Transrectal ultrasound in detecting prostate cancer compared with serum total prostate-specific antigen levels

We carried out a retrospective study to review the efficiency of grey-scale transrectal ultrasonography (TRUS) in detecting prostate cancer compared with the data in recent published work, including alternative imaging methods of the prostate gland. Our study group consisted of 830 patients who underwent TRUS-guided biopsy of the prostate between May 2000 and June 2004. The relation between abnormal TRUS findings and serum total prostate-specific antigen (tPSA) levels was evaluated in patients with prostate cancer who were divided into three different groups according to serum tPSA levels. Group I included patients with tPSA levels of 4-9.9 ng/mL, group II included tPSA levels of 10-19.9 ng/mL and group III included patients with tPSA levels of 20 ng/mL or more. In general, TRUS detected 185 (64%) of 291 cancers with a specificity of 89%, a PPV of 76% and an accuracy of 80%. TRUS findings enabled the correct identification of 22 (56%) of the 39 cancers in group I, 28 (30%) of the 93 cancers in group II and 135 (85%) of the 159 cancers in group III. In conclusion, TRUS alone has a limited potential to identify prostate cancer, especially in patients with tPSA levels lower than 20 ng/mL. Therefore, increased numbers of systematically placed biopsy cores must be taken or alternative imaging methods are required to direct TRUS-guided biopsy for improving prostate cancer detection.     

Combining 33 genetic variants with prostate-specific antigen for prediction of prostate cancer: longitudinal study

The aim of this study was to investigate if a genetic risk score including 33 common genetic variants improves prediction of prostate cancer when added to measures of prostate-specific antigen (PSA). We conducted a case-control study nested within the Northern Sweden Health and Disease Cohort (NSHDC), a prospective cohort in northern Sweden. A total of 520 cases and 988 controls matched for age, and date of blood draw were identified by linkage between the regional cancer register and the NSHDC. Receiver operating characteristic curves with area under curve (AUC) estimates were used as measures of prostate cancer prediction. The AUC for the genetic risk score was 64.3% [95% confidence interval (CI) = 61.4-67.2], and the AUC for total PSA and the ratio of free to total PSA was 86.2% (95% CI = 84.4-88.1). A model including the genetic risk score, total PSA and the ratio of free to total PSA increased the AUC to 87.2% (95% CI = 85.4-89.0, p difference = 0.002). The addition of a genetic risk score to PSA resulted in a marginal improvement in prostate cancer prediction that would not seem useful for clinical risk assessment.     

Pretreatment prostate-specific antigen velocity is associated with development of distant metastases and prostate cancer mortality in men treated with radiotherapy and androgen-deprivation therapy

BACKGROUND: In men with prostate cancer, pretreatment prostate-specific antigen (PSA) velocity (PSAV) has been demonstrated as a predictor of biochemical and survival outcomes in patients undergoing radical prostatectomy (RP). The utility of pretreatment PSAV in predicting outcomes after radiotherapy (RT), with or without androgen-deprivation therapy (ADT), is less certain. This study was undertaken to determine whether pretreatment PSAV is associated with biochemical disease-free survival, patterns of recurrence, and survival outcomes in men treated with radiation therapy and ADT. METHODS: Two hundred seventy-seven patients with intermediate- and high-risk prostate cancer treated with RT and ADT formed the study cohort. Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate whether PSAV was associated with disease outcomes. RESULTS: The median age of diagnosis was 70 years, and the median follow-up was 6.8 years. Men with a PSAV in the highest quartile tended to have higher risk disease at presentation (P = .028). After adjustment for known prognostic factors and duration of ADT, men who had a PSAV in the highest quartile had an increased risk of distant metastasis (hazard ratio [HR], 4.0; 95% confidence interval [95% CI], 1.61-9.9 [P = .003]) and prostate cancer-specific mortality (HR, 2.75; 95% CI, 1.27-5.95 [P = .01]) compared with men who had a lower PSAV, but had no increase in the risk of local recurrence (P = .76). CONCLUSIONS: A high pretreatment PSAV was associated with distant metastasis and prostate cancer-specific mortality but not with local recurrence. A high pretreatment PSAV may signify the presence of occult metastatic disease. Randomized trials are needed to determine whether more aggressive intervention is required in men who present with high pretreatment PSAV.     

