Increasing Prostate-specific Antigen Levels Research Articles

Prostate‐specific antigen levels in relation to cadmium exposure and zinc intake: results from the 2001–2002 national health and nutrition examination survey

Cadmium exposure has been suggested as a risk factor for prostate cancer, and experimental literature suggests that the carcinogenic effect of cadmium is modified by the presence of zinc. We evaluated total prostate-specific antigen (PSA) levels in relation to urinary cadmium concentrations and dietary zinc intake. PSA levels were determined in 1,320 men over the age of 40 in the 2001-2002 National Health and Nutrition Examination Survey (NHANES). Urinary cadmium concentrations were measured in about one-third of the sample population, whereas dietary zinc intake was based on participants' 24-hr recall. Information on all three variables was available for 422 men in the 2001-2002 NHANES survey. We performed linear regressions to evaluate the relationships these factors after accounting for age and other covariates. Little evidence for an association between cadmium and elevated PSA level was observed. However, the data provide suggestive evidence for an interaction between zinc intake and cadmium exposure (P for interaction=0.09). Among men with zinc intake less than the median level of 12.67 mg/day, an increase in 1 microg/g creatinine cadmium exposure was associated with a 35% increase in PSA level. In contrast, among men with greater than median zinc intake, little evidence for an association between cadmium and PSA was found. These findings suggest a protective effect of zinc intake on cadmium-induced prostatic injury, and may provide further rationale for investigating the impact of these factors individually and jointly on the etiology of prostate cancer.

PSA Kinetics and PSA Bounce Following Permanent Seed Prostate Brachytherapy

To report the incidence, timing, and magnitude of the benign prostate-specific antigen (PSA) bounce after 125I prostate brachytherapy and correlate the bounce with clinical and/or dosimetric factors. From March 1999 to August 2003, a total of 292 men received 125I prostate brachytherapy without androgen deprivation or supplemental beam radiotherapy and have PSA follow-up >30 months. Implants were preplanned using transrectal ultrasound (TRUS) and performed under transrectal ultrasound/fluoroscopy guidance using preloaded needles. A PSA bounce is defined as an increase >or=0.2 ng/ml with spontaneous return to prebounce level or lower. Resolved PSA bounces were seen in 40% of men with follow-up >30 months. Median onset was 15 months, and median magnitude was 0.76 ng/ml. Magnitude >2 ng/ml was seen in 15%. The only clinical or dosimetric factor predictive of bounce in multivariate analysis was younger age. Median time to increasing PSA level indicative of failure was 30 months. Benign PSA bounces are common after 125I prostate brachytherapy, especially in younger men. An increase >2 ng/ml above the nadir was seen in 15%. Magnitude of increase does not distinguish bounce from failure. Time to the start of the PSA increase can be helpful, but is not absolute. The PSA bounce does not predict subsequent failure. Caution is advised in interpreting an early increasing PSA level in the first 30 months after 125I brachytherapy in favorable-risk patients.

Evaluation of [11C]‐choline positron‐emission/computed tomography in patients with increasing prostate‐specific antigen levels after primary treatment for prostate cancer

To evaluate [(11)C]-choline positron-emission tomography (PET)/computed tomography (CT) for detecting clinical recurrence after primary treatment for prostate cancer. In all, 50 patients with prostate cancer who had had initial therapy (radical prostatectomy in 40, external beam radiation in three and interstitial brachytherapy in seven) had PET/CT using [(11)C]-choline in the presence of an increased or increasing prostate-specific antigen (PSA) level. The mean (range) time to biochemical progression was 22 (2-136) months. Current PSA levels were determined in all patients at the time of examination. The results were correlated with the histopathology reports after targeted biopsy or surgery, and with the clinical follow-up. The mean (median, range) PSA level in patients with positive PET/CT was 3.62 (2.42, 0.5-13.1) ng/mL, and that in patients with a negative scan was 0.90 (0.95, 0.41-1.40) ng/mL. PET/CT was positive in seven of 13 patients with a PSA level of <1.5 ng/mL, and histology was positive in this group in nine. In 17 patients with PSA levels of 1.5-2.5 ng/mL PET/CT was positive in all and the histology was positive in 13; in 11 men with a PSA level of 2.5-5 ng/mL PET/CT was positive in all 11 and the histology was positive in 10; in nine men with PSA levels of >5 ng/mL PET/CT identified all as positive and the histology was positive in eight. The sensitivity at a PSA level of <2.5 ng/mL of PET/CT for detecting recurrence was 91% (95% confidence interval, 71-99%) with a specificity of 50% (16-84)%. [(11)C]-choline PET/CT seems to be useful for re-staging prostate cancer after curative therapy and with increasing PSA levels; this was verified by histological examination. We recommend this method at PSA levels of <2.5 ng/mL.

