total and f/tPSA levels measured; those meeting the biopsy criteria (PSA 1.1-3.99 ng/mL and f/tPSA < or = 20%) were offered a biopsy. The cancer detection rate was then evaluated and compared with other methods of detection. In all, 773 men were screened, of whom 115 met the criteria and agreed to undergo a prostate biopsy. RESULTS: Cancer was detected in 13 of the 115 men (11.3%) of whom most would have been missed by lowering the age-adjusted threshold for total PSA to 2.5 ng/mL. There was no significant difference in total and f/tPSA values in men with and without prostate cancer. Those cancers that could be evaluated were found to be clinically significant. CONCLUSION: In this study prostate cancer was detected solely on the basis of a low f/tPSA value. Most men with cancer would have been missed by simply lowering the age-adjusted threshold for total PSA. Using the f/tPSA level may allow the detection of clinically significant cancer in men at a time when they are most likely to benefit from treatment.     

Longitudinal PSA changes in men with and without prostate cancer: assessment of prostate cancer risk

BACKGROUND: To determine longitudinal PSA changes over a period of 10 years in patients with and without prostate cancer. METHODS: Serial PSA measurements performed over 10 years were evaluated in 353 men who eventually developed prostate cancer and in 2.462 participants of a screening program without prostatic malignancy. RESULTS: In men with cancer, mean tPSA increased from 2.28 ng/ml at 10 years before diagnosis to 6.37 ng/ml at the time of postive biopsy (PSA velocity: 0.409 ng/ml/year). PSA velocity was significantly associated with Gleason scores and pathologic stage. In the benign group (n=2.462), mean tPSA increased from 1.18 to 1.49 ng/ml over a period of 10 years (PSA velocity of 0.03 ng/ml/year). Of the subjects with tPSA levels of 2 ng/ml or less, 2 years prior to cancer diagnosis, 11.4% had tPSA values of more than 4 ng/ml at the time of biopsy. Of the 972 men with tPSA below 1 ng/ml 2 years before the most recent measurement was obtained, 966 (99.4%) had no evidence of prostate cancer 2 years later, while six were found to have malignancies (0.6%). CONCLUSIONS: Longitudinal PSA changes in men with and without prostate cancer are significantly different. Annual testing may not be required in men with baseline tPSA levels of 1 ng/ml or below, whereas in patients with levels higher than 1 ng/ml, it seems to be indicated because of the significant percentage of men presenting with tPSA levels of more than 4 ng/ml two years later.     

Characteristics of prostate cancers detected at low PSA levels

BACKGROUND: When age-referenced PSA levels as recommended by Oesterling et al.1 were used as a biopsy criterion, only 25% of the cancers detected in a population based PSA Screening Project were organ-confined. This observation led to the decision to use low PSA levels as the sole indication for biopsy. Since 1995 age-referenced PSA levels of 1.25-3.25 ng/ml have been used in combination with a percentage free PSA cutoff of 18%. This PSA cutoff reduction led to a statistically significant migration to lower pathological stages with a decreased prostate cancer mortality in the years 1996-2001. However, concerns have been raised that screening with low PSA levels may detect clinically insignificant cancers. MATERIALS AND METHODS: We evaluated prostate cancer patients with low PSA levels in terms of heterogeneity, clinical significance, multifocality, and tumor biology including ploidy and proliferation index. RESULTS: Concerning heterogeneity the Gleason score of the needle biopsy failed to predict the Gleason score of the radical prostatectomy specimen in nearly 40% of prostate cancer patients; regarding multifocality 65% of patients with low PSA levels showed multifocal lesions and 36% exhibited tetraploid DNA distribution; more than 50% of tetraploid tumors were found in patients with tumor volumes of less than 0.5 cm(3). Ploidy correlated with the Ki-67 proliferation index, but not with tumor volume. CONCLUSIONS: These results demonstrate that small prostate cancers with low PSA levels and low tumor volumes exhibit all features of prostate cancers with higher tumor volumes and show the characteristics of malignant cancers, i.e., multifocality, tetraploidy, and high proliferative activity.     

