Joseph C Presti

United States Department of Veterans Affairs, Бедфорд, Massachusetts, United States

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Publications (212)906.75 Total impact

  • [Show abstract] [Hide abstract]
    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. DOI:10.1016/j.urology.2012.10.090 · 2.19 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 11.6 ng/mL (reference = 1.5-20.0 ng/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 05/2013; 39(3):312-319. DOI:10.1590/S1677-5538.IBJU.2013.03.03 · 0.88 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; 65(6). DOI:10.1016/j.eururo.2013.03.058 · 13.94 Impact Factor
  • The Journal of Urology 04/2013; 189(4):e395-e396. DOI:10.1016/j.juro.2013.02.545 · 4.47 Impact Factor
  • The Journal of Urology 04/2013; 189(4):e144-e145. DOI:10.1016/j.juro.2013.02.1744 · 4.47 Impact Factor
  • The Journal of Urology 04/2013; 189(4):e295-e296. DOI:10.1016/j.juro.2013.02.278 · 4.47 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.
    The Prostate 03/2013; 73(4). DOI:10.1002/pros.22582 · 3.57 Impact Factor
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    ABSTRACT: 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; 111(8). DOI:10.1111/j.1464-410X.2012.11687.x · 3.53 Impact Factor
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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; 65(3). DOI:10.1016/j.eururo.2012.11.052 · 13.94 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. DOI:10.1016/j.eururo.2012.08.015 · 13.94 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 05/2012; 99(5):693-8. DOI:10.1002/bjs.8693 · 5.54 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. DOI:10.1016/j.urology.2012.02.036 · 2.19 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. DOI:10.1016/j.juro.2012.01.083 · 4.47 Impact Factor
  • The Journal of Urology 04/2012; 187(4):e67. DOI:10.1016/j.juro.2012.02.213 · 4.47 Impact Factor
  • The Journal of Urology 04/2012; 187(4):e27. DOI:10.1016/j.juro.2012.02.109 · 4.47 Impact Factor
  • The Journal of Urology 04/2012; 187(4):e662. DOI:10.1016/j.juro.2012.02.1455 · 4.47 Impact Factor
  • The Journal of Urology 04/2012; 187(4):e147. DOI:10.1016/j.juro.2012.02.422 · 4.47 Impact Factor
  • The Journal of Urology 04/2012; 187(4):e405-e406. DOI:10.1016/j.juro.2012.02.1098 · 4.47 Impact Factor
  • The Journal of Urology 04/2012; 187(4):e277. DOI:10.1016/j.juro.2012.02.761 · 4.47 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. DOI:10.1016/j.urology.2012.01.034 · 2.19 Impact Factor

Publication Stats

6k Citations
906.75 Total Impact Points


  • 2013
    • United States Department of Veterans Affairs
      Бедфорд, Massachusetts, United States
  • 2004–2013
    • Palo Alto University
      Palo Alto, California, United States
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2003–2013
    • Stanford Medicine
      • Department of Urology
      Stanford, California, United States
  • 2002–2013
    • Stanford University
      • Department of Urology
      Palo Alto, California, United States
  • 2012
    • U.S. Department of Veterans Affairs
      Washington, Washington, D.C., United States
  • 1998–2010
    • CSU Mentor
      Long Beach, California, United States
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 2008
    • Santa Clara Valley Medical Center
      San José, California, United States
  • 2007
    • Duke University Medical Center
      • Department of Surgery
      Durham, NC, United States
  • 2006–2007
    • Duke University
      • Department of Surgery
      Durham, North Carolina, United States
    • Johns Hopkins Medicine
      • Department of Urology
      Baltimore, MD, United States
  • 1989–2001
    • University of California, San Francisco
      • • Department of Urology
      • • Division of Hospital Medicine
      • • Veterans Affairs Medical Center
      San Francisco, California, United States
  • 1996
    • University of California, Davis
      • Department of Radiation Oncology
      Davis, California, United States
  • 1995
    • University of Florida
      • Department of Urology
      Gainesville, Florida, United States