Detection of prostate cancer at low and intermediate serum prostate-specific antigen levels in a country with a low incidence of prostate cancer

BACKGROUND: The objective of this study was to evaluate the cancer detection rate and the pathologic findings of biopsy in men at low and intermediate prostate-specific antigen (PSA) levels in an Asian population. METHODS: Patients between 40 and 79 years were entered into a study and 755 patients with serum PSA level of 2.0-10.0 ng/ml underwent trus-guided systematic biopsy. Patients were divided to low (PSA 2.0-4.0 ng/ml, n = 144) and intermediate (PSA 4.1-10.0 ng/ml, n = 611) PSA groups. RESULTS: Patients in the low PSA group had significantly smaller prostates (P = 0.003) and lower PSA density (P < 0.001). The rate of cancer detection was 16.7% (24 of 144) in the low PSA group and 23.7% (145 of 611) in the intermediate PSA group (P = 0.067). In men with normal digital rectal examination (DRE), prostate cancer was diagnosed in 14 (13.3%) of the 105 men in the low PSA group and 99 (19.5%) of the 508 men in the intermediate PSA group (P = 0.139). In all patients and patients with normal DRE, no statistically significant differences were found in the pathologic findings of biopsy between the two groups. CONCLUSIONS: Our findings provide a rationale to recommend prostate biopsy at lower PSA threshold in this population. At present, however, it is not clear that men who are treated when their cancers are detected at lower PSA levels have better outcomes than those who are treated when the PSA is higher than 4.0 ng/ml.     

Metastatic prostate cancer with a normal prostate-specific antigen level

Prostate-specific antigen (PSA) is the most commonly used tumour marker for prostate cancer; both in screening and in follow-up. However, there are many false positive increases in the presence of other prostate diseases and , currently, there is no consensus regarding sensitivity and specificity of the PSA test, nor what constitutes the upper limit of normality. We report a case of a 67-year-old patient with metastatic prostate cancer who, with increased level of alkaline phosphatase and normal PSA, showed clinical and radiological evidence of progression of the disease     

Prostate cancer progression in the presence of undetectable or low serum prostate-specific antigen level

BACKGROUND: The serum prostate-specific antigen (PSA) level after definitive treatment for prostate cancer (PC) is a powerful predictor of outcome. Occasionally, PC progression can occur despite low or undetectable PSA levels. The authors report on the clinical and pathologic characteristics of patients who experienced PC progression with undetectable or low PSA levels. METHODS: From an electronic database of all patients with PC who were treated at The University of Texas M. D. Anderson Cancer Center between 1999 and 2004, a group of 46 patients was identified who had progression to metastatic PC detected with concomitant PSA levels from 0.1 ng/mL to 2 ng/mL. Patient charts were reviewed for tumor stage, Gleason score, pretreatment PSA level, and the presence of atypical histologic variants (ie, ductal, sarcomatoid, or small cell cancers). The nadir PSA level after treatment and the PSA level at the time metastatic PC was detected were determined. The patients were followed semiannually, and imaging studies were obtained at the discretion of treating physicians. The sites of metastasis and histologic confirmation were reported when available. RESULTS: Twenty-three of 46 patients underwent radical prostatectomy, 11 patients received radiation therapy, and 12 received hormone treatment as their initial form of therapy. Progression to metastatic disease with concomitant, undetectable PSA levels occurred in 10 patients, including 3 patients who had not received treatment with hormones. The sites of metastasis included bone (n = 35 patients), liver (n = 7 patients), retroperitoneal lymph nodes (n = 5 patients), lungs (n = 4 patients), and brain (n = 1 patient). Aggressive and locally advanced PC were common features in these patients: Eighty-five percent had Gleason scores >or=7, 63% had clinical T3 or T4 tumors, and 41% had pretreatment PSA levels >10 ng/mL. Atypical histologic variants were observed in 21 patients (46%) and in 8 of 10 patients who progressed with undetectable PSA levels. In 10 patients (22%), metastasis were detected in the presence of an undetectable PSA level. Eight of those patients had small cell carcinoma. In 19 patients (41%), progression to metastasis occurred without any increase in their PSA from the nadir level. Thirty-one patients (67%) were asymptomatic at the time metastasis was detected, and the detection of metastasis in these patients occurred only because of routine imaging studies. CONCLUSIONS: Progression of PC may occur despite undetectable or low PSA levels. Complete physical evaluation and imaging studies may be indicated in the surveillance of patients with high-grade, locally advanced tumors, especially when atypical histologic variants are present.     

