Peter T Scardino

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

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Publications (643)3575.33 Total impact

  • [Show abstract] [Hide abstract]
    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 of the United States of America. 07/2014;
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    ABSTRACT: 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.
    Urology 07/2014; 84(1):153-7. · 2.42 Impact Factor
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    ABSTRACT: Focal therapy is gaining interest and this organ-preserving treatment is heading towards becoming an alternative for the conventional surgery and radiation. The purpose of this review is to determine what evidence is required to make focal therapy a viable option for treatment of localized prostate cancer. There is still a lack of high-level evidence for the different focal treatment modalities. The early-stage focal therapy trials are conducted including a various selection of patients and different pretreatment assessment and follow-up, resulting in incomparable data. Recent literature shows it is paramount to extend the amount of biopsies and to alter the way of taking the biopsies with the template-assisted or image-guided approach. To date, multiparametric MRI is the most effective imaging technique in selecting patients for focal therapy. Focal therapy trials are at the early stage of clinical development, with the majority still being phase I studies. To make focal therapy an accepted segment of standard therapy, it needs to proceed toward phase II and III trials. These trials should be conducted with an effective trial design, which will lead to more comparable oncological, functional and quality of life outcomes. Furthermore, it is essential to improve the localization of tumor foci in order to increase the accuracy of spatial targeting of cancer.
    Current opinion in urology 03/2014; · 2.50 Impact Factor
  • CancerSpectrum Knowledge Environment 03/2014; · 14.07 Impact Factor
  • Article: Reply.
    Urology 03/2014; 83(3):597-8. · 2.42 Impact Factor
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    ABSTRACT: Background:Androgen receptor (AR)-gene amplification, found in 20-30% of castration-resistant prostate cancer (CRPCa) is proposed to develop as a consequence of hormone-deprivation therapy and be a prime cause of treatment failure. Here we investigate AR-gene amplification in cancers before hormone deprivation therapy.Methods:A tissue microarray (TMA) series of 596 hormone-naive prostate cancers (HNPCas) was screened for chromosome X and AR-gene locus-specific copy number alterations using four-colour fluorescence in situ hybridisation.Results:Both high level gain in chromosome X (4 fold; n=4, 0.7%) and locus-specific amplification of the AR-gene (n=6, 1%) were detected at low frequencies in HNPCa TMAs. Fluorescence in situ hybridisation mapping whole sections taken from the original HNPCa specimen blocks demonstrated that AR-gene amplifications exist in small foci of cells (600 nm, 1% of tumour volume). Patients with AR gene-locus-specific copy number gains had poorer prostate cancer-specific survival.Conclusion:Small clonal foci of cancer containing high level gain of the androgen receptor (AR)-gene develop before hormone deprivation therapy. Their small size makes detection by TMA inefficient and suggests a higher prevalence than that reported herein. It is hypothesised that a large proportion of AR-amplified CRPCa could pre-date hormone deprivation therapy and that these patients would potentially benefit from early total androgen ablation.British Journal of Cancer advance online publication, 30 January 2014; doi:10.1038/bjc.2014.13 www.bjcancer.com.
    British Journal of Cancer 01/2014; · 5.08 Impact Factor
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    ABSTRACT: Focal therapy has been introduced for the treatment of localised prostate cancer (PCa). To provide the necessary data for consistent assessment, all focal therapy trials should be performed according to uniform, systematic pre- and post-treatment evaluation with well-defined end points and strict inclusion and exclusion criteria. To obtain consensus on trial design for focal therapy in PCa. A four-staged consensus project based on a modified Delphi process was conducted in which 48 experts in focal therapy of PCa participated. According to this formal consensus-building method, participants were asked to fill out an iterative sequence of questionnaires to collect data on trial design. Subsequently, a consensus meeting was held in which 13 panellists discussed acquired data, clarified the results, and defined the conclusions. A multidisciplinary board from oncologic centres worldwide reached consensus on patient selection, pretreatment assessment, evaluation of outcome, and follow-up. Inclusion criteria for candidates in focal therapy trials are patients with prostate-specific antigen <15 ng/ml, clinical stage T1c-T2a, Gleason score 3+3 or 3+4, life expectancy of >10 yr, and any prostate volume. The optimal biopsy strategy includes transrectal ultrasound-guided biopsies to be taken between 6 mo and 12 mo after treatment. The primary objective should be focal ablation of clinically significant disease with negative biopsies at 12 mo after treatment as the primary end point. This consensus report provides a standard for designing a feasible focal therapy trial. A variety of ablative technologies have been introduced and applied in a focal manner for the treatment of prostate cancer (PCa). In this consensus report, an international panel of experts in the field of PCa determined pre- and post-treatment work-up for focal therapy research.
