Determining Clinically Based Factors Associated With Reclassification in the Pre-MRI Era using a Large Prospective Active Surveillance Cohort.

OBJECTIVE: To report biopsy-related and oncologic outcomes in a large prospective active surveillance cohort that was initiated in the premagnetic resonance imaging era and to additionally identify clinical factors associated with disease reclassification in order to inform future studies designed to improve enrollment and follow-up on active surveillance. METHODS: Patients were prospectively enrolled at a single institution from 2006 to 2014 and followed until 2016. Men with Gleason 6 or 7 disease were eligible, and those with >6 months follow-up were included in the analysis. Patients were risk stratified based on clinical/pathologic criteria, including based on a combination of baseline and confirmatory biopsy tumor characteristics. Reclassification-free survival, based on tumor volume increase or Gleason score increase, was analyzed using multivariable Cox proportional hazards models. RESULTS: Of 825 enrolled patients, 682 met inclusion criteria. Median follow-up was 40 months (range 6.6-126.8). Disease was reclassified in 249 (36.5%), and 157 (23.0%) underwent treatment. A single positive core with a negative confirmatory biopsy was significantly associated with time to reclassification (median not met vs 43 months, log rank test P <.001). Composite tumor length, defined as the combined tumor length between baseline and confirmatory biopsies, was associated with shorter Gleason upgrade-free survival (hazard ratio 1.24, 95% confidence interval 1.11-1.40, P <.001) in multivariable analysis. CONCLUSION: Baseline stratification using clinical factors including tumor length may refine risk stratification and offer the foundation on which new systems that incorporate modalities such as magnetic resonance imaging may be based.

Prostate specific antigen best practice statement: 2009 update.

PURPOSE: We provide current information on the use of PSA testing for the evaluation of men at risk for prostate cancer, and the risks and benefits of early detection. MATERIALS AND METHODS: The report is a summary of the American Urological Association PSA Best Practice Policy 2009. The summary statement is based on a review of the current professional literature, clinical experience and the expert opinions of a multispecialty panel. It is intended to serve as a resource for physicians, other health care professionals, and patients. It does not establish a fixed set of guidelines, define the legal standard of care or pre-empt physician judgment in individual cases. RESULTS: There are two notable differences in the current policy. First, the age for obtaining a baseline PSA has been lowered to 40 years. Secondly, the current policy no longer recommends a single, threshold value of PSA, which should prompt prostate biopsy. Rather, the decision to proceed to prostate biopsy should be based primarily on PSA and DRE results, but should take into account multiple factors including free and total PSA, patient age, PSA velocity, PSA density, family history, ethnicity, prior biopsy history and comorbidities. CONCLUSIONS: Although recently published trials show different results regarding the impact of prostate cancer screening on mortality, both suggest that prostate cancer screening leads to overdetection and overtreatment of some patients. Therefore, men should be informed of the risks and benefits of prostate cancer screening before biopsy and the option of active surveillance in lieu of immediate treatment for certain men diagnosed with prostate cancer.

Presurgical stress management improves postoperative immune function in men with prostate cancer undergoing radical prostatectomy.

OBJECTIVE: To assess whether stress management (SM) improved immune outcomes in men undergoing surgery for prostate cancer. METHODS: A total of 159 men were assigned randomly to a two-session presurgical SM intervention, a two-session supportive attention (SA) group, or a standard care (SC) group. Men in the SM group discussed their concerns about the upcoming surgery and were taught diaphragmatic breathing, guided imagery; they had an imaginal exposure to the day of surgery and learned adaptive coping skills. Men in the SA group discussed their concerns about the upcoming surgery and had a semistructured medical interview. Blood samples were collected at baseline (1 month before surgery) and 48 hours after surgery. Measures of mood (Profile of Mood States) were collected at baseline, 1 week pre surgery, and the morning of surgery. RESULTS: Men in the SM group had significantly higher levels of natural killer cell cytotoxicity (p = .04) and higher levels of circulating proinflammatory cytokines (interleukin [IL]-12p70, p = .02; IL-1ß, p = .02; tumor necrosis factor-α, p = .05) 48 hours post surgery than men in the SA group and higher levels of natural killer cell cytotoxicity (p = 0.02) and IL-1ß (p = .05) than men in the SC group. Immune parameters increased for the SM group and decreased or stayed the same for the SA and SC groups. The SM group had significantly lower Profile of Mood States scores than the SC group (p = .006), with no other group differences between SA and SC groups. Changes in mood were not associated with immune outcomes. CONCLUSIONS: The finding that SM leads to decreased presurgical mood-disturbance and increased immune parameters after surgery reveals the potential psychological and biological benefits of presurgical SM.

