Pulmonary · PANCE / PANRE

Lung Cancer (Small Cell and Non-Small Cell)

Written & clinically reviewed by Ryan Busch, PA-C · Updated August 2026 · Report an error

Leading cause of cancer death — NSCLC (~85%) and SCLC (~15%) with distinct biology and treatment.

Also known as: lung cancer, NSCLC, SCLC, adenocarcinoma, squamous cell carcinoma, small cell lung cancer

Overview

Malignancy arising from bronchial epithelium or alveolar cells. Two principal categories: non-small cell lung cancer (NSCLC — adenocarcinoma, squamous cell, large cell) and small cell lung cancer (SCLC — neuroendocrine, aggressive). Modern therapy is driven by histology, molecular markers, and PD-L1 status.

Epidemiology

Leading cause of cancer death in the US (~125,000 deaths/year). 5-year overall survival ~25% (improving with screening and targeted therapy). Median age at diagnosis ~70. Adenocarcinoma is most common subtype, including in never-smokers.

Try two board-style Lung Cancer questions

Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.

Question 1PulmonaryEasy
A 65-year-old man who currently smokes and has a 30-pack-year history presents to establish primary care and asks about lung cancer screening. He is asymptomatic, and his physical examination is normal. Which of the following is the most appropriate screening test?
  • AAnnual sputum cytology
  • BAnnual chest radiography
  • CPET scan every 2 years
  • DAnnual low-dose CT chest
Reveal answer & full explanation
Correct answer: D — Annual low-dose CT chest
  • AAnnual sputum cytology
  • BAnnual chest radiography
  • CPET scan every 2 years
  • DAnnual low-dose CT chest✓

Why Annual low-dose CT chest is correct

  • Per current USPSTF guidance, annual low-dose CT (LDCT) is recommended for adults aged 50–80 years with a ≥20 pack-year history who currently smoke or quit within the past 15 years.
  • This 65-year-old current smoker with a 30 pack-year history meets every eligibility criterion.
  • LDCT is the only modality shown to reduce lung cancer mortality (by roughly 20%) in a screening population (National Lung Screening Trial).

Why the others are wrong

  • Annual sputum cytology — Poor sensitivity, especially for peripheral tumors, and not a recommended screening test; a buzzword-matching trap for anyone who equates 'lung cancer' with sampling secretions.
  • Annual chest radiography — The PLCO trial showed chest radiography does not reduce lung cancer mortality, so it is not used for screening; the premature-closure choice based on an abandoned practice.
  • PET scan every 2 years — PET characterizes and stages known or indeterminate nodules rather than screening asymptomatic patients, and carries radiation and false-positive costs; a right-tool-wrong-setting trap.
Question 2PulmonaryMedium
A 68-year-old man with unresectable stage III squamous cell non-small cell lung cancer has just completed concurrent chemoradiotherapy with no evidence of disease progression on restaging. His Eastern Cooperative Oncology Group performance status is 1, and tumor PD-L1 expression is 40%. Which of the following is the most appropriate next step in management?
  • AProphylactic cranial irradiation
  • BDurvalumab consolidation for 12 months
  • CPlatinum-based chemotherapy consolidation
  • DObservation with serial imaging
Reveal answer & full explanation
Correct answer: B — Durvalumab consolidation for 12 months
  • AProphylactic cranial irradiation
  • BDurvalumab consolidation for 12 months✓
  • CPlatinum-based chemotherapy consolidation
  • DObservation with serial imaging

Why durvalumab consolidation for 12 months is correct

  • For unresectable stage III non-small cell lung cancer that has not progressed after concurrent chemoradiotherapy, consolidation with the anti-PD-L1 antibody durvalumab for up to 12 months is the standard of care, established by the PACIFIC trial.
  • Durvalumab improves both progression-free and overall survival compared with observation and is recommended regardless of PD-L1 level.
  • Consolidation should begin promptly (within about 6 weeks) after completion of chemoradiotherapy.
  • The patient's good performance status (ECOG 1) and absence of progression make him an appropriate candidate.

Why the others are wrong

  • Prophylactic cranial irradiation — Cranial irradiation lowers the rate of brain metastases in stage III non-small cell lung cancer but confers no survival benefit and is not standard after chemoradiotherapy; it belongs to limited-stage small cell disease (confused-with small cell).
  • Platinum-based chemotherapy consolidation — Additional consolidation chemotherapy after definitive chemoradiotherapy has not shown a survival benefit and is not standard (right-disease-wrong-step).
  • Observation with serial imaging — Forgoing durvalumab withholds a proven survival advantage and is inferior to consolidation immunotherapy (premature closure on watchful waiting).
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Risk factors

  • Tobacco smoking (causes ~85% of cases; quantified in pack-years)
  • Secondhand smoke
  • Radon exposure (second leading cause overall)
  • Asbestos (synergistic with smoking)
  • Occupational: arsenic, chromium, nickel, silica, diesel exhaust
  • Air pollution, prior radiation therapy, HIV
  • Family history, COPD, pulmonary fibrosis

Pathophysiology

Carcinogen-induced DNA damage accumulates in bronchial/alveolar epithelium → driver mutations (EGFR, KRAS, ALK, ROS1, BRAF, MET, RET, NTRK, HER2) in adenocarcinoma; TP53 and RB inactivation typical in SCLC. Tumor growth, local invasion, lymphatic and hematogenous spread (brain, bone, liver, adrenals).