Prostate-specific antigen kinetics in clinical decision-making during active surveillance for early prostate cancer--a review

CONTEXT: The kinetics of prostate specific antigen (PSA) are generally assumed to be indicative of tumour progression and are therefore used in clinical decision-making in men on active surveillance for early prostate cancer. OBJECTIVE: This review aims to provide support for exploiting PSA kinetics in an active surveillance setting. EVIDENCE ACQUISITION: We searched the Medline database and reviewed the evidence on both the relation between PSA kinetics before radical treatment for prostate cancer and outcome, as well as the role of PSA kinetics during active surveillance. Furthermore, the benefits and setbacks of different derivatives of PSA kinetics, minimum required time interval and number of measurements, practical recommendations, and pitfalls of their use in clinical practice are discussed. EVIDENCE SYNTHESIS: The evidence concerning the prognostic value of the PSA velocity (PSA-V) and PSA doubling time (PSA-DT) is sparse, especially in active surveillance. PSA kinetics should therefore be combined with other diagnostic measures as the trigger for deferred radical treatment or repeat prostate biopsies. There seems to be consensus among several reports on the unfavourable outcome relating to a PSA-DT <3-4 yr and on the favourable prognostic value of a PSA-DT >10 yr or a decreasing PSA level. Online tools provide help with calculations and insight on disease development. The best method of calculation, number of measurements, and time interval between measurements is unknown for now. CONCLUSIONS: Despite the current deficits in our understanding of the natural behaviour of early prostate cancer and its relation to serum PSA levels, and despite several secondary factors playing a role in PSA kinetics, PSA kinetics are a practical parameter we can offer men on active surveillance to assess the status of their disease.     

The issue of prostate cancer evaluation in men with elevated prostate-specific antigen and chronic prostatitis

Elevated levels of prostate-specific antigen (PSA) in men may result from a variety of causes, such as prostate cancer, benign prostatic hyperplasia, acute urinary tract infection, and bacterial prostatitis. In recent years, several studies have also demonstrated a relationship between chronic prostatitis/chronic pelvic pain syndrome and increased PSA levels. However, asymptomatic patients are not routinely screened for this diagnosis before transrectal biopsy is performed to rule out prostate cancer. These asymptomatic men with elevated PSA levels frequently have evidence of inflammation when their expressed prostatic secretions are examined, or on their prostate biopsy specimens. This raises the problem of appropriate evaluation in the presence of chronic prostatitis and elevated PSA levels--not only in prostate cancer screening programmes, but also in cancer-negative biopsy findings. Evidence from the literature indicates that antimicrobial treatment may lower the PSA levels to what is considered the normal range. Despite that, general recommendations for the practical management are lacking and undetected prostate cancer in men with chronic prostatitis remains a difficult issue.     

PSA-based prostate cancer screening: the role of active surveillance and informed and shared decision making

Since the first publication describing the identification of prostate-specific antigen (PSA) in the 1960s, much progress has been made. The PSA test changed from being initially a monitoring tool to being also used as a diagnostic tool. Over time, the test has been heavily debated due to its lack of sensitivity and specificity. However, up to now the PSA test is still the only biomarker for the detection and monitoring of prostate cancer. PSA-based screening for prostate cancer is associated with a high proportion of unnecessary testing and overdiagnosis with subsequent overtreatment. In the early years of screening for prostate cancer, high rates of uptake were very important. However, over time the opinion on PSA-based screening has shifted towards the notion of informed choice. Nowadays, it is thought to be unethical to screen men without them being aware of the pros and cons of PSA testing, as well as the fact that an informed choice is related to better patient outcomes. Now, as the results of three major screening studies have been presented and the downsides of screening are becoming better understood, informed choice is becoming more relevant.     

