Effect of age, family history of prostate cancer, prostate enlargement and seasonality on PSA levels in a contemporary cohort of healthy Italian subjects

We assessed the joint effect of age at enrollment, age at follow-up, family history of prostate cancer, prostate enlargement and seasonality on prostate-specific antigen (PSA) estimated through log-normal mixed-effects modeling in an Italian cohort of healthy, 45- to 65-year-old subjects over a 4-year period. The median ratio was used as the measure of effect. Median and mean baseline PSA were 0.78 (interquartile range: 0.41-1.50) and 1.27 (95% CI: 1.19-1.35) ng/mL, respectively. A similar median annual increase of 5.7% (95% CI: 4.8%-6.5%) was found for age at enrollment and age at follow-up. Individuals with moderate to severe prostate enlargement had a median PSA ratio of 1.040 (95% CI: 0.919-1.176) and 1.318 (95% CI: 1.128-1.539), respectively. Median ratios of 1.200 (95% CI: 0.026-1.404) and 1.300 (95% CI: 0.915-1.845), respectively, were computed for subjects with only one or more than one prostate-cancer-affected relatives. Regarding seasonality, the highest value was shown in summertime, the lowest in wintertime, and the resulting median ratio was 1.280 (95% CI: 1.117-1.468). Irrespective of age, baseline PSA was in most cases about 1.00 ng/mL with a yearly median variation of about 5% over a 4-year period. Indeed, prostate enlargement, prostate cancer family history and seasonality showed a remarkable impact on PSA measurement. This should be considered when counseling patients with a PSA history.     

Lifestyle factors and prostate-specific antigen (PSA) testing in UK Biobank: Implications for epidemiological research

BackgroundThe central role of prostate-specific antigen (PSA) testing in the diagnosis of prostate cancer leads to the possibility that observational studies that report associations between risk factors and prostate cancer could be affected by detection bias. This study aims to investigate whether reported risk factors for prostate cancer are associated with PSA testing in a large middle-aged population-based cohort in the UK.MethodsThe cross-sectional association between a wide range of sociodemographic, lifestyle, dietary and health characteristics with PSA testing was examined in 212,039 men aged 40–69 years in UK Biobank.ResultsA total of 62,022 (29%) men reported they had ever had a PSA test. A wide range of factors was associated with a higher likelihood of PSA testing including age, height, education level, family history of prostate cancer, black ethnic origin, not being in paid/self-employment, living with a wife or partner, having had a vasectomy, being diagnosed with cancer or hypertension and having a high dietary intake of cereal, cooked and salad/raw vegetables, fresh fruit and tea. Conversely, socioeconomic deprivation, Asian ethnic origin, current smoking, low alcohol intake, high body-mass index, high coffee consumption and being diagnosed with diabetes, heart disease or stroke were associated with a lower likelihood of PSA testing.ConclusionsA variety of sociodemographic, lifestyle and health-related characteristics are associated with PSA testing, suggesting that observed associations of some of these traits with risk for prostate cancer in epidemiological studies may be, at least partially, due to detection bias.     

Is Anyone Listening? Variation in PSA Screening among Providers for Men 75+ before and after United States Preventive Services Task Force Recommendations against It: A Retrospective Cohort Study

Background

In 2008, the United States Preventive Services Task Force recommended against prostate specific antigen (PSA) testing for cancer screening in men age 75+.

Purpose

To assess PSA screening by primary care physicians (PCPs) before and after recommendations.

Methods

In 2013, this retrospective cohort study analyzed PCPs in Texas with 20+ male patients aged 75+ in both 2007 and 2010, with Parts A and B Medicare. The main outcome was percent of PCP’s male patients 75+ who received PSA testing ordered by the PCP in 2007 and 2010, with no recent symptoms suggestive of prostate cancer.

