Date Posted, by Alyssa Voss, M.P.H.
These days, we commonly receive reminder emails, texts, or messages from our health care providers reminding us to schedule our regular check-ups, physicals, screenings, or other routine health care appointments. People of a certain age include cancer screenings to that healthcare to-do list – for example, mammograms for women aged 40 and up, and colonoscopies for men and women starting at age 45.
But how do screening tests actually make it to our to-do list? Through research. For recommended screening tests, studies have been conducted to determine that the screening test is effective at reducing the number of deaths due to that type of cancer as well as optimal screening schedules.
The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
More than thirty years ago, NCI announced one such study – an ambitious cancer screening trial to find answers about the utility of cancer screening tests in preventing deaths from four types of cancer. Championed by researchers from NCI’s Division of Cancer Prevention (DCP) and Division of Cancer Epidemiology and Genetics (DCEG), the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial enrolled 154,877 women and men between 1993 and 2001 and followed participants for nearly 30 years. This year, the PLCO trial officially ended its follow-up and sent its final newsletter to participants thanking them for their dedicated participation in the landmark trial.
For an overview of the trial and its findings visit the trial’s webpage Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).
While the primary results of the screening tests were published between 2009 and 2012, more than 1,300 peer-reviewed scientific publications have been produced to date using PLCO data. This is due to the large resource of data and biospecimens that the study collected from participants over the course of the trial and beyond.
Greater Than the Sum of Its Parts
Cancer screening studies are inherently challenging due to the large study sizes, budgets, and duration needed to carry them out, and the design of the PLCO was intended to maximize NCI’s investment. “The PLCO Clinical trial was a very important cancer screening study, but it is a resource that far, far exceeds its importance as a cancer screening study, said Lori Minasian, M.D., deputy director of DCP. “With its data, biospecimens, and clinical annotation that allows investigators to really dig deeply, PLCO has been an enormous resource to investigators around the world.”
At the outset, the PLCO study aimed to develop a repository of data and biological resources for additional studies to assess risk factors and early markers of cancer risk beyond the original trial. What set this effort apart was the plan to systematically collect detailed information and biospecimens, including blood, buccal (cheek) cells, and tissue, from the more than 150,000 participants over time, before and, for many, after a cancer diagnosis. This approach lent itself not only to studies examining a spectrum of factors that might influence risk years before cancer is found, it also provides researchers with a resource they can use to verify and translate new risk models, biomarker panels, and other innovative approaches to cancer risk assessment and early detection at a population level.
“Between the sheer number of cancer-related events and endpoints captured through follow-up and the longitudinal samples, PLCO is unmatched in the amount of data it has from study participants for over nearly thirty years,” said Steven Moore, Ph.D., M.P.H., DCEG senior investigator and PLCO principal investigator. “PLCO is also timeless, as the data and specimens have been leveraged in research about many different types of cancer beyond the original four using novel technologies and advances that were not available when the trial started.”
NCI’s Cancer Data Access System: Data and More
NCI’s Cancer Data Access System is the access point where researchers can view the comprehensive list of PLCO resources and request access. All requests undergo a rigorous review process. Data-only requests are processed within weeks, while requests for biospecimens involve submission to the PLCO Etiologic and Early Marker Studies program for review. An ongoing list of more than 1,500 approved projects is also available.
“One of the really nice things is that we’ve asked recipients that they return some of those results to us so that we can incorporate the information into the database and then provide it for other investigators, added Minasian. “It becomes a nice way for people to not only use this resource but provide feedback and information for the next set of investigators who come to CDAS for PLCO data.”
The stories below highlight some of the research enabled by PLCO.
Hilary Robbins, Ph.D.
Dr. Robbins is a scientist at the International Agency for Research on Cancer in Lyon, France, where she co-leads the Risk Assessment and Early Detection team. She completed a fellowship at NCI in the Division of Cancer Epidemiology and Genetics, but her main experience working with PLCO resources was after her time there.
“PLCO contributes to almost everything we do in my team,” said Robbins, “especially our work on lung cancer.” For example, the DCP-funded Lung Early Proteins (LEAP) project involves a biomarker panel, called INTEGRAL, developed to identify people at increased risk for lung cancer so they can be screened. Robbins’ team is using a sub-sample of PLCO biospecimens to evaluate whether the INTEGRAL panel can better predict lung cancer risk through multiple measurements over time versus a one-time measurement.
“PLCO provides a perfect opportunity to look at this because there were several blood collections for each participant, with multiple samples usually available before cancer diagnosis.” PLCO plays a role in several more of the projects in Robbins’ team including studies of opioids and cancer risk and multi-cancer detection tests. “PLCO contributes to our research in so many ways because the data and samples are relevant to many different domains and because the resources are so accessible,” Robbins added.
Robert “Rocky” Schoen, M.D., M.P.H.
Dr. Schoen is the UPMC Endowed Chair in Gastroenterology, Hepatology and Nutrition and Professor of Medicine & Epidemiology at the University of Pittsburgh. He became involved in PLCO as a gastroenterologist through his colleagues at UPitt and led the flexible sigmoidoscopy screening element of the trial in Pittsburgh beginning in 1992. In 2002 Schoen became the leader of the colon section of the trial and over the years has used PLCO data for additional high value, impactful projects that continue to this day.
“PLCO has been the most formidable project I was ever involved in, and made the most powerful impact on my career,” Schoen stated. “The biorepository in some ways became more significant than the clinical ‘PLCO’ portions, as it provided a lasting, potent resource to test biomarkers for early detection of cancer.”
He continues to use PLCO data and collaborates with other investigators to develop tools to improve colorectal cancer early detection and colonoscopy technologies. Schoen currently is the national Principal Investigator for the FORTE trial. FORTE is a randomized trial of surveillance colonoscopy enrolling 9,500 participants to evaluate optimal colonoscopy follow-up screening intervals, which Schoen says evolved from PLCO data.
“Did I know that PLCO would be the foundation of my research career – absolutely not! All I knew was it was a great opportunity to work with fabulous scientists committed to public health – how lucky I was to be in the right place at the right time.”
Holli Loomans-Kropp, Ph.D.
Dr. Loomans-Kropp is an assistant professor at the Ohio State University College of Medicine leading a program on precision prevention and early detection of gastrointestinal cancers. She completed her postdoctoral work in the NCI Division of Cancer Prevention, working with Drs. Asad Umar and Paul Pinsky using PLCO data to evaluate aspirin and colorectal cancer incidence, survival, and mortality risk – research she credits with helping her define her career path.
“The experience of designing epidemiologic studies and using PLCO data to answer population-level questions about exposures and risk for colorectal cancer inspired the questions driving my current research,” said Loomans-Kropp. “We can take our observations from population data and investigate at a molecular level how these mechanisms are working, then go back and look at the PLCO data or biospecimens to see if and how these mechanisms are reflected at the population level.”
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