Validation of a Genomic Classifier that Predicts Metastasis Following Radical Prostatectomy in an At Risk Patient Population
TL;DR: Results indicate that genomic information from the primary tumor can identify patients with adverse pathological features who are most at risk for metastasis and potentially lethal prostate cancer.
About: This article is published in The Journal of Urology.The article was published on 2013-12-01 and is currently open access. It has received 292 citations till now. The article focuses on the topics: Prostatectomy & Biochemical recurrence.
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Roswell Park Cancer Institute1, Johns Hopkins University2, Duke University3, Brigham and Women's Hospital4, Mayo Clinic5, City of Hope National Medical Center6, Memorial Sloan Kettering Cancer Center7, Fred Hutchinson Cancer Research Center8, Fox Chase Cancer Center9, Yale Cancer Center10, Washington University in St. Louis11, University of California, San Diego12, University of Wisconsin-Madison13, University Hospitals of Cleveland14, University of Alabama at Birmingham15, Vanderbilt University16, Moffitt Cancer Center17, University of Colorado Boulder18, University of Tennessee Health Science Center19, University of California, San Francisco20, Northwestern University21, Ohio State University22, University of Michigan23, Stanford University24, University of Utah25, National Comprehensive Cancer Network26
TL;DR: The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer.
Abstract: The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer. The portions of the guidelines included herein focus on the roles of germline and somatic genetic testing, risk stratification with nomograms and tumor multigene molecular testing, androgen deprivation therapy, secondary hormonal therapy, chemotherapy, and immunotherapy in patients with prostate cancer.
1,218 citations
TL;DR: This guideline attempts to improve a clinician’s ability to treat patients diagnosed with localized prostate cancer, but higher quality evidence in future trials will be essential to improve the level of care for these patients.
662 citations
TL;DR: It is suggested that SChLAP1 contributes to the development of lethal cancer at least in part by antagonizing the tumor-suppressive functions of the SWI/SNF complex.
Abstract: Prostate cancers remain indolent in the majority of individuals but behave aggressively in a minority. The molecular basis for this clinical heterogeneity remains incompletely understood. Here we characterize a long noncoding RNA termed SChLAP1 (second chromosome locus associated with prostate-1; also called LINC00913) that is overexpressed in a subset of prostate cancers. SChLAP1 levels independently predict poor outcomes, including metastasis and prostate cancer-specific mortality. In vitro and in vivo gain-of-function and loss-of-function experiments indicate that SChLAP1 is critical for cancer cell invasiveness and metastasis. Mechanistically, SChLAP1 antagonizes the genome-wide localization and regulatory functions of the SWI/SNF chromatin-modifying complex. These results suggest that SChLAP1 contributes to the development of lethal cancer at least in part by antagonizing the tumor-suppressive functions of the SWI/SNF complex.
597 citations
TL;DR: Nuclear enriched abundant transcript 1 (NEAT1) is identified as the most significantly overexpressed lncRNA in prostate cancer and evidence that NEAT1 drives oncogenic growth by altering the epigenetic landscape of target gene promoters to favour transcription is provided.
Abstract: The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains elusive. Using a combination of chromatin immunoprecipitation (ChIP) and RNA-sequencing data, we identified an ERα-specific non-coding transcriptome signature. Among putatively ERα-regulated intergenic long non-coding RNAs (lncRNAs), we identified nuclear enriched abundant transcript 1 (NEAT1) as the most significantly overexpressed lncRNA in prostate cancer. Analysis of two large clinical cohorts also revealed that NEAT1 expression is associated with prostate cancer progression. Prostate cancer cells expressing high levels of NEAT1 were recalcitrant to androgen or AR antagonists. Finally, we provide evidence that NEAT1 drives oncogenic growth by altering the epigenetic landscape of target gene promoters to favour transcription.
526 citations
Memorial Sloan Kettering Cancer Center1, University of Texas MD Anderson Cancer Center2, Harvard University3, Seattle Cancer Care Alliance4, University of Michigan5, University of Pennsylvania6, Northwestern University7, Huntsman Cancer Institute8, Washington University in St. Louis9, Mayo Clinic10, University of California, San Diego11, Stanford University12, University of Wisconsin-Madison13, University of Nebraska Medical Center14, University of Colorado Boulder15, Ohio State University16, Case Western Reserve University17, University of Tennessee Health Science Center18, National Comprehensive Cancer Network19
TL;DR: The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors and desmoid tumors.
Abstract: The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal cell carcinoma, and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize the NCCN Kidney Cancer Panel discussions for the 2020 update to the guidelines regarding initial management and first-line systemic therapy options for patients with advanced clear cell renal cell carcinoma.
459 citations
References
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TL;DR: This article proposes methods for combining estimates of the cause-specific hazard functions under the proportional hazards formulation, but these methods do not allow the analyst to directly assess the effect of a covariate on the marginal probability function.
