Understanding NSCLC
Non-Small Cell Lung Cancer (NSCLC) accounts for ~85 % of all lung cancers. It is a heterogeneous group of epithelial lung malignancies that behave and are treated differently from Small Cell Lung Cancer (SCLC).
| Feature | NSCLC | SCLC |
|---|---|---|
| Proportion of lung cancers | ~85 % | ~15 % |
| Typical growth rate | Slower doubling time | Very rapid, aggressive |
| Metastatic pattern | Often local/regional first | Early widespread dissemination |
| Primary treatment paradigm | Stage-based: surgery ± adjuvant ± targeted/IO | Chemo-immunotherapy (rarely surgery) |
| Key actionable biomarkers | EGFR, ALK, ROS1, BRAF, KRAS G12C, MET, RET, NTRK, HER2 | Few (DLL3, BCL2 experimental) |
NSCLC is not a single disease. Molecular subtyping now drives first-line therapy for metastatic disease more than histology alone.
Types & Histology
The World Health Organization (WHO) 2021 classification recognises three major subtypes. Histology matters for chemotherapy selection (e.g., pemetrexed only for non-squamous) and biomarker prevalence.
| Subtype | % of NSCLC | Typical Location | Common Mutations | Chemo Sensitivity Notes |
|---|---|---|---|---|
| Adenocarcinoma | 40–50 % | Peripheral (outer lung) | EGFR (10–15 % West, 30–50 % Asia), KRAS (25–30 %), ALK (3–5 %), ROS1 (1–2 %) | Pemetrexed preferred; bevacizumab safe |
| Squamous Cell Carcinoma | 25–30 % | Central (near bronchi) | FGFR1 amp, PIK3CA, DDR2, KEAP1/NFE2L2 | Avoid pemetrexed & bevacizumab (bleeding risk) |
| Large Cell Carcinoma | 2–3 % | Variable | Heterogeneous; often KRAS, STK11, KEAP1 | Treated as non-squamous if no neuroendocrine features |
| Other/rare | <5 % | — | NUT carcinoma, sarcomatoid (high MET exon 14 skipping) | Individualised |
Clinical Pearl: Even in pure squamous histology, broad molecular profiling (NGS)** is now recommended because actionable targets (EGFR, ALK, ROS1, RET, METex14, NTRK) occasionally occur and change therapy.
Staging System (TNM 8th Edition)
Staging uses the TNM system (Tumour, Nodes, Metastasis) → grouped into Stages I–IV. Accurate staging dictates curative vs. palliative intent.
T Category (Primary Tumour)
| T Descriptor | Criteria |
|---|---|
| Tis | Carcinoma in situ (AIS, MIS, SCIS) |
| T1 | ≤3 cm: T1a(≤1), T1b(>1–2), T1c(>2–3) |
| T2 | >3–5 cm OR invades visceral pleura/main bronchus (≥2 cm from carina)/atelectasis to hilum |
| T3 | >5–7 cm OR invades chest wall, pericardium, phrenic nerve, parietal pericardium OR separate nodule same lobe |
| T4 | >7 cm OR invades diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, oesophagus, vertebral body, carina OR separate nodule different ipsilateral lobe |
N Category (Regional Lymph Nodes)
| N Descriptor | Criteria |
|---|---|
| N0 | No regional nodal metastasis |
| N1 | Ipsilateral peribronchial/hilar nodes |
| N2 | Ipsilateral mediastinal/subcarinal nodes |
| N3 | Contralateral mediastinal/hilar/supraclavicular nodes |
M Category (Distant Metastasis)
| M Descriptor | Criteria |
|---|---|
| M0 | No distant metastasis |
| M1a | Separate tumour nodule in contralateral lobe; pleural/pericardial nodules or malignant effusion |
| M1b | Single extrathoracic metastasis |
| M1c | Multiple extrathoracic metastases (≥1 organ) |
Stage Grouping & 5-Year Survival (SEER 2012–2018, all-comers, pre-modern IO/targeted era)
| Stage | TNM Combination | 5-Yr OS (Historical) | Modern Context |
|---|---|---|---|
| IA1 | T1a N0 M0 | 92 % | Surgery ± adjuvant osimertinib (if EGFR+) |
| IA2 | T1b N0 M0 | 83 % | — |
| IA3 | T1c N0 M0 | 77 % | — |
| IB | T2a N0 M0 | 68 % | Consider adjuvant chemo if high-risk features |
