# Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch

Source: https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/  
OnCo record `lung-cancer-evidence-roadmap` (Roadmap). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Lung cancer is where modern cancer epidemiology began: two studies in 1950 tied it to cigarettes, and a fifty-year cohort proved it. This roadmap follows the evidence from there through chemotherapy that barely worked, the scans that find the disease early, the drugs for cancers that depend on one broken gene, immunotherapy, and small-cell disease, to 2032.

## Summary

Lung cancer kills more people than any other cancer, and it is the cancer whose cause is best understood. Wynder and Graham in the United States and Doll and Hill in Britain published within months of each other in 1950; the British Doctors Study then followed a cohort for fifty years and turned an association into a dose-response relationship with a cessation curve attached. Peto's 2000 analysis gave the number that tobacco control still runs on: stopping before middle age avoids more than 90 percent of the risk.

Treatment took much longer. The 1995 individual-patient meta-analysis of 52 trials showed cisplatin-based chemotherapy helped, by about 5 percent at five years after surgery; E1594 in 2002 showed that no combination of cytotoxic drugs beat any other, with a median survival of 7.9 months. The plateau broke twice. In 2004 Lynch and Paez independently found that the minority who responded dramatically to gefitinib had EGFR mutations, and IPASS in 2009 proved that selecting by that mutation was what made the drug work; in 2007 Soda found the EML4-ALK fusion, and crizotinib was approved four years later. In 2012 Topalian's phase 1 showed durable responses to PD-1 blockade in lung cancer, and by 2018 chemotherapy plus pembrolizumab was standard for most patients without a driver.

Early detection followed its own track. PLCO showed in 2011 that chest radiography does nothing; NLST that year and NELSON in 2020 showed that low-dose computed tomography cuts lung cancer deaths. Eligibility is the unsolved part: pack-year thresholds exclude high-risk groups systematically, never-smokers are outside the criteria entirely, and uptake among those who qualify remains a fraction of them.

Since 2017 the direction has been earlier and combined. PACIFIC put consolidation durvalumab after chemoradiotherapy in stage III disease and five-year survival reached 42.9 percent; CheckMate 816, KEYNOTE-671, AEGEAN and IMpower010 moved immunotherapy around the operation; ADAURA and ALINA did the same with targeted drugs for EGFR and ALK. Small-cell lung cancer, static since twice-daily radiotherapy in 1999, finally moved: ADRIATIC lifted median survival in limited-stage disease from 33.4 to 55.9 months, and tarlatamab, a DLL3 T-cell engager, became the first drug built for the disease. What has not moved is resistance, which arrives in one to three years for every targeted drug, and the gap between who is eligible for screening and who gets it.

UK and NHS specifics (Targeted Lung Health Check coverage and uptake, NICE positions and Cancer Drugs Fund status, molecular testing turnaround, thoracic surgery and radiotherapy capacity, audit indicators and trial access) are on the UK and NHS page for lung cancer and are not restated here.

## Fields

- Kind: Roadmap
- Status: active
- Last checked: 2026-09-25
- Also known as: Lung cancer history; Lung cancer evidence roadmap; NSCLC and SCLC roadmap; Thoracic oncology roadmap

## Sources

- NCI PDQ: lung cancer: https://www.cancer.gov/types/lung
- ESMO guidelines: lung and chest tumours: https://www.esmo.org/guidelines/esmo-clinical-practice-guidelines-lung-and-chest-tumours
- IASLC: International Association for the Study of Lung Cancer: https://www.iaslc.org/
- ClinicalTrials.gov NCT01888601: https://clinicaltrials.gov/study/NCT01888601

