Joseph C Presti

Duke University Medical Center, Durham, NC, United States

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Publications (220)842.28 Total impact

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    ABSTRACT: To examine the ability of various postoperative nomograms to predict prostate cancer-specific mortality (PCSM) and to validate that they could predict aggressive biochemical recurrence (BCR). Prostate-specific antigen (PSA), grade, and stage are the classic triad used to predict BCR after radical prostatectomy (RP). Multiple nomograms use these to predict risk of BCR. A previous study showed that several nomograms could predict aggressive BCR (prostate-specific antigen doubling time [PSADT] <9 months) more accurately than BCR. However, it remains unknown if they can predict more definitive endpoints, such as PCSM. We performed Cox analyses to examine the ability of 4 postoperative nomograms, the Duke Prostate Center (DPC) nomogram, the Kattan postoperative nomogram, the Johns Hopkins Hospital (JHH) nomogram, and the joint Center for Prostate Disease Research(CPDR)/Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) nomogram to predict BCR and PCSM among 1778 men in the Shared Equal Access Regional Cancer Hospital (SEARCH) database who underwent RP between 1990 and 2009. We also compared their ability to predict BCR and aggressive BCR in a subset of men. We calculated the c-index for each nomogram to determine its predictive accuracy for estimating actual outcomes. We found that each nomogram could predict aggressive BCR and PCSM in a statistically significant manner and that they all predicted PCSM more accurately than they predicted BCR (ie, with higher c-index values). Currently available nomograms used to predict BCR accurately predict PCSM and other more clinically relevant endpoints. Moreover, not only do they significantly predict PCSM, but do so with generally greater accuracy than BCR.
    Urology 07/2013; 82(1):53-59. · 2.42 Impact Factor
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    ABSTRACT: BACKGROUND: The University of California, San Francisco, Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score uses pathologic data from radical prostatectomy (RP) to predict prostate cancer recurrence and mortality. However, this clinical tool has never been validated externally. OBJECTIVE: To validate CAPRA-S in a large, multi-institutional, external database. DESIGN, SETTING, AND PARTICIPANTS: The Shared Equal Access Regional Cancer Hospital (SEARCH) database consists of 2892 men who underwent RP from 2001 to 2011. With a median follow-up of 58 mo, 2670 men (92%) had complete data to calculate a CAPRA-S score. INTERVENTION: RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main outcome was biochemical recurrence. Performance of CAPRA-S in detecting recurrence was assessed and compared with a validated postoperative nomogram by concordance index (c-index), calibration plots, and decision curve analysis. Prediction of cancer-specific mortality was assessed by Kaplan-Meier analysis and the c-index. RESULTS AND LIMITATIONS: The mean age was 62 yr (standard deviation: 6.3), and 34.3% of men had recurrence. The 5-yr progression-free probability for those patients with a CAPRA-S score of 0-2, 3-5, and 6-10 (defining low, intermediate, and high risk) was 72%, 39%, and 17%, respectively. The CAPRA-S c-index was 0.73 in this validation set, compared with a c-index of 0.72 for the Stephenson nomogram. Although CAPRA-S was optimistic in predicting the likelihood of being free of recurrence at 5 yr, it outperformed the Stephenson nomogram on both calibration plots and decision curve analysis. The c-index for predicting cancer-specific mortality was 0.85, with the caveat that this number is based on only 61 events. CONCLUSIONS: In this external validation, the CAPRA-S score predicted recurrence and mortality after RP with a c-index >0.70. The score is an effective prognostic tool that may aid in determining the need for adjuvant therapy.
