Lung adenocarcinoma — statistics and effect-size ledger
Purpose and interpretation rules
This sheet preserves reusable denominators, effect sizes, confidence intervals, dates, populations, and methods. It is not a treatment algorithm. Unless a row explicitly says adenocarcinoma, the estimate applies to broader lung cancer or NSCLC and must not be silently relabelled.
- HR/RR below 1 favors the first-listed intervention for the adverse endpoint stated.
- Medians cannot be subtracted to estimate an individual's survival gain.
- Single-arm response rates do not rank therapies across trials.
- DFS, EFS, PFS, OS, pCR, ORR, and patient-reported outcomes are not interchangeable.
- Modelled burden, registry incidence, and trial efficacy answer different questions.
- Every PMID below was resolved through live PubMed E-utilities on 2026-08-29.
Global burden and population trends
| Domain |
Population/method |
Estimate |
Boundary |
Source |
| Global lung-cancer burden, 2022 |
GLOBOCAN model, 185 countries |
Lung cancer was the most commonly diagnosed cancer and leading cancer-death cause |
Not histology-specific |
PMID 38572751 |
| Adenocarcinoma distribution, 2022 |
GLOBOCAN/CI5/AFCRN reconstruction |
Leading lung-cancer subtype in most assessed countries |
Modelled subtype estimates |
PMID 39914442 |
| Japan localized adenocarcinoma trend |
62,870 cases, 1993–2015 |
Annual change +4.5% men; +5.7% women |
Detection/classification contribute |
PMID 35138642 |
| Metastatic lung-cancer 1-y survival |
California registry, 186,156 cases, 1990–2014 |
18.4% → 29.4% |
All histologies |
PMID 33414054 |
| US NSCLC mortality |
SEER incidence-linked mortality, men, 2013–2016 |
Mortality −6.3%/y; incidence −3.1%/y |
Temporal attribution, not randomized |
PMID 32786189 |
| US 2-y lung-cancer-specific survival |
Diagnoses 2001 vs 2014 |
26% → 35% |
All NSCLC mix |
PMID 32786189 |
| Deaths averted 1975–2020 |
US national modelling |
Tobacco control dominant; screening/treatment add later gains |
Model-dependent decomposition |
PMID 39636625 |
Tobacco, never-smoking, pollution, and susceptibility
| Exposure/population |
Estimate |
Method/caution |
Source |
| Biochemically confirmed active smoking in women |
RR 7.8 vs non-smokers |
Prospective cohort; historical exposure |
PMID 7669596 |
| Spousal second-hand smoke |
RR 1.24 (95% CI 1.13–1.36) |
37-study meta-analysis; 4,626 never-smoker cases |
PMID 9365295 |
| Spousal second-hand smoke, later synthesis |
RR 1.25 (1.15–1.37) |
51 studies, 7,369 cases |
PMID 12058801 |
| Workplace second-hand smoke |
RR 1.17 (1.04–1.32) |
Observational synthesis |
PMID 12058801 |
| Japanese never-smoking women |
109 lung cancers/28,414 over 13 y; 82 adenocarcinomas |
Prospective cohort; exposure-dependent spousal association |
PMID 17935128 |
| COPD |
SRR 2.06 (1.50–2.85) |
Prospective-cohort meta-analysis; shared smoking confounding |
PMID 29100446 |
| Emphysema |
SRR 2.33 (1.56–3.49) |
Same synthesis |
PMID 29100446 |
| Asian advanced adenocarcinoma EGFR prevalence |
51.4% of 1,450 evaluable tumors |
PIONEER; advanced Asian cohort, not global |
PMID 24419411 |
| Never-smoker geographic KRAS variation |
3.8× more frequent in North America/Europe than East Asia |
