Peter T Scardino

Memorial Sloan-Kettering Cancer Center, New York, New York, United States

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Publications (676)4139.11 Total impact

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    ABSTRACT: Many men with elevated prostate-specific antigen (PSA) levels in serum do not have aggressive prostate cancer and undergo unnecessary biopsy. Retrospective studies using cryopreserved serum suggest that four kallikrein markers can predict biopsy outcome. Free, intact and total PSA, and kallikrein-related peptidase 2 were measured in cryopreserved blood from 6129 men with elevated PSA (≥3.0ng/mL) participating in the prospective, randomized trial Prostate Testing for Cancer and Treatment. Marker levels from 4765 men providing anticoagulated plasma were incorporated into statistical models to predict any-grade and high-grade (Gleason score ≥7) prostate cancer at 10-core biopsy. The models were corrected for optimism by 10-fold cross validation and independently validated using markers measured in serum from 1364 men. All statistical tests were two-sided. The four kallikreins enhanced prostate cancer detection compared with PSA and age alone. Area under the curve (AUC) for the four kallikreins was 0.719 (95% confidence interval [CI] = 0.704 to 0.734) vs 0.634 (95% CI = 0.617 to 0.651, P < .001) for PSA and age alone for any-grade cancer, and 0.820 (95% CI = 0.802 to 0.838) vs 0.738 (95% CI = 0.716 to 0.761) for high-grade cancer. Using a 6% risk of high-grade cancer as an illustrative cutoff, for 1000 biopsied men with PSA levels of 3.0ng/mL or higher, the model would reduce the need for biopsy in 428 men, detect 119 high-grade cancers, and delay diagnosis of 14 of 133 high-grade cancers. Models exhibited excellent discrimination on independent validation among men with only serum samples available for analysis. A statistical model based on kallikrein markers was validated in a large prospective study and reduces unnecessary biopsies while delaying diagnosis of high-grade cancers in few men. © The Author 2015. Published by Oxford University Press.
    CancerSpectrum Knowledge Environment 07/2015; 107(7). DOI:10.1093/jnci/djv095 · 15.16 Impact Factor
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    ABSTRACT: Previous studies of prostate cancer (PCa) risk and anthropometrics (ie, body measurements) were based on single measurements or obtained over limited time spans. To study the association between anthropometrics measured at multiple time points in life and their relation to later diagnosis, metastasis, or death from PCa. This case-control study includes 27 167 Swedish men enrolled in two population-based projects from 1974 to 1996. PCa diagnosis up to December 31, 2006, disease information, gestation time, and anthropometrics at birth, military conscript testing, and adulthood were collected. A total of 1355 PCa cases were matched with 5271 controls. Univariate conditional logistic regression was used to determine whether clinical diagnosis, metastasis, or PCa death was associated with low birth weight (weight <2500g); with small size for gestational age; or with weight, length, or body mass index (BMI) at birth, adolescence (aged 16-22 yr), or early middle age (aged 44-50 yr). Apart from weight at adolescence, which was associated with an increased risk of PCa diagnosis (odds ratio [OR] per 5kg: 1.05; 95% confidence interval [CI], 1.01-1.09; p=0.026), preadulthood measurements were not associated with any PCa end point. Adulthood parameters were not associated with diagnosis. In contrast, weight and BMI at early middle age were significantly associated with metastasis (OR per 5kg: 1.13; 95% CI, 1.06-1.20; p<0.0001, and OR: 1.09; 95% CI, 1.05-1.14; p<0.0001) and death (OR per 5kg: 1.11 (95% CI, 1.03-1.19; p=0.005, and OR: 1.08; 95% CI, 1.03-1.13; p=0.003), respectively. It remains unclear whether these results apply to men of nonwhite origin, to populations with active PCa screening programs, or to countries without socialized health care. The analyses of these large data sets demonstrate that significant effects of body characteristics (with links to metabolic syndrome) measured at early middle age are associated with PCa disease severity, metastatic progression, and outcome. Conversely, measurements at birth and adolescence are not associated with PCa prevalence or outcome. Increased weight and body mass index in adults is associated with a higher risk of prostate cancer metastasis and death. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    European Urology 03/2015; DOI:10.1016/j.eururo.2015.03.017 · 12.48 Impact Factor
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    ABSTRACT: We evaluated the safety and efficacy of a clinical pathway designed and implemented to transition inpatient minimally invasive radical prostatectomy to a procedure with overnight observation.