The complexity of PSA interpretation in clinical practice

Prostate specific antigen (PSA) is central to the diagnosis of prostate cancer. Laboratories quote cut-off reference ranges for PSA but values within these boundaries do not equate with an absence of cancer nor do levels above the range equate with its presence. Convention places the cut-off value at 4 μg/L when calibrated to the Hybritech immunoassay technology and 3.0 or 3.1 μg/L if the PSA methods are calibrated to the WHO IRP 96/670 standard. The prevalence of prostate cancer in screened normal men over 55 years of age with PSA values less than 4 μg/L (Hybritech method) is 10.1% at a PSA of 0.6–1.0 μg/L. About 12.5% of these will be high grade. Two major randomised trials reported on PSA screening. The European trial (ERSPC) reported a risk reduction for prostate cancer death of 21% in the screened group but the US PLCO trial found no benefit. PSA results depend on calibration and there is a 22% difference between the older Hybritech and newer WHO standardisation. Biological variation in PSA is a geometric mean of 7.3%. External quality assessment schemes show wide variation in the performance of PSA analysis. Neither the American College of Physicians nor the UK National Health Service recommends screening except when there is increased risk through family history or ethnicity. Laboratories should detail their method calibration in each report and clinicians should be alerted to the potential misclassification of patients through PSA variation.     

The impact of PSA testing frequency on prostate cancer incidence and treatment in older men

To quantify the downstream impact of PSA testing on cancer characteristics and utilization of cancer therapies among men aged 70 or older, we utilized patients diagnosed with prostate cancer in 2004-2005 in the Surveillance, Epidemiology and End Results (SEER)-Medicare and their Medicare claims before their cancer diagnosis during 2000-2005. Among men in the highest testing group (4-6 PSA tests), 75% were diagnosed with low- or intermediate-risk of disease, but 77% received treatments within 180 days of cancer diagnosis. More than 45% of newly diagnosed patients in 2004-2005 had 4-6 PSA tests before their cancer diagnosis during 2000-2005. Men in the high testing group were 3.57 times more likely to receive cancer treatments (either surgery, radiation or hormonal therapy) when compared with men who had no previous PSA testing during the same time period. Among men aged 75+ diagnosed with low-risk cancer, men in the high testing group were 78% more likely to receive treatment than those who had no previous PSA testing. In conclusion, given the lack of evidence of effective treatment for elderly patients diagnosed with low- and intermediate-risk prostate cancer and our inability to distinguish indolent from aggressive cancer, more frequent PSA testing among elderly population may exacerbate the risk of overdiagnosis and overtreatment.     

Possibility of re-screening intervals of more than one year in men with PSA levels of 4.0 ng/ml or less

BACKGROUND: The optimal re-screening interval is one of the most important issues to evaluate the effectiveness of screening for prostate cancer. METHODS: Between 1992 and 2000, 7,026 men aged 50-78 with baseline PSA levels of 4.0 ng/ml or lower underwent screening for prostate cancer twice or more. The risk of developing prostate cancer relative to elapsed years and baseline PSA levels were investigated. RESULTS: Prostate cancer was detected in a total of 127 cases (1.8%). The detection rate of prostate cancer was high between 1.6% and 5.5% at 1 year after baseline PSA measurements in men with baseline PSA levels of 2.1-4.0 ng/ml. In men with baseline PSA levels of 1.1- 2.0 ng/ml, the detection rate increased from 0.06% to 1.02% with passed years. The proportion of stage >/=T3 was high at 63% in prostate cancer cases detected between 3 and 4 years after baseline PSA levels being 1.1-2.0 ng/ml. In men with baseline PSA levels of 1.0 or lower, the cumulative detection rate of prostate cancer was low at 0.01% within 3 years, however, the detection rate increased to 0.34% after 5 or more years from baseline PSA measurements. CONCLUSIONS: The re-screening interval was recommended to be 1, 1-2, and 3-5 years for men with baseline PSA levels of 2.1-4.0 ng/ml, 1.1-2.0 ng/ml, and 1.0 ng/ml or lower, respectively.     