871 tumors, 28 locations; research cohort |
PMID 40604281 |
| Air-pollution mechanistic cohort set |
32,957 EGFR-driven cases across four within-country cohorts |
PM2.5 association plus mouse/organoid IL-1β experiments |
PMID 37020004 |
| Never-smoker TALENT screening |
High early-stage detection in risk-enriched cohort |
Single arm; no mortality or overdiagnosis comparator |
PMID 38042167 |
Screening efficacy and harms
| Study/policy |
Population |
Benefit |
Harm/implementation |
Source |
| NLST |
53,454 high-risk participants |
Lung-cancer mortality −20.0% (95% CI 6.8–26.7); all-cause −6.7% |
Trial positivity generated many false positives |
PMID 21714641 |
| NLST initial round |
LDCT arm |
Positive screen 27.3%; cancer in 3.8% of positive screens |
Older low positivity threshold |
PMID 23697514 |
| NELSON men |
13,195 men |
10-y lung-cancer mortality rate ratio 0.76 (0.61–0.94) |
Volumetry/doubling-time protocol |
PMID 31995683 |
| NELSON women |
2,594 women |
Smaller subgroup; favorable mortality direction |
Underpowered sex-specific estimate |
PMID 31995683 |
| USPSTF 2021 eligibility |
US adults |
Annual LDCT age 50–80, ≥20 pack-years, current or quit ≤15 y |
Policy threshold, not biologic boundary |
PMID 33687470 |
| Risk-model selection |
US modelling |
More cost-effective at selected thresholds than categorical rules |
Assumptions drive result |
PMID 36745885 |
| Never-smoker screening |
TALENT ages 55–75 with added risks |
Substantial detection, enriched by family history |
No randomization; cannot infer mortality benefit |
PMID 38042167 |
Histology, grade, and staging
| Domain |
Denominator/result |
Interpretation |
Source |
| TCGA adenocarcinoma |
230 resected tumors |
Mean 8.9 somatic mutations/Mb; 18 significantly mutated genes |
Resection cohort, bulk multi-omics |
| AIS/MIA outcome |
Resected cohorts |
Near-100% disease-specific survival after complete resection |
Requires complete sampling/classification |
| STAS staging evaluation |
4,061 pathologic stage-I NSCLCs |
Prognostic descriptor proposed, not T-category determinant |
Retrospective international analysis |
| TNM-9 source database |
124,581 registrations |
76,518 informed stage-group analysis |
International registry; exclusions apply |
| TNM-9 clinical-stage analysis |
58,193 cases |
Used in stage-group proposal |
Histology mixed |
| TNM-9 pathologic-stage analysis |
39,192 cases |
Used in stage-group proposal |
Operated selection |
| TNM-9 best-stage analysis |
62,611 cases |
Used in stage-group proposal |
Mixed clinical/pathologic information |
| TNM-9 metastatic analysis |
14,937 stage IVA–IVB NSCLCs |
Supported M1c single- versus multiple-organ subdivision |
Prognostic, not treatment selector |
Surgery and local consolidation
| Trial/setting |
Comparison |
Estimate |
Boundary |
Source |
| JCOG0802/WJOG4607L |
Segmentectomy vs lobectomy, peripheral ≤2 cm |
OS criterion favored segmentectomy; more local relapse |
Selected Japanese peripheral tumors |
PMID 35461558 |
| CALGB 140503 |
Sublobar vs lobar, peripheral cT1aN0 ≤2 cm |
DFS noninferior; OS similar |
Intraoperative node-negative confirmation |
PMID 36780674 |
| Gomez oligometastatic phase II |