    European Urology 01/2014; · 10.48 Impact Factor
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    ABSTRACT: Although the value of prostate-specific antigen (PSA) velocity or doubling time has never been seriously questioned for aiding the clinical management of recurrent or advanced cancer, there has historically been considerable uncertainty about PSA kinetics for decisions about biopsy and initial treatment. Recent studies, including analyses of cohorts from all the major randomized trials of localized prostate cancer, have failed to find any evidence that PSA velocity and application of PSA cutpoints are of benefit in this setting. Given current data on PSA velocity and doubling time, we propose the following “take home” messages for the practicing urologist: (1) High PSA velocity is not an indication for biopsy; (2) for men with a low total PSA but a high PSA velocity, consideration should be given to having PSA taken at a shorter interval; (3) men with an indication for biopsy should be biopsied irrespective of PSA velocity; (4) changes in PSA after negative biopsy findings do not determine the need for repeat biopsy; (5) monitoring PSA over time can aid judgment in decisions about biopsy, as informed by the clinical context; (6) PSA velocity is uninformative of risk at diagnosis; (7) high PSA velocity is not an indication for treatment in men on active surveillance; (8) PSA velocity at the time of recurrence should be entered into prediction models (or “nomograms”) to aid patient counseling; (9) PSA changes after treatment for advanced disease can help indicate therapeutic response.
    Urology 01/2014; 83(3):592–598. · 2.42 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.
    Urology 01/2014; 84(1):153–157. · 2.42 Impact Factor
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    ABSTRACT: Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing by age and baseline PSA. Estimates of the effects of age on overdiagnosis were based on population based incidence data from the US Surveillance, Epidemiology and End Results database. To investigate the relationship between PSA and overdiagnosis, we used two separate cohorts subject to PSA testing in clinical trials (n = 1,577 and n = 1,197) and a population-based cohort of Swedish men not subject to PSA-screening followed for 25 years (n = 1,162). If PSA testing had been restricted to younger men, the number of excess cases associated with the introduction of PSA in the US would have been reduced by 85%, 68% and 42% for age cut-offs of 60, 65 and 70, respectively. The risk that a man with screen-detected cancer at age 60 would not subsequently lead to prostate cancer morbidity or mortality decreased exponentially as PSA approached conventional biopsy thresholds. For PSAs below 1 ng/ml, the risk of a positive biopsy is 65 (95% CI 18.2, 72.9) times greater than subsequent prostate cancer mortality. Prostate cancer overdiagnosis has a strong relationship to age and PSA level. Restricting screening in men over 60 to those with PSA above median (>1 ng/ml) and screening men over 70 only in selected circumstances would importantly reduce overdiagnosis and change the ratio of benefits to harms of PSA-screening.
    BMC Medicine 01/2014; 12(1):26. · 6.68 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 01/2014; · 2.42 Impact Factor
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    ABSTRACT: Objective. We sought to evaluate the accuracy of transperineal mapping biopsy (TMB) by comparing it to the pathology specimen of patients who underwent radical prostatectomy (RP) for localized prostate cancer. Methods. From March 2007 to September 2009, 78 men at a single center underwent TMB; 17 of 78 subsequently underwent RP. TMB cores were grouped into four quadrants and matched to data from RP whole-mount slides. Gleason score, tumor location and volume, cross-sectional area, and maximal diameter were measured; sensitivity and specificity were assessed. Results. For the 17 patients who underwent RP, TMB revealed 12 (71%) had biopsy Gleason grades ≥ 3 + 4 and 13 (76%) had bilateral disease. RP specimens showed 14 (82%) had Gleason scores ≥ 3 + 4 and 13 (76%) had bilateral disease. Sensitivity and specificity of TMB for prostate cancer detection were 86% (95% confidence interval [CI] 72%-94%) and 83% (95% CI 62%-95%), respectively. Four quadrants negative for cancer on TMB were positive on prostatectomy, and six positive on TMB were negative on prostatectomy. Conclusion. TMB is a highly invasive procedure that can accurately detect and localize prostate cancer. These findings help establish baseline performance characteristics for TMB and its utility for organ-sparing strategies.
    Prostate cancer. 01/2014; 2014:781438.
  • European Urology 10/2013; · 10.48 Impact Factor
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    ABSTRACT: Human endogenous retroviruses (HERV) encode 8% of the human genome. While HERVs may play a role in autoimmune and neoplastic disease, no mechanistic association has yet been established. We studied the expression and immunogenicity of a HERV-K GAG protein encoded on chromosome 22q11.23 in relation to the clinical course of prostate cancer. Experimental design: In vitro expression of GAG-HERV-K was analyzed in panels of normal and malignant tissues, microarrays, and cell lines, and effects of demethylation and androgen stimulation were evaluated. Patient sera were analyzed for seroreactivity to GAG-HERV-K and other self-antigens by ELISA and seromics (protein array profiling). GAG-HERV-K expression was most frequent in prostate tissues, and regulated both by demethylation of the promoter region and by androgen stimulation. Serum screening