Establishing normal reference ranges for PSA change with age in a population-based study: The Krimpen study

BACKGROUND: We aim to establish the normal pattern of prostate specific antigen (PSA) change with age to provide a baseline from which disease progression might be identified in prostate cancer patients included in active surveillance programs. METHODS: In a community-based study, PSA values were determined at baseline and after 2.1 and 4.2 years in men without prostate cancer. A bivariate multilevel growth curve model was used to estimate the pattern of change of PSA with age. RESULTS: The final model showed that PSA was related to age only. The future PSA of an individual can be predicted based on his age and known history of PSA. The model was also used to calculate PSA doubling time for men with different PSA values at different ages. CONCLUSIONS: This method establishes normal PSA levels by age using PSA history in men without prostate cancer. The model provides baseline data from which disease progression might be detected.     

Correlation of serum PSA and Gleason score in Nigerian men with prostate cancer

Objective  Prostate cancer is an important cause of morbidity and mortality worldwide. While the predisposing factors are not fully understood, African descent is an important risk factor, and prostate cancer has become the number-one cancer in Nigerian men. This was a retrospective study of the correlation between serum prostate specific antigen (PSA) and Gleason grade and score in patients of Nigerian descent. Patients and Methods  The University College Hospital (UCH) Ibadan Cancer Registry was used to identify and quantify the incidence of prostate cancers occurring between 1998 and 2000. The histological slides of appropriate cases were reviewed to confirm the Gleason grade and score. The serum PSA values were retrieved from the patients' case notes and laboratory files. The data obtained were subjected to statistical analysis to look for associations and correlations. Results  The study included 67 men with prostate adenocarcinoma and PSA measurements who were diagnosed and treated at the UCH Ibadan between January 1998 and December 2000. There was a positive correlation between serum PSA and Gleason grade, as well as between serum PSA and Gleason score in our cohort of Nigerian African men with prostate cancer. PSA levels were significantly lower in patients with stage B disease than in patients with stage D disease. Conclusion  Serum PSA is significantly higher in metastatic than in localized disease. Further studies are necessary to determine biomarkers that complement serum PSA and the Gleason grading system in the prognostication of prostate cancer in African patients.     

Racial differences in serum prostate-specific antigen (PSA) doubling time, histopathological variables and long-term PSA recurrence between African-American and white American men undergoing radical prostatectomy for clinically localized prostate cancer

OBJECTIVE: To determine if there are significant differences in biochemical characteristics, biopsy variables, histopathological data, and rates of prostate-specific antigen (PSA) recurrence between African-American (AA) and white American (WA) men undergoing radical prostatectomy (RP), as AA men are twice as likely to die from prostate cancer than their white counterparts. PATIENTS AND METHODS: We established a cohort of 1058 patients (402 AA, 646 WA) who had RP and were followed for PSA recurrence. Age, race, serum PSA, biopsy Gleason score, clinical stage, pathological stage, and PSA recurrence data were available for the cohort. The chi-square test of proportions and t-tests were used to assess basic associations with race, and log-rank tests and Cox regression models for time to PSA recurrence. Forward stepwise variable selection was used to assess the effect on the risk of PSA recurrence for race, adjusted by the other variables added one at a time. RESULTS: The AA men had higher baseline PSA levels, more high-grade prostatic intraepithelial neoplasia (HGPIN) in the biopsy, and more HGPIN in the pathology specimen than WA men. The AA men also had a shorter mean (sd) PSA doubling time before RP, at 4.2 (4.7) vs 5.2 (5.9) years. However, race was not an independent predictor of PSA recurrence (P = 0.225). Important predictors for PSA recurrence in a multivariable model were biopsy HGPIN (P < 0.014), unilateral vs bilateral cancer (P < 0.006), pathology Gleason score and positive margin status (both P < 0.001). CONCLUSIONS: This study indicates that while there are racial differences in baseline serum PSA and incidence of HGPIN, race is not an independent risk factor for PSA recurrence. Rather, other variables such as pathology Gleason score, bilateral cancers, HGPIN and margin positivity are independently associated with PSA recurrence. The PSA doubling time after recurrence may also be important, leading to the increased mortality of AA men with prostate cancer.     

