The American Cancer Society National Prostate Cancer Detection Project. Findings on the detection of early prostate cancer in 2425 men.

The American Cancer Society National Prostate Cancer Detection Project (ACS-NPCDP) is a multidisciplinary, multicenter effort to assess the feasibility of early prostate cancer detection by digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate specific antigen (PSA) assay. By June 1990, 2425 men not previously suspected of having prostate cancer had been examined in ten participating clinical centers according to the project protocol. Three hundred ninety-six men (16.3%) were recommended for biopsy on the basis of TRUS or DRE. An analysis of the results of 330 completed biopsies showed 52 cancers detected by DRE and/or TRUS. Forty-four (84.6%) of the men with cancer had positive TRUS examination results compared with 33 (63.5%) with positive DRE. Five additional cancers were discovered as a result of elevated PSA levels. The overall detection rate was 2.4% and this rate varied by age. The detection rate in men 55 to 60 years of age was 1.3% and this rose to 3.3% in men older than 65 years of age. The estimated sensitivity was significantly greater for TRUS compared with DRE (77.2% versus 57.9%; P less than 0.05). The estimated specificity of DRE was greater than that of TRUS (96.3% versus 89.4%; P less than 0.01). The positive predictive value (PPV) for the tests varied as a function of patient and disease characteristics. The overall PPV was 28.0% for DRE and 15.2% for TRUS. The occurrence of elevated PSA levels significantly increased the PPV of both TRUS and DRE. The majority of cancers detected were at early stages. These preliminary data suggest the feasibility of using these techniques to promote cancer control, but additional data and follow-up are needed to assess the significance of the results.     

The relationship of prostate-specific antigen to digital rectal examination and transrectal ultrasonography. Findings of the American Cancer Society National Prostate Cancer Detection Project.

The participating institutions of the American Cancer Society National Prostate Cancer Detection Project did 520 biopsies on 2425 men over a 3.5-year period. A total of 88 cancers were confirmed pathologically, 93% of which clinically were organ confined. In 324 men (62.3%), a recommendation for biopsy was made based solely on the results of transrectal ultrasonography (TRUS); in 69 patients (13.3%), solely on the digital rectal examination (DRE); in 116 patients (22.3%), on abnormal DRE and TRUS examinations; and in 11 patients (2.1%), in whom DRE and TRUS were normal, on elevated prostate-specific antigen (PSA) levels. The TRUS was abnormal in 80.6% of men found to have cancer, and the PSA level and DRE were abnormal for 67% and 50% of cancers, respectively. The influence of PSA level on cancer detection increased as the serum level increased above 4 ng/ml. The positive predictive values of both the DRE and TRUS were influenced significantly by the presence of an elevated PSA level (P = 0.044 and P less than 0.001, respectively). The results of this ongoing multicenter study support the following statements: (1) the prostate cancer detection rate is influenced by this diagnostic triad and (2) the detection rate of organ-confined disease can be improved substantially by early detection programs.     

Prostate-specific antigen use among men without prostate cancer in France (2008-2010)

This study evaluated the rate of prostate-specific antigen (PSA) dosage in men age 40 or older, affiliated to the general social security system in France between 2008 and 2010: 10.9 million men, excluding those with known prostate cancer. In 2010, 30.7% of this male population had at least one dosage of PSA, i.e. 12.3% of those between 40 and 54, 47.7% of those between 55 and 74, and 47.6% of those 75 years old or older. Percentages of men who had at least one dosage in the three-year period were 26.2%, 77.3% and 75.6% for the same age brackets, respectively. Overall, 13% of men age 40 or older, and in particular 21% of men 75 years old or older had more than three PSA dosages during the three-year time period. Eighty-eight percent of PSA dosages performed in 2010 were prescribed by a general practitioner and 3.2% by an urologist. Conflicting with French and internationally published recommendations regarding PSA dosage, the present results demonstrate a shift toward chaotic mass screening of prostate cancer particularly in men aged 75 or older.     

Prostate-specific membrane antigen levels in sera from healthy men and patients with benign prostate hyperplasia or prostate cancer.