## Connected records

- roadmaps: [Cancer prevention roadmap: tobacco control and vaccines → biomarker-guided chemoprevention → interception in carriers](https://onco.cc/roadmaps/prevention-roadmap/), [Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs](https://onco.cc/roadmaps/chemotherapy-roadmap/), [ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment](https://onco.cc/roadmaps/ctdna-tests/), [Diagnostics roadmap: stains → gene panels → blood tests that decide treatment](https://onco.cc/roadmaps/diagnostics-roadmap/), [Early detection roadmap: organ screening → blood tests for many cancers](https://onco.cc/roadmaps/early-detection-roadmap/), [Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity](https://onco.cc/roadmaps/immunotherapy-roadmap/), [KRAS roadmap: undruggable → G12C → pan-RAS](https://onco.cc/roadmaps/kras-roadmap/), [Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH](https://onco.cc/roadmaps/radiation-roadmap/), [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)
- cancers: [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/), [Early Detection & Screening](https://onco.cc/fronts/early-detection/), [Immunotherapy](https://onco.cc/fronts/immunotherapy/), [Prevention & Risk](https://onco.cc/fronts/prevention/), [Radiation Therapy](https://onco.cc/fronts/radiation/), [Surgery & Interventional](https://onco.cc/fronts/surgery/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Most of the world has almost no cancer care](https://onco.cc/bottlenecks/b-global-access/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/), [Prevention we already have is not deployed](https://onco.cc/bottlenecks/b-prevention-adoption/), [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [The brain: barrier and sanctuary](https://onco.cc/bottlenecks/b-brain-delivery/), [The hardest cancers are found late](https://onco.cc/bottlenecks/b-early-detection/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)
- key papers: [Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib](https://onco.cc/key-papers/paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004/), [ADAURA: three years of osimertinib after surgery for EGFR-mutated lung cancer](https://onco.cc/key-papers/paper-adaura-nejm-2020/), [Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010)](https://onco.cc/key-papers/paper-felip-impower010-adjuvant-atezolizumab-lancet-2021/), [Alectinib in resected ALK-positive non-small-cell lung cancer](https://onco.cc/key-papers/paper-wu-alina-adjuvant-alectinib-nejm-2024/), [Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer](https://onco.cc/key-papers/paper-peters-alex-alectinib-crizotinib-nejm-2017/), [Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC](https://onco.cc/key-papers/paper-cho-mariposa-amivantamab-lazertinib-nejm-2024/), [Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer](https://onco.cc/key-papers/paper-kwak-crizotinib-alk-nsclc-nejm-2010/), [Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC](https://onco.cc/key-papers/paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020/), [Beamion LUNG-1: zongertinib in previously treated HER2-mutant non-small-cell lung cancer](https://onco.cc/key-papers/paper-beamion-lung-1-zongertinib-nejm-2025/), [Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer](https://onco.cc/key-papers/paper-wolf-geometry-mono-1-capmatinib-nejm-2020/), [CheckMate 017: nivolumab beats docetaxel in squamous lung cancer after chemotherapy](https://onco.cc/key-papers/paper-checkmate-017-nejm-2015/), [CheckMate 057: nivolumab beats docetaxel after chemotherapy in non-squamous lung cancer](https://onco.cc/key-papers/paper-checkmate-057-nejm-2015/), [CheckMate 816: three cycles of nivolumab plus chemotherapy before lung cancer surgery](https://onco.cc/key-papers/paper-checkmate-816-nejm-2022/), [Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials](https://onco.cc/key-papers/paper-nsclc-collaborative-group-chemotherapy-meta-analysis-bmj-1995/), [Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer](https://onco.cc/key-papers/paper-schiller-ecog-1594-four-chemotherapy-regimens-nejm-2002/), [Comprehensive genomic profiles of small cell lung cancer](https://onco.cc/key-papers/paper-george-sclc-genomic-profiles-nature-2015/), [Crizotinib versus chemotherapy in advanced ALK-positive lung cancer](https://onco.cc/key-papers/paper-alk-nsclc-n-engl-j-med-2013/), [Doll and Hill 1950: the case-control study that tied smoking to lung