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Richard J Babaian

Publications and source records attributed to Richard J Babaian.

18 recordsLinked to original sources

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.

Black or African American↗

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.

Adult↗

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.

Adult↗

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.

Adult↗

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.

Adult↗

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.

Aged↗

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.

Analysis of Variance↗

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.

Antioxidants↗

Androgen receptor polymorphisms and risk of biochemical failure among prostatectomy patients.

BACKGROUND: Little is known about the role of inherited genotypes in prostate cancer (PC) progression. This prospective study evaluated the predictive value of androgen receptor (AR) polymorphisms (CAG and GGC repeats) among prostatectomy patients. METHODS: We studied 354 patients registered at M. D. Anderson Cancer Center from 1991 to 2001. Kaplan-Meier and Cox proportional hazard analyses were used. RESULTS: During an average follow-up of 56 months, 66 (19%) post-prostatectomy patients experienced biochemical failure (BF). Patients with higher CAG repeats (CAG > or = 24) had significantly longer BF-free survival (BFFS) than those with fewer repeats (CAG < or = 23) (P = 0.04). Higher CAG repeats were significantly associated with lower BF risk among Whites and African Americans. Among Whites, longer CAG repeats (relative risk (RR) = 0.45, P = 0.03) and Gleason score > or = 8 (RR = 19.33, P = 0.005) remained significant BFFS predictors in multivariate analysis. GGC repeats were not associated with BF. CONCLUSIONS: Our data showed that an inherited polymorphism (CAG repeats) in the AR is related to differences in genetic susceptibility to BF, supporting the hypothesis that increased AR activity may play a role in PC progression.

Adenocarcinoma↗

A neurocomputational model for prostate carcinoma detection.

BACKGROUND: Current guidelines for prostate carcinoma screening rely primarily on the digital rectal examination (DRE) and prostate specific antigen (PSA). Well described patient risk factors for prostate carcinoma also include age, ethnicity, family history, and complexed PSA. However, due to the nonlinear relation of each of these variables with prostate carcinoma, it is difficult to predict reliably each patient's risk based on linear univariate analysis. The authors investigated a neural network to model the risk of prostate carcinoma by seven readily available clinical features. METHODS: The database for the current study comprised 3268 men recently evaluated for the early detection of prostate carcinoma. The seven clinical features evaluated included age, race, family history, International Prostate Symptom Score (IPSS), DRE, and total and complexed PSA. Three hundred forty-eight subjects in the dataset included men with determined prostate biopsy outcomes and for whom at least 6 of 7 features were available. The dataset was divided randomly into a training set (60%) and a test set (40%), with n1/n2 cross-validation used to evaluate model accuracy, and was modeled with linear and quadratic discriminant function analysis and a neural computational system. After a model with acceptable goodness of fit was achieved, reverse regression analysis using Wilks's generalized likelihood ratio test was performed to evaluate the statistical significance of each input variable. RESULTS: The receiving operating characteristic (ROC) area for the neural computational system in the test set was 0.825, whereas total PSA and complexed PSA alone had ROC areas of 0.678 and 0.697, respectively. The ROC area of logistic regression in the test set was 0.510, linear discriminant function analysis was 0.674, and quadratic discriminant function analysis was 0.011. All were significantly less than the ROC area of the neural computational model (all Ps < 0.002). Reverse regression based on Wilks's generalized likelihood ratio test demonstrated each input feature to be highly significant to the model (all Ps << 0.000001). CONCLUSIONS: The authors modeled a combination of well described patient risk factors for prostate carcinoma using a neural computational system with acceptable goodness of fit. They demonstrated that each of the seven variates on which the model was based was critically significant to model performance. The authors presented this model for clinical use and suggested that clinicians use it in deciding to perform prostate biopsy.

Age Factors↗

Overexpression of hMTH in peripheral lymphocytes and risk of prostate cancer: a case-control analysis.