    European Urology 04/2013; · 10.48 Impact Factor
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    ABSTRACT: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Diabetes is known to be associated with a slightly lower risk of prostate cancer. Only a limited number of studies have examined the impact of diabetes on prostate cancer outcomes, with mixed results. This study builds on our prior work showing that on the whole, diabetes is not a risk factor for progression to metastases after surgery. However, intriguingly we found a significant interaction with obesity for modifying the relationship between diabetes and progression. If confirmed in future studies, this suggests the mechanisms by which diabetes alters prostate cancer aggressiveness may differ in obese and non-obese men. OBJECTIVE: To examine the association between diabetes and metastasis risk after radical prostatectomy (RP) and to determine if race or obesity modifies this relationship. PATIENTS AND METHODS: Patients comprised 2058 US veterans with prostate cancer (PCa) enrolled in the Shared Equal-Access Regional Cancer Hospital (SEARCH) database and treated with RP between 1988 and 2010. The association of diabetes with metastasis risk or secondary treatment rates was examined using Cox proportional hazards, adjusting for preoperative and, separately, clinical and postoperative findings. The effect modification by race (black vs white) and obesity (body mass index [BMI] ≥30 vs <30 kg/m(2) ) was tested via interaction terms. RESULTS: Men with diabetes had higher BMIs and were more likely to be non-white (all P ≤ 0.001). On multivariable analysis, diabetes was not associated with metastasis risk (P ≥ 0.45), but, among men with diabetes, longer diabetes duration was associated with higher metastasis risk (P ≤ 0.035). When stratified by obesity, diabetes was linked with higher metastasis risk in obese but not in non-obese men (P-interaction ≤ 0.037), but there was no significant interaction with race (P-interaction ≥ 0.56). Diabetes also predicted more aggressive secondary treatment among obese men but less aggressive treatment among non-obese men (hazard ratio 1.39 vs 0.63, P-interaction = 0.006). Where applicable, results were similar for both pre- and postoperative models. CONCLUSIONS: Diabetes was not associated with metastasis risk overall. Stratification by obesity yielded significant differences, with diabetes linked to a fourfold higher metastasis risk in obese men, despite predicting more aggressive secondary treatment. Longer diabetes duration was also associated with increased metastasis risk.
    BJU International 01/2013; · 3.05 Impact Factor
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    ABSTRACT: Introduction: To analyze the association between serum levels of folate and risk of biochemical recurrence after radical prostatectomy among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Materials and Methods: Retrospective analysis of 135 subjects from the SEARCH database treated between 1991-2009 with available preoperative serum folate levels. Patients' characteristics at the time of the surgery were analyzed with ranksum and linear regression. Uni- and multivariable analyses of folate levels (log-transformed) and time to biochemical recurrence were performed with Cox proportional hazards. Results: The median preoperative folate level was 11.6ng/mL (reference = 1.5-20.0ng/mL). Folate levels were significantly lower among African-American men than Caucasians (P = 0.003). In univariable analysis, higher folate levels were associated with more recent year of surgery (P < 0.001) and lower preoperative PSA (P = 0.003). In univariable analysis, there was a trend towards lower risk of biochemical recurrence among men with high folate levels (HR = 0.61, 95 %CI = 0.37-1.03, P = 0.064). After adjustments for patients characteristics' and pre- and post-operative clinical and pathological findings, higher serum levels of folate were independently associated with lower risk for biochemical recurrence (HR = 0.42, 95 %CI = 0.20-0.89, P = 0.023). Conclusion: In a cohort of men undergoing radical prostatectomy at several VAs across the country, higher serum folate levels were associated with lower PSA and lower risk for biochemical failure. While the source of the folate in the serum in this study is unknown (i.e. diet vs. supplement), these findings, if confirmed, suggest a potential role of folic acid supplementation or increased consumption of folate rich foods to reduce the risk of recurrence.
    International braz j urol: official journal of the Brazilian Society of Urology 01/2013; 39(3):312-319.
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    ABSTRACT: BACKGROUND: A prostate-specific antigen (PSA) level <0.2 ng/ml 8 mo after starting on androgen-deprivation therapy (ADT) is correlated with better outcomes. However, not all men reach a nadir PSA level within 8 mo. Whether the lowest PSA on ADT-specifically, <0.2 ng/ml-can be used for risk stratification is untested. OBJECTIVE: We examined the predictive value of small but detectable PSA nadir values on prostate cancer (PCa)-specific outcomes in men treated with early ADT after radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of men treated with ADT after RP before metastases from the SEARCH database. We identified 402 men treated with ADT for elevated PSA following RP, of whom 294 men had complete data. Median follow-up after PSA nadir was 49 mo. All men had a PSA nadir <4 ng/ml; 223 men (76%) had an undetectable nadir. INTERVENTION: ADT for an elevated PSA following RP with no radiographic evidence of metastatic disease. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA nadir on ADT was defined as the lowest PSA value during ADT. Proportional hazards models and the C index were used to test the association and predictive accuracy, respectively, between PSA nadir and PCa-specific outcomes. RESULTS AND LIMITATIONS: Men with a PSA nadir between 0.01 and 0.2 ng/ml had a greater risk of progression to castration-resistant PCa (CRPC) (hazard ratio [HR]: 5.14; p<0.001), metastases (HR: 3.98; p=0.006), and PCa-specific mortality (PCSM) (HR: 5.33; p=0.003) than men with an undetectable nadir. When data were restricted to men followed with ultrasensitive PSA values (sensitivity of 0.01 ng/ml), the C index of PSA nadir alone for predicting CRPC, metastases, and PCSM was 0.88, 0.91, and 0.96, respectively. CONCLUSIONS: A PSA nadir on ADT, even at a very low level, strongly predicts progression to CRPC, metastases, and PCSM. Men with a detectable PSA nadir during ADT should be considered for clinical trials.