Results

In both 2007 and 2010, 1,083 PCPs cared for at least 20 men aged 75 or older. The rate of PSA screening ordered by PCPs was 33.2% in 2007 and 30.6% in 2010. In multilevel analyses controlling for patient characteristics, the variation in PSA screening attributable to the PCP (intraclass correlation coefficient) increased from 23% in 2007 to 26% in 2010, p<0.001. Men with PCPs older than age 60 had 9% lower odds (95% CI, 1–17%) in 2010 compared to 2007 of receiving a PSA test, vs. a 4% increase (95% CI, 4% decrease to 12% increase) in men with PCPs aged 50 or younger. Patients with Board Certified PCPs had a 12% lower odds (95% CI, 8% to 16%) from 2007 to 2010, vs. 2% increase (95% CI 11% decrease to 18% increase) in men with PCPs without board certification.

Conclusions

The USPSTF recommendation did not increase consensus among PCPs regarding PSA screening of older men.     

Changes in prostate cancer incidence,mortality and survival in relation to prostate specific antigen testing in New South Wales,Australia

BackgroundTo examine changes in prostate cancer incidence and mortality rates, and 5-year relative survival, in relation to changes in the rate of prostate specific antigen (PSA) screening tests and the use of radical prostatectomy (RP) in the Australian population.MethodsProstate cancer stage-specific incidence rates, 5-year relative survival and mortality rates were estimated using New South Wales Cancer Registry data. PSA screening test rates and RP/Incidence ratios were estimated from Medicare Benefits Schedule claims data. We used multiple imputation to impute stage for cases with “unknown” stage at diagnosis. Annual percentage changes (APC) in rates were estimated using Joinpoint regression.ResultsTrends in the age-standardized incidence rates for localized disease largely mirrored the trends in PSA screening test rates, with a substantial ‘spike’ in the rates occurring in 1994, followed by a second ‘spike’ in 2008, and then a significant decrease from 2008 to 2015 (APC −6.7, 95% CI −8.2, −5.1). Increasing trends in incidence rates were observed for regional stage from the early 2000s, while decreasing or stable trends were observed for distant stage since 1993. The overall RP/Incidence ratio increased from 1998 to 2003 (APC 9.6, 95% CI 3.8, 15.6), then remained relatively stable to 2015. The overall 5-year relative survival for prostate cancer increased from 58.4% (95% CI: 55.0–61.7%) in 1981–1985 to 91.3% (95% CI: 90.5–92.1%) in 2011–2015. Prostate cancer mortality rates decreased from 1990 onwards (1990–2006: APC −1.7, 95% CI −2.1, −1.2; 2006–2017: APC −3.8, 95% CI −4.4, −3.1).ConclusionsOverall, there was a decrease in the incidence rate of localized prostate cancer after 2008, an increase in survival over time and a decrease in the mortality rate since the 1990s. This seems to indicate that the more conservative use of PSA screening tests in clinical practice since 2008 has not had a negative impact on population-wide prostate cancer outcomes.     

The 4Kscore? Test Reduces Prostate Biopsy Rates in Community and Academic Urology Practices