| IIA | T2b N0 M0 | 60 % | Adjuvant chemo ± atezolizumab (PD-L1 ≥1 %) |
| IIB | T1–2a N1 M0 / T3 N0 M0 | 53 % | — |
| IIIA | Heterogeneous (T1–2 N2, T3 N1, T4 N0–1) | 36 % | Multimodal: chemo-IO → surgery or definitive chemoradiation ± durvalumab |
| IIIB | T3–4 N2, T1–2 N3 | 26 % | Definitive chemoradiation ± durvalumab |
| IIIC | T3–4 N3 | 13 % | Definitive chemoradiation ± durvalumab |
| IVA | Any T Any N M1a/b | 10 % | Biomarker-driven systemic therapy ± local consolidative RT |
| IVB | Any T Any N M1c | <5 % | Same as IVA; clinical trial encouraged |
Note:** Survival curves are shifting rapidly with adjuvant immunotherapy (IMpower010, CheckMate 816, KEYNOTE-671) and targeted therapy (ADAURA). Discuss your specific prognosis with your oncology team.
Risk Factors & Prevention
Modifiable Risks (You Can Change)
| Factor | Relative Risk | Actionable Advice |
|---|---|---|
| Cigarette smoking | 15–30× (dose-dependent) | Quit now – risk drops 50 % at 10 yr; never too late. |
| Second-hand smoke | 1.2–1.5× | Smoke-free home/car; advocate workplace bans. |
| Radon exposure | 2nd leading cause (US) | Test home (<4 pCi/L); mitigate if high. |
| Occupational carcinogens (asbestos, silica, diesel, chromium, arsenic) | Varies | PPE, ventilation, occupational health surveillance. |
| Air pollution (PM2.5) | 1.09 per 10 µg/m³ | HEPA filters; limit outdoor exertion on high-AQI days. |
| Diet low in fruits/vegetables | Modest | Mediterranean diet; avoid beta-carotene supplements (↑ risk in smokers). |
Non-Modifiable Risks
- Age (median dx 70 yr), Family history (1.5–2× if 1st-degree relative), Prior chest radiation, Chronic lung disease (COPD, fibrosis), HIV infection.
Screening: Who & How?
| Guideline | Age | Pack-Years | Current/Quit <15 yr | Modality | Interval |
|---|---|---|---|---|---|
| USPSTF 2021 | 50–80 | ≥20 | Yes | Low-dose CT (LDCT) | Annual |
| ACS 2023 | 50–80 | ≥20 | Yes | LDCT | Annual |
| NCCN | ≥50 | ≥20 | Yes (+ other risks) | LDCT | Annual |
Shared Decision-Making** is mandatory before LDCT: discuss false positives (95 % of nodules benign), incidental findings, overdiagnosis, radiation (1.5 mSv/scan).
Signs & Symptoms
Local / Airway Symptoms (Often Early)
- Persistent cough (>3 weeks) or change in chronic “smoker’s cough”
- Haemoptysis (even streaks – never ignore)
- Dyspnoea / wheeze / stridor
- Recurrent pneumonia same lobe (obstructing tumour)
Regional Spread
- Hoarseness (left recurrent laryngeal nerve palsy)
- Superior Vena Cava Syndrome: facial/arm swelling, distended neck veins
- Pancoast Syndrome: shoulder/arm pain, Horner’s triad (ptosis, miosis, anhidrosis)
- Dysphagia (oesophageal compression)
Distant Metastasis (Organ-Specific)
| Site | Symptoms |
|---|---|
| Brain | Headache, seizure, focal weakness, personality change |
| Bone | Pain, pathologic fracture, hypercalcaemia |
| Liver | RUQ pain, weight loss, jaundice (late) |
| Adrenal | Usually asymptomatic; incidental on CT |
Paraneoplastic Syndromes (Remote Effects)
| Syndrome | Mechanism | Key Clue |
|---|---|---|
| SIADH (hyponatraemia) | ADH ectopic production | Euvolaemic hyponatraemia, concentrated urine |
| Cushing’s (ectopic ACTH) | ACTH secretion | Hypokalaemia, metabolic alkalosis, hyperglycaemia |
| Lambert-Eaton (LEMS) | Anti-VGCC antibodies | Proximal weakness improves with exercise, dry mouth |
| Hypertrophic Osteoarthropathy (HOA) | VEGF/PGE2 | Clubbing, periosteal new bone, joint pain |
| Dermatomyositis | Autoimmune | Heliotrope rash, Gottron’s papules, mechanic’s hands |
Red Flag:** Unexplained weight loss >5 % in 6 months + any respiratory symptom → urgent CXR/CT.