Time to an undetectable prostate-specific antigen (PSA) after androgen suppression therapy for postoperative or postradiation PSA recurrence and prostate cancer-specific mortality

BACKGROUND: For men receiving androgen-suppression therapy (AST) for a rising postoperative or postradiation prostate-specific antigen (PSA) recurrence, whether the time to an undetectable (u) PSA was significantly associated with prostate cancer-specific mortality (PCSM) was evaluated. METHODS: The study cohort comprised 585 men with a rising PSA and negative bone scan after surgery (n = 415) or radiation therapy (n = 170) that were treated with AST and achieved a uPSA. Gray's regression was used to evaluate whether the time to a uPSA after AST was significantly associated with the time to PCSM after the uPSA adjusting for known prognostic factors. RESULTS: The median time (interquartile range) to achieve a uPSA was 4.6 (range, 2.8-7.8) months. There were 23 deaths, 4 of which were from prostate cancer. An increasing time to a uPSA (adjusted hazard ratio [HR]: 9.2, 95% confidence interval [CI]: 3.8, 22.1; P < .0001), a decreasing PSA doubling time (DT) (HR: 0.58, 95% CI: 0.43, 0.80; P = .0007), and Gleason score 8 to 10 cancers (HR: 8.6, 95% CI: 1.04, 77; P = .05) were significantly associated with a shorter time to PCSM. CONCLUSIONS: Despite achieving a uPSA after AST, the risk of PCSM increased significantly as the time to the uPSA lengthens, especially in men with a short pre-AST PSA DT and high-grade prostate cancer. These men should be considered for randomized studies evaluating immediate vs delayed chemotherapy after the achievement of the uPSA.     

Association of prostate stem cell antigen gene polymorphisms with the risk of stomach cancer in Japanese

A recent whole‐genome association study identified a strong association between polymorphisms in the prostate stem cell antigen (PSCA) gene and stomach cancer risk. In this case‐control study, we aimed to validate this association, and further to explore environmental factors possibly interacting with PSCA polymorphisms in 708 incident stomach cancer cases and 708 age–sex matched controls. The association between PSCA polymorphisms and Helicobacter pylori infection was also examined. We found that rs2294008 and rs2976392, which were strongly linked to each other (D′ = 1.00), were significantly associated with stomach cancer risk. Per allele odds ratio for rs2994008 was 1.40 (95% confidence interval: 1.19–1.65; p = 3.7 × 10^?5). We found significant interaction with a family history of stomach cancer in first‐degree relatives (p‐heterogeneity = 0.009). Similar to originally reported association, we found significant heterogeneity between diffuse and intestinal type (p‐heterogeneity = 0.007). No association was seen between PSCA polymorphisms and H. pylori infection. In conclusion, PSCA polymorphisms are associated with stomach cancer risk in Japanese. A possible interaction with family history warrants further evaluation. © 2009 UICC     

The influence of serial prostate-specific antigen (PSA) screening on the PSA velocity at diagnosis

BACKGROUND: A prostate-specific antigen (PSA) velocity (PSAV) >2 ng/mL during the year before diagnosis has been associated with an increased risk of prostate cancer-specific mortality (PCSM) after radical prostatectomy (RP) or radiation therapy. The objective of the current study was to examine whether the proportion of men with a PSAV >2 ng/mL per year has changed significantly during the PSA era. METHODS: The authors evaluated 1095 men from a prospective prostate cancer screening study who underwent RP between 1989 and 2002. For the purposes of this analysis, clinicopathologic features were compared between men who were treated during the following 3 periods: before 1995, from 1995 to 1998, and after 1998. Logistic regression analysis was used to evaluate for an association between the year of diagnosis and the proportion of men with a PSAV >2 ng/mL per year. RESULTS: Two hundred sixty-two of 1095 men (24%) had a PSAV >2 ng/mL per year. There was a statistically significant reduction in the proportion of men presenting with a PSAV >2 ng/mL per year over the study period. Specifically, 35% of men presented with a PSAV >2 ng/mL per year in the early period compared with only 22% and 12% in the middle and late periods, respectively (P < .001). Over the studied periods, there also was a significantly greater proportion of men with >2 PSA values obtained before diagnosis (P < .001). CONCLUSIONS: Men who were screened serially with PSA were less likely to present with a PSAV >2 ng/mL per year. This association lends support to the hypothesis that serial PSA-based screening may lead to a decrease in PCSM.     

