# Galleri and organ-specific cancer screening

[Home](../README.md) · [Cancer and early detection](../WATCHLIST.md#cancer-early-detection) · [Calendar](../MILESTONES.md)

Tags: [Screening and earlier detection](../BROWSE.md#screening)

## Current state

SOARA plans to track ovarian blood-screening harms and invasive workups; a separate urine lung-test study validates existing nodules in never-smokers. These registrations add modalities without proving mortality benefit. Galleri's prior primary-endpoint miss and nonbinding FDA vote remain separate.

Status: active. Initial baseline checked 2026-09-12; selective watchlist, not a systematic review.

## Questions to follow

- Added 2026-09-12: organ-specific cancer screening, initially colorectal blood/stool tests and their clinical utility.
- Follow GRAIL's Galleri multi-cancer detection test, readouts from ongoing trials, new trial announcements, longer follow-up, and regulator decisions.
- Identify the relevant NHS-Galleri and PATHFINDER programs during the baseline; verify exact trial identifiers and current status rather than assuming they remain ongoing.
- Separate sensitivity, specificity, positive predictive value, cancer-signal origin accuracy, detection yield, and stage shift from mortality or other demonstrated patient benefit.
- Note which cancers and stages drive performance, false positives, diagnostic workup, missed cancers, overdiagnosis, and repeat-screening effects.
- Track U.S. authorization, intended population, and availability without equating commercial access with proven screening benefit.

## Programs and next milestones

### Focused update — 2026-10-16

<span class="note-anchor" id="note-2026-10-09-natera-mced-breakthrough-designation"></span>

#### Natera reports FDA Breakthrough Device designation for a separate MCED assay

**Development stage:** Natera announced on October 9 that FDA granted Breakthrough Device designation to its cell-free-DNA multi-cancer early detection assay. The release says the submission included performance across 12 cancer types, including sensitivity, specificity and cancer-signal-origin prediction, but it does not disclose the numerical results, validation population, sample size or a trial identifier.

**Evidence and limitations:** Designation may facilitate FDA interaction; it does not validate improved patient outcomes or establish a favorable population-screening benefit–harm balance. This screening assay is separate from tumor-informed Signatera MRD testing after a cancer diagnosis.

**U.S. status:** Breakthrough designation is not marketing clearance or approval. This source does not establish a launch date, coverage or routine availability. The exact date designation was granted is not provided; October 9 is the announcement date.

**Next milestone:** Detailed intended-use validation and prospective clinical-utility evidence; no dependable date disclosed.

**Sources:** [Source 1](https://www.natera.com/company/news/fda-grants-breakthrough-device-designation-for-nateras-multi-cancer-early-detection-assay/).

<span class="note-anchor" id="note-2026-10-16-safe-mri-breast-screening-registration"></span>

#### SAFE-MRI registers one-time abbreviated breast screening at age 45

**Development stage:** SAFE-MRI (NCT07878377), Radboud University Medical Center, was first posted October 16. The single-group, open-label study plans 2,628 Netherlands residents aged exactly 45. It excludes women with CanRisk lifetime breast-cancer risk of 20% or higher and evaluates one abbreviated breast MRI.

**Evidence and limitations:** Registered outcomes include cancer detection per 1,000 screened, tumor size, cost per cancer detected, stage and participant experience. There is no randomized comparison or cancer-mortality endpoint. Detection and stage distribution cannot establish mortality benefit or resolve overdiagnosis. This is organ-specific breast imaging, not whole-body MRI.

**U.S. status:** Netherlands research; this registration does not establish a new U.S. recommendation or coverage policy.

**Next milestones:** Not yet recruiting as of this check. Start January 1, 2027; primary completion December 2028; final completion December 2031, all registry estimates. Registration is not evidence recruitment has started.

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07878377).

**Remaining gaps:** Focused update of current notes, saved trial records, sponsor/regulator leads and newly registered screening programs. All six initial named-record timeouts were resolved on retry. Broad discovery returned 146 records, of which the first 100 were retrieved; the remaining page and every organ-specific alternative were not appraised. Upcoming ESMO October 23–27 is still a meeting window, not delivered data. Galleri panel voting, SOARA and urine-VOC entries already saved October 13 were deduplicated. No full successful-check advancement.

**Informal-source coverage:** Targeted indexed Reddit and investor discussion searches revisited approval-timing speculation. No exact new FDA action date or primary approval document was established in this focused check. Existing approval-timing claim stays unconfirmed; advisory voting is not marketing authorization. Full investor audio/transcript coverage remains incomplete.

[Full coverage record](../updates/2026-10-16_scheduled_research_update.md).


### Focused update — 2026-10-13

<span class="note-anchor" id="note-2026-10-13-soara-evident"></span>

#### SOARA plans to measure ovarian-screening harms and diagnostic burden

**Source date:** First posted October 13, 2026. **SOARA/NCT07872644**, Mercy BioAnalytics, is a prospective single-group decentralized study of the investigational **Evident ovarian cancer blood-screening test**, planning up to **1,750 average-risk postmenopausal women aged at least 50**.

