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Statistics and effect-size ledger¶
Purpose and interpretation rules¶
This sheet preserves reusable denominators, effect sizes, uncertainty, and scope. It is not a treatment algorithm. Unless a row says LUSC, the estimate is from a broader lung-cancer or NSCLC population and must not be silently relabelled as histology-specific.
- HR and RR below 1 generally favour the first-listed intervention for the stated adverse endpoint.
- ORs quantify association, not absolute risk or causality.
- Medians do not describe a typical individual trajectory and cannot be subtracted to obtain an individual survival gain.
- Cross-trial differences are descriptive; they do not rank regimens.
- Subgroup estimates are labelled, especially when exploratory or not multiplicity-protected.
- Older PubMed source links were re-queried through E-utilities on 2026-08-30; later sweep rows carry their own provenance. The 2026-10-17 SEER row was verified directly against the portal.
Burden and exposures¶
| Domain | Population and denominator | Estimate | Scope / caution | Source |
|---|---|---|---|---|
| US projected burden, 2026 | All lung and bronchus cancers; ACS projections presented by NCI SEER | 229,410 new cases; 124,990 deaths | Projections from earlier reported data, not observed 2026 counts; all histologies, not LUSC. Rechecked 2026-10-24; same figures as 2026-10-17 | NCI SEER — “Cancer Stat Facts: Lung and Bronchus Cancer”, source, accessed 2026-10-24 |
| Global incidence, 2022 | Modelled worldwide LUSC | 616,769 incident cases: 461,171 men and 155,598 women | Incidence, not deaths; estimates depend on registry coverage and histology coding | [PMID 39914442](https://pubmed.ncbi.nlm.nih.gov/39914442/){target="_blank" rel="noopener"} |
| Histology share, 2022 | Modelled lung cancers | LUSC: 29.4% of male and 17.1% of female lung cancers | Global aggregate hides regional variation | [PMID 39914442](https://pubmed.ncbi.nlm.nih.gov/39914442/){target="_blank" rel="noopener"} |
| Global incidence, 2020 | Modelled worldwide LUSC | 351,807 men and 91,070 women; age-standardised rates 7.7 and 1.6 per 100,000 | Different model year; do not treat change from 2020 to 2022 as a measured trend | [PMID 37837979](https://pubmed.ncbi.nlm.nih.gov/37837979/){target="_blank" rel="noopener"} |
| Cigarette intensity | Case-control analysis | >30 cigarettes/day: OR 103.5 (95% CI 74.8–143.2) in men; 62.7 (31.5–124.6) in women | Very large relative association; residual confounding and retrospective exposure measurement remain | [PMID 22052329](https://pubmed.ncbi.nlm.nih.gov/22052329/){target="_blank" rel="noopener"} |
| Smoking intensity, Mendelian randomization | FinnGen squamous-cell carcinoma, 365 cases; 23 genetic instruments for cigarettes/day | OR 5.95 per SD increase (95% CI 3.12–11.37); survived multiple-testing correction | Instrumental estimate of intensity, not pack-years; smoking-status instruments were weaker. LUSC as FinnGen phenotype | [PMID 42888622](https://pubmed.ncbi.nlm.nih.gov/42888622/){target="_blank" rel="noopener"} |
| Residential radon | 28 studies; 13,748 cases, 23,112 controls | LUSC OR 1.43 (1.18–1.74); all lung cancer OR 1.48 (1.26–1.73) | Meta-analysis of observational studies; exposure estimation varies | [PMID 32102460](https://pubmed.ncbi.nlm.nih.gov/32102460/){target="_blank" rel="noopener"} |
| Occupational asbestos | Pooled men; 17,705 cases, 21,813 controls | LUSC OR 1.24 (1.18–1.31) | Occupational ascertainment and co-exposure to smoking matter | [PMID 28141674](https://pubmed.ncbi.nlm.nih.gov/28141674/){target="_blank" rel="noopener"} |