Local consolidation vs maintenance/observation |
PFS 14.2 vs 4.4 mo; OS 41.2 vs 17.0 mo |
49 selected patients; older systemic era |
PMID 31067138 |
| Iyengar phase II |
SABR + maintenance vs maintenance |
PFS 9.7 vs 3.5 mo |
Small trial stopped early for efficacy |
PMID 28973074 |
| SABR-COMET |
SABR vs standard care, mixed cancers |
Long-term OS benefit |
NSCLC subset small |
PMID 32484754 |
Adjuvant and perioperative therapy
| Trial/analysis |
Comparison |
Effect size |
Key boundary |
Source |
| LACE |
Cisplatin chemotherapy vs none; 4,584 resected NSCLCs |
OS HR 0.89 (0.82–0.96); 5-y absolute benefit 5.4% |
Historical, mixed histology |
PMID 18506026 |
| LACE stage IA |
Same |
OS HR 1.40 |
No demonstrated benefit |
PMID 18506026 |
| LACE stage IB |
Same |
OS HR 0.93 |
Modest/uncertain |
PMID 18506026 |
| LACE stage II |
Same |
OS HR 0.83 |
Benefit-concentrated subgroup |
PMID 18506026 |
| LACE stage III |
Same |
OS HR 0.83 |
Benefit-concentrated subgroup |
PMID 18506026 |
| ADAURA stage II–IIIA |
Osimertinib vs placebo |
DFS HR 0.17 |
EGFR exon19del/L858R; optional chemotherapy |
PMID 32955177 |
| ADAURA stage IB–IIIA |
Osimertinib vs placebo |
DFS HR 0.20 |
Three-year planned therapy |
PMID 32955177 |
| ADAURA OS |
Osimertinib vs placebo |
Death HR 0.49; 5-y OS 88% vs 78% |
Salvage patterns evolve |
PMID 37272535 |
| CheckMate 816 |
Nivolumab-chemo vs chemo |
EFS 31.6 vs 20.8 mo; HR 0.63 (97.38% CI 0.43–0.91) |
Mixed NSCLC, driver caveats |
PMID 35403841 |
| CheckMate 816 pCR |
Same |
24.0% vs 2.2% |
pCR prognostic, not individual switch rule |
PMID 35403841 |
| CheckMate 816 surgery |
Same |
Surgery 83.2% vs 75.4% |
Protocol-selected resectable population |
PMID 35403841 |
| CheckMate 816 grade 3–4 AE |
Same |
33.5% vs 36.9% |
Treatment-related |
PMID 35403841 |
| KEYNOTE-671 |
Perioperative pembrolizumab vs placebo |
24-mo EFS 62.4% vs 40.6%; HR 0.58 |
Cannot isolate adjuvant component |
PMID 37272513 |
| KEYNOTE-671 pCR |
Same |
18.1% vs 4.0% |
Mixed histology |
PMID 37272513 |
| KEYNOTE-671 grade ≥3 AE |
Same |
44.9% vs 37.3% |
Treatment-related |
PMID 37272513 |
| AEGEAN |
Perioperative durvalumab vs placebo |
EFS HR 0.68 (0.53–0.88); pCR 17.2% vs 4.3% |
EGFR/ALK excluded from efficacy analysis |
PMID 37870974 |
| AEGEAN grade 3–4 AE |
Same |
42.4% vs 43.2% |
Treatment-related |
PMID 37870974 |
| IMpower010 |
Atezolizumab vs supportive care after chemotherapy |
DFS HR 0.66 in stage II–IIIA PD-L1 ≥1% |
Hierarchical analysis |
PMID 34555333 |
| KEYNOTE-091 |
Pembrolizumab vs placebo |
DFS HR 0.76 overall; PD-L1 ≥50% HR 0.82, not significant at interim |
PD-L1 pattern differs from metastatic setting |
PMID 36108662 |
| PACIFIC five-year |
Durvalumab vs placebo after chemoradiation |
OS 42.9% vs 33.4%; PFS 33.1% vs 19.0% |
Unresectable stage III, mixed histology |
PMID 35108059 |
EGFR-targeted therapy
| Trial |
Comparison/population |
Efficacy |
Safety/interpretation |
Source |
| IPASS mutation-positive |
Gefitinib vs carboplatin-paclitaxel |
PFS HR 0.48 |
Predictive interaction |
PMID 19692680 |
| IPASS mutation-negative |
Same |
Gefitinib HR 2.85, favoring chemotherapy |
Clinical phenotype cannot replace genotype |
PMID 19692680 |