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    ABSTRACT: A disadvantage of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) is that many men must be screened, biopsied, and diagnosed to prevent one death. To increase the specificity of screening for lethal PCa at an early stage. We conducted a case-control study nested within a population-based cohort. PSA and three additional kallikreins were measured in cryopreserved blood from a population-based cohort in Västerbotten, Sweden. Of 40379 men providing blood at ages 40, 50, and 60 yr from 1986 to 2009, 12542 men were followed for >15 yr. From this cohort, the Swedish Cancer Registry identified 1423 incident PCa cases, 235 with distant metastasis. Risk of distant metastasis for different PSA levels and a prespecified statistical model based on the four kallikrein markers. Most metastatic cases occurred in men with PSA in the top quartile at age 50 yr (69%) or 60 yr (74%), whereas 20-yr risk of metastasis for men with PSA below median was low (≤0.6%). Among men with PSA >2 ng/ml, a prespecified model based on four kallikrein markers significantly enhanced the prediction of metastasis compared with PSA alone. About half of all men with PSA >2 ng/ml were defined as low risk by this model and had a ≤1% 15-yr risk of metastasis. Screening at ages 50-60 yr should focus on men with PSA in the top quartile. A marker panel can aid biopsy decision making. For men in their fifties, screening should focus on those in the top 10% to 25% of PSA values because the majority of subsequent cases of distant metastasis are found among these men. Testing of four kallikrein markers in men with an elevated PSA could aid biopsy decision making. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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    ABSTRACT: Objective To build a predictive model of urinary continence recovery following radical prostatectomy that incorporates magnetic resonance imaging parameters and clinical data.Patients and Methods We conducted a retrospective review of data from 2,849 patients who underwent pelvic staging magnetic resonance imaging prior to radical prostatectomy from November 2001 to June 2010.We used logistic regression to evaluate the association between each MRI variable and continence at 6 or 12 months, adjusting for age, body mass index (BMI), and American Society of Anesthesiologists (ASA) score and then used multivariable logistic regression to create our model.A nomogram was constructed using the multivariable logistic regression models.ResultsIn total, 68% (n=1,742/2,559) and 82% (n=2,205/2,689) regained function at 6 and 12 months, respectively.In the base model, age, BMI, and ASA score were significant predictors of continence at 6 or 12 months on univariate analysis (p <0.005).Among the preoperative magnetic resonance imaging measurements, membranous urethral length, which showed great significance, was incorporated into the base model to create the full model.For continence recovery at 6 months, the addition of membranous urethral length increased the AUC to 0.664 for the validation set, an increase of 0.064 over the base model. For continence recovery at 12 months, the AUC was 0.674, an increase of 0.085 over the base model.Conclusions Using our model, the likelihood of continence recovery increases with membranous urethral length and decreases with age, body mass index, and ASA score.This model could be used for patient counseling and for the identification of patients at high risk for urinary incontinence in whom to study changes in operative technique that improve urinary function after radical prostatectomy.This article is protected by copyright. All rights reserved.