血清FPSA/TPSA 比值在前列腺癌鉴别诊断中的应用

目的：探讨游离前列腺特异性抗原／总前列腺特异性抗原（FPSA／TPSA）比值在鉴别诊断前列腺癌中的应用价值。方法：随机选取我院2005年1月-2006年8月住院的前列腺炎患者44例，良性前列腺增生42例，前列腺癌患者54例，排除前列腺疾病的健康体检者63例，测定血清TPSA和FPSA，并计算FPSA／TPSA比值。应用SPSS10．0软件进行统计学分析。结果：FPSA／TPSA比值界值为≤1．8时对前列腺癌鉴别诊断与只检测TPSA相比在敏感性相近的情况下特异性明显提高（TPSA特异性为57．5％，FPSA／TPSA特异性为81．3％）。结论：FPSA／TPSA比值在敏感性相近的情况可明显提高前列腺癌鉴别诊断的特异性，是较为理想的前列腺癌鉴别诊断新指标。     

Protective effect of green tea against prostate cancer: a case-control study in southeast China

To investigate whether green tea consumption has an etiological association with prostate cancer, a case-control study was conducted in Hangzhou, southeast China during 2001-2002. The cases were 130 incident patients with histologically confirmed adenocarcinoma of the prostate. The controls were 274 hospital inpatients without prostate cancer or any other malignant diseases, and matched to the age of cases. Information on duration, quantity and frequency of usual tea consumption, as well as the number of new batches brewed per day, were collected by face-to-face interview using a structured questionnaire. The risk of prostate cancer for tea consumption was assessed using multivariate logistic regression adjusting for age, locality, education, income, body mass index, physical activity, alcohol consumption, tobacco smoking, total fat intake, marital status, age at marriage, number of children, history of vasectomy and family history of prostate cancer. Among the cases, 55.4% were tea drinkers compared to 79.9% for the controls. Almost all the tea consumed was green tea. The prostate cancer risk declined with increasing frequency, duration and quantity of green tea consumption. The adjusted odds ratio (OR), relative to non-tea drinkers, were 0.28 (95% CI = 0.17-0.47) for tea drinking, 0.12 (95% CI = 0.06-0.26) for drinking tea over 40 years, 0.09 (95% CI = 0.04-0.21) for those consuming more than 1.5 kg of tea leaves yearly, and 0.27 (95% CI = 0.15-0.48) for those drinking more than 3 cups (1 litre) daily. The dose response relationships were also significant, suggesting that green tea is protective against prostate cancer.     

Inhibition of prostate-specific membrane antigen (PSMA)-positive tumor growth by vaccination with either full-length or the C-terminal end of PSMA