    European Urology 12/2012; · 10.48 Impact Factor
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    ABSTRACT: INTRODUCTION: Active surveillance (AS) is increasingly accepted as appropriate management for low-risk prostate cancer (PC) patients. It is unknown whether delaying radical prostatectomy (RP) is associated with increased risk of biochemical recurrence (BCR) for men with intermediate-risk PC. METHODS: We performed a retrospective analysis of 1,561 low and intermediate-risk men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database treated with RP between 1988 and 2011. Patients were stratified by interval between diagnosis and RP (≤3, 3-6, 6-9, or >9 months) and by risk using the D'Amico classification. Cox proportional hazard models were used to analyze BCR. Logistic regression was used to analyze positive surgical margins (PSM), extracapsular extension (ECE), and pathologic upgrading. RESULTS: Overall, 813 (52%) men were low-risk, and 748 (48%) intermediate-risk. Median follow-up among men without recurrence was 52.9 months, during which 437 men (38.9%) recurred. For low-risk men, RP delays were unrelated to BCR, ECE, PSM, or upgrading (all P > 0.05). For intermediate-risk men, however, delays >9 months were significantly related to BCR (HR: 2.10, P = 0.01) and PSM (OR: 4.08, P < 0.01). Delays >9 months were associated with BCR in subsets of intermediate-risk men with biopsy Gleason score ≤3 + 4 (HR: 2.51, P < 0.01), PSA ≤ 6 (HR: 2.82, P = 0.06), and low tumor volume (HR: 2.59, P = 0.06). CONCLUSIONS: For low-risk men, delayed RP did not significantly affect outcome. For men with intermediate-risk disease, delays >9 months predicted greater BCR and PSM risk. If confirmed in future studies, this suggests delayed RP for intermediate-risk PC may compromise outcomes. Prostate © 2012 Wiley Periodicals, Inc.
    The Prostate 09/2012; · 3.84 Impact Factor
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    ABSTRACT: Obesity is associated with an increased risk of biochemical recurrence (BCR) after radical prostatectomy (RP). It is unclear whether this is due to technical challenges related to operating on obese men or other biologic factors. To examine whether obesity predicts higher prostate-specific antigen (PSA) nadir (as a measure of residual PSA-producing tissue) after RP and if this accounts for the greater BCR risk in obese men. A retrospective analysis of 1038 RP patients from 2001 to 2010 in the multicenter US Veterans Administration-based Shared Equal Access Regional Cancer Hospital database with median follow-up of 41 mo. All patients underwent RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We evaluated the relationship between body mass index (BMI) and ultrasensitive PSA nadir within 6 mo after RP. Adjusted proportional hazards models were used to examine the association between BMI and BCR with and without PSA nadir. Mean BMI was 28.5kg/m(2). Higher BMI was associated with higher PSA nadir on both univariable (p=0.001) and multivariable analyses (p<0.001). Increased BMI was associated with increased BCR risk (hazard ratio [HR]: 1.06; p=0.007). Adjusting for PSA nadir slightly attenuated, but did not eliminate, this association (HR: 1.04, p=0.043). When stratified by PSA nadir, obesity only significantly predicted BCR in men with an undetectable nadir (p=0.006). Unfortunately, other clinically relevant end points such as metastasis or mortality were not available. Obese men are more likely to have a higher PSA nadir, suggesting that either more advanced disease or technical issues confound an ideal operation. However, even after adjusting for the increased PSA nadir, obesity remained predictive of BCR, suggesting that tumors in obese men are growing faster. This provides further support for the idea that obesity is biologically associated with prostate cancer progression.
    European Urology 08/2012; 62(5):910-6. · 10.48 Impact Factor
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    ABSTRACT: To assess the performance characteristics of prostate-specific antigen (PSA) for predicting the volume of total or high-grade cancer in men undergoing radical prostatectomy. It is known that the performance characteristics of PSA are improved for predicting the presence of high-grade prostate cancer. We identified 1459 patients from the Stanford Radical Prostatectomy Database with clinical Stage T1c (n = 783) and T2 (n = 676) disease who underwent surgery from 1988 to 2003 with detailed morphometric mapping. We generated receiver operating characteristic curves for PSA levels according to the total and high-grade (Gleason score 4 or 5) cancer volume and compared the areas under the curve (AUC) for the various total and high-grade cancer volumes. For patients with Stage T1c disease, the AUC for the PSA ROC curve increased in a stepwise fashion as both the total cancer volume and the high-grade cancer volume increased. Significant differences between the AUCs for low and high volumes of total and high-grade disease were observed. For T2 disease, the AUCs for predicting high-grade cancer volume were generally greater than the corresponding AUCs for T1c disease, although no incremental increase was observed. In patients with Stage T1c disease, in whom the PSA level was the driving force for biopsy, the PSA performance improved in a stepwise fashion with greater total and high-grade cancer volumes as evidenced by improved ROC. Previous studies have shown that PSA performs better for detecting the presence of high-grade disease. We have shown that PSA performs better in predicting greater volumes of high-grade disease in radical prostatectomy specimens.