There is significant concern regarding prostate cancer screening because of the potential for overdiagnosis and overtreatment of men who are discovered to have abnormal prostate specific antigen (PSA) levels and/or digital rectal examination (DRE) results. The 4Kscore® Test (OPKO Diagnostics, LLC) is a blood test that utilizes four kallikrein levels plus clinical information in an algorithm to calculate an individual’s percentage risk (< 1% to > 95%) for aggressive prostate cancer (Gleason score ≥ 7) on prostate biopsy. The 4Kscore Test, as a follow-up test after abnormal PSA and/or DRE test results, has been shown to improve the specificity for predicting the risk of aggressive prostate cancer and reduce unnecessary prostate biopsies. A clinical utility study was conducted to assess the influence of the 4Kscore Test on the decision to perform prostate biopsies in men referred to urologists for abnormal PSA and/or DRE results. The study population included 611 patients seen by 35 academic and community urologists in the United States. Urologists ordered the 4Kscore Test as part of their assessment of men referred for abnormal PSA and/or DRE test results. Results for the patients were stratified into low risk (< 7.5%), intermediate risk (7.5%–19.9%), and high risk (≥ 20%) for aggressive prostate cancer. The 4Kscore Test results influenced biopsy decisions in 88.7% of the men. Performing the 4Kscore Test resulted in a 64.6% reduction in prostate biopsies in patients; the actual percentage of cases not proceeding to biopsy were 94.0%, 52.9%, and 19.0% for men who had low-, intermediate-, and high-risk 4Kscore Test results, respectively. A higher 4Kscore Test was associated with greater likelihood of having a prostate biopsy (P < 0.001). Among the 171 patients who had a biopsy, the 4Kscore risk category is strongly associated with biopsy pathology. The 4Kscore Test, as a follow-up test for an abnormal PSA and/or DRE results, significantly influenced the physician and patient shared decision in clinical practice, which led to a reduction in prostate biopsies while increasing the probability of detecting aggressive cancer.Key Words: Prostate cancer, Prostate-specific antigen, Digital rectal examination, Biopsy rate, Gleason score, 4Kscore Test, Prostate cancer prognosisWidespread screening for prostate cancer with serum prostate-specific antigen (PSA) began in 1991, and subsequently a 45% decline in prostate cancer mortality has been observed.¹ A recent large European randomized clinical trial also reported a 29% reduction in death from prostate cancer in men undergoing routine screening.² However, because of a US study that showed no mortality benefits to organized PSA screening,³ and the net physical and psychologic burden of secondary adverse events triggered by PSA testing versus the number of lives saved, the United States Preventative Services Task Force (USPSTF) recently advised against routine PSA screening for prostate cancer.⁴ The concern of the USPSTF is based on the fact that most men diagnosed with prostate cancer have a tumor that is unlikely to pose a threat to life expectancy. A recent systematic analysis suggested that up to 60% of prostate cancers diagnosed in contemporary studies might be safely observed without a need for immediate intervention.⁵One of the primary challenges for urologists is the potential for under-grading of Gleason 6 prostate cancer due to biopsy sampling error; as a result, up to 90% of men with a Gleason 6 prostate cancer still proceed to prostate cancer treatment despite the advent of active surveillance programs. Approximately 66% of patients who are diagnosed with Gleason 6 disease at biopsy will be confirmed to have Gleason 6 cancer after radical prostatectomy.⁶ Some of these men are considered to have undergone overtreatment, because Gleason 6 cancer is not considered life threatening.⁷ This subset of men has the potential for developing complications following surgery, including erectile dysfunction, urinary incontinence, and changes in health-related quality of life with disruption of psychologic, sexual, and urinary function.^8–12The prostate biopsy procedure is invasive, and has significant costs and complications such as bleeding, urinary retention, and life-threatening infection. A recent population-based study from Ontario, Canada, revealed a fourfold increase to 4.1% for the rate of hospital admissions after prostate biopsy from 1996 to 2005, with 72% of admissions due to infection.¹³ These risks, combined with the anxiety involved in undergoing the procedure, present a significant burden to any man considering prostate cancer screening.The impact of the USPSTF has been a decrease in overall biopsy rates with a subsequent decline in the detection rate of Gleason 7 to 10 high-grade prostate cancers.¹⁴ The elimination of PSA screening means that the 20% to 30% of men who would have presented with an abnormal PSA level and been found to have high-grade prostate cancer may lose an opportunity for a possible cure.¹⁵ Clearly, there is a need for better risk-stratification tools for men presenting with an abnormal PSA level and/or digital rectal examination (DRE) result in order to both reduce the number of prostate biopsies performed and decrease the rate of Gleason 6 diagnosis and treatment.⁶The 4Kscore® Test (OPKO Diagnostics, LLC) incorporates measured blood levels of four kallikrein proteins: total PSA, free PSA, intact PSA, and human kallikrein 2 plus clinical information (age, DRE findings, and a history of prior negative biopsy result) into a proprietary algorithm to calculate an individual man’s percentage risk (< 1% to > 95%) of having Gleason score ≥ 7 if a prostate biopsy were to be performed. The 4Kscore Test has been extensively validated through a total of 12 prospective and retrospective studies published in peer-reviewed journals involving over 22,000 patients from both the United States and Europe.^16–23 These studies of men with elevated PSA levels involved cohorts of unscreened and screened men, and those with negative prior prostate biopsy results. Based on analyses published in these studies, the 4Kscore Test would have theoretically resulted in a 45% reduction in prostate biopsies while delaying the diagnosis of aggressive prostate cancer in only a few men (1.3%–4.7%).The 4Kscore Test is used to accurately determine percentage risk for aggressive prostate cancer (Gleason score ≥ 7) and provide additional information for men being considered for prostate biopsy because of abnormal PSA levels and/or DRE results. This allows urologists to better risk stratify men for biopsy and ultimately results in more selective treatment of those men with aggressive disease. Conversely, those men not harboring life-threatening disease are able to safely avoid prostate biopsy and overtreatment of indolent disease.With the introduction of any new diagnostic test such as the 4Kscore Test into clinical practice, it is important to assess whether its implementation, in this case as a follow-up test for an abnormal PSA and/or DRE result, influences and changes the physician-patient shared decision-making process and leads to an actual reduction in prostate biopsies. Herein we evaluated the influence of the 4Kscore Test on urologist-patient decisions about proceeding with biopsy in men who have an abnormal PSA and/or DRE result from multiple academic and community urology clinical practices in the United States.     