Diagnostic Workup
1. Imaging Staging (Standard Baseline)
| Modality | Indication | Key Details |
|---|---|---|
| Contrast-enhanced CT Chest/Abdomen | All new diagnoses | Liver, adrenals, nodes; 5 mm slices |
| PET-CT (FDG) | Stage IB–III (curative intent) & IV (oligometastatic?) | SUVmax >2.5 suspicious; false + in granulomas; false – in AIS/ground-glass |
| Brain MRI (contrast) | Stage II–IV mandatory; Stage IB if high-risk | 10–15 % asymptomatic brain mets at dx; CT misses small mets |
| Bone Scan / PET-CT | If bone pain/alk phos ↑ | PET replaces bone scan in most centres |
2. Tissue Diagnosis – Get Enough for Biomarkers!
| Approach | Yield | Best For | Biomarker Adequacy |
|---|---|---|---|
| CT-guided core biopsy | 90–95 % | Peripheral nodules | Excellent (core > FNA) |
| EBUS-TBNA (Endobronchial US) | 85–90 % | Mediastinal nodes (N2/N3) | Good (multiple passes) |
| Navigational Bronchoscopy / Robotic | 70–80 % | Peripheral, small (<2 cm) | Good |
| Surgical (VATS/Robotic) | 100 % | Indeterminate SPN, need wedge resection | Excellent |
| Liquid Biopsy (ctDNA NGS) | 60–80 % (shedding-dependent) | Inadequate tissue, repeat biopsy | Complementary only – tissue gold standard |
Critical: Request comprehensive NGS panel (DNA + RNA) on all non-squamous & consider in squamous. Minimum: EGFR, ALK, ROS1, BRAF, KRAS, METex14, RET, NTRK, HER2, PD-L1 (TPS). Turnaround 10–14 days – wait for results before starting systemic therapy** whenever clinically feasible.
3. Pathology Report Essentials (Check Your Report)
- [ ] Histologic type + grade
- [ ] PD-L1 TPS (22C3 or SP263 assay) & IC score
- [ ] Molecular results: variant, allele frequency, exon
- [ ] TMB (if reported, mutations/Mb)
- [ ] Sample adequacy statement
Treatment by Stage
Stage I–II (Early, Resectable)
| Step | Standard | Key Trials / Nuances |
|---|---|---|
| Primary | Lobectomy (open/VATS/Robotic) + systematic nodal dissection | Sublobar (segmentectomy) non-inferior for ≤2 cm, GGO ≥50 % (JCOG0802, CALGB 140503) |
| Adjuvant Chemo | Cisplatin-based doublet (vinorelbine/gemcitabine/docetaxel/pemetrexed*) × 4 cycles | Pemetrexed only non-squamous; benefit clear for ≥4 cm or N1; discuss for 3–4 cm |
| Adjuvant Immunotherapy | Atezolizumab (PD-L1 ≥1 %) or Pembrolizumab (PD-L1 ≥1 %) × 1 yr | IMpower010, KEYNOTE-091, CheckMate 816 (neoadjuvant) |
| Adjuvant Targeted | Osimertinib 80 mg daily × 3 yr for EGFR exon 19del/L858R (Stage IB–IIIA) | ADAURA: 88 % vs 52 % 5-yr DFS – new standard |
| Radiation (SBRT) | If medically inoperable | 50–60 Gy / 3–5 fractions; local control >90 % |
Stage III (Locally Advanced, Unresectable or Borderline)
Multidisciplinary Tumour Board Mandatory.