    Urology 04/2012; 79(6):1336-9. · 2.42 Impact Factor
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    ABSTRACT: Patients question whether multiple biopsy sessions cause worse prostate cancer outcomes. Therefore, we investigated whether there is an association between the number of prior biopsy sessions and biochemical recurrence after radical prostatectomy. Men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database who underwent radical prostatectomy between 1988 and 2010 after a known number of prior biopsies were included in the analysis. Number of biopsy sessions (range 1 to 8) was examined as a continuous and categorical (1, 2 and 3 to 8) variable. Biochemical recurrence was defined as a prostate specific antigen greater than 0.2 ng/ml, 2 values at 0.2 ng/ml or secondary treatment for an increased prostate specific antigen. The association between number of prior biopsy sessions and biochemical recurrence was analyzed using the Cox proportional hazards model. Kaplan-Meier estimates of freedom from biochemical recurrence were compared among the groups. Of the 2,739 men in the SEARCH database who met the inclusion criteria 2,251 (82%) had only 1 biopsy, 365(13%) had 2 biopsies and 123 (5%) had 3 or more biopsies. More biopsy sessions were associated with higher prostate specific antigen (p<0.001), greater prostate weight (p<0.001), lower biopsy Gleason sum (p=0.01) and more organ confined (pT2) disease (p=0.017). The Cox proportional hazards model demonstrated no association between number of biopsy sessions as a continuous or categorical variable and biochemical recurrence. Kaplan-Meier estimates of freedom from biochemical recurrence were similar across biopsy groups (log rank p=0.211). Multiple biopsy sessions are not associated with an increased risk of biochemical recurrence in men undergoing radical prostatectomy. Multiple biopsy sessions appear to select for a low risk cohort.
    The Journal of urology 04/2012; 187(6):2056-60. · 3.75 Impact Factor
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    ABSTRACT: To investigate whether salvage radiation therapy (SRT) may promote prostate cancer (PCa) transformation to more aggressive phenotypes. To accomplish that, we identified men who underwent SRT after radical prostatectomy for PCa and failed SRT. PSA doubling time (PSADT) was used as a surrogate endpoint for cancer aggressiveness. We compared PSADT calculated before start of SRT and after SRT failure. Of 287 men in the SEARCH database since 1988 who underwent SRT, we detected 78 with SRT failure defined as PSA ≥ 0.2 ng/mL above the post-SRT nadir. Of these, 39 had PSADT available before and after SRT, which was compared using Wilcoxon's paired test with men serving as their own controls. We tested predictors of PSADT change using multivariable logistic regression. There were no differences in PSADT before and after SRT (10.2 vs 12.6 months; P = .46). However, in some individual cases, large changes were observed. Only seminal vesicle invasion showed a trend towards an association with a shorter post-SRT PSADT relative to the pre-SRT PSADT (P = .13). Overall, the PSADT after and before SRT were statistically identical, suggesting that after SRT failure, PCa does not emerge with more aggressive biological features. Further studies are needed to identify predictors and the clinical relevance of individual PSADT changes noted in our study.