Trends in Prostate Specific Antigen (PSA) testing and prostate cancer incidence and mortality in Australia: A critical analysis

BackgroundPopulation trends in PSA testing and prostate cancer incidence do not perfectly correspond. We aimed to better understand relationships between trends in PSA testing, prostate cancer incidence and mortality in Australia and factors that influence them.MethodsWe calculated and described standardised time trends in PSA tests, prostate biopsies, treatment of benign prostatic hypertrophy (BPH) and prostate cancer incidence and mortality in Australia in men aged 45–74, 75–84, and 85 + years.ResultsPSA testing increased from its introduction in 1989 to a peak in 2008 before declining in men aged 45–84 years. Prostate biopsies and cancer incidence fell from 1995 to 2000 in parallel with decrease in trans-urethral resections of the prostate (TURP) and, latterly, changes in pharmaceutical management of BPH. After 2000, changes in biopsies and incidence paralleled changes in PSA screening in men 45–84 years, while in men ≥85 years biopsy rates stabilised, and incidence fell. Prostate cancer mortality in men aged 45–74 years remained low throughout. Mortality in men 75–84 years gradually increased until mid 1990s, then gradually decreased. Mortality in men ≥ 85 years increased until mid 1990s, then stabilised.ConclusionAge specific prostate cancer incidence largely mirrors PSA testing rates. Most deviation from this pattern may be explained by less use of TURP in management of BPH and consequent less incidental cancer detection in TURP tissue specimens. Mortality from prostate cancer initially rose and then fell below what it was when PSA testing began. Its initial rise and fall may be explained by a possible initial tendency to over-attribute deaths of uncertain cause in older men with a diagnosis of prostate cancer to prostate cancer. Decreases in mortality rates were many fold smaller than the increases in incidence, suggesting substantial overdiagnosis of prostate cancer after introduction of PSA testing.     

Newer potential biomarkers in prostate cancer

Prostate-specific antigen (PSA) screening has led to a significant rise in the number of men diagnosed with prostate cancer and an associated increase in biopsies performed. Despite its limitations, including a positive predictive value of only 25%-40%, PSA remains the only generally accepted biomarker for prostate cancer. There is a need for better tools to not only identify men with prostate cancer, but also to recognize those with potentially lethal disease who will benefit from intervention. A great deal of work has been done worldwide to improve our knowledge of the genetics behind prostate cancer and the specificity of PSA by developing assays for different PSA isoforms. Common genetic alterations in prostate cancer patients have been identified, including CpG hypermethylation of GSPT1 and TMPRSS2:ERG gene fusion. Serum and urine detection of RNA biomarkers (eg, PCA3) and prostate cancer tissue protein antibodies (eg, EPCA) are being evaluated for detection and prognostic tools. This article reviews some of the promising developments in biomarkers.     