For experimental immunotherapy of prostate cancer, we used a model system to target a defined region of the extracellular domain of prostate-specific membrane antigen (PSMA). PSMA is a surface antigen expressed by prostate epithelium that is upregulated approximately 10-fold in most prostate tumors. We vaccinated BALB/c mice with NIH3T3 cells cotransfected with pST/neo plus pEF-BOS-based vectors expressing either the full-length 750-amino acid human PSMA or only the C-terminal 180-amino acid region (PSMc). PSMc lies C-terminal to the transferrin receptor-like sequence in the extracellular domain of PSMA. BALB/c mice were injected i.p. 4 times at weekly intervals with vaccine cells. Vaccinated mice were then challenged s.c. with Renca/PSMA, a BALB/c renal cell carcinoma line transfected to express human PSMA. Growth of Renca/PSMA tumors was substantially retarded and host survival significantly prolonged in mice prevaccinated with either 3T3/PSMA or 3T3/PSMc. Furthermore, antiserum from vaccinated mice intensely immunocytochemically stained LNCaP, a PSMA-positive human prostate cancer cell line. In contrast, control mice similarly prevaccinated i.p. with 3T3/neo (NIH3T3 cells transfected with pST/neo alone) developed Renca/PSMA tumors, which were palpable within 2 weeks and lethal by 5 weeks. Serum from 3T3/neo-vaccinated mice did not immunocytochemically stain LNCaP cells. The antitumor activity induced by vaccination with 3T3/PSMc was also demonstrated via growth inhibition of established LNCaP tumors xenografted in athymic mice following passive transfer of immune serum from vaccinated mice. Our results suggest that vaccination with PSMc induces adaptive humoral activity, which is directed against the extracellular region of human PSMA and can significantly inhibit human prostate cancer growth in athymic mice, and that administration of antibodies to PSMA may provide a passive treatment modality for immunocompromised patients.     

Test sensitivity of prostate-specific antigen in the Finnish randomised prostate cancer screening trial

We estimated the sensitivity of serum prostate-specific antigen (PSA) as a screening test for prostate cancer in the Finnish randomised, population-based prostate cancer screening trial. The study population consisted of 80,458 men aged 55-67 years identified from the national population registry and randomised to the screening or control arm of the trial. The screening algorithm was based on determination of serum PSA concentration. Test sensitivity was estimated based on interval cancer incidence during the first 4 years of follow-up among screening participants with a negative screening test. Interval cancers were defined as those occurring among men with a negative screening test. Altogether, 19 interval cancers were detected among 17,897 men with serum PSA < 3 ng/ml during the first screening interval. A further 5 cases were diagnosed among 811 men with PSA 3.0-3.9 ng/ml with a benign digital rectal examination or free total PSA ratio > or = 0.16. Test sensitivity based on serum PSA of 3 ng/ml was estimated to be 0.89 (95% confidence interval 0.84-0.93) and that based on PSA of 4 ng/ml combined with an ancillary test (digital rectal examination or free total PSA ratio in the PSA range 3.0-3.9) was 0.87 (0.82-0.92). Test sensitivity achieved with serum PSA in prostate cancer screening appears excellent in the context of a population-based effectiveness trial.     

The impact of prostate-specific antigen level at diagnosis on the relative survival of 28,531 men with localized carcinoma of the prostate

BACKGROUND: To evaluate the predictive value of prostate-specific antigen (PSA) in a population-based cohort, the authors analyzed relative survival in all men with localized prostate cancer who were registered in the Swedish National Prostate Cancer Register (NPCR) from 1996 to 2005. METHODS: All men aged <75 years with localized tumors were identified in the NPCR. A Poisson regression analysis was performed using observed death as response and the expected death rate as offset. The expected and observed numbers of survivors were calculated with stratification for PSA level and 3 categories of tumor differentiation (Gleason score 2-6, 7, and 8-10). The regression model included PSA as linear splines with a breakpoint at a PSA level of 4 ng/mL and with tumor differentiation as a categoric variable. RESULTS: The Poisson regression analysis indicated a U-shaped curve for all 3 groups, with a negative correlation between PSA and relative survival in men with PSA levels <4 ng/mL and a positive correlation for men with PSA levels >4 ng/mL. The correlation was significant for all 3 groups, but the negative correlation between PSA and relative survival was significantly more pronounced in the group with Gleason scores from 8 to 10 than in the other 2 Gleason score groups. CONCLUSIONS: The demonstration of an inverse correlation between PSA level and relative survival in the group of men with PSA levels <4 ng/mL indicated the presence of a small but clinically important subgroup with undifferentiated tumors who have cells that have lost the ability to secrete PSA. This group should be taken into consideration when deciding on treatment and when choosing a cutoff level in PSA screening programs.     