Prostate-Specific Antigen Level at Initiation of Hormonal Therapy After Prostate-Specific Antigen Failure Following Prostatectomy or Radiotherapy and Therapeutic Response

To determine the pretreatment factors associated with an undetectable prostate-specific antigen (PSA) nadir after 8 months of androgen suppression therapy (AST). The study cohort comprised 137 men with an increasing PSA level after surgery or radiotherapy performed for localized prostate cancer who had undergone AST. Cox regression multivariate analyses were used to identify the factors associated with a PSA nadir of 0.2 ng/mL or less 8 months after AST initiation. The PSA level at the initiation of AST was associated with a PSA nadir of 0.2 ng/mL or less after 8 months of AST, as both a continuous variable (adjusted odds ratio [OR] 0.44, P = 0.0001) and a categorical variable, with PSA greater than 10 ng/mL (OR 0.16, P = 0.007). The percentage of patients with a PSA nadir of 0.2 ng/mL or less was 86%, 72%, 75%, 67%, and 25% for men with a PSA level at the initiation of AST of 4 ng/mL or less, greater than 4 to 10 ng/mL, greater than 10 to 20 ng/mL, greater than 20 to 50 ng/mL, and greater than 50 ng/mL, respectively. An elevated PSA level before the initiation of AST was significantly associated with a decreased chance of a PSA nadir of 0.2 ng/mL or less after 8 months of AST. Given the association between the PSA nadir after AST and prostate-cancer specific mortality, men with increasing PSA levels could be considered for Phase II and III clinical trials evaluating the effect of adding novel systemic therapies to AST on the interval to prostate-cancer specific mortality.

Effect of Nutritional Supplement Challenge in Patients with Isolated High-Grade Prostatic Intraepithelial Neoplasia

To investigate, through a prospective follow-up study, the effects of a dietary supplementation challenge in men with isolated high-grade prostatic intraepithelial neoplasia (HGPIN). The effects of a 6-month supplementation challenge with selenium, vitamin E, and soy isoflavonoids in men diagnosed with isolated HGPIN on biopsy were evaluated. A total of 100 patients entered the study. Of the 100 men, 29 were excluded because they refused additional biopsies or were noncompliant with the protocol, 71 underwent repeat biopsies at 3 months, and 58 underwent a third set at 6 months. The prostate-specific antigen (PSA) level was recorded at inclusion and before each set of biopsies. The study endpoint was defined as the diagnosis of PCa at 3 months or the histopathologic status at 6 months. At the study endpoint, PCa had been found in 24 men (33.8%), HGPIN in 34 (47.9%), and no HGPIN or carcinoma in 13 (18.3%). The PCa risk throughout the study period was 25.0% in the group with a stable or decreasing PSA level (n = 48, 67.6%) and 52.2% in the group with an increasing PSA level (n = 23, 32.4%). This difference was statistically significant (P = 0.0458). Isolated HGPIN remaining at the first repeat biopsy and the percentage of initial cores with HGPIN were significant predictors of PCa at additional biopsies. The results of our study have shown that a decrease in the PSA level while taking a selenium, vitamin E, and soy isoflavonoids supplement predicts for a significantly lower risk of PCa in future biopsies. The percentage of initial biopsy cores with HGPIN and isolated HGPIN remaining at the first repeat biopsy are significant predictors of PCa in future biopsies.

Palliative Treatment of Bone Metastases in Hormone-Refractory Prostate Cancer: Effects of Pamidronate on the Carboxyterminal Telopeptide of Type-I Collagen Level in Patients with Increasing Prostate-Specific Antigen Levels

Purpose: Bisphosphonates have been reported to be effective in reducing bone pain and skeletal-related events associated with bone metastases in hormone-refractory prostate cancer (HRPC). However, whether bone resorption is reduced primarily by these particular drugs is difficult to evaluate because patients with HRPC are usually treated with secondary or tertiary hormonal manipulations including second-line antiandrogens, high-dose diethylstilbestrol, or low-dose dexamethasone therapies, some of which may also be effective. Thus, we assessed changes in the level of the carboxyterminal telopeptide of type-I collagen (ICTP), a bone resorption marker, before and after pamidronate administration in HRPC patients with increasing prostate-specific antigen (PSA) levels. Patients and Methods: Twenty-one HRPC patients with bone metastases and increasing PSA levels were intravenously treated with pamidronate at a dose of 30 mg either every 2 or every 4 weeks. Pamidronate administration was started immediately after confirmation of three consecutive increases in the PSA level. Results: In 14 patients (67%), the ICTP levels decreased after the administration of pamidronate, despite increasing PSA levels. In 7 of these cases, the ICTP levels were lower than those recorded for 6 months or longer before the start of pamidronate administration. The characteristics of the responders were compared with those of the non-responders. Conclusion: In 67% of the HRPC patients with increasing PSA levels, pamidronate reduced the accelerated turnover of bone metabolism caused by metastases of prostate cancer.

Fluctuating prostate‐specific antigen levels in patients with initial negative biopsy: should we be reassured?

To evaluate whether the risk of having a positive repeat prostate biopsy is lower in patients with fluctuating prostate-specific antigen (PSA) levels than in patients with a steady or steadily increasing PSA level. Files were extracted from the 2000-2003 databases of two teaching hospitals; 191 patients who had a first negative biopsy followed by one or more sets of biopsies and at least two PSA measurements were included. A 'fluctuating PSA level' in a patient was defined as a PSA series including at least one PSA value lower than the one immediately preceding it. The median PSA level at the first biopsy was 7 ng/mL, while that for the second, third and fourth biopsies were 8.0, 8.0 and 8.7 ng/mL, respectively. The median time between the first and second, and the second and third PSA tests was 290 and 317 days, respectively. Prostate cancer was eventually detected in 53 men (27.7%) in whom 39 it was at the first repeat biopsy. Among the 79 patients with a fluctuating PSA level, 17 (22%) had prostate cancer, vs 36 (32%) among the 112 with a 'steady' PSA level; the difference was not significant (P=0.14). When considering the 53 patients diagnosed with prostate cancer, the 17 with a fluctuating PSA level and the 36 others had no significant difference in age, T stage, first PSA level and Gleason score. In the present study, by contrast with the common and unfounded view, the risk of having a positive repeat prostate biopsy was no lower in men with a fluctuating PSA level than in those with a steady or steadily increasing PSA level. The practical and economical implications warrant further studies to confirm these findings.

Comparison of calcaneal bone density in operative versus non-operative army personnel