    BJU International 02/2015; DOI:10.1111/bju.13087 · 3.13 Impact Factor
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    ABSTRACT: Background:The diffusion of minimally invasive radical prostatectomy (MIRP) in the United States may have led to adverse patient outcomes due to rapid surgeon adoption and collective inexperience. We hypothesized that throughout the early period of minimally invasive surgery, MIRP patients had inferior outcomes as compared with those who had open radical prostatectomy (ORP).Methods:We used the Surveillance, Epidemiology and End Results-Medicare dataset and identified men who had ORP and MIRP for prostate cancer from 2003-2009. Study endpoints were receipt of subsequent cancer treatment, and evidence of postoperative voiding dysfunction, erectile dysfunction (ED) and bladder outlet obstruction. We used proportional hazards regression to estimate the impact of surgical approach on each endpoint, and included an interaction term to test for modification of the effect of surgical approach by year of surgery.Results:ORP (n=5362) and MIRP (n=1852) patients differed in their clinical and demographic characteristics. Controlling for patient characteristics and surgeon volume, there was no difference in subsequent cancer treatments (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.76-1.05), although MIRP was associated with a higher risk of voiding dysfunction (HR 1.31, 95% CI 1.20-1.43) and ED (HR 1.43, 95% CI 1.31-1.56), but a lower risk of bladder outlet obstruction (HR 0.86, 95% CI 0.75-0.97). There was no interaction between approach and year for any outcome. When stratifying the analysis by year, MIRP consistently had higher rates of ED and voiding dysfunction with no substantial improvement over time.Conclusions:MIRP patients had adverse urinary and sexual outcomes throughout the diffusion of minimally invasive surgery. This may have been a result of the rapid adoption of robotic surgery with inadequate surgeon preparedness.Prostate Cancer and Prostatic Disease advance online publication, 16 December 2014; doi:10.1038/pcan.2014.49.
    Prostate Cancer and Prostatic Diseases 12/2014; 18(1). DOI:10.1038/pcan.2014.49 · 2.83 Impact Factor
  • Behfar Ehdaie, Peter T Scardino
    Nature Reviews Urology 10/2014; DOI:10.1038/nrurol.2014.284 · 4.52 Impact Factor
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    ABSTRACT: The natural history of prostate-specific antigen (PSA)-defined biochemical recurrence (BCR) of prostate cancer (PCa) after definitive local therapy is highly variable. Validated prediction models for PCa-specific mortality (PCSM) in this population are needed for treatment decision-making and clinical trial design.
    European Urology 10/2014; DOI:10.1016/j.eururo.2014.09.019 · 12.48 Impact Factor
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    ABSTRACT: A paucity of data exists on the insignificant disease potentially suitable for active surveillance (AS) among men with intermediate-risk prostate cancer (PCa). We tried to identify pathologically insignificant disease and its preoperative predictors in men who underwent radical prostatectomy (RP) for intermediate-risk PCa.
    World Journal of Urology 09/2014; DOI:10.1007/s00345-014-1413-3 · 3.42 Impact Factor
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    ABSTRACT: The lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response. Using a 3D organoid system, we report success in long-term culture of prostate cancer from biopsy specimens and circulating tumor cells. The first seven fully characterized organoid lines recapitulate the molecular diversity of prostate cancer subtypes, including TMPRSS2-ERG fusion, SPOP mutation, SPINK1 overexpression, and CHD1 loss. Whole-exome sequencing shows a low mutational burden, consistent with genomics studies, but with mutations in FOXA1 and PIK3R1, as well as in DNA repair and chromatin modifier pathways that have been reported in advanced disease. Loss of p53 and RB tumor suppressor pathway function are the most common feature shared across the organoid lines. The methodology described here should enable the generation of a large repertoire of patient-derived prostate cancer lines amenable to genetic and pharmacologic studies.