Risk factors for prostate cancer: A national case-control study

Statutory notification of cancer in New Zealand provided an opportunity to investigate risk factors for prostate cancer in a large national population-based case-control study. We analyzed data obtained from telephone interviews with 923 cases and 1,224 controls. For inclusion in the study, all subjects had to have been married at some time. We found an increased risk of prostate cancer among those with a history of prostate cancer in first degree relatives (RR 2.6; 95% CI, 1.9-3.7) and an increased risk of prostate cancer with length of marriage among men married only once and still married at interview. For a consecutive subgroup of 550 cases and 819 controls, data on height and weight at age 20 and at 5 years before interview were collected. Men less than or equal to 1.7 m in height at age 20 years had a lower risk of prostate cancer than men taller at that age. There was no association between weight or body mass index and risk of prostate cancer.     

Long-term outcomes of radical prostatectomy with multimodal adjuvant therapy in men with a preoperative serum prostate-specific antigen level > or =50 ng/mL

BACKGROUND.

The authors evaluated the long‐term outcomes of men with prostate cancer and very high (≥50 ng/mL) preoperative serum prostate‐specific antigen (PSA) values that were treated with radical prostatectomy.

METHODS.

This study included 236 men with preoperative serum PSA values ≥50ng/mL who underwent radical retropubic prostatectomy between 1987 and 2004. For comparison, the study cohort was divided into 2 groups: patients with PSA levels between 50 and 99 ng/mL and patients with PSA levels ≥100 ng/mL. Biochemical recurrence was defined as a single postoperative serum PSA value of 0.4 ng/mL or greater. Systemic disease progression was defined as the development of a local recurrence or systemic metastases, and any death resulting from prostate cancer or its treatment was defined as a cancer‐specific mortality.

RESULTS.

Biochemical recurrence‐free survival rates in the groups of patients with a PSA level 50 to 99 ng/mL and ≥100 ng/mL were 43% and 36% at 10 years, respectively. Systemic progression‐free survival rates in the PSA 50 to 99 ng/mL and PSA ≥100 ng/mL groups were 83% and 74% at 10 years, respectively. Estimated overall cancer‐specific survival was 87% at 10 years.

CONCLUSIONS.

Patients with prostate cancer and a serum PSA level ≥50 ng/mL have very high‐risk prostate cancer that carries a high likelihood of being pathologically advanced. Although the probability of realizing long‐term survival in these high‐risk patients is less than in patients with more favorable disease, 10‐year survival outcomes remain excellent and argue for aggressive management of these cases. Cancer 2008. © 2008 American Cancer Society.     

Higher prostate-specific antigen levels predict improved survival in patients with hormone-refractory prostate cancer who have skeletal metastases and normal serum alkaline phosphatase

BACKGROUND: Higher prostate-specific antigen (PSA) and alkaline phosphatase (ALK-P) levels predicted worse survival in men with metastatic hormone-refractory prostate cancer (HRPC). In the current study, the authors evaluated the combined effects of PSA and ALK-P on survival. METHODS: Two hundred twenty-four men who had HRPC with bone metastases and who were receiving chemotherapy were identified, and 143 of those men had data available on both ALK-P and PSA levels at chemotherapy initiation. The primary endpoint of the study was overall survival (OS) after chemotherapy. The men were dichotomized into normal and abnormal ALK-P groups according to levels based on institutional normal ranges. The effect of PSA was evaluated as both a categorical value and a continuous value using Cox regression. RESULTS: Eighty-nine of 143 patients (62%) had elevated ALK-P levels. The median PSA was 147 ng/mL (93 ng/mL in patients with normal ALK-P, 171 ng/mL in patients with elevated ALK-P). At a median follow-up of 30 months after chemotherapy initiation, 93 patients had died. The median OS after chemotherapy was 15.8 months (95% confidence interval, 12.8-18.4 months) and was significantly longer if ALK-P was in the normal range (21.3 months vs 14 months; P = .005). For the group with normal ALK-P levels, the median OS was 12.5 months, 24.5 months, and 36.9 months for patients with low, medium, and high PSA levels, respectively. In contrast, the effect of PSA on survival was not as evident in the group with elevated ALK-P levels (16.5 months vs 11.9 months vs 12.1 months, respectively; P = .14 for interaction). Age-adjusted multivariate analysis demonstrated statistically significant interactions of PSA and ALK-P with OS (P = .02). CONCLUSIONS: ALK-P significantly predicted OS in men with HRPC who had bone metastases. In patients with normal ALK-P levels, higher PSA levels were associated with improved survival.