Positive screens trigger transvaginal ultrasound; further management stays with clinicians. Twelve-month primary measures include test/procedure/screening adverse events, specificity, and the **ratio of invasive follow-up procedures to confirmed ovarian cancers**. Psychological burden is secondary.

**Limits/safety/U.S.:** Not yet recruiting, with no accuracy or safety results. No control arm or mortality endpoint establishes improved outcomes from ovarian screening. High specificity alone would not eliminate unnecessary imaging or surgery in this low-prevalence population. The registry explicitly identifies an unapproved device; registration is not FDA marketing authorization.

**Next:** November 2026 estimated start and May 2028 estimated primary/final completion. Verify actual initiation and diagnostic resolution; these estimates are not publication dates.

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07872644).

<span class="note-anchor" id="note-2026-10-13-urine-voc-neversmoker"></span>

#### A urine lung-cancer test enters prospective validation in never-smokers

**Source date:** First posted October 13, 2026; registry lists **actual start September 15, 2026** and recruiting. **NCT07871656**, Thomas Jefferson University with EARLY Labs, plans **87 never-smoking adults** undergoing biopsy or resection for an indeterminate pulmonary nodule at least 6 mm.

A machine-learning urine volatile-organic-compound biosensor will distinguish histologically malignant from benign nodules. Sensitivity and specificity with 95% intervals are primary; additional biobank and risk-reclassification analyses are secondary/exploratory.

**Limits/safety/U.S.:** This is a nodule-selected case-control validation, not screening randomly selected asymptomatic never-smokers. It cannot by itself establish population predictive values, stage shift, fewer lung-cancer deaths, or avoidance of biopsy. No posted results or new screening authorization. Diagnostic workup remains necessary.

**Next:** March 1, 2028 estimated primary/final completion; no announced readout date.

**Sources:** [Source 1](https://clinicaltrials.gov/study/NCT07871656).

**Remaining gaps:** Read current Galleri/organ-specific page/state, September 5 overlap and all six named registries; no duplicate EDCC poster or prior nonbinding FDA-vote event. New SOARA and urine-VOC human-study registrations appraised with screening/diagnostic populations distinct.; New-study query returned 134 matches; first 100 screened, remaining page not retrieved. Broad query contains incidental cancer/screening terms. All organ-specific breast/colorectal/lung trials, FDA final-status/label database records and downstream-outcomes inventory remain incompletely refreshed.; October 8 BMJ Galleri opinion located as opinion, not a new trial result. No FDA approval inferred from its title, commercial access, press headlines or advisory vote. ESMO Oct 25/26 workup analyses remain scheduled.

**Informal-source coverage:** Targeted original/indexed Galleri informal searches did not yield a distinct new attributable trial/decision rumor. Misleading panel-approval headlines do not establish FDA marketing approval. Informal/podcast coverage incomplete.

[Full coverage record](../updates/2026-10-13_scheduled_research_update.md).


### Focused update — 2026-10-09

#### EDCC poster reports fewer emergency cancer diagnoses with Galleri

**Source date:** October 7 GRAIL evidence-hub posting; EDCC was October 6–8. Individual delivery was unverified. **Evidence:** Sponsor-funded conference poster using randomized NHS-Galleri data.

Across three annual rounds plus approximately 12 months of follow-up after each, **225 cancers were diagnosed through an emergency presentation in the intervention arm versus 286 in control**, a **21.3% reduction**. For the 12 prespecified high-mortality types, the corresponding counts were **135 versus 188 (28.2%)**. The poster supplies no uncertainty intervals or significance tests for these comparisons.

**Limits:** These are counts of emergency diagnoses, not counts of lives saved. The estimate of **4,861 fewer emergency presentations annually in England at 70% uptake** is a population projection assuming a linear uptake relationship. It is not an observed nationwide outcome, and does not reverse the trial's unsuccessful combined stage III/IV primary endpoint or establish survival benefit.

**U.S. status / next milestone:** No new FDA approval from this poster. Await mortality follow-up and full peer-reviewed secondary reporting; dates undisclosed.

[Original EDCC poster](https://grail.com/wp-content/uploads/2026/10/EDCC-2026_Ellis_Routes-to-Dx_Poster_FINAL.pdf).

#### NHS-Galleri model estimates a preclinical detection window

**Source date:** October 6 GRAIL hub posting; EDCC October 6–8. **Evidence:** Post hoc model of NHS-Galleri incidence for 12 prespecified cancers.

The model estimates mean detectable preclinical windows of **1.49 years for cancers clinically diagnosed at stage I (95% CI 0.58–2.86), 1.80 at stage II (0.87–2.88), 1.24 at stage III (0.66–2.09), and 1.69 at stage IV (1.16–2.42)**. At a modeled annual interval, episode sensitivity is **22%, 44%, 47%, and 65%**, respectively; these differ from estimated sensitivity at the moment of clinical diagnosis.