| Smoking cessation after diagnosis | Meta-analysis | NSCLC mortality RR 0.77 (0.66–0.90); all lung-cancer mortality RR 0.71 (0.64–0.80) | Mainly observational; healthier-quitter and treatment-adherence effects possible | [PMID 34995798](https://pubmed.ncbi.nlm.nih.gov/34995798/){target="_blank" rel="noopener"} |
| Continued smoking after early diagnosis | Early lung cancer cohorts | Mortality HR 2.94; recurrence HR 1.86 versus cessation | Evidence quality limited, but direction supports immediate cessation care | [PMID 20093278](https://pubmed.ncbi.nlm.nih.gov/20093278/){target="_blank" rel="noopener"} |
Screening and early detection¶
| Study / policy | Population | Benefit estimate | Harm or implementation estimate | Source |
|---|---|---|---|---|
| NLST | 53,454 high-risk participants | Lung-cancer mortality reduced 20.0% (95% CI 6.8–26.7); all-cause mortality reduced 6.7% | 96.4% of positive screens across rounds were false positive under the trial threshold; this is not the probability of an invasive procedure | [PMID 21714641](https://pubmed.ncbi.nlm.nih.gov/21714641/){target="_blank" rel="noopener"} |
| NELSON | 13,195 men and 2,594 women | Men: 10-year lung-cancer mortality rate ratio 0.76 (0.61–0.94) | 9.2% had at least one additional CT; referral rate 2.1% under a volume/doubling-time protocol | [PMID 31995683](https://pubmed.ncbi.nlm.nih.gov/31995683/){target="_blank" rel="noopener"} |
| USPSTF evidence review | 7 RCTs; 86,486 participants | NLST incidence-rate ratio 0.85, NNS 323 over 6.5 years; NELSON IRR 0.75, NNS 130 over 10 years | NLST: 17 invasive procedures per 1,000 screened due to false-positive findings; fewer than 1 major complication per 1,000 | [PMID 33687468](https://pubmed.ncbi.nlm.nih.gov/33687468/){target="_blank" rel="noopener"} |
| USPSTF eligibility | US adults | Annual LDCT, age 50–80, at least 20 pack-years, current smoking or quit within 15 years | A policy threshold, not an individual biological boundary | [PMID 33687470](https://pubmed.ncbi.nlm.nih.gov/33687470/){target="_blank" rel="noopener"} |
| Community implementation | 2,003 screened participants | — | Any invasive procedure 5.1%; invasive procedure for a false-positive nodule 0.4% | [PMID 36781101](https://pubmed.ncbi.nlm.nih.gov/36781101/){target="_blank" rel="noopener"} |
| Comorbidity and benefit | Modelled screening cohort | Highest comorbidity quintile lung-cancer mortality HR 0.99 (0.79–1.23) | Illustrates competing mortality and reduced net benefit; not a universal exclusion rule | [PMID 39798695](https://pubmed.ncbi.nlm.nih.gov/39798695/){target="_blank" rel="noopener"} |
| CT-occult central LUSC | Bronchoscopy referral series; 10,851 lung cancers | 115 CT-occult central LUSCs | Referral denominator cannot estimate population screening sensitivity | [PMID 38443800](https://pubmed.ncbi.nlm.nih.gov/38443800/){target="_blank" rel="noopener"} |
Pathology and precursor lesions¶
| Question | Evidence | Estimate | Interpretation | Source |
|---|---|---|---|---|
| p40 diagnostic performance | 85 studies; 17,893 patients | Sensitivity 0.92 (0.89–0.95); specificity 0.94 (0.93–0.96); diagnostic OR 377 | Squamous differentiation, not pulmonary origin | [PMID 35126682](https://pubmed.ncbi.nlm.nih.gov/35126682/){target="_blank" rel="noopener"} |
| p63 diagnostic performance | Same meta-analysis | Sensitivity 0.92 (0.90–0.94); specificity 0.83 (0.80–0.86); diagnostic OR 70 | Similar sensitivity but lower specificity than p40 | [PMID 35126682](https://pubmed.ncbi.nlm.nih.gov/35126682/){target="_blank" rel="noopener"} |