Evaluation of the needs of male carriers of mutations in BRCA1 or BRCA2 who have undergone genetic counseling

To date, the concerns of men at risk of inheriting a BRCA1 mutation or a BRCA2 mutation have received little attention. It had been anticipated that few men would be interested in predictive testing when a BRCA mutation was identified in their family. However, these men are often affected emotionally by diagnoses of breast cancer in their relatives and may themselves harbor fears that cancer will develop. Male carriers of BRCA1/2 mutations are at increased risk of development of cancers of several types, including those of the breast and prostate. We conducted an evaluation of the needs and experiences of 59 male carriers of BRCA1/2 mutations followed at either the University of Toronto or Creighton University. We assessed their motivations for seeking genetic counseling and testing, involvement in family discussions of breast and ovarian cancer, risk perception, changes in cancer-screening practices, and overall satisfaction with the genetic-counseling process. The principal motivation for seeking genetic counseling was concern for their daughters. The majority (88%) of men participated in family conversations about breast and ovarian cancer, and 47% participated in conversations about prophylactic surgery. Most men believed that they were at increased risk of development of cancer (prostate, breast, colorectal, and skin cancers). However, fewer than one-half (43%) of the men with no previous diagnosis of cancer stated that their prostate cancer-surveillance practices had changed after they had received genetic test results. More than one-half (55%) had intrusive thoughts about their cancer risk. Although levels of satisfaction were high, practitioners should be aware of (a) potential pressures influencing men to request predictive testing, (b) the difficulties that men encounter in establishing surveillance regimens for breast and prostate cancer, and (c) the general lack of information about men's particular experiences in the medical community.     

The contribution of prostatic acid phosphatase and prostatic specific antigen in the diagnosis of prostatic cancer

Prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) were measured by immunochemical methods using test preparations from two different companies. In 66 patients with benign hyperplasia of the prostate a good correlation was found only between PSA levels (orthogonal regression analysis: y = 1.77 x -0.68; r = 0.995). Discrimination analysis between benign hyperplasia and new prostatic cancer (28 patients), using ROC curves, revealed a sensitivity for prostatic cancer of about 30 percent using both PAP methods and of about 58 percent using both PSA methods at the 95-percentile of benign hyperplasia. The PSA methods were both more sensitive in detecting prostatic cancer than the PAP methods.     

Prostate Cancer Specificity of PCA3 Gene Testing: Examples from Clinical Practice

A specific marker for early prostate cancer would fill an important void. In initial evaluations of the prostate cancer antigen 3 (PCA3) gene vis-à-vis serum prostate-specific antigen (PSA) levels, the gene offers great promise. At the cellular level, PCA3 specificity for cancer is nearly perfect because of the gross overexpression of the gene by cancer cells. As a clinical test for early prostate cancer, heightened specificity is also seen in urine containing prostate cells from men with the disease. PCA3 gene testing holds valuable potential in PSA quandary situations: (1) men with elevated PSA levels but no cancer on initial biopsy; (2) men found to have cancer despite normal levels of PSA; (3) men with PSA elevations associated with varying degrees of prostatitis; and (4) men undergoing active surveillance for presumed microfocal disease.     