**Limits:** The window is inferred from incidence, control/test-negative cases, and a parametric decay model. It is not a directly measured duration spent in a cancer stage. Annual compatibility does not establish the optimal interval, benefit from more frequent testing, or mortality reduction.

**U.S. status / next milestone:** No new approval or screening recommendation. Prospective interval comparisons and survival evidence remain needed; no announced date.

[Original detection-window poster](https://grail.com/wp-content/uploads/2026/10/EDCC-2026_Hubbell_PS-Screening-Interval_FINAL.pdf).

#### PATHFINDER 2 subgroup analysis leaves uncertainty about equal performance

**Source date:** October 7 GRAIL hub posting; EDCC October 6–8. **Evidence:** Descriptive PATHFINDER 2 subgroup poster, **NCT05155605**.

The performance population was **32,007**. Overall specificity was **99.64% (95% CI 99.57–99.70)** and episode sensitivity **39.3% (34.9–44.0)**. Specificity was at least 99.3% in the reported racial/ethnic groups. Sensitivity estimates were much less precise: **50.0% (15.0–85.0)** among American Indian/Alaska Native participants, with only **four cancers**, and **38.9% (24.8–55.1)** among Black participants, with **36 cancers**.

**Limits:** Race/ethnicity was self-reported and categories can overlap. There were no formal hypothesis tests or prespecified equivalence criteria. Similar point estimates and high specificity do not prove equally effective screening, equal access to diagnostic resolution, or equal clinical benefit. Detection accuracy is distinct from mortality benefit.

**U.S. status / next milestone:** No new approval. Await larger diverse prospective samples and subgroup workup/outcome data; no announced date.

[Original health-equity poster](https://grail.com/wp-content/uploads/2026/10/EDCC-2026_Demeure_Health-Equity-Poster_FINAL-1.pdf).

#### Claims analysis finds no mammography decline after a negative Galleri result

**Source date:** October 7 GRAIL hub posting; EDCC October 6–8. **Evidence:** Retrospective Komodo claims analysis.

Among **2,820 women aged 42–72** with a negative first Galleri test in July 2022–June 2023 and continuous insurance coverage for 24 months before and after, any mammography occurred in **2,317 (82.2%) before versus 2,357 (83.6%) after**. This includes diagnostic mammography; screening-only use was approximately 78% in both periods. Most participants had commercial insurance.

**Limits:** No untreated comparison group, statistical uncertainty, or randomized adherence intervention. Continuous-coverage and selection requirements substantially narrow the sample. The analysis does not prove Galleri improves adherence, exclude substitution in other populations, or establish cancer-outcome benefit. Galleri does not replace established breast screening.

**U.S. status / next milestone:** No new authorization or mammography recommendation. Controlled implementation studies and broader populations remain needed; timing unknown.

[Original mammography-adherence poster](https://grail.com/wp-content/uploads/2026/10/EDCC-2026_McDonnell_MammographyAdherenceMCED_Poster_FINAL.pdf).

#### Galleri poster catalogs histologic cancer types rather than 204 independent screening targets

**Source date:** October 7 GRAIL hub posting; EDCC October 6–8. **Evidence:** Descriptive analysis of PATHFINDER 2 and NHS-Galleri.

Investigators classified **1,100 Galleri-detected invasive cancers** among approximately **105,000 screened participants** into **204 histologically distinct site-and-histology combinations** using ICD-O-3. Some colon subsites are counted separately; hormone-receptor/HER2 categories and molecular markers are not comprehensively represented.

**Limits:** This counts the spectrum among cancers that were found. It supplies neither sensitivity for each of 204 types nor evidence that every subtype is reliably detected. It does not mean 204 organ sites, predict an individual's likelihood of detection, or establish mortality benefit. The underlying studies were conducted in 2021–2025; this is a new classification analysis rather than another trial.

**U.S. status / next milestone:** No new approval. Independent subtype-specific performance and outcome data remain needed; timing unknown.

[Original spectrum poster](https://grail.com/wp-content/uploads/2026/10/EDCC-2026_Clarke_PS-MCED-Detectable-Cancer-Types_Poster_FINAL-1.pdf).

**Remaining gaps:** Read current topic/state and September5 overlap; live API retrieved all six saved registries, including October6 Vanguard update. Registry administrative refresh is not a new results announcement.; Closed prior EDCC gap: appraised actual October6–7 sponsor PDFs for emergency routes, detection-window modeling, health equity, mammography adherence, cancer spectrum and stage-associated life-expectancy modeling. Exact hub posting dates retained separately from conference6–8 window.; Organ-specific breast/colorectal/lung/precancer programs received targeted discovery searches; not an exhaustive registry/publication census. FDA September23 panel follow-through and labels were not independently reappraised in full. Life-expectancy-by-stage modeling not promoted as observed screening survival benefit.