    Urology 03/2012; 79(5):1105-10. · 2.42 Impact Factor
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    ABSTRACT: The impact of race and socioeconomic status (SES) in prostate cancer (CaP) outcomes has been well-studied, but controversy remains. The associations of race/SES with intermediate CaP outcomes, including positive surgical margin (PSM) and biochemical recurrence (BCR), were explored in an equal-access setting. Data were retrospectively collected from 2502 men in the Shared Equal Access Regional Cancer Hospitals (SEARCH) database who underwent radical prostatectomy from 1989 to 2010. SES (income, education, employment, and poverty) was estimated from linkage of home ZIP code to census data. Logistic regression with adjustment for pre- and postoperative covariates estimated risk for associations between race/SES and pathologic outcomes. Cox proportional hazards models estimated risk for associations between race/SES and time to BCR. Black men were more likely to have lower SES than white men (P < .001). On multivariate analysis, race was not associated with PSM, but higher SES was associated with less PSM and fewer Gleason sum ≥ 7 pathologic tumors when SES was assessed by education, employment, or poverty (P trend ≤ .051) and income, employment, or poverty (P trend ≤ 0.059), respectively. Crude Cox models showed black men had higher BCR risk (hazards ratio = 1.20, 95% confidence interval = 1.05-1.38, P = .009) that persisted after adjustment for covariates including SES (hazards ratio ≥ 1.18, P ≤ .040). Higher SES measured by income and poverty were associated with less BCR, but only for black men (P trend ≤ .048). Even in an equal-access setting, higher SES predicted lower PSM risk, and race persisted in predicting BCR despite adjustment for SES. Low SES black patients may be at greatest risk for postprostatectomy BCR. Cancer 2012. © 2012 American Cancer Society.
    Cancer 03/2012; 118(20):4999-5007. · 5.20 Impact Factor
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    ABSTRACT: Bladder plasmacytoid carcinoma is an invasive urothelial carcinoma subtype that is emphasized for its morphological overlap with plasma cells and metastatic carcinoma. Our experience suggests frequent intraperitoneal spread that is not typical of conventional urothelial carcinoma. We identified cases of plasmacytoid urothelial carcinoma diagnosed on radical cystectomy. Patient age, gender, American Joint Committee on Cancer (7th edition) stage, metastatic spread/recurrence sites and clinical disease status at last followup were recorded. A total of 10 male and 5 female patients 42 to 81 years old were identified. One tumor was pT2, 11 pT3 and 3 pT4. Six of 15 patients (40%) presented with lymph node metastasis and 5 (33%) had intraperitoneal metastasis at cystectomy. These initial sites of metastatic spread included the prerectal space, ovary and vagina, ovary and fallopian tube, bowel serosa, and omentum and bowel serosa in 1 case each. Three patients had subsequent metastasis involving the prerectal space, pleural fluid and small bowel serosa, and bowel serosa in 1 each. Eight patients had followup information available, including 3 who died of disease, 3 with disease and 2 with no evidence of disease. Of the patients 33% with the plasmacytoid variant of urothelial carcinoma presented with intraperitoneal disease spread and 20% had subsequent metastasis involving serosal surfaces. The possibility of noncontiguous intraperitoneal spread involving serosal surfaces should be recognized to ensure proper intraoperative staging and clinical followup for patients with plasmacytoid carcinoma.
    The Journal of urology 03/2012; 187(3):852-5. · 3.75 Impact Factor
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    ABSTRACT: Obese men have lower serum levels of testosterone, dehydroepiandrosterone (DHEA) and prostate-specific antigen (PSA), but an increased risk of dying from prostate cancer. The aim of this study was to examine the effect of surgically induced weight loss on serum testosterone, DHEA and PSA levels in obese men. Consecutive men undergoing Roux-en-Y gastric bypass (RYGB) participated in a prospective, longitudinal study. Main outcomes were changes were body mass index (BMI), percentage excess weight loss, serum levels of testosterone, DHEA and PSA, PSA mass and plasma volume, measured before operation and 3, 6 and 12 months later. In 64 patients, mean BMI fell from 48.2 kg/m(2) before operation to 39.2, 35.6 and 32.4 kg/m(2) at 3, 6 and 12 months after RYGB. Testosterone levels rose significantly from 259 ng/dl to 386, 452 and 520 ng/dl respectively. Serum PSA levels increased significantly from 0.51 ng/ml to 0.67 ng/ml at 12 months. There were no significant changes in DHEA or PSA mass. RYGB normalizes the serum testosterone level. PSA levels increase with weight loss and may be inversely correlated with changes in plasma volume, indicating that PSA levels may be artificially low in obese men owing to haemodilution.
    British Journal of Surgery 02/2012; 99(5):693-8. · 4.84 Impact Factor
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    ABSTRACT: The objective of this study was to examine the association between calcium intake and prostate cancer risk. We hypothesized that calcium intake would be positively associated with lower risk for prostate cancer. We used data from a case-control study conducted among veterans between 2007 and 2010 at the Durham Veterans Affairs Medical Center. The study consisted of 108 biopsy-positive prostate cancer cases, 161 biopsy-negative controls, and 237 healthy controls. We also determined whether these associations differed for blacks and whites or for low-grade (Gleason score <7) and high-grade prostate cancer (Gleason score ≥7). We administered the Harvard food frequency questionnaire to assess diet and estimate calcium intake. We used logistic regression models to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Intake of calcium from food was inversely related to risk for prostate cancer among all races in a comparison of cases and biopsy-negative controls (P = .05) and cases and healthy controls (P = .02). Total calcium was associated with lower prostate cancer risk among black men but not among white men in analyses of healthy controls. The highest tertile of calcium from food was associated with lower risk for high-grade prostate cancer in a comparison of high-grade cases and biopsy-negative controls (OR, 0.37; 95% CI, 0.15-0.90) and high-grade cases and healthy controls (OR, 0.38; 95% CI, 0.17-0.86). Calcium from food is associated with lower risk for prostate cancer, particularly among black men, and lower risk for high-grade prostate cancer among all men.