| Scenario | Preferred Approach | Evidence |
|---|---|---|
| Potentially Resectable (IIIA N2 single station) | Neoadjuvant Chemo-IO (nivolumab + chemo × 3 cycles) → Surgery → Adjuvant IO (nivolumab × 1 yr) | CheckMate 816, 77T (pCR 24 % vs 2.2 %); KEYNOTE-671 (pembrolizumab) |
| Unresectable / N2 Multi-station / IIIB–C | Definitive Concurrent Chemoradiation (60–66 Gy / 30–33 fx + cisplatin/etoposide or carboplatin/paclitaxel) → Consolidation Durvalumab 10 mg/kg q2w × 1 yr (start ≤42 d post-RT) | PACIFIC: 4-yr OS 49.6 % vs 36.3 % |
| EGFR-mutant III | Ongoing trials (LAURA: osimertinib post-CRT); current standard = CRT → durvalumab (PD-L1 agnostic) | LAURA PFS benefit presented 2023 |
Stage IV (Metastatic) – Biomarker-First Algorithm
“`mermaid
flowchart TD
A[Stage IV NSCLC] –> B{Driver Mutation?}
B — EGFR ex19del/L858R –> C[Osimertinib 80 mg daily]:::preferred
B — EGFR exon 20 ins –> D[Amivantamab + chemo OR Mobocertinib]:::preferred
B — ALK rearrangement –> E[Lorlatinib OR Alectinib/Brigatinib]:::preferred
B — ROS1 rearrangement –> F[Entrectinib OR Repotrectinib (post-crizotinib)]:::preferred
B — BRAF V600E –> G[Dabrafenib + Trametinib]:::preferred
B — MET exon 14 skip –> H[Capmatinib OR Tepotinib]:::preferred
B — RET fusion –> I[Selpercatinib OR Pralsetinib]:::preferred
B — NTRK fusion –> J[Larotrectinib OR Entrectinib]:::preferred
B — KRAS G12C –> K[Sotorasib OR Adagrasib]:::preferred
B — HER2 mut –> L[Trastuzumab Deruxtecan]:::preferred
B — No Driver / PD-L1 ≥50% –> M[Pembrolizumab mono OR + chemo]:::preferred
B — No Driver / PD-L1 1-49% –> N[Pembro + Chemo]:::preferred
B — No Driver / PD-L1 <1% –> O[Chemo-IO (Pembro/Atezo + Chemo) OR Chemo + Bev + Atezo (non-sq)]:::preferred
classDef preferred fill:#e8f5e9,stroke:#2e7d32,stroke-width:2px;
“`
Test → Wait → Treat.** Starting chemo-IO while waiting for NGS may preclude later targeted therapy (toxicity, efficacy).
First-Line Regimens Cheat-Sheet (No Driver)
| Histology | PD-L1 | Preferred Regimen | Cycles / Duration |
|---|---|---|---|
| Non-Squamous | ≥50 % | Pembrolizumab 200 mg q3w (± pemetrexed/platinum × 4) | IO 2 yr; maintenance pembro + pemetrexed |
| Non-Squamous | 1–49 % | Pembrolizumab + pemetrexed + platinum × 4 → maint pembro + pemetrexed | — |
| Non-Squamous | <1 % | Option A: Pembro + pemetrexed + platinum → maint pembro + pemetrexed<br>Option B: Atezolizumab + bevacizumab + carboplatin + paclitaxel × 4–6 → maint atezo + bev | IMpower150 strong in liver mets |
| Squamous | Any | Pembrolizumab + carboplatin + (nab-)paclitaxel × 4 → maint pembro | KEYNOTE-407 |
| Any (Frailty) | Any | Carboplatin + pemetrexed (non-sq) or Carboplatin + nab-paclitaxel (sq) ± IO | Adjust dose; geriatric assessment |
Maintenance & Subsequent Lines
- Maintenance: Continue immunotherapy ± pemetrexed (non-sq) until progression/toxicity (max 2 yr).
- Progression on Targeted Therapy: Biopsy (tissue/liquid) for resistance mechanism → match next-gen inhibitor (e.g., osimertinib → C797S → clinical trial; MET amp → osimertinib + savolitinib).