**Informal-source coverage:** Targeted original Reddit/Galleri and informal meeting searches did not yield a distinct attributable fresh rumor. This is a limited search, not proof there are no rumors; no inference of FDA approval from an advisory vote or poster.

[Full coverage record](../updates/2026-10-09_scheduled_research_update.md).


### Focused update — 2026-10-06

#### Galleri adds October presentations on repeat screening, equity and diagnostic-workup safety

**Source/event date:** October 5, 2026. **Evidence:** Sponsor conference announcement, not a completed-results appraisal.

GRAIL schedules six EDCC abstracts in Edinburgh, October 6–8, and two ESMO abstracts in Madrid, October 23–27. EDCC: NHS-Galleri preclinical-detection window on **October 6**; PATHFINDER2 cancer-type spectrum and race/ethnicity performance, mammography adherence and emergency-diagnosis analyses on **October 7**. ESMO: real-world positive-test diagnostic workups (**1164P, October 25, 12:00–12:45 local program time**) and PATHFINDER2 cancer-signal-origin-guided workup efficiency/safety (**1151, October 26, 14:45–16:15 session window**, Salamanca Auditorium/Hall 10).

**Limits/safety:** The announcement supplies no new full numerical estimates or subgroup/harms tables. Stage shifts, inferred preclinical windows and emergency-presentation associations do not establish mortality benefit, optimal interval or absence of overdiagnosis. Preserve the previously missed NHS primary endpoint and post-data-lock PATHFINDER serious-workup-event caveat.

**U.S. status:** The October 5 release explicitly says Galleri is **not FDA-cleared or approved**; prescription laboratory access remains separate. No FDA decision date is verified.

**Next milestone:** Obtain actual EDCC October 6–7 and ESMO October 25–26 material; these scheduled events are not guaranteed positive findings.

[October 5 announcement](https://grail.com/press-releases/grail-to-present-new-data-from-nhs-galleri-and-pathfinder-2-at-edcc-and-esmo-congress-2026/).

**Coverage:** Galleri FDA approval October 2026 September 2026 colorectal screening results; genomic newborn screening polygenic risk pharmacogenomics trial September October 2026 after:2026-09-25 before:2026-10-07

**Remaining gaps:** Read topic/current panel and paper events; searched since September5 with October2–6 emphasis. Opened new October5 GRAIL announcement and current news center.; October5 official sponsor source explicitly still says Galleri not FDA-cleared or approved. This is current verification separate from advisory vote.; EDCC/ESMO actual posters and full FDA meeting transcript not appraised. Organ-specific colorectal registry census and SDC2 full-paper gap remain; no complete-topic no-news conclusion.

**Informal-source coverage:** Searched Galleri FDA timing/Reddit. September24 r/EverythingScience discussion repeats advisory vote and uncertainty; September28 r/ProactiveHealth price discussion is access/anecdote. No original new approval deadline or efficacy rumor verified. Existing approval-timing speculation stays unresolved.

[Full coverage record](../updates/2026-10-06_scheduled_research_update.md).


### Focused update — 2026-10-02

No additional material finding was verified in this focused pass. Coverage remains incomplete; this is not a full-topic “no news” conclusion.

**Coverage:** Galleri FDA approval September October 2026 advisory panel; colorectal stool blood screening September 2026 SDC2; Galleri FDA approval Reddit September 2026.

**Remaining gaps:** No final FDA approval verified. September 23 nonbinding panel vote already captured and is not new approval. Full organ-specific registry census, panel transcript and newly located SDC2 papers remain unappraised.

**Informal-source coverage:** Unresolved; no new corroboration; Reddit approval timing remains speculation; no official action date identified. [Original source](https://www.reddit.com/r/biotech_stocks/comments/1wp74ld/fda_approval/)

**Next update:** FDA decision timing remains unannounced; GRAIL forecasts coming months. Longer-term patient outcomes and repeat-screening utility remain unresolved.

[Full coverage record](../updates/2026-10-02_scheduled_research_update.md).

### Focused update — 2026-09-27

#### Galleri advisory panel votes favorably; FDA decision remains pending

**Source date:** 2026-09-23. **Event date:** 2026-09-23. **Evidence:** FDA advisory-committee record.

Panel votes favored safety 10–0, effectiveness 6–4, and benefit versus risk 7–2 with one abstention. The committee assessed reasonable assurance of safety and effectiveness and whether benefits outweigh risks for the proposed screening use. Several favorable votes were conditional on labeling changes, provider education and postapproval follow-up.

**Limitations:** Nonbinding advice is not FDA approval. Members questioned early-detection wording and limited stage I performance. Mortality benefit, overdiagnosis and optimal testing intervals remain unresolved; standard cancer screening should continue.

**Safety:** False positives can trigger unnecessary investigations; negative tests can miss cancer. A positive signal requires diagnostic workup.

**U.S. status:** No FDA approval established by this vote; existing laboratory-test access is a separate status.

**Next milestone:** FDA decision has no verified exact date. GRAIL forecasts coming months; this is sponsor guidance, not an FDA deadline.