Purpose: To study the response of nonmalignant prostatic tissue to ionizing irradiation in terms of the resultant changes in serum prostate specific antigen (PSA) levels.Methods and Materials: Weekly serum PSA values were determined during radiotherapy (RT)_in nine patients (“treatment group”) without clinical evidence of prostate cancer (PC), and who received pelvic RT for other indications. Slopes fr the rate of change in PSA was determined using model: log PSA = β0 + β1∗week + β2∗week2 + error. These results are compared with 17 normal volunteers (“control group”) who were not exposed to ionizing irradiation. an attempt is made to compare any similarities and differences in subsets of 64 T1–T4NOMO PC patients who received pelvic RT.Results: An elevation in the serum PSA levels were noted in eight of nine patients in the “treatment group” with a median time of 4.2 weeks to reach the maximum serum PSA values. After an initial increase, PSA values declined. In some patients, manifold increase in PSA was noted, for exampel, from 1.8 to 13.5 ng/ml and 3.3 to 9.8 ng/ml in two patients. The PSA increase ranged from 50–650%. The median slope was 0.601 week−1 (range 0.192–3.045 week−1). No such increases were seen in the “control group” (median slope = 0.03 week−1; range, 0.18–0.13 week−1). When diffrences between the mean increase/decrease for each week compared to pretreatment values were analyzed, the irradiated group had statistically significant elevations in the PSA for weeks 3 (p = 0.034), 4 (p = 0.24). A similar ternd of increasing PSA levels during radiotherapy was noted in prostate cancer patients whose initial PSA values were ≤ 20 ng/ml: whereas positive slopes (i.e., increasing PSA levels during radiotherapy course) was seen in 7.1% of those with > 20 ng/ml preradiotherapy PSA values, such trends were seen in52.7% of those with ≤ 20 ng/ml preradiotherapy PSA values.Conclusion: (a) Incidental exposure of noncancerous prostate to ionizing irradiation appears to lead to an initial elevation followed by a decline in serum PSA. (b) Similar elevations in serum (PSA) levels are seen in over 50% of prostate cancer patients with ≤ 20 ng/ml pretreatment PSA. (c) Acinal cell death and sudden release of PSA into the circulation is the most likely explanation for our observations, although other mechanism cannot be excluded. (d) Our observations have to be considered in modeling PSA kinetics induced by RT and in correlating such kinetics to long-term outcomes. (e0 Our findings in the control group indicate that there appears to be no significant variation in serum PSA over many weeks under physiological conditions in normal healthy ambulatory men.

Influence of body mass index on prostate‐specific antigen failure after androgen suppression and radiation therapy for localized prostate cancer

Increasing body mass index (BMI) is associated with shorter time to prostate-specific antigen (PSA) failure after radical prostatectomy. Whether BMI is associated with time to PSA failure was investigated in men treated with androgen suppression therapy (AST) and radiation therapy (RT) for clinically localized prostate cancer. The observational prospective cohort study consisted of 102 men with clinically localized prostate cancer who received 70 Gy RT with 6 months of AST on a single arm of a randomized trial between December 1995 and April 2001. Height and weight data were available at baseline for 99 (97%) of the men, from which BMI was calculated. Adjusting for age (continuous) and known prognostic factors including PSA level (continuous), Gleason score, and T-category, Cox regression analyses were performed to analyze whether BMI (continuous) was associated with time to PSA failure (PSA >1.0 ng/mL and increasing >0.2 ng/mL on 2 consecutive visits). Median age and median BMI (interquartile range [IQR]) at baseline was 72 (69.1-74.7) years and 27.4 (24.8-30.7) kg/m,(2) respectively. In addition to an increasing PSA level (P = .006) and Gleason 8-10 cancer (P = .024), after a median follow-up (IQR) of 6.9 (5.6-8.5) years, an increasing BMI was also significantly associated with a shorter time to PSA failure (adjusted hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.01-1.19; P = .026) after RT and AST. After adjusting for known prognostic factors, baseline BMI is significantly associated with time to PSA failure after RT and AST for men with clinically localized prostate cancer. Further study is warranted to assess the impact of an increasing BMI after AST administration on PSA failure, prostate cancer-specific, and all-cause mortality.

Long-term effectiveness of luteinizing hormone-releasing hormone agonist or antiandrogen monotherapy in elderly men with localized prostate cancer (T1-2) : a retrospective study

To evaluate the long-term effectiveness, side effects and compliance rates of two types of drugs (luteinizing hormone-releasing hormone [LHRH] agonist and antiandrogen) that were used individually to treat patients with localized prostate cancer (T1-2) at our institution. Ninety-seven patients who were diagnosed in the period from April 1997 to January 2000 as having clinically localized prostate cancer (T1-2) received either LHRH agonist (leuprolide acetate 7.5 mg/month) monotherapy (group 1, n = 62) or antiandrogen monotherapy (group 2, n = 35; 18 received bicalutamide 50 mg q.d., 13 received nilutamide 150 mg t.i.d. and 4 received flutamide 250 mg t.i.d.). The mean age in both groups was 76 years. The mean follow-up time was (50.8 +/- 8.5) months in group 1 and (43.1 +/- 2.2) months in group 2. Prostate-specific antigen (PSA) levels rose in only 1 of the 62 patients (1.6%) in group 1, and in 20 of the 35 patients (57.1%) in group 2. In group 2, 10 of the 20 patients (50%) with increasing PSA levels were treated with LHRH salvage therapy, and eight (80%) responded. Hot flashes (54.8%) and lethargy (41.9%) were the most common side effects in group 1. In contrast, nipple-tenderness (40%) and light-dark adaptation (17.1%) were more often seen in group 2. Only 1 of the 62 patients (1.6%) in group 1 switched to another medication because of adverse side effects; whereas 8 of the 35 patients (22.9%) in group 2 did so. Unlike antiandrogen monotherapy, LHRH agonist monotherapy provided long-term durable control of localized prostate cancer (T1-2). It can also be an effective treatment option for patients whose disease failed to respond to antiandrogen monotherapy. The limitations of our study are the lack of health outcomes analysis and a small sample size.