General Practitioners’ Experiences of,and Responses to,Uncertainty in Prostate Cancer Screening: Insights from a Qualitative Study

BackgroundProstate-specific antigen (PSA) testing for prostate cancer is controversial. There are unresolved tensions and disagreements amongst experts, and clinical guidelines conflict. This both reflects and generates significant uncertainty about the appropriateness of screening. Little is known about general practitioners’ (GPs’) perspectives and experiences in relation to PSA testing of asymptomatic men. In this paper we asked the following questions: (1) What are the primary sources of uncertainty as described by GPs in the context of PSA testing? (2) How do GPs experience and respond to different sources of uncertainty?MethodsThis was a qualitative study that explored general practitioners’ current approaches to, and reasoning about, PSA testing of asymptomatic men. We draw on accounts generated from interviews with 69 general practitioners located in Australia (n = 40) and the United Kingdom (n = 29). The interviews were conducted in 2013–2014. Data were analysed using grounded theory methods. Uncertainty in PSA testing was identified as a core issue.FindingsAustralian GPs reported experiencing substantially more uncertainty than UK GPs. This seemed partly explainable by notable differences in conditions of practice between the two countries. Using Han et al’s taxonomy of uncertainty as an initial framework, we first outline the different sources of uncertainty GPs (mostly Australian) described encountering in relation to prostate cancer screening and what the uncertainty was about. We then suggest an extension to Han et al’s taxonomy based on our analysis of data relating to the varied ways that GPs manage uncertainties in the context of PSA testing. We outline three broad strategies: (1) taking charge of uncertainty; (2) engaging others in managing uncertainty; and (3) transferring the responsibility for reducing or managing some uncertainties to other parties.ConclusionOur analysis suggests some GPs experienced uncertainties associated with ambiguous guidance and the complexities of their situation as professionals with responsibilities to patients as considerably burdensome. This raises important questions about responsibility for uncertainty. In Australia in particular they feel insufficiently supported by the health care system to practice in ways that are recognisably consistent with ‘evidence based’ professional standards and appropriate for patients. More work is needed to clarify under what circumstances and how uncertainty should be communicated. Closer attention to different types and aspects of the uncertainty construct could be useful.     

Incorporating Known Genetic Variants Does Not Improve the Accuracy of PSA Testing to Identify High Risk Prostate Cancer on Biopsy

Introduction

Prostate-specific antigen (PSA) testing is a widely accepted screening method for prostate cancer, but with low specificity at thresholds giving good sensitivity. Previous research identified four single nucleotide polymorphisms (SNPs) principally associated with circulating PSA levels rather than with prostate cancer risk (TERT rs2736098, FGFR2 rs10788160, TBX3 rs11067228, KLK3 rs17632542). Removing the genetic contribution to PSA levels may improve the ability of the remaining biologically-determined variation in PSA to discriminate between high and low risk of progression within men with identified prostate cancer. We investigate whether incorporating information on the PSA-SNPs improves the discrimination achieved by a single PSA threshold in men with raised PSA levels.

Materials and Methods

Men with PSA between 3-10ng/mL and histologically-confirmed prostate cancer were categorised as high or low risk of progression (Low risk: Gleason score≤6 and stage T1-T2a; High risk: Gleason score 7–10 or stage T2C). We used the combined genetic effect of the four PSA-SNPs to calculate a genetically corrected PSA risk score. We calculated the Area under the Curve (AUC) to determine how well genetically corrected PSA risk scores distinguished men at high risk of progression from low risk men.

Results

The analysis includes 868 men with prostate cancer (Low risk: 684 (78.8%); High risk: 184 (21.2%)). Receiver operating characteristic (ROC) curves indicate that including the 4 PSA-SNPs does not improve the performance of measured PSA as a screening tool for high/low risk prostate cancer (measured PSA level AU C = 59.5% (95% CI: 54.7,64.2) vs additionally including information from the 4 PSA-SNPs AUC = 59.8% (95% CI: 55.2,64.5) (p-value = 0.40)).

Conclusion

We demonstrate that genetically correcting PSA for the combined genetic effect of four PSA-SNPs, did not improve discrimination between high and low risk prostate cancer in men with raised PSA levels (3-10ng/mL). Replication and gaining more accurate estimates of the effects of the 4 PSA-SNPs and additional variants associated with PSA levels and not prostate cancer could be obtained from subsequent GWAS from larger prospective studies.     