Critical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging.

BACKGROUND: Knowledge about the staging significance of the prostate cancer antigen 3 (PCA3) score to better identify pathologic features after radical prostatectomy (RP) is limited and controversial. OBJECTIVE: Our aim was to study the clinical staging significance of PCA3 to identify pathologic favorable and/or unfavorable features in the RP specimen. DESIGN, SETTING, AND PARTICIPANTS: Complete retrospective clinical and pathologic data of consecutive men who had undergone RP from three tertiary referral centers including preoperative PCA3 scores (n=305) and computer-assisted planimetrically measured tumor volume data (n=160) were available. INTERVENTION: All patients were treated with RP. MEASUREMENTS: PCA3 scores were assessed using the PROGENSA assay (Gen-Probe, San Diego, CA, USA). Beyond standard risk factors (age, digital rectal examination, prostate-specific antigen, prostate volume, biopsy Gleason score, percentage of positive cores), five different PCA3 codings were used in logistic regression models to identify five distinct pathologic end points: (1) low-volume disease (<0.5 ml), (2) insignificant prostate cancer (PCa) according to the Epstein criteria, (3) extracapsular extension (ECE), (4) seminal vesicle invasion (SVI), and (5) aggressive disease defined as Gleason sum ≥7. Accuracy estimates of each end point were quantified using the area under the curve (AUC) of the receiver operator characteristic analysis in models with and without PCA3. RESULTS AND LIMITATIONS: PCA3 scores were significantly lower in low-volume disease and insignificant PCa (p ≤ 0.001). AUC of multivariable low-volume disease (+2.4 to +5.5%) and insignificant PCa models (+3 to +3.9%) increased when PCA3 was added to standard clinical risk factors. In contradistinction, regardless of its coding, PCA3 scores were not significantly elevated in pathologically confirmed ECE (p=0.4) or SVI (p=0.5), respectively. Higher PCA3 scores were associated with aggressive disease (p<0.001). Importantly, the addition of PCA3 to multivariable intermediate- and high-grade models did not improve prediction. Despite reporting the largest pathologic PCA3 study, the main limitation resides in its small sample size. CONCLUSIONS: PCA3 was confirmed as a valuable predictor of pathologically confirmed low-volume disease and insignificant PCa. Further exploration of its role as an additional marker to select patients for active surveillance may be warranted. In contradistinction, assessment of pathologically advanced or aggressive PCa is not improved using PCA3.

Prostate specific antigen best practice statement: 2009 update.

PURPOSE: We provide current information on the use of PSA testing for the evaluation of men at risk for prostate cancer, and the risks and benefits of early detection. MATERIALS AND METHODS: The report is a summary of the American Urological Association PSA Best Practice Policy 2009. The summary statement is based on a review of the current professional literature, clinical experience and the expert opinions of a multispecialty panel. It is intended to serve as a resource for physicians, other health care professionals, and patients. It does not establish a fixed set of guidelines, define the legal standard of care or pre-empt physician judgment in individual cases. RESULTS: There are two notable differences in the current policy. First, the age for obtaining a baseline PSA has been lowered to 40 years. Secondly, the current policy no longer recommends a single, threshold value of PSA, which should prompt prostate biopsy. Rather, the decision to proceed to prostate biopsy should be based primarily on PSA and DRE results, but should take into account multiple factors including free and total PSA, patient age, PSA velocity, PSA density, family history, ethnicity, prior biopsy history and comorbidities. CONCLUSIONS: Although recently published trials show different results regarding the impact of prostate cancer screening on mortality, both suggest that prostate cancer screening leads to overdetection and overtreatment of some patients. Therefore, men should be informed of the risks and benefits of prostate cancer screening before biopsy and the option of active surveillance in lieu of immediate treatment for certain men diagnosed with prostate cancer.