    Preventing chronic disease 01/2012; 9:E39. · 1.82 Impact Factor
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    ABSTRACT: What's known on the subject? and What does the study add? Much of our understanding of the pathological basis of prostate cancer comes from our analysis of radical prostatectomy specimens. Prostate cancer diagnosed by transrectal ultrasonography-guided biopsy is more likely to be posterior and basal in orientation rather than anterior or apical. Quantitative tissue analyses have not been undertaken both with details and in an unselected population, e.g. prostate specimens from autopsy cystoprostatectomy series from bladder cancer. Quantitative tissue analysis of incidentally detected prostate cancer such as largest cancer surface area, volume, site of origin, multifocality and laterality could be of paramount importance when trying to understand the findings of screen-detected programmes and focal therapy. Cancers were found in 30% of prostates. In the 96 prostates, 215 cancer foci were identified (mean 2.24). Prostate cancer was multifocal in 60% and bilateral in 80% of cases. The site of origin was in the peripheral and transition zone (TZ) in 75% and 25%, respectively. Overall, 90% of cancer foci were clinically insignificant with volume of <0.5 mL and no grades 4-5. In all, 75% of the cancer foci were in the peripheral zone, the remainder were within the TZ. One third of cancer foci were anteriorly located beyond the area sampled by posterior biopsies. One fifth of cancer foci were ≤ 6 mm of the apex. • To describe multifocality, volume and location of prostate cancers incidentally found in cystoprostatectomy specimens. Quantitative tissue analysis of prostate cancer in a population free of the evaluation bias associated with prostate-specific antigen level and biopsy is important as some men are likely to be offered tissue-preserving therapeutic strategies in the future. • Cystoprostatectomy specimens for bladder cancer from 345 consecutive patients without clinically manifest prostate cancer were included. • Cancers were found in 104/345 (30%) of prostates. Cases with largest cancer >2 mL (eight patients) were excluded from morphometric study. Quantitative tissue analysis of 3-mm step-sectioned glands included largest cancer surface area, volume, site of origin, multifocality and laterality. • In the 96 prostates, 215 cancer foci were identified (mean 2.24). Prostate cancer was multifocal in 58% and bilateral in 79% of cases. • Of the 215 cancers, 90% were <0.5 mL and 79% <0.2 mL. Overall, 88% of cancer foci were clinically insignificant with a volume of <0.5 mL and no grades 4-5. • In all, 75% of the cancer foci were in the peripheral zone, the remainder were within the transition zone. • One third of cancer foci were anteriorly located beyond the area sampled by posterior biopsies. One fifth of cancer foci were ≤ 6 mm of the apex. • Limitations include the fact that cystoprostatectomy cancer foci are at an earlier stage than screened-detected cancers. • This detailed morphometric analysis of prostate cancer foci in a population that is free from the selection bias associated with screening can help inform our diagnostic and treatment strategies.
    BJU International 12/2011; 110(4):517-23. · 3.05 Impact Factor
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    ABSTRACT: Several radical prostatectomy series have linked small prostates with high grade cancer based on the hypothesis that a small prostate results from a low androgen milieu that selects for less hormone dependent, more aggressive tumors. We previously reported that this association resulted from ascertainment bias from the performance characteristics of prostate specific antigen rather than from tumor biology in our radical prostatectomy cohort. In this study we analyzed this association in a more generalized population of men who underwent prostate needle biopsy. The prostate needle biopsy database at our institution was queried for all initial biopsies. Included patient characteristics were age, race, family history of prostate cancer, prostate specific antigen, abnormal digital rectal examination and prostate volume in ml on transrectal ultrasound. Multivariate logistic regression was used to determine the influence of prostate volume on the odds of high grade cancer. The study population included 1,295 patients during 2000 to 2010, of whom 582 (44.9%) had prostate cancer and 398 (30.7%) had high grade cancer. When all patients were pooled, the OR for high grade cancer was 0.85 (95% CI 0.78-0.92) for each 10 ml increase in prostate volume. When patients were divided by clinical T stage, the corresponding ORs for those with T1c disease was 0.83 (95% CI 0.74-0.93) and for those with T2 or greater disease it was 0.99 (0.98-1.00). The association between small prostates and high grade cancer exists only in men with clinical T1c (normal digital rectal examination) prostate cancer. It likely resulted from ascertainment bias due to the performance characteristics of prostate specific antigen rather than tumor biology.