Oxidative damage is an important factor in prostate carcinogenesis, and overexpression of human MutT homolog (hMTH), a repair gene that removes oxidative damage, is a molecular marker of cellular oxidative stress. Therefore, we tested the hypothesis that overexpression of hMTH in unaffected (normal) surrogate tissue is associated with risk of prostate cancer in a pilot study of 51 patients with diagnosed prostate cancer and 50 age- and ethnicity-matched controls. Total RNA was extracted from phytohemagglutinin-stimulated peripheral blood lymphocytes of these subjects. We performed the real-time reverse transcription-polymerase chain reaction assay to evaluate the relative mRNA expression of three oxidative-damage-repair genes, human MutM homolog (hMMH), hMTH, and human MutY homolog (hMYH), with beta-actin and human O(6)-methylguanine DNA methyltransferase (hMGMT) as the internal controls. The relative gene expression levels of hMMH and hMTH were borderline higher in the cases than in controls (15.3% and 28.8% higher, respectively; P = 0.046 and P = 0.035, respectively), whereas no increase was observed for hMYH and hMGMT. With the median of the controls' values as the cutoff point, we observed that a high expression level of hMTH, but not of other genes, was associated with a significantly increased risk of prostate cancer (odds ratio = 2.62; 95% confidence interval = 1.13-6.75) after adjustment for age and ethnicity. These results suggested that increased expression of hMTH in peripheral lymphocytes may be a risk factor for prostate cancer and support our priori hypothesis. Although our findings were biologically plausible and consistent with the literature, they were preliminary and need to be confirmed in larger studies. In addition, a correlation between the expression level of hMTH and the level of oxidative DNA damage in the target tissues needs to be established as well.

Actins↗

Volume indexes of total, free, and complexed prostate-specific antigen enhance prediction of extraprostatic disease extension in men with nonpalpable prostate cancer.

OBJECTIVES: To analyze the ability of volume-adjusted total, complexed, and free prostate-specific antigen (PSA) to predict organ-confined cancer at radical prostatectomy in patients with nonpalpable disease. METHODS: Collected sera were assayed for total PSA (tPSA), complexed PSA (cPSA), and free PSA (fPSA) in 78 men who underwent radical prostatectomy with nonpalpable prostate cancer. The pathologic results (organ-confined versus extraprostatic extension [EPE]), tPSA, cPSA, fPSA/tPSA ratio, cPSA/tPSA ratio, fPSA/cPSA ratio, tPSA density (tPSAD), cPSA density (cPSAD), and fPSA density (fPSAD) were compared by the Mann-Whitney U test and receiver operating characteristic curves. RESULTS: Fifteen men (19.2%) had pathologic EPE. After stratifying the patients on the basis of the Beckman tPSA, the cPSAD, tPSAD, and fPSAD were significant predictors of EPE when comparing their respective medians in individuals with tPSA greater than 4.0 ng/mL. Statistically significant differences were noted between patients with and without EPE for tPSAD (P = 0.0015), cPSAD (P = 0.0018), and fPSAD (P = 0.0022), but not for the fPSA/tPSA, cPSA/tPSA, and fPSA/cPSA ratios. The area under the receiver operating characteristic curve was similar for tPSA (0.539) and cPSA (0.542), as it was for tPSAD (0.708), cPSAD (0.700), and fPSAD (0.731). The specificity and diagnostic accuracy of tPSAD, cPSAD, and fPSAD were significantly greater than those of tPSA and cPSA (specificity P <0.001; diagnostic accuracy P <0.05). CONCLUSIONS: In men with nonpalpable prostate cancer, the density parameters of tPSA, cPSA, and fPSA performed equivalently and appeared to enhance the predictability of EPE.

Adenocarcinoma↗

Identification of factors predicting response to adjuvant radiation therapy in patients with positive margins after radical prostatectomy.