- Progression on IO: Docetaxel ± ramucirumab (REVEL); docetaxel + nintedanib (LUME-Lung 1, adeno only); T-DXd for HER2 mut; Amivantamab for EGFR ex20ins post-platinum.
Biomarker-Driven Therapy Deep Dive
| Biomarker | Prevalence (Adeno) | FDA-Approved 1st-Line TKI | Key Resistance Mechanisms | Next-Line Options |
|---|---|---|---|---|
| EGFR ex19del/L858R | 10–15 % (W) / 30–50 % (A) | Osimertinib (FLAURA) | C797S (cis/trans), MET amp, HER2 amp, SCLC transdiff, PIK3CA | Osimertinib + savolitinib (MET), amivantamab + lazertinib, chemo |
| EGFR exon 20 ins | 2–3 % | Amivantamab + chemo (PAPILLON) / Mobocertinib (withdrawn US, avail elsewhere) | — | Amivantamab-based combos, clinical trials |
| ALK rearrangement | 3–5 % | Lorlatinib (CROWN) > Alectinib (ALEX) > Brigatinib (ALTA-1L) | ALK kinase mutations (G1202R, L1196M), ALK amplification | Next-gen ALKi per mutation; lorlatinib covers most |
| ROS1 rearrangement | 1–2 % | Entrectinib (integrated) / Repotrectinib (TRIDENT-1, post-crizotinib) | ROS1 G2032R (solvent front) | Repotrectinib, taletrectinib, clinical trials |
| KRAS G12C | 13 % | Sotorasib (CodeBreaK 200) / Adagrasib (KRYSTAL-1) | KRAS Y96C, KRAS amplification, bypass (MET, EGFR) | Combo with EGFRi (ERBITUX), SHP2 inhibitors, chemo-IO |
| MET exon 14 skip | 3–4 % | Capmatinib (GEOMETRY) / Tepotinib (VISION) | MET D1228, MET amplification | Savolitinib, tepotinib + osimertinib (if EGFR co-mut) |
| RET fusion | 1–2 % | Selpercatinib (LIBRETTO-001) / Pralsetinib (ARROW) | RET solvent front (G810), MET amp | Next-gen RETi (bofutinib), cabozantinib |
| NTRK 1/2/3 fusion | <0.5 % | Larotrectinib / Entrectinib | TRK solvent front | Repotrectinib, taletrectinib |
| HER2 (ERBB2) mutation | 2–4 % | Trastuzumab Deruxtecan (T-DXd) (DESTINY-Lung02) | Heterogeneity, HER2 ECD shedding | T-DXd + tucatinib, clinical trials |
| PD-L1 TPS | Continuous | Pembrolizumab (KEYNOTE-024/042) | Primary (cold TME, STK11/LKB1 loss) or acquired | Chemo-IO, ADCs, clinical trials |
TMB-High (≥10 mut/Mb): Pembrolizumab approved agnostic (KEYNOTE-158), but not standard 1st-line in NSCLC** if driver present.
