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Identify Genes/Pathways Responsible for Progression From Low Risk to Higher Risk Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03789253
Recruitment Status : Not yet recruiting
First Posted : December 28, 2018
Last Update Posted : December 28, 2018
Information provided by (Responsible Party):
National Taiwan University Hospital

Brief Summary:
In Taiwan, about 70% of new incident prostate cancer patients have localized disease. Most patients were detected by PSA screening. Among them, many had low-risk PC, which is very likely latent in nature, progresses slowly, and rarely leads to death. Most patients died of other causes, such as other cancers, cardiovascular diseases, and diabetes mellitus. Many guidelines recommend that active surveillance (AS) or watchful waiting (WW) is a good option for low risk patients to avoid overtreatment-related complications. However, 30% of patients on AS will finally need definitive treatments due to disease progression within 10 years. We hypothesize that there are differential gene expressions between progressive and non-progressive tumors. If we can identify key genes or pathways that are responsible for progression of low risk PC to higher risk diseases, PC progression could be reduced substantially by regulating these genes or pathways and maintain long-term cancer latency to control non-metastatic PC. In light of the high prevalence rate of latent PC in adult men, the strategy is in fact the best strategy for preventing clinical PC.

Condition or disease
Prostate Cancer Stage I

Detailed Description:

At the Department of Urology, NTUH, we have established a largest Chinese AS/WW cohort, which were prospectively collected since 2013. There were already 280 AS and 100 WW patients. Most AS patients have undergone serial prostate re-biopsies every 1 to 2 years, which is actually our cutting edge in the field. 87 men had at least twice biopsies at our hospital (mean interval 15 months). 26 of them showed pathological progression (Group As) who have been treated aggressively. The other 61 men had no progression even after multiple biopsies (Group Bs). So, we may compare the genetic changes in each subject in Group A to reveal genetic changes responsible for progression. We can also compare baseline expressions between Group A and B to predict progression. We also can correlate genetic alterations in Group A with cancer phenotypes and short-term post-treatment outcomes.

Here are the four Specific Aims:

Aim-1. To investigate the role of known genes or pathways in mediating progression from low risk to higher risk by using serial biopsy paraffin embedded tissue blocks from our AS patients. These known genes/pathways are selected from published reports, which are found to be related to progression from low to higher grade PC, such as Ki-67, PTEN loss, and chromosome 8 alterations.

Aim-2. There was only one cDNA microarray gene bank (GSE37199) published in the literature (Lancet Oncol. 2012; 13:1114) that was associated with differential expression between AS and mCRPC cohorts. We will proceed with the Gene Set Enrichment Analysis (GSEA) to identify more potential genes or pathways that have NOT been specifically demonstrated relating to AS progression. These new genes or pathways will then be studied in Aim-1.

Aim-3. We will perform global cDNA microarray sing non-cancer part of the serial biopsy paraffin tissue blocks from our AS cohort, followed by GSEA to reveal differential gene expression between Group A and B patients. Hopefully we can identify genes/pathways that are related to progression of low risk or latent PC in Taiwanese.

Aim-4. To conduct multivariate analyses considering not only key genetic alterations but also multiple clinicopathological parameters to build up a model predicting progression from low to higher risk PC.

In fact, the only one published study (Lancet Oncol. 2012;13:1114) was to reveal differential cDNA expression in blood cells between AS and mCRPC cohorts, but not between progressive and non-progressive patients. Therefore, the study design was defective because the obtained differential expression may not reflect what really happened in low risk cancer progression. To our knowledge, there has been no differential genetic expression study or the GSEA study for AS cohort. In addition, we have the largest Taiwanese/Chinese cohort on AS/WW and abundant serial biopsy specimens. In summary, our study which focuses on genomic research on AS cohort is a new strategy to prevent clinical PC and is of high novelty and clinical implications.

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Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Identify Genes/Pathways Responsible for Progression From Low Risk to Higher Risk Prostate Cancer—A New Strategy for Prostate Cancer Prevention
Estimated Study Start Date : January 2, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

AS cohort with progression
AS cohort with tumor progression
AS cohort without progression
AS cohort without tumor progression

Primary Outcome Measures :
  1. Difference of Gene expression [ Time Frame: 3 years ]
    Using GESA to analyze different stage of prostate cancer

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Low or intermediate risk prostate cancer patients receiving active surveillance

Inclusion Criteria:

  1. Historically or cytologically confirmed adenocarcinoma of prostate.
  2. Have or ever received active Surveillance as the main conservative management at NTUH (National Taiwan University Hospital).
  3. Have or will receive prostate biopsy to confirm tumor progression after the diagnosis of prostate cancer.

Exclusion Criteria:

  1. Have received systemic chemotherapy, pelvic radiotherapy or androgen deprivation therapy (ADT) before the obtainment of pathological specimen from prostate operation or biopsy.
  2. Subjects who disagree with signing the informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03789253

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Contact: Yeong-Shiau Pu, PhD 886-2-23123456 ext 65950
Contact: Chung-Hsin Chen, PhD 886-2-23123456 ext 65242

Sponsors and Collaborators
National Taiwan University Hospital
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Principal Investigator: Yeong-Shiau Pu, PhD National Taiwan University

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Responsible Party: National Taiwan University Hospital Identifier: NCT03789253     History of Changes
Other Study ID Numbers: 201712093RINB
First Posted: December 28, 2018    Key Record Dates
Last Update Posted: December 28, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Taiwan University Hospital:
active surveillance, microarray, latent, GSEA, latent
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases