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Prostate Cancer Program

Motivation

Improvements in early detection of prostate cancers and accurate determination of their potential lethality promises to save thousands of lives per year and to avert greater numbers of unnecessary radical treatments.

Prostate cancer is the most commonly diagnosed cancer in men in North America and the second most commonly diagnosed cancer in men worldwide.2 In 2007, over 250,000 men died from this disease worldwide, including over 28,000 men in the United States.3 Current prostate cancer screening strategies, which combine blood tests for prostate specific antigen (PSA) with digital rectal examinations (DRE), effectively detect many early prostate cancers but still miss a significant fraction of ultimately lethal cancers. As with other cancers, early detection is critical to survival: 10-year survival is nearly 100% when the disease is diagnosed early but decreases dramatically when the cancer is not detected prior to metastasis (Figures 2 and 3).4 Thus, we have an opportunity to save lives by improving upon current screening strategies, thereby detecting a greater fraction of lethal cancers at an early, curable stage.

Figure 2: Stage at Diagnosis4 Figure 3: 10-year Survival by Stage at Diagnosis4

A diagnosis of prostate cancer is complicated by the fact that the vast majority of prostate cancers would never be lethal even if left untreated, yet our ability to predict which cancers can safely be left untreated is far from perfect. Furthermore, current treatment of prostate cancer (usually radical prostatectomy) commonly results in a significantly reduced quality of life. The scale of problem is enormous; studies suggest that for every six men that underwent radical prostatectomy, only one of them was helped by it, while the rest would not have died from their cancer. These staggering overtreatment statistics have led to the emergence of "watchful waiting" and "active surveillance" approaches to prostate cancer management whereby patients with lower-risk prostate cancer are closely monitored for early signs of progression, and radical treatments can be postponed or avoided altogether. A major goal of the Canary Prostate Program is to develop tools to more accurately discriminate lethal from non-lethal cancers, thus informing critical treatment decisions and sparing many thousands of men from unnecessary radical treatments.

Research

Canary-supported researchers are applying a collaborative approach to develop diagnostic tests for early detection of lethal prostate cancers and discrimination of lethal versus non-lethal cases.

The specific goals of the Canary Foundation Prostate program are to develop tests that can: 1) Identify lethal prostate cancers at an early (curable) stage 2) Classify prostate cancers as either a) potentially lethal: best treated with aggressive therapy b) non-lethal: suitable for continued monitoring without aggressive treatment. Given the large body of published but unvalidated candidate markers for prostate cancer, we are focusing our initial efforts on evaluating the performance of a selected set of promising biomarkers. Candidate biomarkers are evaluated based on their ability to detect lethal prostate cancers at an early (curable) stage and to discriminate lethal from non-lethal prostate cancer. We are focusing on blood-based biomarkers for early detection and considering both blood-based and tissue-based biomarkers for prognostic applications.

Core Resources

Prospective studies, in which samples are systematically collected from a defined group of men whose treatment and monitoring are consistent and systematically documented, are essential for rigorously testing our ability to predict the course of the disease using specimens obtained before the course of the cancer was known. The accompanying well-characterized biological resource bank (blood, tissue, DNA and attendant pathological and clinical data) is invaluable for development and evaluation of candidate biomarkers.

Prostate Active Surveillance Study (PASS)
One of our most important undertakings has been to support and coordinate the planning, development and execution of the Prostate Active Surveillance Study (PASS), an ambitious multi-institution study of active surveillance (rather than immediate surgery) following diagnosis of prostate cancer. This ground-breaking study will enable not only collection of valuable biospecimens but also the identification of specific clinical, pathological, or other features that can be used to determine whether and when intervention is needed.

Tissue Microarrays
In order to facilitate rapid and efficient evaluation of candidate biomarkers in predicting the potential lethality of prostate cancers, we are supporting the construction and application of tissue microarrays that include altogether thousands of prostate cancer samples, well-annotated with respect to the course of the disease.

Blood-Based Biomarkers

We are working to identify and develop new blood-based molecular biomarkers that, perhaps in combination with PSA, can reliably detect prostate cancer at a curable stage and predict which of these cancers require immediate intervention and which can safely be managed by attentive surveillance.

  • Assay Development - A critical bottleneck in biomarker validation is the availability of assays to measure the levels of target biomarkers in the blood. Canary has addressed this bottleneck by supporting an assay development team in Victoria, Canada, and is leveraging this expertise to evaluate novel blood-based candidate biomarkers for prostate cancer.
  • Retrospective Cross-Sectional Validation - Candidate blood-based biomarkers will be tested using a carefully curated common set of blood specimens from men with lethal prostate cancer and from men with non-lethal prostate cancer. Such specimens provide a filter for access to more precious specimens obtained from prospective studies.
  • Retrospective Longitudinal Validation - Candidate biomarkers that look promising in retrospective cross-sectional validation studies will be critically evaluated using blood and tissue samples from the Canary Prostate Active Surveillance Study (PASS). These results allow us to determine whether or not the candidate biomarkers can truly detect prostate cancer at a curable stage and/or selectively identify potentially lethal prostate cancers.
  • Prospective Validation - The infrastructure provided by the PASS study will give us the opportunity to put the most promising biomarker candidates to the definitive test - assessing their ability to save or improve lives when used to screen men for prostate cancer or to guide decisions about treatment.

Tissue-Based Biomarkers

While tissue-based biomarkers by definition require an invasive procedure (biopsy), they could still be extremely valuable post-biopsy in determining which men can be safely spared from radical prostatectomies.

  • Retrospective Cross-Sectional Validation - Candidate biomarkers will be evaluated for their ability to stratify prostate cancers based on their risk of progression in prostate cancer biopsy tissues. Our tissue microarrays that include large numbers of prostate cancer samples (from radical prostatectomies) that are well-annotated with respect to disease progression will allow us to carry out these analyses rigorously, rapidly and efficiently.
  • Retrospective Longitudinal Validation - Markers that look promising in retrospective cross-sectional studies of radical prostatectomy specimens will then be tested in biopsy specimens obtained from the Canary Prostate Active Surveillance Study (PASS). We will assess each marker's ability to predict whether a prostate cancer, left untreated, will progress significantly in men under active surveillance.
  • Prospective Validation - The infrastructure provided by the PASS study will give us the opportunity to put the most promising biomarker candidates to the definitive test - assessing their ability to improve the lives of men with prostate cancer by specifically identifying the small fraction of men who need aggressive treatment, and sparing the others from unnecessary surgery.

View Canary Funded Projects

Citations

  1. Figure 1: http://www.cdc.gov/cancer/prostate/publications/decisionguide/
  2. Garcia M, Jemal A, Ward EM, Center MM, Hao Y, Siegel RL, Thun MJ. 2007. Global Cancer Facts & Figures 2007. Atlanta, GA: American Cancer Society.
  3. Cancer Facts & Figures 2008. American Cancer Society, Atlanta, GA, 2008.
  4. Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER 9 Regs Limited-Use, Nov 2006 Sub (1973-2004 varying) - Linked To County Attributes - Total U.S., 1969-2004 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2007, based on the November 2006 submission.