Side-Effect Management
Targeted Therapy Toxicity Quick Reference
| Drug Class | Common (≥20 %) | Grade 3/4 Watch-List | Monitoring & Mitigation |
|---|---|---|---|
| EGFR TKIs (osimertinib) | Rash, diarrhoea, dry skin, paronychia, ↑LFTs | ILD/pneumonitis (3–4 %), QTc prolongation, cardiomyopathy (LVEF ↓) | Baseline + q3mo LVEF; ECG if risk factors; hold for new respiratory symptoms → CT chest |
| ALK TKIs (lorlatinib) | Hyperlipidaemia (80 % ↑chol/trig), oedema, weight gain, neuropathy, cognitive effects | Severe hyperlipidaemia, AV block, seizures | Fasting lipids baseline + q4–8 wks; statin ready; neurocognitive screen |
| KRAS G12C inhibitors | Diarrhoea, nausea, fatigue, ↑LFTs | Hepatotoxicity (adagrasib > sotorasib), ILD (<2 %) | LFTs q3w × 8 wks then q3mo; hold for ALT/AST >5× ULN |
| MET inhibitors | Oedema (peripheral/periorbital), nausea, hypoalbuminaemia | ILD (2–3 %) | Daily weights; low-salt diet; diuretic if symptomatic |
| RET inhibitors | Hypertension, ↑LFTs, constipation, fatigue | Hypertensive crisis, ILD, QT prolongation (pralsetinib) | Home BP log; weekly BP × 4 wks then q2w; ECG baseline/q3mo |
Immunotherapy (IO) Immune-Related Adverse Events (irAEs)
| Organ | Incidence (Any Grade) | Red-Flag Symptoms | First-Line Management |
|---|---|---|---|
| Thyroid (hypo/hyper) | 5–10 % | Fatigue, cold intolerance, palpitations | TSH q6w; levothyroxine / beta-blocker; continue IO if hypothyroid |
| Pneumonitis | 3–5 % | New dyspnoea, dry cough, fever, O₂ drop | Hold IO; high-dose steroids (pred 1–2 mg/kg); CT chest; pulmonology co-mgmt |
| Colitis | 1–3 % | Bloody diarrhoea, abdominal pain, ≥4 stools/day | Hold IO; budesonide (mild) → pred 1–2 mg/kg (mod/sev); infliximab if steroid-refractory |
| Hepatitis | 5–10 % (↑LFTs) | Asymptomatic usually; jaundice if severe | LFTs q3w; hold IO if AST/ALT >3× ULN (or >5× if baseline elevated); steroids |
| Endocrine (hypophysitis, adrenal insufficiency) | 1–2 % | Headache, visual changes, hypotension, electrolyte chaos | Morning cortisol, ACTH, pituitary MRI; hormone replacement; IO often held |
| Dermatologic | 30–40 % | Rash, pruritus, vitiligo, Stevens-Johnson (rare) | Topical steroids, antihistamines; hold IO if Grade ≥3 |
| Cardiac (myocarditis) | <1 % | Chest pain, troponin ↑, arrhythmia, HF symptoms | EMERGENCY – stop IO, high-dose steroids ± infliximab/IVIG, cardiology ICU |
Patient Rule: Any new symptom = call oncology nurse line. Do not self-medicate steroids. Carry irAE wallet card** listing immunotherapy drug.
Follow-Up & Survivorship
Surveillance Schedule (NCCN / ASCO Consensus)
| Time Post-Curative Intent | History/Exam | Imaging | Labs / Other |
|---|---|---|---|
| 0–2 yr | q3–6 mo | Chest CT q6 mo (contrast if indicated) | CBC, CMP q6 mo; TSH if prior IO |
| 2–5 yr | q6–12 mo | Chest CT annually (low-dose OK) | As clinically indicated |
| >5 yr | Annually | Low-dose CT annually (lung cancer screening protocol) | — |
| Any recurrence symptoms | Immediate | Targeted imaging (PET-CT, brain MRI, bone scan) | — |
Survivorship Priorities
- Smoking cessation – reduces second primary risk, improves QoL.
- Cardiovascular health – anthracycline/radiation legacy; statin, BP control, exercise.
- Bone health – DEXA baseline if steroids/AI; calcium/vit D; denosumab if osteopenia + fracture risk.
- Pulmonary rehab – post-lobectomy/SBRT; improves dyspnoea, exercise capacity.
- Psychosocial – distress screening (NCCN Distress Thermometer); fear of recurrence; financial toxicity navigation.
- Second primary screening – colon, breast, prostate, skin per age guidelines; LDCT annually for life.