Transdermal oestrogen therapy as a second‐line hormonal intervention in prostate cancer: a bad experience

To compare transdermal oestrogen with oral diethylstilbestrol (DES) as a second- or third-line hormonal therapy in the treatment of prostate cancer. In all, 32 assessable patients who, having already had a relapse on at least one line of hormonal therapy, received transdermal oestrogen therapy as an alternative to oral DES, when DES became unavailable. Whereas DES had controlled the prostate-specific antigen (PSA) level for a median of 29 weeks in a group of 15 patients in remission, all but one had an increase in PSA level (median 86% increase above the starting PSA level) within a median of 8 weeks after introducing transdermal therapy. This increase was reversed in seven of the 12 patients who recommenced DES therapy. Although the use of transdermal oestrogen is currently attracting enthusiasm as a first-line treatment for prostate cancer, these results show that for second- or third-line therapy further cautious research with careful monitoring is necessary.

2309: The Influence of Body Mass Index on PSA Failure Following Androgen Suppression and Radiation Therapy for Localized Prostate Cancer

Increasing body mass index (BMI) has been shown to be associated with a shorter time to prostate specific antigen (PSA) failure following radical prostatectomy. We investigated whether BMI is associated with time to PSA failure in men treated with radiation therapy (RT) and androgen suppression therapy (AST) for clinically localized prostate cancer. Between December 1995 and April 2001, 102 of 206 men with clinically localized prostate cancer, enrolled on a prospective randomized trial, received 70 Gy 3-dimensional conformal RT with 6 months of AST. Height and weight data were available at randomization for 99 of the 102 (97%) men and from which BMI was calculated. Adjusting for age (continuous) and the known prognostic factors including the PSA level (continuous), Gleason score (GS) and T-category, Cox regression analyses were performed to analyze whether BMI (continuous) was associated with time to PSA failure (PSA>1.0 ng/ml and increasing >0.2 ng/ml on 2 consecutive visits). The median age and median BMI [interquartile range (IQR)] at randomization was 72 (69.1 to 74.7) years and 27.4 (24.8 to 30.7) kg/m2, respectively. As shown in the Table, in addition to an increasing PSA level (p=0.006) and Gleason 8 to 10 cancer (p=0.024), after a median follow-up (IQR) of 6.9 (5.6 to 8.5) years, an increasing BMI was also significantly associated with a shorter time to PSA failure [adjusted hazard ratio (HR) 1.10; 95% confidence interval (CI) 1.01 to 1.19; p=0.026] following RT and AST.Tabled 1CovariateNo. MenPSA FailureNo. EventsUVAMVAHR [95% CI]P-ValueHR [95% CI]P-ValueBMI (continuous)99251.11 (1.02, 1.20)0.0181.10 (1.01, 1.19)0.026PSA (continuous)99251.06 (1.02, 1.11)0.0041.07 (1.02, 1.13)0.006Age (continuous)99250.94 (0.87, 1.01)0.0860.98 (0.91, 1.06)0.624GS 6 or less3381.0—1.0—GS 756120.88 (0.36, 2.15)0.7771.36 (0.46, 4.0)0.580GS 8 to 101052.56 (0.84, 7.85)0.0994.35 (1.22, 15.5)0.024T154101.0—1.0—T245152.14 (0.96, 4.78)0.0621.69 (0.73, 3.94)0.223UVA: univariable analysis; MVA: multivariable analysis. Open table in a new tab UVA: univariable analysis; MVA: multivariable analysis. After adjusting for known prognostic factors, baseline BMI is significantly associated with time to PSA failure following RT and AST for men with clinically localized prostate cancer. Further study is warranted to assess the impact of an increasing BMI following AST administration on PSA failure, prostate cancer-specific and all-cause mortality.