Carbohydrate structure and differential binding of prostate specific antigen to Maackia amurensis lectin between prostate cancer and benign prostate hypertrophy

Serum prostate-specific antigen (PSA) assay is widely used for detection of prostate cancer. Because PSA is also synthesized from normal prostate, false positive diagnosis cannot be avoided by the conventional serum PSA test. To apply the cancer-associated carbohydrate alteration to the improvement of PSA assay, we first elucidated the structures of PSA purified from human seminal fluid. The predominant core structure of N-glycans of seminal fluid PSA was a complex type biantennary oligosaccharide and was consistent with the structure reported previously. However, we found the sialic acid alpha2-3 galactose linkage as an additional terminal carbohydrate structure on seminal fluid PSA. We then analyzed the carbohydrate moiety of serum PSA from the patients with prostate cancer and benign prostate hypertrophy using lectin affinity chromatography. Lectin binding was assessed by lectin affinity column chromatography followed by determining the amount of total and free PSA. Concanavalin A, Lens culinaris, Aleuria aurantia, Sambucus nigra, and Maackia amurensis lectins were tested for their binding to the carbohydrates on PSA. Among the lectins examined, the M. amurensis agglutinin-bound fraction of free serum PSA is increased in prostate cancer patients compared to benign prostate hypertrophy patients. The binding of PSA to M. amurensis agglutinin, which recognizes alpha2,3-linked sialic acid, was also confirmed by surface plasmon resonance analysis. These results suggest that the differential binding of free serum PSA to M. amurensis agglutinin lectin between prostate cancer and benign prostate hypertrophy could be a potential measure for diagnosis of prostate cancer.     

前列腺特异性抗原在前列腺癌诊断中的应用进展

已经证明,前列腺特异性抗原（PSA）是一种有价值的前列腺癌（PCa)肿瘤标记物,血清PSA的广泛使用提高了前列腺癌的检出率,使晚期癌患得明显减少。然而,PSA对PCa的检测缺乏特异性,由于其高的假阳性率,引起许多不必要的活检。为了提高PSA对PCa诊断的特异性,降低不必要的活检,众多学正在探讨与PSA相关的几项参数的临床应用价值,本就此作一综述。     

Initial experience with single-agent docetaxel as neoadjuvant therapy in men with locally advanced prostate cancer

Patients with locally advanced prostate cancer have worse outcomes after radical prostatectomy (RP) than patients with more favorable parameters. The findings of large, contemporary, RP series have led investigators at a number of centers to evaluate the potential role of neoadjuvant chemotherapy in patients with locally advanced disease. A currently ongoing study of 28 patients explores the antitumor response of a regimen of single-agent, docetaxel, 40 mg/m(2), administered intravenously on a weekly schedule for 6 weeks to patients with locally advanced prostate cancer before RP. Docetaxel has demonstrated significant antitumor activity in patients with advanced, androgen-independent disease. Study results showed that 75% of patients had reductions in prostate-specific antigen (PSA) levels ranging from 9%-79% at the completion of docetaxel therapy. In 25% of the patients, PSA levels increased by 2%-18% from baseline to completion of chemotherapy. In addition, noncastrate levels of testosterone were maintained in all patients. The docetaxel therapy has also been relatively well tolerated. Reporting of the primary endpoint of pathologic response is pending completion of accrual and surgery.     

The role of the urologist in treating patients with hormone-refractory prostate cancer

Objectives: To ascertain what percentage of urologists' oncology practice is dedicated to the care of prostate cancer patients and to determine urologists' attitudes towards the treatment of patients with metastatic and hormone-refractory prostate cancer (HRPC). An additional objective is to determine urologists' interest in administering various types of chemotherapy in HRPC patients.Materials and Methods: The American Urological Association (AUA) directory of practicing urologists was obtained, and 3000 randomly selected members of the AUA, as well as the complete list of 168 Society of Urologic Oncology (SUO) members, were chosen for the mailing of a 16-item questionnaire. The urologists were asked about how many of their patients have prostate cancer, how many have metastatic disease, and how many have HRPC and are currently receiving intravenous (IV) chemotherapy. In addition, the urologists were queried regarding their level of interest in learning about chemotherapy options as well as learning how to administer chemotherapy.Results: A total of 654 survey questionnaires were completed and returned for tabulation, resulting in a 21% effective response rate. Sixty-four percent of the responding urologists' cancer patients had prostate cancer, 21% had metastatic disease, and 19% had HRPC; only 4% of the urologists currently administer IV chemotherapy themselves. When asked to describe their interest in learning how to deliver and be reimbursed for IV chemotherapy, 26% expressed an extremely low level of interest, 23% a low level of interest, 31% a high level of interest, and 17% an extremely high level of interest. The results of other questions are presented and correlated with the number of years the urologists have been in practice and other demographic data.Conclusions: The management of prostate cancer comprises a major portion of urologists' practices. Almost one half (48%) of the urologists in this survey were interested in administering and being reimbursed for IV chemotherapy. Several chemotherapy regimens have been shown to improve quality of life in patients with HRPC, yet only about 30% of these patients were referred for chemotherapy. If more urologists were able to deliver these drugs, then the number of patients referred for chemotherapy would likely increase, as would accrual to important clinical trials in HRPC. The results of this survey suggest that methods to implement the training and reimbursement of urologists in the use of chemotherapy regimens should be investigated.     

Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene

Studies of families with breast cancer have indicated that male carriers of BRCA2 mutations are at increased risk of prostate cancer, particularly at an early age. To evaluate the contribution of BRCA2 mutations to early-onset prostate cancer, we screened the complete coding sequence of BRCA2 for germline mutations, in 263 men with diagnoses of prostate cancer who were 相似文献   

UNINFORMED CONSENT: MASS SCREENING FOR PROSTATE CANCER

While medicine may agree in principle that cancer screening requires informed consent, such consent is not, in fact, common practice. In the case of prostate‐cancer screening this means that men in large numbers undergo PSA testing with little understanding of its liabilities – in particular, that it may or may not decrease mortality, often detects cancer of questionable significance, and may lead to unnecessary surgery. Given that prostate cancer is known to be overtreated and that family history is a risk factor, it follows that a man diagnosed with prostate cancer, even if it is of no clinical significance, automatically promotes his son into the high‐risk category; and given that those so categorized are subject to heightened medical surveillance and that the more diligently medicine searches for prostate cancer the more likely it is to find it, it follows that the sons of men diagnosed as a result of PSA testing are at risk of being overdiagnosed (and overtreated) precisely because their father was. Twenty years into the PSA revolution, its generational consequences have not been discussed in the medical literature.     

Newly registered elderly patients: who are they and why such delay in the transfer of their medical records?

The time taken to transfer the records of elderly patients registering with a new general practice was investigated. Thirty five (5%) of a total of 671 patients aged 75 and over were entered as new patients on to the age-sex register of an urban group practice during one year. Twenty nine had moved into the area and six had changed their general practitioner for personal and other reasons. An average of 141 (range 71-296) days elapsed before dispatch of their medical records to the new practice. During this period an average of 3·5 (range 0-15) consultations with a general practitioner were recorded, indicating the need of such patients for medical care. The long delays were caused by the processing of medical records at the central register and the transfer of records between family practitioner committees and general practitioners. Delays were most apparent in the time taken for general practitioners to dispatch the necessary documents to the family practitioner committees, and these should be minimised.The use of a summary card written and updated by the general practitioner and retained by the patient would facilitate continuing care should patients change to a new practice. Meanwhile, assessment of elderly patients after registration with a new practice by a member of the primary health care team may identify problems before the records have been transferred and may help the resettlement of these high risk elderly patients.