cancer](https://onco.cc/key-papers/paper-doll-hill-smoking-lung-cancer-bmj-1950/), [Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer](https://onco.cc/key-papers/paper-cheng-adriatic-durvalumab-limited-stage-sclc-nejm-2024/), [Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN)](https://onco.cc/key-papers/paper-paz-ares-caspian-durvalumab-es-sclc-lancet-2019/), [Efficacy and Safety of Rovalpituzumab Tesirine in Third-Line and Beyond Patients with DLL3-Expressing, Relapsed/Refractory Small-Cell Lung Cancer: Results From the Phase II TRINITY Study](https://onco.cc/key-papers/paper-dll3-sclc-clin-cancer-res-2019/), [EGFR mutation and resistance of non-small-cell lung cancer to gefitinib](https://onco.cc/key-papers/paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005/), [EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy](https://onco.cc/key-papers/paper-paez-egfr-mutations-gefitinib-science-2004/), [Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial](https://onco.cc/key-papers/paper-egfr-nsclc-lancet-oncol-2012/), [Evaluation of USPSTF Lung Cancer Screening Guidelines Among African American Adult Smokers](https://onco.cc/key-papers/paper-aldrich-uspstf-screening-african-american-smokers-jama-oncol-2019/), [Fifty years of the British Doctors Study: smokers lose ten years of life, quitting gives most of it back](https://onco.cc/key-papers/paper-doll-peto-50-year-doctors-bmj-2004/), [First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer](https://onco.cc/key-papers/paper-impower133-n-engl-j-med-2018/), [First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer](https://onco.cc/key-papers/paper-shaw-crown-lorlatinib-crizotinib-nejm-2020/), [Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer](https://onco.cc/key-papers/paper-spigel-pacific-five-year-survival-jco-2022/), [FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer](https://onco.cc/key-papers/paper-flaura-nejm-2018/), [Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma](https://onco.cc/key-papers/paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009/), [Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR](https://onco.cc/key-papers/paper-egfr-nsclc-n-engl-j-med-2010/), [Genomic and evolutionary classification of lung cancer in never smokers](https://onco.cc/key-papers/paper-zhang-lung-cancer-never-smokers-nat-genet-2021/), [Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors](https://onco.cc/key-papers/paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011/), [Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer](https://onco.cc/key-papers/paper-soda-eml4-alk-fusion-nature-2007/), [KEYNOTE-001 (Garon 2015): pembrolizumab in non-small-cell lung cancer and the 50% PD-L1 cut-off](https://onco.cc/key-papers/paper-keynote-001-pembrolizumab-nsclc-nejm-2015/), [KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer](https://onco.cc/key-papers/paper-keynote-024-nejm-2016/), [KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation](https://onco.cc/key-papers/paper-keynote-189-nejm-2018/), [LIBRETTO-001: selpercatinib in RET fusion-positive non-small-cell lung cancer](https://onco.cc/key-papers/paper-libretto-001-selpercatinib-nsclc-nejm-2020/), [Lung adenocarcinoma promotion by air pollutants](https://onco.cc/key-papers/paper-hill-lung-adenocarcinoma-air-pollutants-nature-2023/), [Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group](https://onco.cc/key-papers/paper-lace-adjuvant-cisplatin-pooled-analysis-jco-2008/), [Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data](https://onco.cc/key-papers/paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019/), [NELSON: volume-based CT screening reduces lung cancer deaths with fewer false alarms](https://onco.cc/key-papers/paper-nelson-nejm-2020/), [NLST: yearly low-dose CT scans cut lung cancer deaths in heavy smokers](https://onco.cc/key-papers/paper-nlst-nejm-2011/), [Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC](https://onco.cc/key-papers/paper-lu-laura-osimertinib-stage-iii-nejm-2024/), [Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer](https://onco.cc/key-papers/paper-osimertinib-nsclc-n-engl-j-med-2017/), [Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC](https://onco.cc/key-papers/paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023/), [PACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancer](https://onco.cc/key-papers/paper-pacific-nejm-2017/), [Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer](https://onco.cc/key-papers/paper-sandler-ecog-4599-bevacizumab-nsclc-nejm-2006/), [Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer](https://onco.cc/key-papers/paper-keynote-407-n-engl-j-med-2018/), [Perioperative