    The Journal of urology 12/2011; 187(2):477-80. · 3.75 Impact Factor
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    ABSTRACT: Study Type - Prognosis (cohort series). Level of Evidence 2a. What's known on the subject? and What does the study add? The incidence and prevalence of obesity in the USA and Europe is increasing. Higher body mass index is associated with a lower risk of overall prostate cancer diagnosis but also with an increased risk of high grade prostate cancer. Obese men undergoing primary therapy with radical prostatectomy or external beam radiation are more likely to experience a biochemical recurrence after treatment compared with normal weight men. Finally, obesity is associated with increased prostate-cancer-specific mortality. We hypothesized that obese men on androgen deprivation therapy may be at increased risk for prostate cancer progression. Previous studies have shown that obese men have lower levels of testosterone compared with normal weight men. Additionally, one previous study found that obese men have higher levels of testosterone on androgen deprivation therapy. Men with higher levels of testosterone on androgen deprivation therapy are at increased risk of prostate cancer progression. We found that men with higher body mass index were at increased risk of progression to castration-resistant prostate cancer, development of metastases and prostate-cancer-specific mortality. When we adjusted for various clinicopathological characteristics, obese men were at increased risk of progression to castration-resistant prostate cancer and development of metastases. The results of our study help generate hypotheses for further study regarding the mechanisms between obesity and aggressive prostate cancer. • To investigate whether obesity predicts poor outcomes in men starting androgen deprivation therapy (ADT) before metastasis, since previous studies found worse outcomes after surgery and radiation for obese men. • A retrospective review was carried out of 287 men in the SEARCH database treated with radical prostatectomy between 1988 and 2009. • Body mass index (BMI) was categorized to <25, 25-29.9 and ≥ 30 kg/m2. • Proportional hazards models were used to test the association between BMI and time to castration-resistant prostate cancer (PC), metastases and PC-specific mortality adjusting for demographic and clinicopathological data. • During a median 73-month follow-up after radical prostatectomy, 403 men (14%) received early ADT. • Among 287 men with complete data, median BMI was 28.3 kg/m2. • Median follow-up from the start of ADT was 52 months during which 44 men developed castration-resistant PC, 34 developed metastases and 24 died from PC. • In multivariate analysis, higher BMI was associated with a trend for greater risk of progression to castration-resistant PC (P= 0.063), a more than threefold increased risk of developing metastases (P= 0.027) and a trend toward worse PC-specific mortality (P= 0.119). • Prognostic biomarkers did not differ between BMI groups. • Among men treated with early ADT, our results suggest that obese men may have increased risk of PC progression. • These data support the general hypothesis that obesity is associated with aggressive PC, although validation of these findings and further study of the mechanisms linking obesity and poor PC outcomes are required.
    BJU International 11/2011; 110(4):492-8. · 3.05 Impact Factor
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    ABSTRACT: We examined the relationship between weight change in the year before radical prostatectomy (RP) and biochemical recurrence (BCR) and adverse pathology. We abstracted data from 359 men undergoing RP in the SEARCH (Shared Equal Access Regional Cancer Hospital) database between 2001-2007. Logistic regression and Cox proportional hazards models were used to test the association between weight change in the year before surgery and adverse pathology and BCR, respectively. In all, 152 (42%) men gained weight, 193 (54%) lost weight and 14 (4%) had the same weight. Among weight gainers, median gain was 2.4 kg and among weight losers, median loss was 2.7 kg. As a continuous variable, weight change was not associated with adverse pathology or BCR (all P>0.05). In secondary analysis, on multivariate analysis, men gaining ≥ 2.5 kg were at higher BCR risk (hazards ratio=1.65, 95% confidence interval (CI): 1.03-2.64, P=0.04) while weight loss ≥ 2.5 kg was not associated with BCR (hazards ratio=0.83, 95% CI: 0.54-1.29, P=0.41).Conclusions:As a continuous variable, weight change was not associated with outcome. In secondary hypothesis-generating analyses, weight gain ≥ 2.5 kg in the year before surgery, regardless of final body mass index, was associated with increased BCR following RP. If validated, these data suggest weight gain ≥ 2.5 kg may promote prostate cancer progression.