PURPOSE: Radical prostatectomy (RP) is a highly effective treatment for patients with prostate cancer. However, patients with positive surgical margins after radical prostatectomy have less than ideal outcomes with 5-year progression rates between 36% and 50%. Postoperative radiation therapy (RT) is often advocated for improving these outcomes. We identified predictors of response to adjuvant RT given for positive margins after RP. MATERIALS AND METHODS: We retrospectively reviewed the clinical records of men who underwent RP between 1987 and 1999 at our institution and who received adjuvant RT for positive surgical margins. Only patients in whom prostate specific antigen (PSA) was undetectable after RP as well as before the initiation of RT were included. Numerous clinicopathological variables, including pre-RP PSA, pathological stage, margin length and location, and extracapsular extension or seminal vesicle involvement, were assessed for their adverse effect on the biochemical recurrence rate after adjuvant RT. RESULTS: A total of 62 men met our inclusion criteria. Median age at surgery was 60.7 +/- 6.1 years and median PSA at presentation was 9.0 ng/ml (range 1.4 to 64.9). The median RT dose was 60.0 +/- 3.6 Gy. RT was started a median of 5.0 +/- 3.6 months after RP. The 5 and 10-year biochemical disease-free survival rates for the whole group were 90.2% and 87.9%, respectively. Of all parameters tested only Gleason score 4 + 3 or greater (p = 0.037) and pre-RP PSA greater than 10.9 ng/ml (p = 0.040) were predictive of biochemical recurrence after adjuvant RT on univariate analysis. On multivariate analysis only pre-RP PSA greater than 10.9 ng/ml remained an independent predictor (p = 0.031). CONCLUSIONS: In the setting of true adjuvant RT in patients with positive margins after RP and undetectable PSA those with predominant Gleason grade 4 or greater, or PSA greater than 10.9 ng/ml at presentation are at increased risk for recurrence after adjuvant RT.

Aged↗

Cavernous nerve reconstruction to preserve erectile function following non-nerve-sparing radical retropubic prostatectomy: a prospective study.

Erectile dysfunction following radical prostatectomy for treatment of clinically localized prostate cancer remains a problem that deters many men from seeking surgical treatment. Sparing the cavernous nerves has been popularized as a method of preserving potency, but men with locally advanced disease may be at increased risk for positive margins with this technique. In this study, sural nerve grafting of the cavernous nerve bundles, to preserve postoperative potency while potentially maximizing cancer control, was examined. Thirty men were enrolled in this prospective phase I study and underwent non-nerve-sparing radical prostatectomy performed by one of two protocol surgeons. Preoperative erectile function was assessed both objectively, using a RigiScan (Timm Medical Technologies, Inc., Eden Prairie, Minn.), and subjectively. The cavernous nerves were identified and resected during the operation with the use of an intraoperative mapping device (CaverMap; Alliant Medical Technologies, Norwood, Mass.). Bilateral autologous sural nerve grafting to the cavernous nerve stumps was performed by one of two protocol plastic surgeons. Postoperative erectile dysfunction therapy, using intracorporeal injection, a vacuum pump, and/or oral sildenafil therapy, was instituted 6 weeks after the operation. Spontaneous erectile activity was subjectively and objectively measured every 3 months after the operation. Follow-up periods ranged from 13 to 33 months (mean, 23 months). Overall, 18 of 30 patients (60 percent) demonstrated both objective and subjective evidence of spontaneous erectile activity. Of those 18 men, 13 (72 percent) were able to have intercourse (seven unassisted and six with the aid of sildenafil). No disease or biochemical recurrences have been noted in this group of patients with locally advanced disease. In conclusion, autologous sural nerve grafting after non-nerve-sparing radical prostatectomy is an effective means of preserving spontaneous erectile activity after the operation while maximizing cancer control potential.

Aged↗

Cancer worry is associated with abnormal prostate-specific antigen levels in men participating in a community screening program.