The effects of a presurgical stress management intervention for men with prostate cancer undergoing radical prostatectomy.

PURPOSE This study assessed the short-term and long-term efficacy of a presurgical stress management intervention at reducing mood disturbance and improving quality of life (QOL) in men undergoing radical prostatectomy (RP) for prostate cancer. PATIENTS AND METHODS One hundred fifty-nine men were randomly assigned to a two-session (plus two boosters) presurgical stress management intervention (SM), a two-session (plus two boosters) supportive attention group (SA), or a standard care group (SC). Assessments occurred 1 month before surgery; 1 week before surgery; the morning of surgery; 6 weeks after surgery, and 6 and 12 months after surgery. Results Results indicated significant group differences in mood disturbance before surgery (P = .02), such that men in the SM group had significantly less mood disturbance than men in the SC group (P = .006), with no significant differences between the SM and SA or SA and SC groups. In the year after surgery, there were significant group differences on Medical Outcomes Study 36-item short form survey (SF-36) physical component summary (PCS) scores (P = .004); men in the SM group had significantly higher PCS scores than men in the SC group (P = .0009), and there were no significant differences between the SM and SA or SA and SC groups. There were no group effects on prostate-specific QOL or SF-36 mental health scores. CONCLUSION These findings demonstrate the efficacy of a brief presurgical stress management intervention in improving some short-term and long-term outcomes. If these results are replicated, it may be a useful adjunct to standard care for men with prostate cancer undergoing surgery.

National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers.

BACKGROUND: Updated National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed. METHODS: Published reports relevant to use of tumor markers for 5 cancer sites--testicular, prostate, colorectal, breast, and ovarian--were critically reviewed. RESULTS: For testicular cancer, alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are recommended for diagnosis/case finding, staging, prognosis determination, recurrence detection, and therapy monitoring. alpha-Fetoprotein is also recommended for differential diagnosis of nonseminomatous and seminomatous germ cell tumors. Prostate-specific antigen (PSA) is not recommended for prostate cancer screening, but may be used for detecting disease recurrence and monitoring therapy. Free PSA measurement data are useful for distinguishing malignant from benign prostatic disease when total PSA is <10 microg/L. In colorectal cancer, carcinoembryonic antigen is recommended (with some caveats) for prognosis determination, postoperative surveillance, and therapy monitoring in advanced disease. Fecal occult blood testing may be used for screening asymptomatic adults 50 years or older. For breast cancer, estrogen and progesterone receptors are mandatory for predicting response to hormone therapy, human epidermal growth factor receptor-2 measurement is mandatory for predicting response to trastuzumab, and urokinase plasminogen activator/plasminogen activator inhibitor 1 may be used for determining prognosis in lymph node-negative patients. CA15-3/BR27-29 or carcinoembryonic antigen may be used for therapy monitoring in advanced disease. CA125 is recommended (with transvaginal ultrasound) for early detection of ovarian cancer in women at high risk for this disease. CA125 is also recommended for differential diagnosis of suspicious pelvic masses in postmenopausal women, as well as for detection of recurrence, monitoring of therapy, and determination of prognosis in women with ovarian cancer. CONCLUSIONS: Implementation of these recommendations should encourage optimal use of tumor markers.

Comparison of cancers detected at only a sextant or alternative location.

OBJECTIVES: To evaluate the effect of the tumour-positive biopsy site at extended biopsy on tumour volume and potential biological significance of prostate cancer. PATIENTS AND METHODS: We retrospectively evaluated radical prostatectomy specimens from 247 consecutive men diagnosed with prostate cancer by extended biopsy. Men who had both a positive sextant and alternative site were excluded, resulting in 132 evaluable men. We assessed age, pretreatment prostate-specific antigen (PSA) level, prostate volume, pathological stage, Gleason score, total tumour volume, and location (sextant or alternative site) of the positive biopsy. Patients were grouped by location of the positive biopsy, i.e. sextant site only or alternative site only, including anterior horn, midline region and transition zone. RESULTS: A biopsy from a sextant-only or an alternative site only was positive in 42% (56/132) and 58% (76/132) of men, respectively. There was no significant difference in PSA level, number of positive cores, pathological stage, Gleason score, total tumour volume or the incidence of low-volume/low-grade cancer (volume <0.5 mL and a Gleason score of

A randomized prospective trial evaluating testosterone, haemoglobin kinetics and quality of life, during and after 12 months of androgen deprivation after prostatectomy: results from the Postoperative Adjuvant Androgen Deprivation trial.