    Cell 09/2014; 159(1). DOI:10.1016/j.cell.2014.08.016 · 33.12 Impact Factor
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    ABSTRACT: Introduction Anesthesia technique has been associated with cancer outcomes after radical prostatectomy (RP). These studies are limited by variability in surgeon experience, bias in patient selection, and in some cases, sample size. We evaluated the impact of anesthesia technique for RP on biochemical recurrence (BCR) using a large cohort of patients operated on by a single experienced surgeon. Methods We retrospectively reviewed data from a prospective institutional oncologic database on 929 patients treated with RP by a single surgeon from 1999-2008. Spinal anesthesia was used for patients from 2002-2006. We compared outcomes of these patients (n = 264) with outcomes of patients who underwent general anesthesia (n = 665) at Memorial Sloan-Kettering Cancer Center from 1999-2001 and 2006-2008. Cox proportional hazards regression was used to assess differences in BCR rates between the anesthesia groups adjusting for differences in postoperative factors related to anesthetic technique and tumour pathologic characteristics associated with BCR after RP. Results Median follow-up among patients free from BCR was 4.6 yr. On multivariable analysis, spinal anesthesia did not independently predict the rate of BCR (hazard ratio = 1.10; 95% confidence interval 0.7 to 1.74; P = 0.7). Independent predictors of BCR were preoperative prostate-specific antigen (PSA), pathologic Gleason grade, extracapsular extension, and seminal vesicle invasion. Conclusions We did not find an association between anesthesia technique and disease recurrence in men with prostate cancer treated with RP. Anesthesia technique is unlikely to alter disease recurrence following RP independent of surgical and pathological factors.
    Canadian Journal of Anaesthesia 08/2014; 61(12). DOI:10.1007/s12630-014-0221-y · 2.50 Impact Factor
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    ABSTRACT: Primary prostate cancer is the most common malignancy in men but has highly variable outcomes, highlighting the need for biomarkers to determine which patients can be managed conservatively. Few large prostate oncogenome resources currently exist that combine the molecular and clinical outcome data necessary to discover prognostic biomarkers. Previously, we found an association between relapse and the pattern of DNA copy number alteration (CNA) in 168 primary tumors, raising the possibility of CNA as a prognostic biomarker. Here we examine this question by profiling an additional 104 primary prostate cancers and updating the initial 168 patient cohort with long-term clinical outcome. We find that CNA burden across the genome, defined as the percentage of the tumor genome affected by CNA, was associated with biochemical recurrence and metastasis after surgery in these two cohorts, independent of the prostate-specific antigen biomarker or Gleason grade, a major existing histopathological prognostic variable in prostate cancer. Moreover, CNA burden was associated with biochemical recurrence in intermediate-risk Gleason 7 prostate cancers, independent of prostate-specific antigen or nomogram score. We further demonstrate that CNA burden can be measured in diagnostic needle biopsies using low-input whole-genome sequencing, setting the stage for studies of prognostic impact in conservatively treated cohorts.
    Proceedings of the National Academy of Sciences 07/2014; 111(30). DOI:10.1073/pnas.1411446111 · 9.81 Impact Factor
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    ABSTRACT: OBJECTIVE To investigate the relationship between prostate volume measured from preoperative imaging and adverse pathologic features at the time of radical prostatectomy and evaluate the potential effect of clinical stage on such relationship. METHODS In 1756 men who underwent preoperative magnetic resonance imaging and radical prostatectomy from 2000 to 2010, we examined associations of magnetic resonance imaging-measured prostate volume with pathologic outcomes using univariate logistic regression and with postoperative biochemical recurrence using Cox proportional hazards models. We also analyzed the effects of clinical stage on the relationship between prostate volume and adverse pathologic features via interaction analyses. RESULTS In univariate analyses, smaller prostate volume was significantly associated with high pathologic Gleason score (P <.0001), extracapsular extension (P <.0001), and positive surgical margins (P = .032). No significant interaction between clinical stage and prostate volume was observed in predicting adverse pathologic features (all P >. 05). The association between prostate volume and recurrence was significant in a multivariable analysis adjusting for postoperative variables (P = .031) but missed statistical significance in the preoperative model (P = .053). Addition of prostate volume did not change C-Indices (0.78 and 0.83) of either model. CONCLUSION Although prostate size did not enhance the prediction of recurrence, it is associated with aggressiveness of prostate cancer. There is no evidence that this association differs depending on clinical stage. Prospective studies are warranted assessing the effect of initial method of detection on the relationship between volume and outcome. (C) 2014 Elsevier Inc.