    Prostate cancer and prostatic diseases 09/2011; 14(4):361-6. · 2.10 Impact Factor
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    ABSTRACT: Prior radical prostatectomy series have shown an inverse association between prostate size and high grade cancer. It has been suggested that smaller size prostates arise in a low androgen environment, enabling development of more aggressive cancer. We propose that this observation is the result of ascertainment bias driven by prostate specific antigen performance. We identified 1,404 patients from the Stanford Radical Prostatectomy Database with clinical stage T1c (723) and T2 (681) disease who underwent surgery between 1988 and 2002, and underwent detailed morphometric mapping by a single pathologist. Multivariate linear regression was performed to assess for the effects of age, prostate weight and prostate specific antigen on total and high grade (Gleason grade 4/5) cancer volume and percentage of high grade disease. In patients who underwent biopsy due to abnormal prostate specific antigen (stage T1c), prostate weight was negatively associated (p = 0.0002) with total cancer volume, volume of high grade disease and percentage of high grade disease. For patients who underwent biopsy based on abnormal digital rectal examination (stage T2) these associations were not observed. Improved prostate specific antigen performance for high grade disease results in ascertainment bias in patients with T1c disease. Thus, the association between prostate size and high grade disease may be a consequence of grade dependent performance of prostate specific antigen rather than true tumor biology.
    The Journal of urology 06/2011; 185(6):2108-11. · 3.75 Impact Factor
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    ABSTRACT: • To better understand the natural history of weight change with androgen-deprivation therapy (ADT), we investigated the effect of ADT on body weight among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. • Men undergoing ADT lose lean muscle but gain fat mass, contributing to an overall gain in weight. • We identified 132 men in SEARCH who received ADT after radical prostatectomy. • 'Weight change' was defined as the difference in weight before starting ADT (6 months before ADT) and the on-ADT weight (between 6 and 18 months after starting ADT). • In a subanalysis, baseline characteristics of weight-gainers and -losers were analysed using univariate and multivariate analysis to test association with weight change. • In all, 92 men (70%) gained weight, and 40 (30%) either lost or maintained a stable weight. • On average, weight on ADT was 2.2 kg higher than the weight before ADT, with the mean change for weight-gainers and -losers being +4.2 kg and -2.4 kg, respectively. • This compared with no significant weight change in the year before starting ADT (paired t-test, change -0.7 kg, P= 0.19) or in the second year on ADT (paired t-test, change -0.5 kg, P= 0.46) for 84 men in whom these additional weight values were recorded. • There was no significant association between any of the features examined and weight change on univariate and multivariate analysis. • In this longitudinal study, ADT was accompanied by significant weight gain (+2.2 kg). This change occurred primarily in the first year of therapy, with men neither losing nor gaining additional weight thereafter.
    BJU International 03/2011; 107(6):924-8. · 3.05 Impact Factor

Publication Stats

6k Citations
842.28 Total Impact Points

Institutions

  • 2007–2013
    • Duke University Medical Center
      • Department of Surgery
      Durham, NC, United States
    • Medical College of Georgia
      Augusta, Georgia, United States
  • 2003–2013
    • Stanford Medicine
      • Department of Urology
      Stanford, California, United States
  • 2012
    • U.S. Department of Veterans Affairs
      Washington, Washington, D.C., United States
  • 2010–2012
    • University of California, San Diego
      • Division of Urology
      San Diego, CA, United States
    • University of Southern California
      • Department of Urology
      Los Angeles, California, United States
  • 2002–2011
    • Stanford University
      • • Department of Urology
      • • Stanford Stroke Center
      • • Department of Radiation Oncology
      Stanford, CA, United States
    • University of California, Los Angeles
      • • Department of Urology
      • • Department of Medicine
      Los Angeles, California, United States
  • 2008
    • Palo Alto University
      Palo Alto, California, United States
    • Wayne State University
      • Division of Hematology and Oncology
      Detroit, MI, United States
  • 1988–2007
    • University of California, San Francisco
      • • Department of Surgery
      • • Department of Urology
      • • Division of Hospital Medicine
      San Francisco, CA, United States
  • 2006
    • Johns Hopkins University
      • Department of Pathology
      Baltimore, Maryland, United States
  • 2004–2006
    • Johns Hopkins Medicine
      • Department of Urology
      Baltimore, MD, United States
  • 1998–2006
    • CSU Mentor
      Long Beach, California, United States
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 1991–2000
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Pathology
      • • Department of Surgery
      • • Urology Service
      New York City, NY, United States