Active surveillance versus radical treatment for favorable-risk localized prostate cancer

Widespread prostate-specific antigen (PSA) screening in North America has resulted in a profound stage migration and a marked increase in incidence. One in six men is now diagnosed, many with small-volume, low-grade cancer. This incidence is dramatically higher than the 3% lifetime risk of prostate cancer death that characterized the pre-screening era. This article summarizes the case for active surveillance for "favorable-risk" prostate cancer with selective delayed intervention for rapid biochemical progression, assessed by increasing PSA levels, or grade progression. The results of a large phase II trial using this approach are reviewed. To date, this study has shown that virtually all men with favorable-risk prostate cancer managed in this fashion will die of unrelated causes. Based on the Swedish randomized trial of radical prostatectomy versus watchful waiting, the Connecticut observation series, and the Toronto active surveillance experience, a number needed to treat analysis of the benefit of radical treatment of all newly diagnosed favorable-risk prostate cancer patients, compared with a strategy of active surveillance with selective delayed intervention, is presented. This suggests that approximately 73 patients will require radical treatment for each prostate cancer death averted. This translates into a 3- to 4-week survival benefit, unadjusted for quality of life. This figure is confirmed based on an analysis of the 2004 D'Amico et al. PSA velocity data in favorable-risk disease. The approach of active surveillance with selective delayed intervention based on PSA doubling time and repeat biopsy represents a practical compromise between radical therapy for all patients (which results in overtreatment for patients with indolent disease) and watchful waiting with palliative therapy only (which results in undertreatment for those with aggressive disease).

Mass screening for prostate cancer in patients with end‐stage renal disease: a comparative study

To determine the usefulness of prostate-specific antigen (PSA) screening for prostate cancer in patients with end-stage renal disease (ESRD), as although serum PSA is effective in the early detection of this cancer in the general population, there are few reports of its utility in patients with ESRD. Blood samples were obtained for PSA screening from April 2002 to September 2003; 1250 men with ESRD aged >50 years were compared with 1007 healthy control men aged >55 years, all in Kumamoto Prefecture, Japan. All men with a serum PSA level of >4.0 ng/mL were categorized as PSA-positive and were further assessed, including a prostate biopsy. There was a statistically significantly greater increase in PSA level with age in the ESRD group than in the healthy controls. The rate of cancer detection among men with a PSA level of >10 ng/mL was significantly higher in patients with ESRD than in healthy controls. Thirteen patients with ESRD and five healthy control men were finally diagnosed with prostate cancer. The serum PSA level was slightly higher and the incidence of prostate cancer at higher PSA levels appeared to be greater in men with ESRD than in healthy controls. The findings of this large study suggest that PSA screening is useful for the diagnosis of prostate cancer in these patients.

Prostate volume and prostate-specific antigen levels in men enrolled in a large screening trial

Objectives Prostate volume correlates both with prostate-specific antigen (PSA) values and with the presence of benign prostatic hyperplasia (BPH). Here we examine the relationship between prostate volume and PSA level in a large, geographically diverse sample of men undergoing prostate cancer screening. Methods We followed 35,323 men enrolled in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Each man was screened with digital rectal examination (DRE) and PSA levels for up to 4 years. Prostate volume was estimated by DRE performed by trained examiners at the PLCO sites. Linear and logistic regression was used to assess the effect of prostate volume and age on PSA levels. Regression coefficients were adjusted for the effect of prostate volume measurement error. Results Prostate volume estimated by DRE showed considerable measurement error. Averaging volume over screening visits and accounting for examiner bias greatly reduced this error. Linear regression analysis showed a slope of 0.030/cm 3 of log PSA on prostate volume when correcting for measurement error (95% confidence interval [CI], 0.029 to 0.031). Age was independently associated with (log) PSA, with a slope of 0.022 per year. Logistic regression analysis of the risk of having an elevated PSA value (exceeding 4 ng/mL) showed an odds ratio of 1.9 (95% CI, 1.8 to 2.0) associated with a 10 cm 3 increase in prostate volume. The correlation of log PSA and prostate volume was 0.37. Prostate volume was not correlated with body mass index and showed weak correlation ( r = 0.14) with age. Conclusions Prostate volume and age are independently associated with increased PSA levels in a population of men undergoing screening.