OBJECTIVE: To assess testosterone and haemoglobin kinetics in the Postoperative Adjuvant Androgen Deprivation (PAAD) trial, and correlate these with quality of life (QoL) in this prospective randomized study. PATIENTS AND METHODS: Forty-three patients met the criteria for high-risk cancer after RRP (Gleason score > or = 8, pT3c or Gleason score 7 concomitant with pT3a/b and positive surgical margins) and were prospectively randomized to either observation or AD for 12 months. Haemoglobin and testosterone levels were determined and QoL surveyed at regular intervals for 24 months. RESULTS: Serum testosterone levels were castrate in 19 of 21 treated patients at 3 months and all at 6 months after starting AD. Levels failed to return to normal at 6 months after stopping treatment in six of 16 (38%) patients, and at 12 months in three of 17 (18%). AD caused a delay in the recovery of haemoglobin levels to normal after RRP. There was no statistically significant decline in the Short Form-36 QoL score with AD. Scores on the University of California-Los Angeles Sexual Functioning Scale were decreased during AD, but returned to a level not statistically significantly different from controls after stopping treatment. CONCLUSION: A year of adjuvant AD after RRP affected serum haemoglobin, testosterone and sexual function reversibly, with return to control levels within the subsequent year in most patients. No significant effect on overall QoL with AD was detected in the study.

African-American men with nonpalpable prostate cancer exhibit greater tumor volume than matched white men.

BACKGROUND: Although prostate cancer (PC) mortality disproportionately affects African-American (AA) men, limited data exist comparing the pathologic characteristics of white and AA patients with nonpalpable PC (clinical stage T1c). METHODS: The authors reviewed the radical prostatectomy (RP) specimens from 37 consecutive AA men with clinical stage T1c PC and 35 white men who were matched for age, clinical stage, serum prostate-specific antigen (PSA) level, year of surgery, prostate weight, and prostate biopsy strategy. Pathologic characteristics were compared after mapping tumor foci and calculating tumor volumes by using computer software. RESULTS: For AA men, the median age (57.7 years), mean serum PSA level (9.3 ng/mL), mean prostate weight (43 g), and biopsy strategy (73% sextant) were matched with the cohort of 35 white men (median age, 57.1 years; mean PSA, 9.3 ng/mL;, mean prostate weight, 43 g; biopsy strategy, 66% sextant). Despite similar biopsy characteristics between the 2 groups (Gleason score > or =7 in 43% of AA men vs. 37% of white men), AA men exhibited significantly higher prostatectomy Gleason scores (> or =7 in 76% of AA men vs. 34% of white men; P = .01). AA men also had a higher mean tumor volume (1.82 cm3 vs. 0.72 cm3; P = .001) and had 2.8 times more tumor per ng/mL of serum PSA (0.22 cm3 per ng/mL vs. 0.079 cm3 per ng/mL; P = .001). CONCLUSIONS: Compared with a cohort of white men with similar clinical features at the time of biopsy, AA men with nonpalpable PC had higher prostatectomy Gleason scores, greater cancer volume, and greater tumor volume per ng/mL of serum PSA. These data provide additional support for the concept of early PC detection using a serum PSA threshold of 2.5 ng/mL for biopsy among AA men.

Impact of fellowship training on pathologic outcomes and complication rates of radical prostatectomy.