An accumulating body of research suggests that psychological factors can affect physiological parameters. We assessed the association between the perceived risk of prostate cancer, prostate cancer-specific worry, and cancer-related symptoms and prostate-specific antigen (PSA) levels or the findings from digital rectal examination (DRE) in a large sample of men undergoing a free prostate cancer screening. Participants (n = 1635) completed a background questionnaire and a questionnaire that assessed their prostate cancer history, screening behavior, perceived risk of prostate cancer, and prostate cancer worry. PSA levels were then determined, and a DRE was conducted. A PSA level of >or=4.0 ng/ml was considered abnormal. The sample size for the multivariate analyses was reduced because of missing data on certain items. Participants who had an abnormal PSA level reported a significantly higher perceived cancer risk (P = 0.02), cancer worry (P = 0.004), and a greater percentage indicated the reason for the current screening was cancer-related symptoms (P = 0.014) than did participants who had normal PSA levels. Multivariate logistic regression analyses controlling for age, past screening behavior, past screening results, and reason for current screening revealed that perceived cancer risk [P = 0.01; odds ratio (OR), 1.5; 95% confidence interval (CI), 1.1-2.1], cancer worry (P = 0.001; OR, 3.3; 95% CI, 1.7-6.5), and cancer-related symptoms (P = 0.05; OR, 3.4; 95% CI, 1.1-10.3) remained significantly associated with an abnormal PSA level. When perceived cancer risk, cancer worry, and cancer-related symptoms were entered in the same multivariate analysis, only cancer worry remained in the model. The present findings suggest that prostate cancer-specific worry was associated significantly with an abnormal PSA level.

Adult↗

Complexed prostate-specific antigen for early detection of prostate cancer in men with serum prostate-specific antigen levels of 2 to 4 nanograms per milliliter.

Complexed PSA (cPSA) has been shown to improve specificity in the detection of prostate cancer over that of total PSA (tPSA) testing in men with tPSA values greater than the cutoff value of 4.0 ng/mL. However, recent studies have reported a 25% incidence of prostate cancer in men with tPSA values in the 2.5- to 4.0-ng/mL range. We performed a multicenter study of cPSA in a population of men who underwent prostate biopsies because of elevated PSA levels or abnormal digital rectal examination (DRE). As part of this study, we sought to assess the clinical value of cPSA in comparison to tPSA, the free/tPSA ratio (f/tPSA) and the complexed/tPSA ratio (c/tPSA) in early detection of prostate cancer in men with tPSA values in the range of 2 to 4 ng/mL. The study was performed at 7 centers. Sera were drawn from men who underwent biopsy procedures consisting of >10 prostate tissue cores. Receiver operating characteristic (ROC) analysis was performed from the results of patients with tPSA values in the range of 2 to 4 ng/mL, including men with suspicious as well as unremarkable findings on DRE. Sera were collected and tested with the Bayer tPSA and cPSA assay and the Beckman free PSA and tPSA assays. ROC analysis was performed for all samples in the 2- to 4-ng/mL PSA range. At biopsy, 158 men had no evidence of malignancy and 57 (26.5%) were diagnosed with prostate cancer. ROC analysis indicated that the area under the curve (AUC) for cPSA was 0.64, which was statistically significantly greater than that achieved for tPSA (AUC, 0.57; P <0.0001). The AUC for f/tPSA and c/tPSA were 0.60 and 0.63, respectively, which was not statistically significantly different from that of tPSA or cPSA (P >or=0.252). A cutpoint of 2.5 ng/mL for tPSA and 2.1 ng/mL for cPSA provided a specificity of 20.3% and 34.2%, respectively, and sensitivity levels of 86%. Using cutpoints of 25% for f/tPSA and 74% for c/tPSA provided a specificity of 11.0% and 21.5%, respectively, and sensitivity levels of 97%. In all, >92% of the cancers treated with radical prostatectomy were organ confined, and the histologic grading of the tumors ranged from moderately to poorly differentiated with Gleason scores from 5 to 9. These data confirm that there is a high incidence of clinically significant prostate cancer in men with tPSA levels <4.0 ng/mL. Measurement of cPSA proved useful in stratifying men with tPSA values in the 2- to 4-ng/mL range into high- and low-risk groups for prostate cancer. The use of cPSA as a single test was found to enhance detection of prostate cancer over that of testing with tPSA and PSA ratios in men with tPSA values in the range of 2 to 4 ng/mL.