Effect of the consumption of tomato paste on plasma prostate-specific antigen levels in patients with benign prostate hyperplasia

The consumption of tomatoes and tomato products has been associated with a reduced risk of prostate cancer. We observed a decrease of 10.77% in prostate-specific antigen (PSA) levels in patients with benign prostate hyperplasia who were submitted to daily ingestion of tomato paste. This was an experimental rather than a controlled study with a sample of 43 men ranging in age from 45 to 75 years, all with histological diagnoses of benign prostate hyperplasia and plasma PSA levels of 4-10 ng/mL. All patients received 50 g of tomato paste once a day for 10 consecutive weeks and PSA levels were analyzed before, during and after the consumption of tomato paste. ANOVA for repeated measures was used to compare PSA levels before, during and after the consumption of tomato paste. The mean +/- SD PSA level was 6.51 +/- 1.48 ng/mL at baseline and 5.81 +/- 1.58 ng/mL (P = 0.005) after 10 weeks. Acceptance was good in 88.3, regular in 9.3, and poor in 2.3% of the patients. Dietary ingestion of 50 g of tomato paste per day for 10 weeks significantly reduced mean plasma PSA levels in patients with benign prostate hyperplasia, probably as a result of the high amount of lycopene in tomato paste. This was not a prostate cancer prevention study, but showed some action of tomato paste in prostate biology. The development of prostate cancer is typically accompanied by an increase in plasma PSA levels, thus any intervention that affects plasma PSA levels can suggest an impact in the progression of disease.

A phase II trial of imatinib mesylate in patients with biochemical relapse of prostate cancer after definitive local therapy

To determine the biological effects of imatinib mesylate (STI-571, Gleevec; Novartis Pharmaceuticals, Inc., East Hanover, NJ, USA), as measured by prostate-specific antigen (PSA) kinetics in men with biochemical relapse of prostate cancer after definitive local therapy. Men with prostate cancer, who had had definitive local therapy, with nonmetastatic recurrent disease as manifested by a rising PSA level, were enrolled on this phase II trial. Men received 400 mg of imatinib mesylate orally twice daily and continuously until disease progression or unacceptable toxicity. The PSA level was measured monthly. In all, 20 men with biochemically relapsed prostate cancer were treated. The median pretreatment PSA level was 5.4 ng/mL. Of the 19 evaluable men, one achieved a >or= 50% reduction in PSA level and two had decreases of <50%. For the 16 men in whom the on-treatment PSA doubling time (PSADT) could be calculated (those with increasing PSA level) the median PSADT did not increase significantly (5.8 vs 7.2 months, P = 0.64). Eleven of 20 men discontinued therapy due to toxicity and the trial was stopped early due to toxicity. Based on the lack of PSA modulation and pronounced toxicities leading to early closure of this trial, further study of single-agent imatinib mesylate at this dose (400 mg twice daily) cannot be recommended in this patient population.

MRI-Guided Biopsy of the Prostate Increases Diagnostic Performance in Men with Elevated or Increasing PSA Levels after Previous Negative TRUS Biopsies