Early detection of prostate cancer in 2007. Part 1: PSA and PSA kinetics

OBJECTIVE: This is the first of two review papers attempting to clarify the best way to detect prostate cancer (PCa) in 2007. Screening for PCa has not yet been shown to lower PCa mortality. Still, opportunistic screening is wide spread in Europe and in most other parts of the world. METHODS: Current literature and data from screening studies are reviewed and discussed. Prostate-specific antigen (PSA) has been and remains one of the corner stones of early detection of PCa. Traditionally used cut-off values cannot be applied in an uncritical fashion after it was shown that a significant amount of overdiagnosis and that large proportions of cancers and poorly differentiated cancers are present in the low PSA ranges. The paper addresses the continued relevance of PSA cut-off values. The diagnostic value of PSA velocity is reviewed in conjunction with PSA cut-off values and as a possible replacement of total PSA. A need for more selective screening in the low PSA ranges is pointed out. RESULTS AND CONCLUSIONS: The data show that men presenting initially with PSA values below 1 do not have to be rescreened for a period of 8 yr. In the PSA range 1-2.9 ng/ml, new parameters are needed that improve specificity and are selective for screening for aggressive lesions. PSA velocity so far has not been shown to be useful in the early detection of PCa but may be useful in detecting aggressive PCa selectively. For the time being, it seems sensible to continue using PSA cut-off values such as 3.0 or 4.0 ng/ml provided overtreatment is decreased by using available nomograms.     

Annual PSA tests are not necessary for men with a PSA level below 2 ng/mL: Findings of the Imari prostate cancer screening program

BACKGROUND: Annual changes in prostate specific antigen (PSA) levels detected by the Imari prostate cancer screening program were evaluated to establish a more efficient and cost-saving screening system, especially for men with low PSA levels. METHODS: Prostate specific antigen-based annual mass screenings for prostate cancer were conducted for men aged 60-69 in the Imari district, Saga, Japan. Between 1992 and 2000, 1822 men had their PSA levels tested. A total of 4661 PSA tests were conducted. Changes in PSA levels over the following 1 to 5 years were analyzed in men with PSA levels of 3 ng/mL or less, a range in which the detection rate of prostate cancer would seem to be negligibly low. RESULTS: The overall detection rate of prostate cancer between 1992 and 2000 was 0.73%. The detection rate in men with a PSA level between 3.1 and 3.9 ng/mL, and between 4 and 9.9 ng/mL was 1.6% and 8.3%, respectively. Of 4661 determinations of PSA, 2553 (54.8%) were found to be < or = 1 ng/mL, 1273 (27.3%) were between 1.1 and 2 ng/mL, and 401 (8.6%) were between 2.1 and 3 ng/mL. Four hundred and thirty-four men (9.3%) had PSA levels > or = 3.1 ng/mL, with possible indications for prostate biopsy. Of the men tested, 1.4% with an initial PSA level of < or = 2 ng/mL and 22.3% with an initial level between 2.1 and 3 ng/mL had a PSA level of > or = 3.1 ng/mL after 1 year. Almost the same rate of PSA increase was observed between the two PSA tests conducted at 2 to 5-year intervals. Of the men tested, 2.2% with an initial PSA level of < or = 2 ng/mL, and 21.9% with an initial level between 2.1 and 3 ng/mL, had a level of > or = 3.1 ng/mL after 5 years. CONCLUSION: Levels of PSA in men with an initial level below 2 ng/mL remained stable for up to 5 years. Levels of PSA in 97.8- 98.8% of men remained below 3 ng/mL after 1 to 5 years. In contrast, 18-35.3% of men with an initial PSA level between 2.1 and 3 ng/mL showed PSA progression to 3.1 ng/mL or more within 5 years. Our present data suggest that annual PSA testing is not necessary for men with a PSA level below 2 ng/mL. Prostate specific antigen testing could therefore be conducted at longer intervals in such individuals.