[FDA 24-hour panel summary](https://www.fda.gov/media/195032/download); [GRAIL vote and timing announcement](https://grail.com/press-releases/fda-advisory-committee-votes-in-favor-of-approval-of-grails-galleri-multi-cancer-early-detection-test/).

**Coverage:** Read FDA September 23 24-hour summary and sponsor vote announcement; deduplicated prior September 22 repeat-screening papers. Followed elapsed advisory milestone.

**Remaining gaps:** Full meeting transcript/webcast not appraised; organ-specific colorectal and other screening registries require further refresh. FDA final decision remains pending in reviewed sources.

**Informal-source coverage:** September 23–24 Reddit posts repeat verified votes or speculate about approval without a new evidenced date; no separate alert. https://www.reddit.com/r/Wiseek/comments/1wok3yj/gral_fda_panel_backs_grails_galleri_cancer_test/

**Next update:** FDA decision timing remains unannounced; GRAIL forecasts coming months. Longer-term patient outcomes and repeat-screening utility remain unresolved.

[Full coverage record](../updates/2026-09-27_scheduled_research_update.md).

### Focused update — 2026-09-22

#### Galleri FDA briefing package and exact voting questions reviewed

**Verified:** 2026-09-22; original posting date not established. **Evidence:** Regulator briefing; verified September 22, original posting date not specified.

The September 23 advisory panel will vote separately on reasonable assurance of safety, effectiveness, and whether benefits outweigh risks. Its recommendation is nonbinding, not marketing approval. FDA evaluates a revised Galleri assay retrospectively on stored samples, distinct from the MCED-V2 version used prospectively. FDA Table A3 reports 12-month episode sensitivity of 35.0% (106/303; 95% CI 29.8–40.5) in PATHFINDER 2 and 31.6% (259/820; 28.5–34.8) in NHS-Galleri. Specificity is 99.85% and 99.74%; PPV is 77.0% and 66.2%. These must not replace historical prospective-assay results. NHS figures cover the first screening round with 12-month follow-up; specificity and PPV use weighted retrospective sampling.

**Limitations:** These are test-performance analyses, not mortality benefit. FDA asks whether the stage-specific evidence supports the word “early” in the indication, how to communicate limitations, and whether postapproval studies would be needed.

**Safety:** Prospective MCED-V2 workup safety differs from revised-assay performance: PATHFINDER 2 had adverse events in 9/218 positive-test participants, including one serious event overall. Four participants had study-related events; none of those study-related events were serious. False negatives and workup burden remain relevant.

**U.S. status:** Prescription laboratory-test access is distinct from FDA marketing authorization; no approval established.

**Next milestone:** September 23, 2026, 09:00–18:00 Eastern: scheduled FDA advisory meeting. No vote had occurred at this check.

[FDA meeting and package](https://www.fda.gov/advisory-committees/advisory-committee-calendar/september-23-2026-molecular-and-clinical-genetics-panel-medical-devices-advisory-committee-meeting); [FDA executive summary, pp16–17,38–39,45](https://www.fda.gov/media/194909/download); [FDA voting questions](https://www.fda.gov/media/194908/download); [FDA discussion questions](https://www.fda.gov/media/194907/download).

#### NHS-Galleri peer-reviewed report quantifies performance across three screening rounds

**Source date:** 2026-09-22. **Event date:** 2026-09-22. **Evidence:** Peer-reviewed descriptive secondary-endpoint analysis within randomized trial.

All-cancer episode sensitivity was 37.2%, 27.1% and 26.7% in annual rounds 1–3, with PPV 58.0%, 50.4% and 45.8%. Specificity remained about 99.5–99.6%. Lower repeat-round detection concerns the changing prevalent/incident cancer pool, not evidence of technical deterioration.

**Study population:** 142,250 randomized (71,122 intervention; 71,128 control), aged 50–77 at invitation / 50–78 at enrollment in eight English NHS regions. Only eligible/evaluable intervention participants enter these performance analyses; 93.6% White in round 1.

| Annual round | Evaluable tests | Episode sensitivity, % (95% CI) | Positive predictive value, % (95% CI) |
| --- | --- | --- | --- |
| 1 | 70325 | 37.2 (34.4–40.0) | 58.0 (54.4–61.6) |
| 2 | 64498 | 27.1 (24.4–30.0) | 50.4 (46.1–54.7) |
| 3 | 62323 | 26.7 (24.0–29.6) | 45.8 (41.7–49.9) |

Table 2 aggregate N=197,146 counts tests, not unique people. Episode sensitivity divides test-detected primary cancers by all participants diagnosed with primary cancer within the round follow-up: 419/1,127; 261/963; 257/961. Later rounds exclude prior trial cancer diagnoses.