revealed that antibodies to GAG-HERV-K are found in a subset of prostate cancer patients (33/483, 6.8%), but rarely in male healthy donors (1/55, 1.8%). Autoantibodies to GAG-HERV-K occurred more frequently in advanced prostate cancer patients (29/191 in stage III-IV, 21.0%) than in early prostate cancer (4/292 in stage I-II, 1.4%). Presence of GAG-HERV-K serum antibody was correlated with worse survival of prostate cancer patients, with a trend for faster biochemical recurrence in patients with antibodies to GAG-HERV-K. Preferential expression of GAG-HERV-K ch22q11.23 in prostate cancer tissue and increased frequency of autoantibodies observed in advanced prostate cancer patients make this protein one of the first bona fide retroviral cancer antigens in humans, with potential as a biomarker for progression and biochemical recurrence rate of prostate cancer.
    Clinical Cancer Research 09/2013; · 7.84 Impact Factor
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    ABSTRACT: We demonstrate that the androgen receptor (AR) regulates a transcriptional program of DNA repair genes that promotes prostate cancer radioresistance, providing a potential mechanism by which androgen deprivation therapy (ADT) synergizes with ionizing radiation (IR). Using a model of castration-resistant prostate cancer, we show that second-generation antiandrogen therapy results in downregulation of DNA repair genes. Next, we demonstrate that primary prostate cancers display a significant spectrum of AR transcriptional output which correlates with expression of a set of DNA repair genes. Employing RNA-seq and ChIP-seq, we define which of these DNA repair genes are both induced by androgen and represent direct AR targets. We establish that prostate cancer cells treated with IR plus androgen demonstrate enhanced DNA repair and decreased DNA damage and furthermore that antiandrogen treatment causes increased DNA damage and decreased clonogenic survival. Finally, we demonstrate that antiandrogen treatment results in decreased classical non-homologous end joining.
    Cancer Discovery 09/2013; · 10.14 Impact Factor
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    ABSTRACT: Prostate biopsy-related infectious complications are associated with significant morbidity. The risk of infectious complications in prostate cancer patients on active surveillance (AS) remains understudied. 591 consecutive men who underwent prostate biopsy were prospectively enrolled in a study evaluating prostate biopsy-related complications between January 2011 and January 2012. Of these, 403 were previously diagnosed with prostate cancer and included in this study. They received a 14-core transrectal ultrasound guided prostate biopsy as part of an AS regimen. A nurse contacted all men within 14 days of biopsy, and information was collected on potential complications, antibiotics received and bacterial culture results. Fourteen patients (3.5%) had infectious complications including 13 requiring hospitalization. Five patients had positive urine cultures and fluoroquinolone (FQ)-resistant isolates were identified in 4 patients, including 2 patients with extended-spectrum beta-lactamase (ESBL)-producing isolates. We evaluated the impact of risk factors including diabetes, benign prostatic hypertrophy (BPH), and antibiotic regimen; however only the number of previous prostate biopsies was significantly associated with an increased risk of infectious complications (p=0.041). For every previous biopsy, odds of an infection increases 1.3 times (odds ratio 1.33, 95% confidence interval 1.01-1.74). In men with prostate cancer on AS, the number of previous prostate biopsies is associated with significant risk of infectious complications and every previous biopsy increases the risk of infectious complication. FQ-resistant and ESBL-producing isolates represent the most commonly identified organisms. Men with prostate cancer on AS should be informed of the risks associated with serial repeat prostate biopsies.
    The Journal of urology 09/2013; · 4.02 Impact Factor
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    ABSTRACT: Active surveillance (AS) is becoming an increasingly common management strategy for low-grade prostate cancer and involves repeated prostate biopsies over time. It has been hypothesized that serial biopsies can lead to reduced erectile function (EF) in patients on AS. We explored this hypothesis in a longitudinally followed cohort. We identified 342 men on AS whose first biopsy occurred between 2000 and 2009. We investigated EF using patient-reported outcomes, namely the six erectile function questions from the International Index of Erectile Function (IIEF-6). We estimated the change in EF over time using locally-weighted scatterplot smoothing. The median age in this cohort was 64 (IQR 58-68) years. Median follow-up on AS was 3.5 years (IQR 2.3-5.0), and the median number of biopsies was 5 (IQR 3-6). Over the first 4 years on AS, EF declined 1.0 points/year (95% confidence interval [CI], 0.2, 1.7) on the IIEF-6 (scale 1-30). When stratified by comorbidities or number of biopsies, we see an almost identical drop in EF over time. The use of Phosphodiesterase-5 inhibitors increased from 5% to 27% from baseline to year 5 on AS. In this longitudinally followed active surveillance cohort we observed a small decline of erectile function and an increased use of Phosphodiesterase-5 inhibitors over time. While we cannot separate out the effect of multiple biopsies from that of the natural aging process on erectile function in this observational study, our data suggests AS-related biopsies do not have a large impact on erectile function.
    The Journal of urology 09/2013; · 4.02 Impact Factor