Clinical Trials & Emerging Therapies
| Modality | Target / Mechanism | Notable Agents / Trials | Phase / Status |
|---|---|---|---|
| Antibody-Drug Conjugates (ADCs) | TROP2, HER3, CEACAM5, B7-H3 | Datopotamab deruxtecan (TROP2) + osimertinib (TROPION-Lung07); Patritumab deruxtecan (HER3) | Ph3 / Ph2 |
| Bispecific Antibodies | EGFR×MET, EGFR×cMET, PD-1×CTLA-4, PD-1×LAG3 | Amivantamab (EGFR×MET) – approved ex20ins; Ivonescimab (PD-1×VEGF) – China approval; Tebotelimab (PD-1×LAG3) | Approved / Ph3 |
| KRAS Non-G12C | G12D, G12V, G12R, G13D | Mrtx1133 (G12D), RMC-6236 (pan-KRAS) | Ph1/2 |
| Neoantigen Vaccines | Personalised mRNA / peptide | mRNA-4157 (V940) + pembrolizumab (KEYNOTE-942 melanoma; lung cohort enrolling) | Ph2/3 |
| CAR-T / TCR-T | DLL3 (SCLC), MUC1, NY-ESO-1 | Autologous TCR-T for KRAS G12D/V (TCR-NSCLC) | Ph1 |
| Radiopharmaceuticals | SSTR2, FAPI, PSMA | Lu-177-DOTATATE (SSTR2+ NSCLC), Ac-225-FAPI | Ph1/2 |
| Peri-operative IO Combinations | Neoadjuvant chemo-IO ± adjuvant IO ± targeted | CheckMate 77T (nivo+chemo → surg → nivo), KEYNOTE-671, AEGEAN (durva+chemo → surg → durva) | Ph3 positive / regulatory review |
How to Find a Trial: • ClinicalTrials.gov (filter: condition “Non-Small Cell Lung Cancer”, status “Recruiting”, location) • My Cancer Genome (Vanderbilt) – matches mutations to trials • LUNGevity Clinical Trial Finder – patient-friendly interface • Ask your oncologist for molecular tumour board referral.
Questions for Your Care Team (Print & Bring)
Diagnosis & Staging
- [ ] What exact histologic subtype and stage do I have?
- [ ] Has PD-L1 and comprehensive NGS (DNA+RNA) been ordered? When will results return?
- [ ] Was brain MRI performed? If not, why?
- [ ] Is my case discussed at a multidisciplinary tumour board?
Treatment Planning
- [ ] What is the goal of treatment (curative vs. palliative / life-prolonging vs. symptom control)?
- [ ] What are my biomarker-driven options vs. standard chemo-immunotherapy?
- [ ] If targeted therapy: which specific mutation, which drug, expected duration, monitoring plan?
- [ ] If immunotherapy: irAE education plan, wallet card, emergency contact?
- [ ] Clinical trial options – here or referral centre?
- [ ] Financial counselling – drug assistance, travel, time-off-work resources?
During Treatment
- [ ] How will we monitor response (CT schedule, tumour markers, ctDNA)?
- [ ] Dose modification rules for my specific regimen?
- [ ] Supportive care referrals: palliative care, nutrition, physio, psychosocial, integrative oncology?
- [ ] Fertility / sexual health preservation discussion (if applicable)?
Survivorship / Long-Term
- [ ] Surveillance schedule tailored to my stage/treatment?
- [ ] Late-effect screening plan (cardiac, pulmonary, endocrine, second cancers)?
- [ ] Survivorship care plan document for my PCP?
- [ ] Advance care planning / goals-of-care revisited regularly?
Resources & References (Harvard Style)
Clinical Practice Guidelines
- National Comprehensive Cancer Network (2024) NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 3.2024. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (Accessed: 15 May 2024).
- Planchard, D. et al. (2023) ‘Metastatic non-small cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up’, Annals of Oncology, 34(12), pp. 1049–1070. https://doi.org/10.1016/j.annonc.2023.09.014.
- Ettinger, D.S. et al. (2021) ‘NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 1.2022’, Journal of the National Comprehensive Cancer Network, 19(1), pp. 26–37. https://doi.org/10.6004/jnccn.2021.0003.
- Detterbeck, F.C. et al. (2017) ‘The IASLC Lung Cancer Staging Project: Methodology and Validation Used in the Development of Proposals for Revision of the Stage Classification of NSCLC in the Forthcoming (Eighth) Edition of the TNM Classification of Lung Cancer’, Journal of Thoracic Oncology, 12(10), pp. 1433–1446. https://doi.org/10.1016/j.jtho.2017.05.016.
Landmark Clinical Trials (Selection)
- Soria, J.C. et al. (2018) ‘Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer (FLAURA)’, New England Journal of Medicine, 378(2), pp. 113–125. https://doi.org/10.1056/NEJMoa1713137.