**Limitations:** No hypothesis testing; no new mortality or overdiagnosis result. Follow-up ends at 12 months, next blood draw, death, emigration or withdrawal, whichever first. Episode sensitivity cannot distinguish missed existing cancers from newly developed interval cancers. Primary PPV excludes recurrences; counting adjudicated recurrences increases it to 60.4/51.7/48.0%. No systematic time-to-resolution data. GRAIL-funded, with disclosed employment/advisory interests. Keep separate from FDA revised-assay retrospective bridging metrics.

**Safety:** Detailed safety is delegated to Sasieni et al., NEJM, cited as in press. This paper cites <1% adverse events but does not provide a fresh complete harms table. Do not interpret high specificity or negative predictive value as absence of harm or exclusion of cancer.

**U.S. status:** No new authorization from publication; September 23 panel remains an advisory milestone, not approval.

**Next milestone:** FDA panel September 23; longer follow-up, mortality/overdiagnosis and healthcare/psychological outcomes have no verified publication date here.

[NHS-Galleri original full report, published September 22](https://www.nature.com/articles/s41591-026-04652-8); [Original Table 2, fully retrieved and checked](https://www.nature.com/articles/s41591-026-04652-8/tables/2).

#### PATHFINDER 2 peer-reviewed publication clarifies denominators and the locked safety dataset

**Source date:** 2026-09-22. **Event date:** 2026-09-22. **Evidence:** Peer-reviewed prospective single-arm interventional study.

PPV 60.3% (173/287), specificity99.64%, all-cancer episode sensitivity39.3%, 12-cancer subgroup69.8%; median diagnostic resolution48 days. Core values match the existing conference note. 213/35,335 (0.6%) had invasive procedures after a positive test, but among the 290 positive-result participants evaluated the proportion was213/290 (73.4%). They underwent295 invasive procedures,267/295 (90.5%) nonsurgical. In targeted evaluation,46.3% of false-positive participants had invasive procedures; four had surgery, all yielding benign neoplasms.

**Study population:** Adults 50+ without clinical suspicion of cancer or cancer diagnosis/treatment within 3 years. 35,878 enrolled December8,2021–July10,2024; data lock February11,2026. 35,350 analyzable; 32,007 performance; 35,335 safety; 35,850 cleaned clinical data for broader AE summary. These sets differ.

**Limitations:** No randomized comparator, formal hypothesis test or predefined success criterion; one prevalence round; incomplete 12-month assessment for some participants; sponsor covered diagnostic costs. Earlier test returned up to2 CSOs; newer commercial algorithm returns1 plus supplemental information. Does not prove mortality benefit or equivalence of current assay.

**Safety:** Locked dataset:9/290 had10 AEs during evaluation;5 study-related, none serious;5 unrelated included1 serious hyponatremia. Broader cleaned dataset56/35,850 (0.2%) study-related AEs, none serious at lock. Crucially preserve existing May31 sponsor disclosure of a workup-related serious AE identified AFTER lock; unqualified no serious events would be wrong. The paper says extended-follow-up AEs will be reported later.

**U.S. status:** Publication does not change approval status.

**Next milestone:** Longitudinal screening adherence and further diagnostic-journey/safety analyses; no firm release date.

[PATHFINDER 2 full publication, September22](https://www.nature.com/articles/s41591-026-04618-w).

**Coverage:** Read FDA meeting, exact voting/discussion questions, revised-assay performance and workup safety sections; discovered September22 repeat-round performance paper. Prior missing briefing gap materially closed.

**Remaining gaps:** Full sponsor briefing, all FDA subgroup appendices, organ-specific screening interval outcomes and mortality publications not fully reappraised. Meeting has not occurred at check.

**Informal-source coverage:** September21 Reddit market commentary calls briefing favorable; that inference is not an FDA endorsement. Automated secondhand CEO timing attribution lacked an original source and was not promoted. https://www.reddit.com/r/Wiseek/comments/1wmi37e/gral_fda_briefing_doc_backs_galleri_cancer_test/

[Full coverage record](../updates/2026-09-22_scheduled_research_update.md).

**Next update:** **September 23, 2026:** FDA advisory votes on safety, effectiveness and benefit–risk. No vote or approval established at this check.

### Focused update — 2026-09-18

No additional finding was verified in this focused search. The incomplete coverage below does not establish that nothing changed across the full topic.

**Coverage:** FDA September 23 notice, PATHFINDER2/REACH/Vanguard registry refresh and screening discovery; no new clinical outcome verified. This is a focused review, not a complete re-review of every program.

**Remaining gaps:** Substantive panel briefing package not located; full NHS/PATHFINDER tables and all Shield/Cologuard interval evidence not reappraised.

**Informal-source coverage:** Recent panel speculation and podcast searches did not supply an original new quantified efficacy or approval rumor; investor recording not fully reviewed.

[Full coverage record](../updates/2026-09-18_scheduled_research_update.md).

**Next update:** **September 23, 2026:** announced FDA advisory panel. Further NHS and colorectal repeat-round results have no firm near-term release date.