BACKGROUND: The study was conducted to assess the results of radical prostatectomy (RP) performed by fellowship-trained surgeons in the first year of independent practice. METHODS: A prospective cohort study of 66 men who underwent RP performed by 2 recently graduated fellowship-trained surgeons (C.J.R., n = 27; A.M.K., n = 39) in their first year of independent practice was undertaken. Preoperative, operative, and postoperative data were collected and analyzed. Median follow-up of the cohort is 12.5 months. RESULTS: The median patient age was 61.2 +/- 6.9 years (range, 44-74 years), the median prostate-specific antigen level was 5 ng/mL (range, 1.2-39.4 ng/mL), and the median prostate biopsy-determined Gleason score was 7. Of the 66 men, 25 (38%) underwent a bilateral nerve-sparing RP, 20 (30%) underwent a unilateral nerve-sparing RP, and 21 (32%) underwent a nonnerve-sparing procedure. Forty-two men (63%) underwent a pelvic lymph node dissection. The median operative time was 201 minutes. Median estimated blood loss was 734 mL (range, 300-1600 mL). There were 4 major complications--a pulmonary embolism in 3 patients and an intraoperative rectal injury in 1. Pathologic classification was as follows: pT2, 74%; pT3a, 23%; pT3b, 2%; and pN+, 2%. The positive margin rate was 14% overall and only 2% in men with pT2 disease. CONCLUSIONS: Results of RP performed by fellowship-trained surgeons in their first year of practice compare favorably with results of RP in a large series reported by more experienced surgeons. Being trained in an environment where an experienced surgeon serves as first assistant to the trainee appears to abbreviate the learning curve associated with this procedure.

Demographic and past screening behaviors of men attending a free community screening program for prostate cancer.

This study characterizes demographic and past prostate screening behaviors of men who participated in a free screening for prostate cancer. Demographics, past prostate screening behavior, perceived risk, and cancer worry were assessed in 1,680 men. Mean age was 58.2 years, 56% were White, and 76% had health insurance. Men with insurance were more likely to have had a previous prostate-specific antigen (PSA) test and digital rectal exam (DRE). White men were more likely to have had a previous PSA and DRE and to have discussed PSA testing with a physician than African American men. African American men reported greater perceived risk and more worry than White men. Screening differences between African American and White men were explained by insurance status. These results may help guide the development of and promotion for future screening programs. Future efforts should be directed at increasing awareness about screening procedures for prostate cancer.

Obesity, weight gain, and risk of biochemical failure among prostate cancer patients following prostatectomy.

PURPOSE: Several lines of evidence suggest that diet and weight gain may be important environmental factors implicated in prostate carcinogenesis, especially in tumor progression. The purpose of this study was to evaluate obesity at different ages in a well-characterized cohort of prostate cancer patients treated with prostatectomy and to develop a prognostic model that incorporates body mass index (BMI) as a measure of obesity. EXPERIMENTAL DESIGN: We carried out a prospective study of 526 patients registered at the M.D. Anderson Cancer Center from 1992 to 2001. Kaplan-Meier and Cox proportional hazard analyses were done. RESULTS: During an average follow-up of 54 months, 97 (18%) post-prostatectomy patients experienced biochemical failure. Patients who were obese (BMI > or = 30 kg/m2) at diagnosis had a higher rate of biochemical failure than nonobese men (P = 0.07). Those obese at 40 years had an even greater rate of biochemical failure (P = 0.001). Higher BMI at diagnosis [hazard ratio (HR), 1.07; P = 0.01] and Gleason score = 7(4 + 3) and > or =8 (HR, 3.9; P = 0.03 and HR, 10.0; P < or = 0.001, respectively) remained significant independent predictors of biochemical failure in multivariate analysis. Men who gained weight at the greatest rate (>1.5 kg/y) between 25 years and diagnosis progressed significantly sooner (mean time, 17 months) than those who exhibited a slower weight gain (mean time, 39 months; P(trend) = 0.005). The inclusion of obesity to the clinical nomogram improved performance. CONCLUSIONS: Our findings validate the importance for a role of obesity in prostate cancer progression and suggest a link to the biological basis of prostate cancer progression that can be therapeutically exploited.

Outcome of salvage radiotherapy for biochemical failure after radical prostatectomy with or without hormonal therapy.