| Minimal IHC panel | 263 prospective biopsies | Morphology classified 53.2%; p40/TTF-1 reduced NSCLC-NOS from 46.7% to 14.4%; 90% concordance with available resections | Single cohort; tissue preservation remains part of the outcome | [PMID 29168459](https://pubmed.ncbi.nlm.nih.gov/29168459/){target="_blank" rel="noopener"} |
| High-risk HPV in lung SCC | 114 primary, 11 pulmonary metastatic SCC | HR-HPV RNA-ISH 0/114 primary vs 9/11 metastatic; p16+ in 27.2% of primaries; p16+/Rb partial loss only in HPV+ metastases | Small metastatic denominator; supports HPV-specific testing over p16 alone | [PMID 42758332](https://pubmed.ncbi.nlm.nih.gov/42758332/){target="_blank" rel="noopener"} |
| 3q amplification in airway lesions | 19 serial biopsies | Present in high-grade lesions, absent in low-grade lesions; 8/10 high-grade lesions progressed | Small, lesion-level study; does not validate population bronchoscopy | [PMID 20299530](https://pubmed.ncbi.nlm.nih.gov/20299530/){target="_blank" rel="noopener"} |
Molecular architecture and targetability¶
| Signal | Denominator | Estimate | Clinical meaning | Source |
|---|---|---|---|---|
| TCGA genomic complexity | 178 LUSC tumours | Mean 360 coding mutations, 165 rearrangements, 323 copy-number segments per tumour | High complexity does not equal many actionable drivers | [PMID 22960745](https://pubmed.ncbi.nlm.nih.gov/22960745/){target="_blank" rel="noopener"} |
| Cell-cycle pathway | TCGA | CDKN2A/RB1 pathway altered in 72% | Common biology; CDK4/6 biomarker matching did not establish efficacy | [PMID 22960745](https://pubmed.ncbi.nlm.nih.gov/22960745/){target="_blank" rel="noopener"} |
| PI3K pathway | TCGA | Altered in 47% | Broad pathway labels were insufficient selectors in Lung-MAP | [PMID 22960745](https://pubmed.ncbi.nlm.nih.gov/22960745/){target="_blank" rel="noopener"} |
| Erdafitinib, FGFR-altered NSCLC (FIND) | 44,537 screened → 26 enrolled; 22 treated; 73% squamous | Fusion cohort 2/7 PR (one unconfirmed); mutation cohort best response SD (n=8) | Simon stage I only; hyperphosphataemia 45.5% | [PMID 42848441](https://pubmed.ncbi.nlm.nih.gov/42848441/){target="_blank" rel="noopener"} |
| Squamous differentiation | TCGA | Altered in 44% | Lineage architecture, not a validated drug-selection rule | [PMID 22960745](https://pubmed.ncbi.nlm.nih.gov/22960745/){target="_blank" rel="noopener"} |
| Oxidative-stress pathway | TCGA | NFE2L2/KEAP1 altered in 34% | Prognostic/resistance hypothesis; no standard matched drug | [PMID 22960745](https://pubmed.ncbi.nlm.nih.gov/22960745/){target="_blank" rel="noopener"} |
| NFE2L2 and metastatic progression | Surgically resected stage I–III lung cancer, >5-year follow-up | NFE2L2 mutations associated with metastatic disease or brain metastasis in LUSC; adenocarcinoma had higher brain-metastasis risk than LUSC overall | Observational; authors call rarer-alteration findings exploratory. Not a surveillance rule | [PMID 42909660](https://pubmed.ncbi.nlm.nih.gov/42909660/){target="_blank" rel="noopener"} |
| FGFR1 amplification | Early validation cohort | 22% | Amplification prevalence did not translate into reliable FGFR-inhibitor benefit | [PMID 21160078](https://pubmed.ncbi.nlm.nih.gov/21160078/){target="_blank" rel="noopener"} |
| DDR2 mutation | Discovery cohort | Approximately 3.8% | Compelling preclinical dependency; no validated routine matched therapy | [PMID 22328973](https://pubmed.ncbi.nlm.nih.gov/22328973/){target="_blank" rel="noopener"} |