    Urology 07/2014; 84(1):153-7. DOI:10.1016/j.urology.2014.04.006 · 2.13 Impact Factor
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    ABSTRACT: Summary of the discussion at a public workshop cosponsored by the U.S. Food and Drug Administration (FDA) and the American Urological Association reviewing potential trial designs for product and device development for the treatment of localized prostate cancer. Product development for treatment of localized prostate cancer has been stymied by the impracticality of using overall survival as an endpoint in patients with localized disease and the lack of acceptable surrogate endpoints. A workshop evaluating potential trial designs for the development of therapies for localized prostate cancer was held in San Diego, CA, in May 2013. Invited experts represented multiple stakeholders, including urology, medical oncology, radiation oncology, industry, and patient advocates. The expert panel discussed development of products for all risk strata of clinically localized prostate cancer. The panel responded to specific questions from FDA, discussing trial design for patients with low-, intermediate-, and high-risk prostate cancer, focal therapy for prostate cancer, patients who have undergone definitive radiation therapy, and adjuvant therapy for patients undergoing radiation therapy or surgery. Expert commentary provided by the panel will inform a planned FDA guidance on pathways for product and device development for treatment of localized prostate cancer and will be discussed at meetings of the FDA's Oncologic Drugs Advisory Committee. FDA intends to develop a set of principles that can be used to promote the development of new products or devices for the treatment of this disease.
    Urology 05/2014; DOI:10.1016/j.urology.2013.10.087 · 2.13 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e765. DOI:10.1016/j.juro.2014.02.2102 · 3.75 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e859-e860. DOI:10.1016/j.juro.2014.02.2343 · 3.75 Impact Factor
  • European Urology Supplements 04/2014; 13(1):e262. DOI:10.1016/S1569-9056(14)60258-X · 3.37 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e459. DOI:10.1016/j.juro.2014.02.1198 · 3.75 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e462. DOI:10.1016/j.juro.2014.02.1205 · 3.75 Impact Factor

Publication Stats

33k Citations
4,139.11 Total Impact Points

Institutions

  • 1999–2015
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Surgery
      • • Urology Service
      • • Epidemiology & Biostatistics Group
      • • Department of Pathology
      New York, New York, United States
  • 2013–2014
    • Cornell University
      Итак, New York, United States
  • 2012
    • University of Utah
      • Huntsman Cancer Institute
      Salt Lake City, Utah, United States
  • 2007–2010
    • University of Turku
      Turku, Varsinais-Suomi, Finland
    • University of Hamburg
      Hamburg, Hamburg, Germany
  • 2009
    • University of Michigan
      • Department of Urology
      Ann Arbor, Michigan, United States
  • 2008–2009
    • Columbia University
      New York, New York, United States
    • Weill Cornell Medical College
      • Department of Urology
      New York City, New York, United States
  • 1987–2006
    • Baylor College of Medicine
      • Department of Urology
      Houston, Texas, United States
  • 2005
    • State University of New York Downstate Medical Center
      • Department of Urology
      Brooklyn, NY, United States
  • 2003
    • University Medical Center Hamburg - Eppendorf
      • Department of Urology
      Hamburg, Hamburg, Germany
  • 2002
    • The University of Tennessee Medical Center at Knoxville
      • Department of Surgery
      Knoxville, TN, United States
    • Medical University of South Carolina
      • Department of Urology
      Charleston, SC, United States
  • 2000
    • Wake Forest School of Medicine
      Winston-Salem, North Carolina, United States
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
    • University of California, San Francisco
      San Francisco, California, United States
    • Harper University Hospital
      Detroit, Michigan, United States
  • 1991–2000
    • Houston Methodist Hospital
      Houston, Texas, United States
  • 1995
    • University of Southern California
      • Department of Urology
      Los Angeles, California, United States
  • 1994–1995
    • Prostate Cancer Research Institute
      Los Angeles, California, United States
    • Loyola University Medical Center
      • Department of Urology
      Maywood, IL, United States
  • 1993
    • National Cancer Institute (USA)
      Maryland, United States
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 1990
    • Methodist Hospitals
      Gary, Indiana, United States