BACKGROUND: This study analyzed the outcome of salvage radiotherapy for biochemical failure after radical prostatectomy (RP). By comparing the outcomes for patients who received RT alone and for those who received combined RT and hormonal therapy, we assessed the potential benefits of hormonal therapy. PATIENTS AND METHODS: This cohort was comprised of 101 patients who received salvage RT between 1990 and 2001 for biochemical failure after RP. Fifty-nine of these patients also received hormone. Margin status (positive vs. negative), extracapsular extension (yes vs. no), seminal vesicle involvement (yes vs. no), pathologic stage, Gleason score, pre-RP PSA, post-RP PSA, pre-RT PSA, hormonal use, radiotherapy dose and technique, RP at M. D. Anderson Cancer Center, and time from RP to salvage RT were analyzed. Statistically significant variables were used to construct prognostic groups. RESULTS: Independent prognostic factors for the RT-alone group were margin status and pre-RT PSA. RP at M. D. Anderson Cancer Center was marginally significant (p = 0.06) in multivariate analysis. Pre-RT PSA was the only significant prognostic factor for the combined-therapy group. We used a combination of margin status and pre-RT PSA to construct a prognostic model for response to the salvage treatment based on the RT group. We identified the favorable group as those patients with positive margin and pre-RT PSA < or = 0.5 ng/mL vs. the unfavorable group as otherwise. This stratification separates patients into clinically meaningful groups. The 5-year PSA control probabilities for the favorable vs. the unfavorable group were 83.7% vs. 61.7% with radiotherapy alone (p = 0.03). Androgen ablation seemed to be most beneficial in the unfavorable group. CONCLUSION: After prostatectomy, favorable-group patients may fare well with salvage radiotherapy alone. These patients may be spared the toxicity of androgen ablation. The other patients may benefit most from a combined approach with hormonal treatment. We further suggest that salvage radiotherapy should be given early when the PSA is still low.

Efficacy of prostatic fossa biopsy in detecting local recurrence after radical prostatectomy.

OBJECTIVES: To evaluate retrospectively the efficacy of prostatic fossa biopsy in detecting local recurrence of prostate cancer in men with biochemical failure after radical prostatectomy. METHODS: Between January 1997 and December 2002, 100 men without prior adjuvant therapy after radical prostatectomy underwent transrectal ultrasound (TRUS)-guided biopsy of the prostatic fossa. The TRUS findings, digital rectal examination (DRE) findings, serum total prostate-specific antigen (PSA) level at TRUS, PSA velocity, and pathologic stage and Gleason score of the radical prostatectomy specimen were correlated with the biopsy results. RESULTS: Overall, 29 (29%) of the 100 men who underwent biopsy had documented local recurrence. The sensitivity and specificity of DRE to detect biopsy-proven local recurrence was 72.4% and 64.8%, respectively. The corresponding values for TRUS were 86.2% and 53.5%. None of the men with a serum PSA concentration of less than 0.5 ng/mL at biopsy who had normal results for both TRUS and DRE had a biopsy-proven local recurrence. By stepwise multivariate logistic regression analysis, abnormal TRUS findings and serum PSA concentration at biopsy were independent predictors for positive fossa biopsy results. The combination of TRUS and serum PSA concentration was the best predictive model for a positive fossa biopsy result. CONCLUSIONS: Prostatic fossa biopsy should be avoided in patients with both or either normal DRE or TRUS findings when the PSA level is less than 0.5 ng/mL.

Changes in serum proteomic patterns by presurgical alpha-tocopherol and L-selenomethionine supplementation in prostate cancer.