| NRF2/KEAP1 protein state | Resected lung tumours | NRF2 positivity 38% in LUSC vs 18% adenocarcinoma; low KEAP1 46%; OS HR 2.09 for adverse state | Retrospective IHC; assay and causal interpretation uncertain | [PMID 20534738](https://pubmed.ncbi.nlm.nih.gov/20534738/){target="_blank" rel="noopener"} |
| Real-world actionability | 130 evaluable LUSCs | 38% had an alteration qualifying for Lung-MAP, another trial, or approved therapy; 24% of submitted specimens insufficient | Broad definition includes trial eligibility, not proven benefit | [PMID 31855703](https://pubmed.ncbi.nlm.nih.gov/31855703/){target="_blank" rel="noopener"} |
Lung-MAP feasibility and negative-target ledger¶
| Step / substudy | Denominator or result | Estimate | Reading rule | Source |
|---|---|---|---|---|
| Screening enrollment | 1,864 | 1,841 tissue submissions (98.9%) | Operational feasibility | [PMID 33125909](https://pubmed.ncbi.nlm.nih.gov/33125909/){target="_blank" rel="noopener"} |
| Genomic results | 1,841 submissions | 1,674 results (90.9%) | Assay success among submissions | [PMID 33125909](https://pubmed.ncbi.nlm.nih.gov/33125909/){target="_blank" rel="noopener"} |
| Substudy assignment | 1,674 results | 1,404 assigned (83.9%) | Assignment is not enrollment or response | [PMID 33125909](https://pubmed.ncbi.nlm.nih.gov/33125909/){target="_blank" rel="noopener"} |
| Substudy registration | 1,404 assignments | 655 registered (46.7%) | Attrition quantifies the implementation gap | [PMID 33125909](https://pubmed.ncbi.nlm.nih.gov/33125909/){target="_blank" rel="noopener"} |
| Targeted cohorts | 143 treated | 10 responses (7.0%) | Aggregate hides heterogeneous agents and markers | [PMID 33125909](https://pubmed.ncbi.nlm.nih.gov/33125909/){target="_blank" rel="noopener"} |
| Immunotherapy cohorts | 315 treated | 53 responses (16.8%) | Historical platform aggregate, not a current-line benchmark | [PMID 33125909](https://pubmed.ncbi.nlm.nih.gov/33125909/){target="_blank" rel="noopener"} |
| Docetaxel control | 56 treated | 3 responses (5.4%) | Small common-control experience | [PMID 33125909](https://pubmed.ncbi.nlm.nih.gov/33125909/){target="_blank" rel="noopener"} |
| Dovitinib / FGFR | Phase II | ORR 11.5% (95% CI 0.8–23.8); median PFS 2.9 months | Amplification alone was an inadequate selector | [PMID 27315356](https://pubmed.ncbi.nlm.nih.gov/27315356/){target="_blank" rel="noopener"} |
| AZD4547 / FGFR | Lung-MAP S1400D | ORR 7% (0–17); median PFS 2.7 months; OS 7.5 months | No practice-changing signal | [PMID 31195180](https://pubmed.ncbi.nlm.nih.gov/31195180/){target="_blank" rel="noopener"} |
| Taselisib / PI3K | Lung-MAP S1400B | ORR 5% (0–24) | Broad PI3K-positive category failed | [PMID 31158500](https://pubmed.ncbi.nlm.nih.gov/31158500/){target="_blank" rel="noopener"} |
| Palbociclib / cell cycle | Lung-MAP S1400C | ORR 6% (0–15) | Pathway alteration did not predict adequate dependence | [PMID 31302234](https://pubmed.ncbi.nlm.nih.gov/31302234/){target="_blank" rel="noopener"} |
| TAK-228 / mTOR | Biomarker-selected phase II | ORR 25%; median PFS 8.9 months | Small signal requiring confirmation; not standard care | [PMID 36240971](https://pubmed.ncbi.nlm.nih.gov/36240971/){target="_blank" rel="noopener"} |
Curative-intent treatment¶
| Setting / trial | Comparison | Efficacy estimate | Safety / boundary | Source |
|---|---|---|---|---|
| Resected NSCLC, LACE | Cisplatin-based adjuvant chemotherapy vs no chemotherapy; 4,584 patients | OS HR 0.89 (0.82–0.96); absolute five-year benefit 5.4 percentage points | Histology interaction not significant | [PMID 18506026](https://pubmed.ncbi.nlm.nih.gov/18506026/){target="_blank" rel="noopener"} |