### Tracked programs and current evidence

NHS-Galleri (NCT05611632); PATHFINDER 2 (NCT05155605); REACH/Galleri-Medicare (NCT05673018); Galleri FDA review. NCI Vanguard (NCT06995898) is tracked as relevant field context, not a Galleri trial.

### Baseline evidence

#### 2026-09-12 — Initial evidence baseline

**NHS-Galleri has already read out, and its primary endpoint was missed.** This randomized trial enrolled more than 142,000 adults aged 50–77 and tested three annual screening rounds alongside usual NHS screening. Topline findings appeared February 19, 2026; fuller results were presented May 30 at ASCO. There was no statistically significant reduction in the prespecified combined stage III/IV endpoint for 12 cancers. Secondary analyses found fewer stage IV diagnoses, including 22% and 26% reductions in rounds two and three, and 16% more stage I/II diagnoses overall. Increased stage III detection, especially in the first round, contributed to the primary-endpoint result. These findings support a stage-shift signal; they do not establish reduced cancer mortality or eliminate overdiagnosis. The investigators plan another analysis with 12 additional months of data; mortality follow-up takes longer. Evidence here is the trial team's conference-results summary, not a fully appraised peer-reviewed final outcomes paper. [February topline](https://grail.com/press-releases/landmark-nhs-galleri-trial-demonstrates-a-substantial-reduction-in-stage-iv-cancer-diagnoses-increased-stage-i-and-ii-detection-of-deadly-cancers-and-four-fold-higher-cancer-detection-rate/); [Trial-team report, May 30](https://www.nhs-galleri.org/trial-updates/nhs-galleri-trial-reports-fewer-diagnoses-of-the-most-advanced-cancers); [NCT05611632](https://clinicaltrials.gov/study/NCT05611632).

**PATHFINDER 2 supplies prospective performance and workup evidence.** The May 31, 2026 sponsor report of the ASCO presentation covers 35,878 participants. Positive predictive value was 60.3%: cancer was diagnosed in 173 of 287 people with a cancer signal. Specificity was 99.6%, but all-cancer episode sensitivity was 39.3% over 12 months; the 69.8% figure applies to the prespecified 12-cancer group. Thus, a negative result still misses many cancers. Cancer-signal origin accuracy was 91.3%, and median diagnostic resolution took 48 days. One serious workup-related adverse event was identified after data lock. Increased screen detection is not proof of mortality benefit. This remains sponsor-reported conference evidence; prioritize the full publication, cancer/stage-specific performance and later safety analyses. The registry lists active, not recruiting, actual primary completion February 11, 2026 and estimated study completion April 30, 2028. [Sponsor readout](https://grail.com/press-releases/grail-presents-pathfinder-2-results-of-more-than-35000-participants-showing-the-galleri-test-substantially-increased-cancer-detection-with-robust-performance-and-favorable-safety-at-2026-a/); [NCT05155605](https://clinicaltrials.gov/study/NCT05155605).

**REACH/Galleri-Medicare addresses older U.S. populations.** The recruiting study targets 50,000 participants, began July 2024 and estimates completion in September 2030. Its primary endpoint is stage IV cancer incidence over three years, with invasive workups, test performance, screening adherence and healthcare use also tracked. It uses a nonrandomized contemporaneous usual-care comparator, so selection and confounding require scrutiny. No outcome readout was located in this baseline. [Registry, updated May 22, 2026](https://clinicaltrials.gov/study/NCT05673018).

**The next concrete near-term milestone is FDA review.** Galleri remains commercially available by prescription without FDA clearance/approval in the checked sources. Its PMA is scheduled for an FDA advisory-panel discussion and vote on **September 23, 2026**. That meeting is future as of this baseline; neither a scheduled panel nor its eventual recommendation equals FDA approval. Watch briefing documents, intended-use wording, the vote, FDA's decision and evidence requirements. [FDA meeting notice](https://www.fda.gov/advisory-committees/advisory-committee-calendar/september-23-2026-molecular-and-clinical-genetics-panel-medical-devices-advisory-committee-meeting).

**Relevant new-trial context:** NCI's recruiting Vanguard pilot (NCT06995898), up to 24,000 people, tests **Avantect and Shield MCD**, not Galleri. It studies feasibility and diagnostic workflows ahead of a larger benefits/harms trial; it is not yet mortality proof for the field. [NCI study explanation](https://www.cancer.gov/research/areas/screening/vanguard-study).

**Expected-update timing:** September 23, 2026 is an announced FDA panel date. NHS-Galleri plans 12 more months of follow-up but gives no firm public release date; mortality results are several years away. PATHFINDER 2 has no verified next readout date (April 2028 is estimated study completion). REACH estimates September 2030 completion, not a guaranteed results date. No analyst-derived release dates are assigned.

Remaining gaps: full peer-reviewed NHS-Galleri/PATHFINDER 2 outcome papers and complete subgroup/workup tables were not appraised in this initial brief. Track new evidence rather than inferring benefit from detection counts, projected survival or marketing claims.