Publication Stats

26k Citations
3,575.33 Total Impact Points

Institutions

  • 1999–2014
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Surgery
      • • Epidemiology & Biostatistics Group
      • • Urology Service
      New York City, New York, United States
  • 2011–2012
    • University of Utah
      • • Department of Surgery
      • • Division of Urology
      Salt Lake City, UT, United States
    • Queen Mary, University of London
      • Centre for Molecular Oncology
      London, ENG, United Kingdom
  • 2010
    • Ontario Institute for Cancer Research
      Toronto, Ontario, Canada
    • Montefiore Medical Center
      • Department of Urology
      New York City, New York, United States
  • 2009
    • University of Illinois at Chicago
      Chicago, Illinois, United States
    • University of Michigan
      • Department of Urology
      Ann Arbor, Michigan, United States
    • University of Southern California
      • Department of Urology
      Los Angeles, CA, United States
    • Medical University of Vienna
      • Universitätsklinik für Urologie
      Vienna, Vienna, Austria
    • Dana-Farber Cancer Institute
      • Lank Center for Genitourinary Oncology
      Boston, MA, United States
  • 1987–2009
    • Baylor College of Medicine
      • Department of Urology
      Houston, Texas, United States
  • 2008
    • Weill Cornell Medical College
      New York City, New York, United States
    • University of Chicago
      • Section of Nephrology
      Chicago, IL, United States
    • Institute of Cancer Research
      Londinium, England, United Kingdom
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      • Prostate Cancer Program
      Milano, Lombardy, Italy
    • Lund University
      Lund, Skåne, Sweden
  • 2006
    • University of London
      Londinium, England, United Kingdom
  • 2005
    • State University of New York Downstate Medical Center
      • Department of Urology
      Brooklyn, NY, United States
    • Colorado State University
      Fort Collins, Colorado, United States
  • 2003
    • University Medical Center Hamburg - Eppendorf
      • Department of Urology
      Hamburg, Hamburg, Germany
    • Cornell University
      • Department of Urology
      Ithaca, NY, United States
  • 2002
    • The University of Tennessee Medical Center at Knoxville
      • Department of Surgery
      Knoxville, TN, United States
    • University of Hamburg
      • Department of Urology
      Hamburg, Hamburg, Germany
    • Medical University of South Carolina
      • Department of Urology
      Charleston, SC, United States
    • William Beaumont Army Medical Center
      El Paso, Texas, United States
  • 2000
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
    • Wake Forest School of Medicine
      Winston-Salem, North Carolina, United States
    • University of California, San Francisco
      San Francisco, California, United States
    • Harper University Hospital
      Detroit, Michigan, United States
  • 1993–2000
    • Houston Methodist Hospital
      Houston, Texas, United States
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
  • 1998
    • Iwate Medical University
      • Department of Urology
      Morioka, Iwate, Japan
  • 1994–1997
    • Prostate Cancer Research Institute
      Los Angeles, California, United States
    • Loyola University Medical Center
      • Department of Urology
      Maywood, IL, United States
  • 1996
    • Mayo Clinic - Rochester
      • Department of Laboratory Medicine & Pathology
      Rochester, MN, United States
  • 1994–1995
    • University of Washington Seattle
      • Department of Surgery
      Seattle, WA, United States
  • 1990
    • Methodist Hospitals
      Gary, Indiana, United States