| LACE by stage | Same | IA HR 1.40; IB 0.93; II 0.83; III 0.83 | Subgroup pattern supports stage selection; not an isolated LUSC rule | [PMID 18506026](https://pubmed.ncbi.nlm.nih.gov/18506026/){target="_blank" rel="noopener"} |
| CheckMate 816 | Neoadjuvant nivolumab + chemotherapy vs chemotherapy | Median EFS 31.6 vs 20.8 months; HR 0.63 (97.38% CI 0.43–0.91); pCR 24.0% vs 2.2% | Surgery 83.2% vs 75.4%; grade 3–4 treatment-related AEs 33.5% vs 36.9% | [PMID 35403841](https://pubmed.ncbi.nlm.nih.gov/35403841/){target="_blank" rel="noopener"} |
| CheckMate 816 final | Same | OS HR 0.72 (0.523–0.998); five-year OS 65.4% vs 55.0% | Among pCR vs no pCR, five-year OS 95.3% vs 55.7%; ctDNA-clearance association 75.0% vs 52.6% | [PMID 40454642](https://pubmed.ncbi.nlm.nih.gov/40454642/){target="_blank" rel="noopener"} |
| KEYNOTE-671 | Perioperative pembrolizumab vs placebo, both with neoadjuvant chemotherapy | 24-month EFS 62.4% vs 40.6%; HR 0.58; pCR 18.1% vs 4.0%; MPR 30.2% vs 11.0% | Grade ≥3 treatment-related AEs 44.9% vs 37.3%; design cannot isolate adjuvant contribution | [PMID 37272513](https://pubmed.ncbi.nlm.nih.gov/37272513/){target="_blank" rel="noopener"} |
| KEYNOTE-671 OS update | Same | 36-month OS 71% vs 64%; HR 0.72 (0.56–0.93) | Mixed histology | [PMID 39288781](https://pubmed.ncbi.nlm.nih.gov/39288781/){target="_blank" rel="noopener"} |
| AEGEAN | Perioperative durvalumab vs placebo, both with chemotherapy | EFS HR 0.68 (0.53–0.88); pCR 17.2% vs 4.3% | Grade 3–4 treatment-related AEs 42.4% vs 43.2%; mixed histology | [PMID 37870974](https://pubmed.ncbi.nlm.nih.gov/37870974/){target="_blank" rel="noopener"} |
| AEGEAN updated (2026) | Same; second interim EFS analysis, modified ITT n=740, median follow-up 25.9 months | EFS HR 0.69 (0.55–0.88); DFS HR 0.66 (0.47–0.92); OS HR 0.89 (0.70–1.14), interim | Adjuvant-phase maximum grade 3–4 AEs 15.4% vs 10.6%; mixed histology; OS immature | [PMID 42664473](https://pubmed.ncbi.nlm.nih.gov/42664473/){target="_blank" rel="noopener"} |
| CheckMate 77T ctDNA (biomarker-evaluable) | Perioperative nivolumab vs placebo; 98/229 and 92/232 had evaluable biomarkers | Presurgical ctDNA clearance 50/76 (66%) vs 24/64 (38%); pCR given clearance 25/50 vs 3/24; 0/25 nivolumab patients without clearance had pCR | Exploratory subset (41% of randomized). Squamous histology was a top machine-learning predictor of prolonged EFS. Mixed histology | [PMID 42587156](https://pubmed.ncbi.nlm.nih.gov/42587156/){target="_blank" rel="noopener"} |
| CheckMate 77T squamous EFS (extended data) | Same; unstratified histology subgroups | 30-month EFS 95% CIs: squamous 57–75% vs 35–55%; non-squamous 45–65% vs 31–50% (nivolumab vs placebo) | Point HRs not stated in the figure caption; mixed-trial subgroup | [PMID 42587156](https://pubmed.ncbi.nlm.nih.gov/42587156/){target="_blank" rel="noopener"} |
| Perioperative ICI, age ≥65 (Cochrane 2026) | ICI ± chemotherapy vs placebo/no treatment ± chemotherapy; 11 RCTs, 3,152 of 6,788 participants aged ≥65 | OS HR 0.88 (0.61–1.26; 3 RCTs, n=590; moderate certainty); EFS HR 0.61 (0.52–0.71; 7 RCTs); DFS HR 0.85 (0.73–0.99; 3 RCTs); pCR RR 5.07 (3.40–7.54; low certainty) | No age-specific QoL data; ≥75 and PD-L1 strata not estimable; not histology-specific | [PMID 42440312](https://pubmed.ncbi.nlm.nih.gov/42440312/){target="_blank" rel="noopener"} |