| FLAURA |
Osimertinib vs gefitinib/erlotinib |
PFS 18.9 vs 10.2 mo; HR 0.46 |
Classical EGFR mutations |
PMID 29151359 |
| FLAURA OS |
Same |
OS 38.6 vs 31.8 mo; HR 0.80 |
Crossover/subsequent therapy matter |
PMID 31751012 |
| FLAURA2 |
Osimertinib + platinum-pemetrexed vs osimertinib |
PFS 25.5 vs 16.7 mo; HR 0.62 |
Added chemotherapy burden |
PMID 37937763 |
| MARIPOSA |
Amivantamab-lazertinib vs osimertinib |
PFS 23.7 vs 16.6 mo; HR 0.70 |
Infusion, rash, edema, VTE |
PMID 38924756 |
| AURA3 |
Osimertinib vs platinum-pemetrexed in T790M |
PFS 10.1 vs 4.4 mo; HR 0.30 |
Post-earlier-generation setting |
PMID 27959700 |
| PAPILLON |
Amivantamab-chemo vs chemo, EGFR exon20ins |
PFS 11.4 vs 6.7 mo; HR 0.40 |
First-line exon-20 insertion |
PMID 37870976 |
Fusion-driver therapy
| Driver/trial |
Population |
Estimate |
Boundary |
Source |
| ROS1 crizotinib |
Advanced ROS1-positive NSCLC |
ORR 72%; median PFS 19.2 mo |
Single-arm expansion |
PMID 25264305 |
| RET selpercatinib |
RET-fusion NSCLC |
High response including CNS activity |
Single-arm foundational cohorts |
PMID 32846060 |
| LIBRETTO-431 |
Selpercatinib vs platinum-pemetrexed ± pembrolizumab |
Median PFS 24.8 vs 11.2 mo |
Interim efficacy population |
PMID 37870973 |
| NTRK larotrectinib |
TRK-fusion cancers |
High pooled response |
Tissue-agnostic; small lung subset |
PMID 29466156 |
| ALINA |
Alectinib vs platinum chemotherapy after resection |
Large DFS/CNS benefit |
Mature OS and chemo additivity unresolved |
PMID 38598794 |
KRAS, BRAF, MET, and HER2 therapy
| Trial |
Population |
Efficacy |
Major caution |
Source |
| CodeBreaK 100 |
Previously treated KRAS G12C NSCLC |
ORR 37.1%; median PFS 6.8 mo |
Single arm |
PMID 34096690 |
| CodeBreaK 200 |
Sotorasib vs docetaxel |
PFS HR 0.66; 5.6 vs 4.5 mo |
No demonstrated OS advantage; crossover |
PMID 36764316 |
| KRYSTAL-1 |
Adagrasib, previously treated G12C |
ORR 42.9%; median PFS 6.5 mo |
Single arm |
PMID 35658005 |
| MET capmatinib |
METex14 cohorts |
Higher ORR untreated than pretreated |
Single-arm; edema |
PMID 32877583 |
| MET tepotinib |
METex14 cohorts |
Clinically meaningful response |
Single-arm; assay and edema |
PMID 32469185 |
| DESTINY-Lung01 |
T-DXd, HER2-mutant NSCLC |
ORR 55%; duration 9.3 mo; PFS 8.2 mo |
ILD 26%, including deaths |
PMID 34534430 |
| DESTINY-Lung02 |
T-DXd 5.4 vs 6.4 mg/kg cohorts |
Activity preserved at lower dose |
Lower dose favored benefit-risk |
PMID 37694347 |
Driver-negative immunotherapy
| Trial |
Comparison |
Estimate |
Boundary |
Source |
| KEYNOTE-024 |
Pembrolizumab vs chemo, TPS ≥50% |
PFS 10.3 vs 6.0 mo; HR 0.50; ORR 44.8% vs 27.8% |
EGFR/ALK-negative selected group |
PMID 27718847 |
| KEYNOTE-189 |
Pembrolizumab-platinum-pemetrexed vs chemotherapy |
Initial OS HR 0.49; PFS HR 0.52 |
Metastatic nonsquamous, EGFR/ALK-negative |
PMID 29658856 |
| IMpower150 |
Atezolizumab-bevacizumab-carboplatin-paclitaxel vs bevacizumab-chemo |
OS/PFS benefit |
Four-drug burden; mixed biomarkers |
PMID 29863955 |
| PD-L1-negative pooled 5-y |
Pembrolizumab-chemo vs chemo |
OS HR 0.64 (0.51–0.79); PFS HR 0.66 (0.54–0.81); 5-y OS 12.5% vs 9.3% |
Squamous+nonsquamous pooled |
PMID 38642841 |
| EGFR-mutant PD-L1-positive pilot |