durvalumab for resectable non-small-cell lung cancer](https://onco.cc/key-papers/paper-heymach-aegean-perioperative-durvalumab-nejm-2023/), [Perioperative nivolumab and chemotherapy in stage III non-small-cell lung cancer](https://onco.cc/key-papers/paper-provencio-nadim-ii-perioperative-nivolumab-stage-iii-nejm-2023/), [Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer](https://onco.cc/key-papers/paper-keynote-671-n-engl-j-med-2023/), [Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution](https://onco.cc/key-papers/paper-abbosh-phylogenetic-ctdna-lung-cancer-nature-2017/), [Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission](https://onco.cc/key-papers/paper-auperin-prophylactic-cranial-irradiation-sclc-nejm-1999/), [Prophylactic cranial irradiation in extensive small-cell lung cancer](https://onco.cc/key-papers/paper-slotman-n-engl-j-med/), [Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial](https://onco.cc/key-papers/paper-plco-chest-radiograph-lung-cancer-mortality-jama-2011/), [Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement](https://onco.cc/key-papers/paper-uspstf-lung-cancer-screening-jama-2021/), [Sotorasib for Lung Cancers with KRAS p.G12C Mutation](https://onco.cc/key-papers/paper-kras-nsclc-n-engl-j-med-2021/), [Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRAS G12C mutation: a randomised, open-label, phase 3 trial](https://onco.cc/key-papers/paper-de-langen-codebreak-200-sotorasib-docetaxel-lancet-2023/), [Tarlatamab for patients with previously treated small-cell lung cancer](https://onco.cc/key-papers/paper-ahn-dellphi-301-tarlatamab-sclc-nejm-2023/), [Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy](https://onco.cc/key-papers/paper-tarlatamab-sclc-n-engl-j-med-2025/), [The mortality of doctors in relation to their smoking habits; a preliminary report](https://onco.cc/key-papers/paper-doll-hill-mortality-of-doctors-smoking-bmj-1954/), [Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma; a study of 684 proved cases](https://onco.cc/key-papers/paper-wynder-graham-tobacco-bronchiogenic-carcinoma-jama-1950/), [Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer](https://onco.cc/key-papers/paper-topalian-anti-pd1-nejm-2012/), [Tracking the evolution of non-small-cell lung cancer](https://onco.cc/key-papers/paper-jamal-hanjani-tracerx-evolution-nsclc-nejm-2017/), [Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide](https://onco.cc/key-papers/paper-turrisi-twice-daily-thoracic-radiotherapy-limited-sclc-nejm-1999/)
- ideas: [Close the United Kingdom lung cancer gaps the UK page names: screening rollout, diagnostic pathway, molecular testing and drug access](https://onco.cc/ideas/idea-lung-uk-screening-testing-and-access-gaps/), [Decide who is screened for lung cancer by individual risk, not by pack-years](https://onco.cc/ideas/idea-lung-screening-eligibility-by-risk-not-pack-years/), [Evaluate clean-air policies using lung cancer in never-smokers](https://onco.cc/ideas/idea-prev-clean-air-never-smoker-endpoints/), [Lung screening eligibility by risk score, not pack-years, including high-risk never-smokers](https://onco.cc/ideas/idea-prev-lung-screening-risk-model-eligibility/), [Make resistance a diagnosis: sequence at every progression and choose the next line from what the tumour became](https://onco.cc/ideas/idea-lung-resistance-directed-sequencing-at-every-progression/), [Measure brain metastasis prevention as a primary endpoint, not as a secondary one](https://onco.cc/ideas/idea-lung-brain-metastasis-prevention-as-a-primary-endpoint/), [Prevention trials aimed only at brain metastasis](https://onco.cc/ideas/idea-bio2-brain-met-prevention-trials/), [Run small-cell lung cancer as one platform with shared controls and subtype stratification](https://onco.cc/ideas/idea-lung-small-cell-platform-with-shared-controls-and-subtypes/), [Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)](https://onco.cc/ideas/idea-sclc-subtype-directed/), [Take lung screening scanners to supermarket car parks in the poorest areas](https://onco.cc/ideas/idea-prev-mobile-lung-screening-deprived-areas/), [Treat lung cancer in never-smokers as its own disease, with its own detection programme](https://onco.cc/ideas/idea-lung-never-smoker-disease-its-own-programme/), [Treat the deprivation gradient in lung cancer as a defect in delivery that can be fixed and measured](https://onco.cc/ideas/idea-lung-deprivation-gradient-treated-as-a-defect-in-delivery/)

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