| IMpower010 | Adjuvant atezolizumab vs best supportive care after chemotherapy | DFS HR 0.66 in stage II–IIIA PD-L1 ≥1%; 0.79 in all stage II–IIIA; 0.81 in stage IB–IIIA ITT | Hierarchical analysis, assay/cutoff and jurisdiction matter | [PMID 34555333](https://pubmed.ncbi.nlm.nih.gov/34555333/){target="_blank" rel="noopener"} |
| PEARLS/KEYNOTE-091 | Adjuvant pembrolizumab vs placebo | Median DFS 53.6 vs 42.0 months; HR 0.76; PD-L1 ≥50% HR 0.82, not significant at interim analysis | Mixed histology; PD-L1 pattern differed from a simple enrichment expectation | [PMID 36108662](https://pubmed.ncbi.nlm.nih.gov/36108662/){target="_blank" rel="noopener"} |
| PACIFIC primary | Durvalumab vs placebo after concurrent chemoradiation | Median PFS 16.8 vs 5.6 months; HR 0.52; OS HR 0.68; 24-month OS 66.3% vs 55.6% | Unresectable stage III, mixed histology | [PMID 28885881](https://pubmed.ncbi.nlm.nih.gov/28885881/){target="_blank" rel="noopener"}; [PMID 30280658](https://pubmed.ncbi.nlm.nih.gov/30280658/){target="_blank" rel="noopener"} |
| PACIFIC five-year | Same | Five-year OS 42.9% vs 33.4%; five-year PFS 33.1% vs 19.0% | Long-term landmark; subsequent therapies can affect OS | [PMID 35108059](https://pubmed.ncbi.nlm.nih.gov/35108059/){target="_blank" rel="noopener"} |
Metastatic and recurrent treatment¶
| Trial / setting | Comparison | Efficacy estimate | Safety / interpretation | Source |
|---|---|---|---|---|
| KEYNOTE-407 | Pembrolizumab + carboplatin/taxane vs chemotherapy in 559 metastatic LUSCs | OS 15.9 vs 11.3 months; HR 0.64 (0.49–0.85); PFS 6.4 vs 4.8 months; HR 0.56 (0.45–0.70) | Grade ≥3 AEs 69.8% vs 68.2%; direct LUSC evidence | [PMID 30280635](https://pubmed.ncbi.nlm.nih.gov/30280635/){target="_blank" rel="noopener"} |
| KEYNOTE-407 five-year | Same | OS HR 0.71 (0.59–0.85); PFS HR 0.62 (0.52–0.74); five-year OS 18.4% vs 9.7% | Long-term tail does not identify beforehand who benefits | [PMID 36735893](https://pubmed.ncbi.nlm.nih.gov/36735893/){target="_blank" rel="noopener"} |
| KEYNOTE-407 PRO | Same | Week-18 global health/QoL between-group difference 4.9 points (1.4–8.3) | Group mean can conceal severe individual toxicity and attrition | [PMID 31751163](https://pubmed.ncbi.nlm.nih.gov/31751163/){target="_blank" rel="noopener"} |
| CheckMate 017 | Nivolumab vs docetaxel after platinum in LUSC | OS 9.2 vs 6.0 months; HR 0.59 (0.44–0.79); one-year OS 42% vs 24%; ORR 20% vs 9% | Grade 3–4 treatment-related AEs 7% vs 55%; direct LUSC evidence | [PMID 26028407](https://pubmed.ncbi.nlm.nih.gov/26028407/){target="_blank" rel="noopener"} |
| CheckMate 227 | Nivolumab + ipilimumab vs chemotherapy, PD-L1 ≥1% NSCLC | OS 17.1 vs 14.9 months; two-year OS 40.0% vs 32.8% | NSCLC-wide; CTLA-4 toxicity and early progression matter | [PMID 31562796](https://pubmed.ncbi.nlm.nih.gov/31562796/){target="_blank" rel="noopener"} |
| POSEIDON | Tremelimumab + durvalumab + chemotherapy vs chemotherapy | OS HR 0.77 (0.65–0.92), medians 14.0 vs 11.7 months; PFS HR 0.72 | Grade 3–4 treatment-related AEs 51.8% vs 44.4%; mixed histology | [PMID 36327426](https://pubmed.ncbi.nlm.nih.gov/36327426/){target="_blank" rel="noopener"} |
| REVEL | Ramucirumab + docetaxel vs docetaxel after platinum; 1,253 NSCLCs | OS 10.5 vs 9.1 months; HR 0.86 (0.75–0.98); PFS 4.5 vs 3.0 months; HR 0.76 (0.68–0.86) | Modest absolute effect; neutropenia and bleeding-risk selection | [PMID 24933332](https://pubmed.ncbi.nlm.nih.gov/24933332/){target="_blank" rel="noopener"} |
| LUX-Lung 8 | Afatinib vs erlotinib in pretreated LUSC | PFS 2.4 vs 1.9 months; HR 0.82; OS 7.9 vs 6.8 months; HR 0.81 | Limited modern niche; not equivalent to EGFR-mutant targeted therapy | [PMID 26156651](https://pubmed.ncbi.nlm.nih.gov/26156651/){target="_blank" rel="noopener"} |