- Wu, Y.-L. et al. (2023) ‘Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer (ADAURA)’, New England Journal of Medicine, 389(16), pp. 1473–1485. https://doi.org/10.1056/NEJMoa2304240.
- Antonia, S.J. et al. (2017) ‘Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer (PACIFIC)’, New England Journal of Medicine, 377(20), pp. 1919–1929. https://doi.org/10.1056/NEJMoa1709937.
- Mok, T. et al. (2022) ‘Pembrolizumab versus Chemotherapy for Previously Untreated, PD-L1–Expressing, Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (KEYNOTE-042)’, The Lancet, 393(10183), pp. 1819–1830. https://doi.org/10.1016/S0140-6736(19)30037-8.
- Forde, P.M. et al. (2022) ‘Neoadjuvant Nivolumab plus Chemotherapy in Resectable Non-Small-Cell Lung Cancer (CheckMate 816)’, New England Journal of Medicine, 386(21), pp. 1973–1985. https://doi.org/10.1056/NEJMoa2202170.
- Skoulidis, F. et al. (2021) ‘Sotorasib for Lung Cancers with KRAS p.G12C Mutation (CodeBreaK 100)’, New England Journal of Medicine, 384(25), pp. 2371–2381. https://doi.org/10.1056/NEJMoa2102301.
- Li, B. et al. (2022) ‘Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer (DESTINY-Lung02)’, Nature Medicine, 28, pp. 1154–1162. https://doi.org/10.1038/s41591-022-01786-9.
Screening & Prevention
- USPSTF (2021) ‘Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement’, JAMA, 325(10), pp. 962–970. https://doi.org/10.1001/jama.2021.1117.
- National Lung Screening Trial Research Team (2011) ‘Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening’, New England Journal of Medicine, 365(5), pp. 395–409. https://doi.org/10.1056/NEJMoa1102873.
Biomarkers & Molecular Testing
- Lindeman, N.I. et al. (2018) ‘Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors: Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology’, Journal of Molecular Diagnostics, 20(2), pp. 129–159. https://doi.org/10.1016/j.jmoldx.2017.11.001.
- Rolfo, C. et al. (2021) ‘Liquid Biopsy for Non-Small Cell Lung Cancer: A Perspective from the IASLC’, Journal of Thoracic Oncology, 16(10), pp. 1647–1662. https://doi.org/10.1016/j.jtho.2021.06.014.
Patient-Focused Resources
- LUNGevity Foundation – Patient education, clinical trial finder, support services. https://www.lungevity.org
- GO2 Foundation for Lung Cancer – Helpline, biomarker testing guidance, advocacy. https://go2.org
- American Lung Association – Lung HelpLine, Freedom From Smoking®, screening eligibility quiz. https://www.lung.org
- Cancer.Net (ASCO) – Doctor-approved NSCLC guide, side-effect management, questions to ask. https://www.cancer.net/cancer-types/lung-cancer-non-small-cell
- National Cancer Institute (NCI) – PDQ® Patient & Health Professional versions, trial search. https://www.cancer.gov/types/lung
- My Cancer Genome (Vanderbilt) – Gene-variant–trial matching. https://www.mycancergenome.org
Survivorship & Quality of Life
- Ganz, P.A. (2021) ‘Cancer Survivorship Care: The Lancet Oncology Commission’, The Lancet Oncology, 22(6), pp. e228–e246. https://doi.org/10.1016/S1470-2045(21)00063-1.
- Dutch Lung Cancer Information Centre (2023) ‘Living with Lung Cancer: A Practical Guide’. Available at: https://www.longkanker.nl (Accessed: 15 May 2024).
Disclaimer
This article is for informational purposes only and does not constitute medical advice.
Treatment algorithms evolve rapidly; always discuss your individual case with a qualified multidisciplinary lung cancer team (medical oncologist, radiation oncologist, thoracic surgeon, pulmonologist, pathologist, radiologist, nurse navigator, palliative care).
In case of medical emergency (e.g., sudden shortness of breath, haemoptysis >30 mL, new neurological deficit, fever >38 °C on immunotherapy), call emergency services or present to the nearest emergency department immediately.
Last clinical content review: October 2023. Next scheduled review: April 2024.
Content developed in accordance with HONcode principles for trustworthy health information.