#### 2026-09-12 — Scope expansion: organ-specific cancer screening

**Added scope:** colorectal blood and stool tests, including Shield, next-generation stool DNA tests, FIT and new entrants. Follow evidence for screening participation, precancer detection, interval cancers, colonoscopy completion, complications, incidence and mortality. Other organ-specific platforms can be added as meaningful human clinical-utility evidence emerges. Galleri remains active; a colorectal-only test answers a different question.

**Current clinical position:** the ACS 2026 guideline prefers visual examinations and stool-based methods. Blood tests are an additional option but are not preferred because of weaker detection of precancer and stage I cancer. Any positive non-colonoscopy screen requires diagnostic colonoscopy; a convenient first test is only one part of a completed screening pathway. This is guideline tracking, not a personal test recommendation. [ACS 2026 guideline summary](https://www.cancer.org/health-care-professionals/american-cancer-society-prevention-early-detection-guidelines/colorectal-cancer-screening-guidelines.html).

**Shield — Guardant Health, ECLIPSE (NCT04136002).** FDA approved the blood test July 26, 2024 for average-risk adults aged 45 and over. Its pivotal evaluable population included 7,861 people: overall cancer sensitivity was approximately 83%, specificity approximately 90%, but advanced precancerous-lesion detection approximately 13%. Those endpoints must remain separate; an overall cancer-detection number obscures much poorer prevention potential through polyp detection. FDA approval does not establish equivalence to colonoscopy or stool testing for long-term outcomes. [FDA device summary](https://www.fda.gov/medical-devices/recently-approved-devices/shield-p230009); [NCI evidence explanation](https://www.cancer.gov/news-events/cancer-currents-blog/2024/shield-blood-test-colorectal-cancer-screening).

**Cologuard Plus — Exact Sciences, BLUE-C (NCT04144738).** FDA approved the next-generation multitarget stool DNA test October 3, 2024. The peer-reviewed study assessed 20,176 participants with colonoscopy as reference. Cancer sensitivity was 93.9%, advanced-precancer sensitivity 43.4%, and specificity among those without advanced neoplasia 90.6%. The study's FIT comparator had lower single-round sensitivity but greater specificity. This was diagnostic-performance research, not a randomized mortality comparison. Cross-trial comparisons with Shield also do not substitute for a direct test comparison or repeated-screening study. [FDA approval record](https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P230043); [BLUE-C paper](https://www.nejm.org/doi/full/10.1056/NEJMoa2310336).

**Next updates:** follow repeat-round performance and completed diagnostic workups. Shield has an FDA-required post-approval study assessing two consecutive screening intervals, with the second compared against colonoscopy. No reliable near-term public results date was verified. The ACS update is already published in 2026; it is baseline context, not an upcoming decision. Keep the separately scheduled September 23 Galleri panel as Galleri-specific. [FDA post-approval study](https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma_pas.cfm?c_id=7952&t_id=787465).

## Dated history

### 2026-10-02 — Scheduled focused review

0 newly recorded findings or milestones; primary evidence, uncertainty and incomplete coverage are detailed above and in the [run record](../updates/2026-10-02_scheduled_research_update.md). Full-topic successful-check dates remain unchanged.

- **2026-09-27:** 1 sourced entries and 0 cross-topic links from a focused scheduled check. [Coverage and remaining gaps](../updates/2026-09-27_scheduled_research_update.md).

- **2026-09-22:** Focused scheduled research retry; 3 sourced entries and 0 cross-topic links. [Coverage and gaps](../updates/2026-09-22_scheduled_research_update.md).

### 2026-09-14 — Focused ad-hoc update

**Regulatory milestone unchanged:** The [FDA meeting notice](https://www.fda.gov/advisory-committees/advisory-committee-calendar/september-23-2026-molecular-and-clinical-genetics-panel-medical-devices-advisory-committee-meeting) still schedules the Galleri discussion for **September 23, 2026**. The complete substantive briefing package was not available in the materials checked. No panel vote or FDA approval has occurred as of this check. [GRAIL’s news center](https://grail.com/news-center/) did not supply a new clinical outcome readout beyond the existing baseline; employment-grant and conference-attendance notices are not efficacy evidence.

**Coverage:** Focused regulator, sponsor-news, recent trial-news and informal/investor searches. Speculative approval timing was not promoted to an announced milestone. The September investor-conference original transcript, full NHS-Galleri/PATHFINDER 2 papers and organ-specific alternatives were not fully appraised. Broader last-successful-check status is unchanged.

### Dated findings

The dated baseline entries are preserved under [Baseline evidence](#baseline-evidence).

### 2026-09-18 — Scheduled focused review

FDA September 23 notice, PATHFINDER2/REACH/Vanguard registry refresh and screening discovery; no new clinical outcome verified. Original event dates, safety and limitations are retained in the September 18 update above. The complete-topic successful-check date was not advanced because the listed gaps remain. [Run record](../updates/2026-09-18_scheduled_research_update.md).