The science and clinical implementation of multi-cancer early detection.
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I have no financial relationships with GRAIL, Exact Sciences, Guardant Health, or any company developing MCED technology. This newsletter represents independent analysis and does not constitute medical or investment advice. Full disclosures
I am a hematologist and medical oncologist. My research has focused on how liquid biopsies can be incorporated into clinical practice, with publications in journals such as the Nature portfolio and presentations at ASCO and ESMO.
Before Stage One is my way of maintaining the part of my professional life that involves reading papers, thinking carefully about what they mean, and writing the pertinent points down to share with others.
Before Stage One is written by Michael LaPelusa, MD in his personal capacity. Views expressed are his own and do not represent the views of any institution. Content is provided for informational purposes only and should not be relied upon as medical, legal, business, investment, or tax advice. Nothing here is a recommendation to undergo, avoid, prescribe, or order any medical test or treatment, nor a recommendation to buy or sell any security. Readers should consult their own physicians and advisers regarding clinical, financial, and legal decisions. The author does not hold positions in any company discussed unless explicitly disclosed in the post. See full disclosures.
On September 23, the FDA’s Molecular and Clinical Genetics Panel reviewed GRAIL’s premarket approval application for the Galleri test and voted 10 to 0 on safety, 6 to 4 on effectiveness, and 7 to 2 with one abstention on benefit-risk. My Expert Commentary for ASCO Daily News on what the vote changes for oncologists, and the two papers published the day before…
Read moreOn September 23, the FDA’s Molecular and Clinical Genetics Panel will meet to review GRAIL’s premarket approval application (PMA) for Galleri. No other multi-cancer early detection (MCED) test has gotten this far in FDA review. What the meeting means depends on who is asking, so this post is split into three seats…
Read moreNHS-Galleri is the largest randomized controlled trial ever conducted for an MCED test. It was launched in England in 2021 and randomized 142,250 adults aged 50 to 77 with no symptoms or suspicion of cancer.
Read moreIn the two years since GRAIL's Galleri became commercially available in the US, a second MCED test was launched commercially at a lower price point (Exact Sciences’ Cancerguard), a third company obtained FDA Breakthrough Device Designation for its own MCED test (Guardant’s Shield MCD), Medicare…
Read moreIn the US, a clinical laboratory test can reach patients through one of two main pathways.
Read moreIf you've been reading this newsletter, you know that I believe MCED testing has a trajectory that points toward a future where MCED testing may be integrated into preventive care, like mammograms and colonoscopies are.
Read moreIn April 2025, Guardant presented clinical validation data for its MCED test (Shield MCD) at AACR. The presentation evaluated samples from 778 participants in a blinded case-control design (similar to CCGA and DETECT-A). Of these 778 participants, 375 had a known cancer diagnosis, while 403 did not have cancer.
Read moreThe CancerSEEK test, the MCED test used in DETECT-A, was an early version of what became Cancerguard. The CancerSEEK concept was first described in a landmark 2018 paper published in Science. That study was a case-control analysis of 1,005 patients with known, nonmetastatic cancers of eight types…
Read morePATHFINDER 2 was a prospective, multi-center, interventional study conducted at healthcare institutions across the US and Canada, spanning academic centers like Mayo Clinic, Duke, Oregon Health & Science University, and Weill Cornell, alongside community sites like Ochsner Health, Henry Ford, and Hoag Memorial.
Read morePATHFINDER was a prospective cohort study conducted at seven US health networks, including both oncology and primary care outpatient clinics. Between December 2019 and December 2020, the investigators enrolled a "convenience sample" (a non-probabilistic sampling method where participants are chosen…
Read moreThe Circulating Cell-free Genome Atlas (CCGA) was a large, prospective, case-control, observational study that enrolled 15,254 participants across 142 sites in North America between August 2016 and February 2019. 8,584 participants had a recent cancer diagnosis, and 6,670 did not.
Read moreIn the posts ahead, I will delve into clinical studies. Those posts are full of statistical terms like sensitivity, specificity, positive predictive value, and more. I encourage you to bookmark this post, as I'll reference the terms in it frequently.
Read moreI'm going to start with a primer on biology. If you already have a working knowledge of DNA, gene expression, and epigenetics, skip ahead to "More about Methylation" below.
Read moreMy name is Michael LaPelusa and I'm a hematologist and medical oncologist. I graduated from hematology and medical oncology fellowship in 2026. This post is about why I started this newsletter.
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