Prostate-specific membrane antigen (PSMA) serum levels have been proposed to be of prognostic significance in patients with advanced prostate disease. The objective of the present study was to confirm PSMA serum expression by Western blot techniques, to determine whether such data could assist in the differentiation of benign from malignant prostatic disease, and to determine the suitability of serum PSMA measurements in predicting recurrent or progressive prostate malignancies. We measured PSMA, a transmembrane glycoprotein identified in prostate epithelial cells, in the sera of 236 normal individuals and cancer patients by Western blot analysis. Within the normal male population, PSMA levels increase with age and were found to be significantly elevated in subjects more than 50 years of age when compared to those of younger men. We did not confirm previous reports that serum PSMA measurements could distinguish late-stage prostate carcinoma from early-stage prostate carcinoma, nor did we find PSMA to be more effective than prostate-specific antigen in monitoring prostate cancer patient prognosis. Furthermore, we found elevated serum PSMA in healthy females, and, similar to the healthy male population, the levels increased with age, with the highest levels found in the sera from breast cancer patients. These latter observations further support that PSMA is not a specific biomarker for prostate cancer and that a variety of normal and diseased tissue may contribute to the serum levels of PSMA.     

Prostate-specific antigen levels and subsequent prostate cancer: potential for screening.

Prostate-specific antigen levels are increased in men with prostatic disease, including prostate cancer, and have been used clinically to monitor the response of prostate cancer to therapy. More recently, prostate-specific antigen levels, usually in combination with digital rectal examination or transrectal prostatic ultrasonography, have been suggested to be useful for the detection of prostate cancer. To evaluate the association between a single serum prostate-specific antigen level and the subsequent development of prostate cancer, we measured serum levels in 35 men who donated blood to a community-based serum bank in 1974 and who subsequently developed prostate cancer and in 35 matched controls from the same group of volunteers. Levels of prostate-specific antigen were significantly higher in men who went on to develop prostate cancer, up to 6 years prior to the time of diagnosis in the cases. The level of prostate-specific antigen decreased with increasing time to diagnosis. The mean level for prostate cancer cases diagnosed within the first 3 years of follow-up was 16.2 micrograms/liter compared to 2.4 micrograms/liter for controls (P = 0.002). The mean level for cancer cases diagnosed in years 4 through 6 following blood sampling was 9.6 micrograms/liter compared to 1.3 micrograms/liter for controls (P = 0.0002). The sensitivity and specificity of a prostate-specific antigen level > or = 4 micrograms/liter up to 3 years prior to the time of clinical diagnosis were both 75% and up to 6 years were 67% and 85%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostate-specific antigen and external beam radiation therapy in prostate cancer.

This study of 133 patients with localized prostate cancer (Stages A2 to C), treated by external beam radiation therapy (XRT), was undertaken for two reasons: (1) to investigate the usefulness of pretreatment serum prostate-specific antigen (PSA) levels in evaluating patients before XRT; and (2) to investigate post-XRT changes in PSA values and their likely clinical significance. It was found that pretreatment PSA values in patients with localized disease exhibit wide patient to patient variability with a greater than 100-fold difference between the lowest and highest values. Although mean PSA values were significantly higher in Stage C disease (51 patients; mean PSA, 17.3 ng/ml) than in Stage A2 disease (31 patients; mean PSA, 9.0 ng/ml), Stage B1 disease (23 patients; mean PSA, 9.1 ng/ml), or Stage B2 disease (28 patients; mean PSA, 10.6 ng/ml), individual values were of virtually no help in assigning individual patients to a clinical stage. PSA levels did not correlate with grade. After XRT, PSA values fell significantly and dramatically in virtually all patients (98%) by 3 months follow-up. Mean PSA fell from 12.5 to 2.6 ng/ml, and median PSA fell from 6.6 to 1.9 ng/ml. In most patients, PSA continued to fall up to 12 months after XRT and then stabilized at 21 months. Although PSA values fell dramatically after XRT, PSA was detectable in the serum of all patients. PSA values tended to transiently and mildly elevate during XRT. In a small proportion of patients, rising PSA values were observed after 6 months. The full significance of this requires further follow-up, of four such patients, one has relapsed. PSA is a more sensitive marker of prostatic radiation than prostatic acid phosphatase.     

Prostate cancer screening in high-risk men: African American Hereditary Prostate Cancer Study Network

BACKGROUND: There are scant data available on prostate cancer screening among high-risk African American men with positive family histories. It is important to determine whether or not their screening rates differ from those in the general population. METHODS: This study computed rates of previous digital rectal examination (DRE) and prostate-specific antigen (PSA) screening for prostate cancer in cancer-free (unaffected) relatives age 40-69 years from African American families that had four or more men with prostate cancer. The rates for these 134 high-risk African American men from the African American Hereditary Prostate Cancer Study (AAHPC) were compared with nationwide estimates obtained from participants in the 1998 and 2000 National Health Interview Survey (NHIS), for which the numbers of demographically comparable subjects were 5583 (4900 Caucasians, plus 683 African Americans) and 3359 (2948 Caucasians, 411 African Americans), respectively. RESULTS: Men in the AAHPC cohort (with a strong positive family history) had significantly less screening than both African Americans and Caucasians in the NHIS cohorts. Only about one-third (35%) of the men in the AAHPC unaffected cohort had ever had a DRE, and only about 45% of them had ever received a PSA test. These rates were much lower than those obtained for African American men in the NHIS: 45% for DRE and 65% for PSA. These discrepancies increased with age. CONCLUSIONS: Older African American men with positive family histories report surprisingly low rates of DRE and PSA screening compared with their counterparts in the NHIS surveys. At-risk men need to be informed of the benefits and limitations of prostate cancer screening and actively involved in decision-making for or against prostate cancer screening.     

American Cancer Society Guideline for the Early Detection of Prostate Cancer: Update 2010

In 2009, the American Cancer Society (ACS) Prostate Cancer Advisory Committee began the process of a complete update of recommendations for early prostate cancer detection. A series of systematic evidence reviews was conducted focusing on evidence related to the early detection of prostate cancer, test performance, harms of therapy for localized prostate cancer, and shared and informed decision making in prostate cancer screening. The results of the systematic reviews were evaluated by the ACS Prostate Cancer Advisory Committee, and deliberations about the evidence occurred at committee meetings and during conference calls. On the basis of the evidence and a consensus process, the Prostate Cancer Advisory Committee developed the guideline, and a writing committee drafted a guideline document that was circulated to the entire committee for review and revision. The document was then circulated to peer reviewers for feedback, and finally to the ACS Mission Outcomes Committee and the ACS Board of Directors for approval. The ACS recommends that asymptomatic men who have at least a 10‐year life expectancy have an opportunity to make an informed decision with their health care provider about screening for prostate cancer after they receive information about the uncertainties, risks, and potential benefits associated with prostate cancer screening. Prostate cancer screening should not occur without an informed decision‐making process. Men at average risk should receive this information beginning at age 50 years. Men in higher risk groups should receive this information before age 50 years. Men should either receive this information directly from their health care providers or be referred to reliable and culturally appropriate sources. Patient decision aids are helpful in preparing men to make a decision whether to be tested. CA Cancer J Clin 2010;60:70–98. © 2010 American Cancer Society, Inc.     

Serum insulin-like growth factor-I is positively associated with serum prostate-specific antigen in middle-aged men without evidence of prostate cancer.

We have examined the relationship between serum insulin-like growth factor-I (IGF-I) and prostate-specific antigen in 367 healthy men without evidence of prostate cancer and found a positive association (P = 0.05). In men without prostate cancer, serum prostate-specific antigen is closely related to prostate size, and our findings, therefore, suggest that IGF-I may induce prostatic epithelial proliferation. Higher circulating levels of IGF-I have been associated with increased risk of both prostate cancer and possibly benign prostatic hyperplasia. Greater rates of cell proliferation induced by IGF-I may be a key biological pathway underlying these disorders.     

Prostate-specific antigen as a marker of disease activity in prostate cancer

Despite the impact of prostate-specific antigen (PSA) testing on the detection and management of prostate cancer, controversy about its usefulness as a marker of disease activity continues. This review, based on a recent roundtable discussion, examines whether PSA measurements can be used rationally in several clinical settings. Following radical prostatectomy and radiation therapy, prediction of survival by PSA level is most reliable in high-risk patients. PSA doubling time after radiation therapy is the strongest predictor of biochemical failure. PSA measurements have been associated with inconsistent results following hormonal treatment; reduced PSA levels may result from antiandrogen treatment, which decreases expression of the PSA gene, and therefore, the level of PSA production. In the setting of primary and secondary cancer prevention, PSA is important in risk stratification when selecting patients for studies. Part 1 of this two-part article, which concludes in the September issue, focuses on the physiology of PSA, its measurement and use in clinical practice, and its predictive value following radical prostatectomy and radiation therapy.     