Abstract: With explanatory covariates, the standard analysis for competing risks data involves modeling the cause-specific hazard functions via a proportional hazards assumption Unfortunately, the cause-specific hazard function does not have a direct interpretation in terms of survival probabilities for the particular failure type In recent years many clinicians have begun using the cumulative incidence function, the marginal failure probabilities for a particular cause, which is intuitively appealing and more easily explained to the nonstatistician The cumulative incidence is especially relevant in cost-effectiveness analyses in which the survival probabilities are needed to determine treatment utility Previously, authors have considered methods for combining estimates of the cause-specific hazard functions under the proportional hazards formulation However, these methods do not allow the analyst to directly assess the effect of a covariate on the marginal probability function In this article we pro
11,109 citations
"Validation of a Genomic Classifier ..." refers methods in this paper
...Cumulative incidence curves were constructed using Fine-Gray competing risks analysis.(20) Survival...
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TL;DR: The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of about 1,024,400 deaths from cancer, which can be accelerated by applying existing cancer control knowledge across all segments of the population, with an emphasis on those groups in the lowest socioeconomic bracket.
Abstract: Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. A total of 1,638,910 new cancer cases and 577,190 deaths from cancer are projected to occur in the United States in 2012. During the most recent 5 years for which there are data (2004-2008), overall cancer incidence rates declined slightly in men (by 0.6% per year) and were stable in women, while cancer death rates decreased by 1.8% per year in men and by 1.6% per year in women. Over the past 10 years of available data (1999-2008), cancer death rates have declined by more than 1% per year in men and women of every racial/ethnic group with the exception of American Indians/Alaska Natives, among whom rates have remained stable. The most rapid declines in death rates occurred among African American and Hispanic men (2.4% and 2.3% per year, respectively). Death rates continue to decline for all 4 major cancer sites (lung, colorectum, breast, and prostate), with lung cancer accounting for almost 40% of the total decline in men and breast cancer accounting for 34% of the total decline in women. The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of about 1,024,400 deaths from cancer. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population, with an emphasis on those groups in the lowest socioeconomic bracket.
10,630 citations
TL;DR: Several clinical parameters help predict the outcomes of men with PSA elevation after radical prostatectomy, and these data may be useful in the design of clinical trials, the identification of men for enrollment into experimental protocols, and counseling men regarding the timing of administration of adjuvant therapies.
Abstract: Context
In men who develop an elevated serum prostate-specific
antigen level (PSA) after having undergone a radical prostatectomy, the
natural history of progression to distant metastases and death due to
prostate cancer is unknown.
Objective
To characterize the time course of disease progression
in men with biochemical recurrence after radical prostatectomy.
Design
A retrospective review of a large surgical series with
median (SD) follow-up of 5.3 (3.7) years (range, 0.5-15 years) between
April 1982 and April 1997.
SettingAn urban academic tertiary referral institution.Patients
A total of 1997 men undergoing radical
prostatectomy, by a single surgeon, for clinically localized prostate
cancer. None received neoadjuvant therapy, and none had received
adjuvant hormonal therapy prior to documented distant metastases.
Main Outcome Measures
After surgery, men were followed up with PSA
assays and digital rectal examinations every 3 months for the first
year, semiannually for the second year, and annually thereafter. A
detectable serum PSA level of at least 0.2 ng/mL was evidence of
biochemical recurrence. Distant metastases were diagnosed by
radionuclide bone scan, chest radiograph, or other body imaging, which
was performed at the time of biochemical recurrence and annually
thereafter.
Results
The actuarial metastasis-free survival for all 1997 men
was 82% (95% confidence interval, 76%-88%) at 15 years after
surgery. Of the 1997 men, 315 (15%) developed biochemical PSA level
elevation. Eleven of these underwent early hormone therapy after the
recurrence and are not included in the study. Of the remaining 304 men,
103 (34%) developed metastatic disease within the study period. The
median actuarial time to metastases was 8 years from the time of PSA
level elevation. In survival analysis, time to biochemical progression
(P<.001), Gleason score (P<.001), and PSA
doubling time (P<.001) were predictive of the probability
and time to the development of metastatic disease. An algorithm
combining these parameters was constructed to stratify men into risk
groups. Once men developed metastatic disease, the median actuarial
time to death was 5 years. The time interval from surgery to the
appearance of metastatic disease was predictive of time until death
(P<.02).
Conclusions
Several clinical parameters help predict the outcomes
of men with PSA elevation after radical prostatectomy. These data may
be useful in the design of clinical trials, the identification of men
for enrollment into experimental protocols, and counseling men
regarding the timing of administration of adjuvant
therapies.
2,854 citations
TL;DR: The USPSTF recommends against PSA-based screening for prostate cancer (grade D recommendation), which applies to men in the general U.S. population, regardless of age.
Abstract: This USPSTF recommendation on screening for prostate cancer considers evidence on the benefits and harms of prostate-specific antigen (PSA)–based screening for prostate cancer, as well as those of ...
2,137 citations
TL;DR: PCa incidence rates increased in nearly all countries considered in this analysis except in a few high-income countries, and the increase in PCa mortality rates mainly occurred in lower resource settings, with declines largely confined to high-resource countries.
1,362 citations
"Validation of a Genomic Classifier ..." refers background in this paper
...7 million new cases and 499,000 deaths annually by 2030.(1) In the approximately 2....
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