Adult↗

Can volume measurement of the prostate enhance the performance of complexed prostate-specific antigen?

We assessed whether volume-based complexed prostate-specific antigen (cPSA) indices could enhance prostate cancer detection in men with serum total PSA (tPSA) between 2.5 and 10.0 ng/mL. Between December 1998 and April 2000, cPSA assay was measured in 480 men who underwent transrectal ultrasound-guided prostate biopsies at 7 institutions. We compared the usefulness of cPSA and its indices with the ratio of free PSA (fPSA) to tPSA (percent fPSA) for early detection of prostate cancer. Overall, 168 men (35%) had cancer. In the 341 men with tPSA between 4.01 and 10.0 ng/mL at approximately 90% sensitivity and areas under the receiver operating characteristics curve, the performances of volume-based parameters were significantly better (P <0.05) than those of tPSA and cPSA. In the 139 men with tPSA between 2.5 and 4.0 ng/mL, at 90% sensitivity, the specificity of the ratio of cPSA to tPSA (percent cPSA) was best, followed by cPSA density (cPSAD). In the 101 men with the history of a previous prostate biopsy, at approximately 90% sensitivity, the specificity of cPSAD was significantly better than those of tPSA and percent fPSA (P <0.05). In the 371 men with a total prostate volume of >or=30 cm(3) at approximately 90% sensitivity, the specificity of the cPSAD was significantly better than that of tPSA, percent fPSA, and cPSA (P <0.05). In the 109 men with a total prostate volume of <30 cm(3), at 90% sensitivity the specificity of cPSA and cPSAD was better than that of percent fPSA. In conclusion, volume-based cPSA can modestly enhance the performance of cPSA.

Humans↗

Complexed prostate-specific antigen as a staging tool: results based on a multicenter prospective evaluation of complexed prostate-specific antigen in cancer diagnosis.

Within a 7-site prospective evaluation of the Bayer complexed prostate-specific antigen PSA (cPSA) assay, we analyzed the ability of cPSA to predict extracapsular extension (ECE) before radical prostatectomy. Included in this analysis were 152 men diagnosed with cancer, who subsequently underwent radical prostatectomy. Sera were tested with the Bayer total PSA (tPSA) and cPSA assays, and the Beckman free PSA (fPSA) and tPSA assays. Treating surgical pathology result as a binary variable (organ confined vs ECE), mean tPSA, cPSA, fPSA/tPSA (f/tPSA) ratios, tPSA density (tPSAD), and cPSA density (cPSAD) were compared by receiver operating characteristic (ROC) curves and univariate analysis. In all, 28 men (18.4%) had pathologically identified ECE. Between those with and without ECE, significant differences were observed for tPSA (P = 0.0127), cPSA (P = 0.0120), tPSAD (P = 0.0001), and cPSAD (P = 0.0002), but not f/tPSA (P = 0.3774) or c/tPSA (P = 0.2882). All tested parameters except f/tPSA (P = 0.376) and c/tPSA (P = 0.288) predicted ECE (P <0.05) by logistic regression. The ROC area under the curve (AUC) was identical for tPSA and cPSA (0.621) and for tPSAD (0.692) and cPSAD (0.691). Kendall-tau correlation coefficients also demonstrated the strongest correlation with ECE for cPSAD and tPSAD. Either alone or as a tPSAD calculation, cPSA carries equivalent staging ability to tPSA. The use of f/tPSA appears to be less effective in staging than either cPSA or tPSA, whereas the use of either cPSAD or tPSAD provides maximal staging accuracy. Therefore, cPSA could be applied as an accurate predictor of ECE independently or in a nomogram along with other predictive variables.

Aged↗