| TROPION-Lung01 LUSC subgroup | Datopotamab deruxtecan vs docetaxel | PFS 2.8 vs 3.9 months; HR 1.41 (0.95–2.08); OS 7.6 vs 9.4 months; HR 1.32 (0.91–1.92) | Histology subgroup was unfavourable; an all-NSCLC headline is misleading | [PMID 39250535](https://pubmed.ncbi.nlm.nih.gov/39250535/){target="_blank" rel="noopener"} |
| PD-(L)1 inhibitor + chemotherapy, stage IIIB–IV squamous NSCLC (meta-analysis 2026) | 14 phase III RCTs, 4,481 patients | OS HR 0.73 (0.67–0.79); PFS HR 0.54 (0.48–0.60); ORR RR 1.50 (1.40–1.61) | Higher total and grade 3–5 immune-related AEs; pooled across different PD-(L)1 agents; LUSC | [PMID 42724878](https://pubmed.ncbi.nlm.nih.gov/42724878/){target="_blank" rel="noopener"} |
| Cisplatin/gemcitabine/necitumumab after platinum + ICI (WJOG14120L) | Single-arm phase II, 46 evaluable LUSC | ORR 26.1% (80% CI 17.7–36.2), below the 40% target; DCR 87.0%; median PFS 4.4 months; median OS 12.2 months | No pneumonitis or treatment-related deaths; uncontrolled; LUSC | [PMID 42816458](https://pubmed.ncbi.nlm.nih.gov/42816458/){target="_blank" rel="noopener"} |
Metastatic patterns, supportive care, and lived outcomes¶
| Context | Denominator / comparison | Estimate | Boundary | Source |
|---|---|---|---|---|
| Selected untreated brain metastases | Pembrolizumab phase II; PD-L1-positive cohort | Intracranial response 11/37, 29.7% (15.9–47.0); none in PD-L1-negative/unevaluable cohort | Asymptomatic 5–20-mm lesions; cannot justify deferring urgent local therapy | [PMID 32251621](https://pubmed.ncbi.nlm.nih.gov/32251621/){target="_blank" rel="noopener"} |
| Oligometastatic consolidation | Randomized phase II; 49 patients | PFS 14.2 vs 4.4 months; OS 41.2 vs 17.0 months | Small, early-closed, selected NSCLC study from an older systemic era | [PMID 31067138](https://pubmed.ncbi.nlm.nih.gov/31067138/){target="_blank" rel="noopener"} |
| Bone metastases | Exploratory lung subgroup: denosumab vs zoledronic acid | NSCLC OS 9.5 vs 8.0 months, HR 0.78; LUSC 8.6 vs 6.4 months, HR 0.68 | Exploratory, not multiplicity-protected; do not choose solely for survival | [PMID 23154554](https://pubmed.ncbi.nlm.nih.gov/23154554/){target="_blank" rel="noopener"} |
| Early palliative care | Randomized metastatic NSCLC; 151 patients | FACT-L at 12 weeks 98.0 vs 91.5; depression 16% vs 38%; aggressive end-of-life care 33% vs 54%; OS 11.6 vs 8.9 months | Single-centre landmark; supports concurrent, needs-based palliative care | [PMID 20818875](https://pubmed.ncbi.nlm.nih.gov/20818875/){target="_blank" rel="noopener"} |
| Postoperative pulmonary complications | 34 studies; 31,696 lung-cancer resections | Pooled complication incidence 18.4% | Definitions and procedure mix heterogeneous; use for counselling, not individual prediction | [PMID 38975138](https://pubmed.ncbi.nlm.nih.gov/38975138/){target="_blank" rel="noopener"} |
Reuse checklist¶
Before copying a number into a page, presentation, or decision aid:
- preserve the population and histology;
- preserve whether the endpoint is OS, PFS, EFS, DFS, pCR, response, toxicity, or quality of life;
- include the CI when reported here;
- retain the comparator and time point;
- distinguish randomized estimates from exploratory subgroups and observational associations;
- do not turn a relative effect into an absolute benefit without the baseline risk;
- re-check guideline status, authorization, and registry status at the date of use.