ObjectivesRepeatedly negative prostate biopsies in individuals with elevated prostate specific antigen (PSA) levels can be frustrating for both the patient and the urologist. This study was performed to investigate if magnetic resonance imaging (MRI)-guided transrectal biopsy increases diagnostic performance in individuals with elevated or increasing PSA levels after previous negative conventional transrectal ultrasound (TRUS)-guided biopsies. Methods27 consecutive men with a PSA >4ng/ml and/or suspicious finding on digital rectal examination, suspicious MRI findings, and at least one prior negative prostate biopsy were included. Median age was 66 years (mean, 64.5±6.8); median PSA was 10.2ng/ml (mean, 11.3±5.5). MRI-guided biopsy was performed with a closed unit at 1.5Tesla, an MRI-compatible biopsy device, a needle guide, and a titanium double-shoot biopsy gun. ResultsMedian prostate volume was 37.4cm3 (mean, 48.4±31.5); median volume of tumor suspicious areas on T2w MR images was 0.83cm3 (mean, 0.99±0.78). The mean number of obtained cores per patient was 5.22±1.45 (median, 5; range, 2–8). Prostate cancer was detected in 55.5% (15 of 27) of the men. MRI-guided biopsy could be performed without complications in all cases. ConclusionAccording to our knowledge, this is the largest cohort of consecutive men to be examined by MRI-guided transrectal biopsy of the prostate in this setting. The method is safe, can be useful to select suspicious areas in the prostate, and has the potential to improve cancer detection rate in men with previous negative TRUS-biopsies.

Correlation between metabolite ratios and ADC values of prostate in men with increased PSA level

Proton magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted imaging (DWI) were carried out in men with increased prostate-specific antigen (PSA) level. Forty subjects [controls (Group I) and patients (Groups II and III with PSA >20 and 4-20 ng/ml, respectively)] were investigated using endorectal coil at 1.5 T prior to transrectal ultrasound (TRUS)-guided biopsy. Metabolite ratio [citrate/(choline+creatine)] and apparent diffusion coefficient (ADC) were calculated for identical voxels. In patients, voxels that showed lower metabolite ratio showed reduced ADC in the peripheral zone (PZ) of the prostate, and voxels with increased metabolite ratio showed higher ADC. Metabolite ratios were used to predict areas of malignancy if the ratio was <1.4 and if ADC value was <1.17 x 10(-3) mm(2)/s. Patients in Group II had lower metabolite ratio and ADC in the PZ compared to controls and Group III. All 13 were positive for malignancy in MR, while 12 of 13 were positive on TRUS-guided sextant biopsy. In Group III, certain voxels of PZ that showed reduced metabolite ratio also showed lower ADC. A positive correlation was observed between metabolite ratio and ADC. MR predicted areas of malignancy in PZ in 15 of 20 patients; however, only six were positive on TRUS-guided biopsy perhaps due to high false-negative rate of TRUS-guided biopsy. Results show positive correlation between MRSI and DWI and their potential in detection of malignancy, thereby improving the diagnosis especially in patients with PSA level of 4-20 ng/ml.

Weekly Docetaxel/Estramustine Phosphate in Patients with Increasing Serum Prostate-Specific Antigen Levels After Primary Treatment for Prostate Cancer: A Phase II Trial of the Minnie Pearl Cancer Research Network

Purpose Docetaxel alone or in combination with estramustine prolongs survival in patients with metastatic hormone-refractory prostate cancer. The role of chemotherapy is undefined in the treatment of patients who develop an increasing serum prostate-specific antigen (PSA) level after primary therapy but have no detectable metastases. This phase II study was performed as a preliminary evaluation of the feasibility and efficacy of weekly docetaxel/estramustine in patients with prostate cancer and increasing serum PSA levels. Patients and Methods Between March 2001 and September 2003, 34 patients entered this phase II trial. All patients had biopsy-proven adenocarcinoma of the prostate and had increasing PSA levels but no clinically or radiographically detected metastases after primary therapy. All patients received docetaxel 35 mg/m 2 intravenously on days 1, 8, and 15 and estramustine phosphate 140 mg 3 times daily for 7 doses, beginning the evening before each dose of docetaxel. Treatment courses were repeated at 28-day intervals, and responding patients received a total of 6 courses. Results Thirty-one patients (91%) completed 6 courses of treatment. Thirty-two of 33 evaluable patients (97%) had a decrease in serum PSA level of > 50% during treatment, and 27 patients (82%) had normalization of serum PSA level. The median progression-free survival was 28 months, with 33% of patients progression free at 3 years. This treatment regimen was well tolerated with no myelosuppression-related complications or uncommon grade 3 nonhematologic toxicity. Conclusion Treatment with weekly docetaxel and estramustine is feasible and active in patients with prostate cancer and increasing serum PSA levels. However, the benefit of early treatment versus treatment when clinical metastases are detected requires demonstration in a randomized phase III trial.