Pembrolizumab, TKI-naive |
No objective responses among eligible EGFR-mutant patients |
Small phase II; stopped for futility |
PMID 29874546 |
ctDNA, MRD, and implementation
| Setting |
Denominator/result |
Meaning |
Source |
| Localized lung-cancer MRD |
Post-treatment ctDNA anticipated radiographic recurrence in some patients |
Strong prognosis; action utility unproven |
PMID 28899864 |
| TRACERx phylogenetic ctDNA |
Personalized subclonal tracking |
Reveals relapse evolution; low-shedding limitation |
PMID 28445469 |
| LUNGCA-1 |
Prospective multicentre postoperative cohort |
ctDNA positivity associated with recurrence |
Not randomized intervention |
| Newly diagnosed metastatic plasma NGS |
Prospective complementary testing |
Added actionable detections to tissue |
Negative plasma non-exclusionary |
| Reflex testing |
Program implementation |
Increased completion and reduced ordering loss |
Center-specific workflow |
Patient experience, palliative care, and safety
| Domain |
Population/result |
Estimate |
Source |
| Early palliative care |
151 metastatic NSCLC patients |
12-wk FACT-L 98.0 vs 91.5; depression 16% vs 38%; aggressive end-of-life care 33% vs 54%; OS 11.6 vs 8.9 mo |
PMID 20818875 |
| T-DXd ILD |
DESTINY-Lung01 |
Adjudicated drug-related ILD 26%, including fatal events |
PMID 34534430 |
| CheckMate 816 severe AE |
Neoadjuvant nivolumab-chemo vs chemo |
Grade 3–4 treatment-related AE 33.5% vs 36.9% |
PMID 35403841 |
| KEYNOTE-671 severe AE |
Perioperative pembrolizumab vs placebo |
Grade ≥3 treatment-related AE 44.9% vs 37.3% |
PMID 37272513 |
| AEGEAN severe AE |
Perioperative durvalumab vs placebo |
Grade 3–4 treatment-related AE 42.4% vs 43.2% |
PMID 37870974 |
Known conflicts and caveats
| Conflict |
Why estimates differ |
Rule for reuse |
| Adenocarcinoma burden |
Registry histology coverage, imputation, diagnostic era |
Keep model, year, sex, and geography |
| Never-smoker fraction |
Definition, geography, sex, referral enrichment |
Do not quote a universal percentage without denominator |
| Screening harms |
Positivity threshold, volumetry, round, work-up algorithm |
Keep trial/program and definition |
| Driver frequency |
Ancestry, smoking, stage, assay, tissue adequacy |
Never use phenotype to skip testing |
| PFS across targeted trials |
Line, comparator, CNS eligibility, follow-up |
No cross-trial ranking |
| PD-L1 |
Assay, cutoff, biopsy site, treatment exposure |
Record clone, score, specimen, date |
| MRD sensitivity |
Tumor burden, shedding, assay and sampling time |
Negative is not proof of cure |
| Perioperative EFS |
Stage editions and therapy architecture differ |
Do not infer adjuvant-component value |
| OS |
Crossover and subsequent therapies vary |
Report treatment switching and follow-up |
Reuse checklist
- Preserve population, histology, stage, genotype, and line.
- Preserve comparator, endpoint, time point, and confidence interval.
- Label randomized, single-arm, observational, or modelled evidence.
- Do not average conflicting estimates.
- Re-query living guidelines and trial status at use.
- Reproduce derived values only with the original numerator and denominator.
Linked evidence layers