Prostate-specific antigen recurrence and mortality after conventional dose radiation therapy in select men with low-risk prostate cancer

BACKGROUND: Prostate-specific antigen (PSA) recurrence, prostate cancer-specific mortality (PCSM), and all-cause mortality (ACM) were evaluated for men age >70 years receiving conventional dose external beam radiation therapy (RT). METHODS: Between January 1, 1989, and December 1, 2002, 358 men were treated with RT for localized prostate cancer at a Harvard Medical School Affiliate in Fall River, MA. Median age was 71.2 (range, 43.2-83.5) years and patients were followed for a median of 4.0 (range, 0.2-13.5) years. RESULTS: Univariable analysis demonstrated that increasing pretreatment PSA velocity was significantly associated with increasing pretreatment PSA (P < .0001), Gleason score (P = .0002), and shorter post-RT PSA doubling time (P = .0007) but not with clinical T-category (P = .09) or percent positive biopsies (P = .08). For the select cohort of men age >70 years with low-risk disease and a pretreatment PSA velocity < or =1.0 ng/mL per year, all deaths observed to date have been from nonprostate cancer etiologies. Whereas PSA recurrence in this group reached 43.3% by 7 years, due to the advanced age of the cohort and less aggressive biology, competing causes of mortality predominated as the cause of death despite PSA failure. CONCLUSIONS: In men age >70 years with low-risk prostate cancer and pretreatment PSA velocity < or =1.0 ng/mL/year, prostate cancer death was not observed despite a modest PSA recurrence rate.     

Prostate-specific antigen as a marker of disease activity in prostate cancer

Despite the impact of prostate-specific antigen (PSA) testing on the detection and management of prostate cancer, controversy about its usefulness as a marker of disease activity continues. This review, based on a recent roundtable discussion, examines whether PSA measurements can be used rationally in several clinical settings. Following radical prostatectomy and radiation therapy, prediction of survival by PSA level is most reliable in high-risk patients. PSA doubling time after radiation therapy is the strongest predictor of biochemical failure. PSA measurements have been associated with inconsistent results following hormonal treatment; reduced PSA levels may result from antiandrogen treatment, which decreases expression of the PSA gene, and therefore, the level of PSA production. In the setting of primary and secondary cancer prevention, PSA is important in risk stratification when selecting patients for studies. Part 2 of this two-part article, which began in the August issue, discusses the role of PSA in hormonal and drug therapies and in primary and secondary chemoprevention.     

Prostate cancer health and cultural beliefs of black men: The Florida Prostate Cancer Disparity Project

Background

Since behavioral factors are significant determinants of population health, addressing prostate cancer (CaP)-related health beliefs and cultural beliefs are key weapons to fight this deadly disease. This study investigated the health beliefs and cultural beliefs of black men relative to CaP, and the key socio-demographic correlates of these beliefs.

Methods

The study design was a cross-sectional survey of 2,864 Florida black men, age 40 to 70, on their perceived susceptibility, perceived severity, attitude, outcomes beliefs, perceived behavioral control, CaP fatalism, religiosity, temporal orientation, and acculturation relative to CaP screening and prevention.

Results

The men reported favorable attitude and positive outcome beliefs, but moderate perceived behavioral control, CaP susceptibility and CaP severity. They also had low level of acculturation, did not hold fatalistic beliefs about CaP, had high religious coping skills and had high future time perspective. Several demographic variables were found to be associated with health beliefs and cultural beliefs.

Discussion

Our study provides rich data with regard to the health and cultural beliefs that might serve to inform the development of CaP control initiative for US-born and foreign-born black men.

     

Dietary supplement use patterns in men with prostate cancer: the Cancer Prostate Sweden Study

BackgroundIn a European setting, we know little about the use of dietary supplements among men with prostate cancer (PCa) and to what extent lifestyle, disease or other factors influence such use.Patients and methodsWe evaluated supplement use in 1127 men with incident PCa and in 900 population controls in Sweden. Age-adjusted binary regression with an identity link was carried out to estimate prevalence differences and corresponding 95% confidence intervals (CIs). Modifying effects of lifestyle- and diet-related factors were explored by statistical assessment of additive interaction.ResultsAmong men with PCa, 542 individuals (48%) had used supplements, which was a 10% (95% CI: 5.9%–15%) higher prevalence than among population controls. Among individuals with high intake of fatty fish, vegetables, and phytoestrogens, but low intake of saturated fat, supplement use was 29% (95% CI: 18%–41%) more common in men with PCa than in population controls. We found no evidence of heterogeneity by categories of education, smoking history, body mass index, fiber, fruit, or phytoestrogen intake, treatment, or disease stage.ConclusionSupplement use is common in Swedish men with PCa, especially among those with a healthy dietary pattern.     