BACKGROUND: Evidence of the chemopreventive effects of the dietary antioxidants alpha-tocopherol (vitamin E) and l-selenomethionine (selenium) comes from secondary analysis of two phase III clinical trials that found treatment with these antioxidants reduced the incidence of prostate cancer. To determine the effects of selenium and vitamin E in blood and prostate tissue, we undertook a preoperative feasibility study complementary to the currently ongoing Selenium and Vitamin E Cancer Prevention Trial. METHODS: Forty-eight patients with clinically localized prostate cancer enrolled on this 2 x 2 factorial design study were randomized to take selenium, vitamin E, both, or placebo for 3 to 6 weeks before prostatectomy. Sera were collected from patients before and after dietary supplementation. Thirty-nine patients were evaluable, and 29 age-matched disease-free men served as controls. Mass profiling of lipophilic serum proteins of lower molecular weight (2-13.5 kDa) was conducted, and mass spectra data were analyzed using custom-designed software. RESULTS: Weighted voting analyses showed a change in sera classification from cancerous to healthy for some patients with prostate cancer after dietary intervention. ANOVA analysis showed significantly different treatment effects on prediction strength changes among the four groups at a 95% confidence level. Eliminating an outlying value and performing post hoc analysis using Fisher's least significant difference method showed that effects in the group treated with the combination were significantly different from those of the other groups. CONCLUSION: In sera from patients with prostate cancer, selenium and vitamin E combined induced statistically significant proteomic pattern changes associated with prostate cancer-free status.

Evaluation of precursor prostate-specific antigen isoform ratios in the detection of prostate cancer.

OBJECTIVE: Disease-associated isoforms of the prostate-specific antigen (PSA) have recently been identified. We evaluated the efficacy of using precursor isoforms of PSA (pPSA) and their ratios for the detection of prostate cancer. METHODS: Serum concentrations of [-2], [-4], and [-7]pPSA, BPSA, and free PSA (fPSA) were retrospectively measured in 43 selected men. Of the 43 men, 15 had clinical T2 prostate cancer with ultrasound-estimated prostate volumes (PVs) of >50 cm(3), 13 had clinical T2 prostate cancer with (PVs) <25 cm(3), and 15 were prostate cancer-free with PV >50 cm(3). We calculated sum pPSA ([-2]+[-4]+[-7]pPSA). We also compared the ratios of: free/total PSA, [-2]pPSA/fPSA, [-2]pPSA/BPSA, [-2]pPSA/(fPSA-BPSA), [-2]pPSA/(fPSA-sum pPSA), and [-2]pPSA/{fPSA-(sum pPSA+BPSA)} among these three groups. RESULTS: The median [-2]pPSA/(fPSA-sum pPSA) ratio was significantly higher in men with prostate cancer with or without large PV compared with men with large PV without prostate cancer. Values for median [-2]pPSA/free PSA ratio were higher in men with prostate cancer with or without large PV compared with men with large PV, and without prostate cancer, but the differences were not statistically significant. CONCLUSIONS: In this preliminary study, [-2]pPSA/(fPSA-sum pPSA) ratio was not associated with prostate gland volume but was associated with prostate cancer. This ratio may be useful in the detection of prostate cancer, particularly in men with larger glands.

Relationship between plasma carotenoids and prostate cancer.

Carotenoids, particularly lycopene, are thought to decrease prostate cancer risk, but the relationship between plasma carotenoid concentrations and risk in various populations has not been well characterized. Comparing 118 non-Hispanic Caucasian men mainly from southeast Texas with nonmetastatic prostate cancer with 52 healthy men from the same area, we conducted a case-control analysis evaluating associations between risk and plasma levels of total carotenoids, beta-cryptoxanthin, alpha- and trans-beta-carotene, lutein and zeaxanthin, total lycopenes, trans-lycopene, total cis-lycopenes, and cis-lycopene isoforms 1, 2, 3, and 5. Risk for men with high plasma levels of alpha-carotene, trans-beta-carotene, beta-cryptoxanthin, and lutein and zeaxanthin was less than half that for those with lower levels. In contrast, we observed no significant associations for total lycopenes, all-trans-lycopene, and cis-lycopene isomer peaks 2, 3, and 5, although high levels of cis-lycopene isomer peak 1 were inversely associated with risk. Analysis of men with aggressive disease (Gleason scores of > or =7, n = 88) vs. less aggressive cases (Gleason scores of <7, n = 30) failed to reveal significant associations between carotenoid levels and the risk of diagnosis with aggressive disease. These findings suggest that, in these men, higher circulating levels of alpha-cryptoxanthin, alpha-carotene, trans-beta-carotene, and lutein and zeaxanthin may contribute to lower prostate cancer risk but not to disease progression.