Prostate stem cell antigen is overexpressed in prostate cancer metastases.

PURPOSE: Prostate stem cell antigen (PSCA) is expressed by a majority of prostate cancers and is a promising therapeutic target. PSCA protein and mRNA expression was examined in prostate cancer bone, lymph node, and visceral metastases to assess the potential of PSCA as an immunotherapeutic target in advanced prostate cancer. EXPERIMENTAL DESIGN: Immunohistochemical analysis of PSCA protein expression and quantitative mRNA expression analysis of PSCA was done on clinical specimens of prostate cancer bone, lymph node, and visceral metastases. PSCA protein and mRNA expression levels were quantified and compared between available matched pairs of bone and lymph node or visceral metastases. RESULTS: Bone metastases stained with higher intensity of PSCA compared with lymph node or liver metastases in seven of eight (87.5%) matched pairs (P = 0.035). PSCA mRNA expression was equal or greater than that of LAPC-9, a PSCA expressing xenograft, in 12 of 24 (50%) cases of prostate cancer metastases and was significantly correlated with PSCA protein expression (sigma = 0.84, P = 0.0019). Overall, PSCA protein expression was detected in 41 of 47 (87.2%), four of six (66.7%), and two of three (66.7%) cases of bone, lymph node, and liver metastases, respectively. Mean PSCA staining intensity was significantly higher in prostate cancer bone metastases compared with lymph node metastases (2.0 +/- 0.02 versus 0.83 +/- 0.31, P = 0.014). CONCLUSIONS: Prostate cancer metastases express PSCA. However, greater PSCA staining intensity and level of PSCA mRNA expression was associated with bone metastases compared with lymph node metastases. This study suggests that PSCA is a promising tumor marker and potential therapeutic target for patients with metastatic prostate cancer.     

Beyond Prostate-specific Antigen - Future Biomarkers for the Early Detection and Management of Prostate Cancer

Prostate-specific antigen is currently commonly used as a screening biomarker for prostate cancer, but it has limitations in both sensitivity and specificity. The development of novel biomarkers for early cancer detection has the potential to improve survival, reduce unnecessary investigations and benefit the health economy. Here we review the use and limitations of prostate-specific antigen and its subtypes, urinary biomarkers including PCA3, alpha-methylacyl-CoA racemase, the TMPRSS2-ERG fusion gene and microseminoprotein-beta, and other novel markers in both serum and urine. Many of these biomarkers are at early stages of development and require evaluation in prospective trials to determine their potential usefulness in clinical practice. Genetic profiling may allow for the targeting of high-risk populations for screening and may offer the opportunity to combine biomarker results with genotype to aid risk assessment.     

Substantial family history of prostate cancer in black men recruited for prostate cancer screening: results from the Prostate Cancer Risk Assessment Program

BACKGROUND.

Black men are at increased risk for prostate cancer (PCA), particularly with a family history (FH) of the disease. Previous reports have raised concern for suboptimal screening of black men with an FH of PCA. The extent of FH of PCA are reported from a prospective, longitudinal PCA screening program for high‐risk men.

METHODS.

Black men ages 35 to 69 years are eligible for PCA screening through the Prostate Cancer Risk Assessment Program (PRAP) regardless of FH. Rates of self‐reported FH of PCA, breast, and colon cancer at baseline were compared with an age‐matched sample of black men from the 2005 National Health Interview Survey (NHIS) using standard statistical methods.

RESULTS.

As of January 2007, 332 black men with pedigree information were enrolled in PRAP and FH of PCA was compared with 838 black men from the 2005 NHIS. Black men in PRAP reported significantly more first‐degree relatives with PCA compared with black men in the 2005 NHIS (34.3% [95% confidence interval (95% CI), 29.2‐39.7] vs 5.7% [95% CI, 3.9‐7.4]). Black men in PRAP also had more FH of breast cancer compared with those in the 2005 NHIS (11.5% [95% CI, 8.2‐15.4] vs 6.3% [95% CI, 4.6‐8.0]).

CONCLUSIONS.

FH of PCA appears to be a motivating factor for black men seeking PCA screening. Targeted recruitment and education among black families should improve PCA screening rates. Efforts to recruit black men without an FH of PCA are also needed. Cancer 2008. © 2008 American Cancer Society.