Clinical presentation

Symptoms

  • Persistent cough, change in chronic cough quality
  • Hemoptysis (any unexplained hemoptysis in smoker >40 warrants imaging)
  • Dyspnea, chest pain (pleuritic if pleural involvement)
  • Constitutional: weight loss, anorexia, fatigue
  • Hoarseness (recurrent laryngeal nerve)
  • Symptoms of metastases: bone pain, focal neurologic deficits, headaches, seizures

Signs / physical exam

  • Fixed monophonic wheeze (endobronchial obstruction)
  • Clubbing, supraclavicular lymphadenopathy
  • Horner syndrome (ptosis, miosis, anhidrosis) and brachial plexopathy — Pancoast (superior sulcus) tumor
  • Superior vena cava syndrome — facial swelling, distended neck and chest veins, plethora (more common in SCLC)
  • Paraneoplastic findings: SIADH (SCLC), Cushing (SCLC), Lambert-Eaton myasthenic syndrome (SCLC), hypercalcemia (squamous), HPOA

Classic findings

Pancoast tumor: shoulder pain + Horner syndrome + arm weakness. SVC syndrome with right upper lobe mass. Hypercalcemia in squamous cell. SIADH or Cushing in SCLC.

Differential diagnosis

  • Pneumonia / lung abscess — Acute febrile course; resolves with antibiotics; non-resolving consolidation should prompt repeat imaging
  • Tuberculosis — Cavitary disease, hemoptysis, weight loss; positive AFB/IGRA
  • Granulomatous disease (sarcoid, histo, cocci) — Bilateral hilar adenopathy + parenchymal nodules; serology and biopsy
  • Pulmonary metastases from other primary — Multiple bilateral nodules with feeding vessel; primary malignancy history; cannonball mets
  • Hamartoma (benign) — Smooth, well-circumscribed, popcorn calcification, low growth rate
  • Carcinoid tumor — Endobronchial mass with recurrent infections; can secrete serotonin (carcinoid syndrome)
  • Lymphoma — Mediastinal mass, B symptoms, lymphadenopathy elsewhere; biopsy

Diagnostic workup

Diagnostic criteria

Definitive diagnosis requires tissue (histology + molecular and immunohistochemistry). TNM staging (8th edition) for NSCLC; SCLC traditionally classified as limited stage (confined to one hemithorax/single radiation port) vs extensive.

Labs

  • CBC, CMP (including calcium), LDH
  • Coagulation studies if procedures planned

Imaging

  • Chest CT with contrast — characterize mass, mediastinal nodes, pleural disease
  • PET-CT — staging (FDG avidity, distant metastases)
  • MRI brain — staging for stage II-IV NSCLC and all SCLC (high incidence of brain mets)
  • Bone scan if PET not available

Other studies

  • Tissue diagnosis: bronchoscopy with biopsy/EBUS, CT-guided percutaneous biopsy, mediastinoscopy, VATS
  • Molecular testing on NSCLC adenocarcinoma: EGFR, ALK, ROS1, BRAF V600E, KRAS G12C, MET exon 14, RET, NTRK, HER2 + PD-L1 IHC
  • Pulmonary function tests, cardiopulmonary assessment for surgical candidates
  • Screening: USPSTF 2021 — annual low-dose CT for ages 50-80 with ≥20 pack-year history who currently smoke or quit within 15 years

Diagnostic algorithm

Subtype% of CasesLocationDistinctive Features
Adenocarcinoma (NSCLC)~40%PeripheralMost common in never-smokers; driver mutations (EGFR, ALK, ROS1); requires molecular testing
Squamous cell (NSCLC)~25-30%CentralCavitation; hypercalcemia via PTHrP; smoking-associated
Large cell (NSCLC)~5%PeripheralPoor differentiation; aggressive
Small cell (SCLC)~15%CentralRapid growth, early mets; paraneoplastic SIADH, Cushing, LEMS; staged as limited/extensive
Lung cancer histologic subtypes — clinical and biologic distinctions.

Treatment

First-line

  • NSCLC Stage I-II (early): surgical resection (lobectomy preferred, VATS) + mediastinal nodal sampling; SBRT for non-surgical candidates
  • NSCLC Stage III: concurrent chemoradiation (cisplatin/carboplatin + etoposide/pemetrexed/paclitaxel + radiation), followed by consolidation durvalumab (PACIFIC trial)
  • NSCLC Stage IV (metastatic), no driver mutation: immunotherapy ± chemotherapy — pembrolizumab monotherapy if PD-L1 ≥50%; pembrolizumab + carboplatin/pemetrexed (nonsquamous) or carboplatin/paclitaxel (squamous) otherwise (KEYNOTE-189, -407)
  • NSCLC driver-positive: targeted therapy — osimertinib (EGFR), alectinib/lorlatinib (ALK), crizotinib/entrectinib (ROS1), dabrafenib+trametinib (BRAF V600E), sotorasib/adagrasib (KRAS G12C), capmatinib (METex14)
  • SCLC limited stage: concurrent chemoradiation (cisplatin/carboplatin + etoposide) + prophylactic cranial irradiation if response
  • SCLC extensive stage: platinum + etoposide + atezolizumab or durvalumab (IMpower133, CASPIAN)
  • Smoking cessation at any stage

Second-line / adjunct

  • NSCLC second-line: docetaxel ± ramucirumab; nivolumab/pembrolizumab if not previously used; targeted therapy switch for acquired resistance (e.g., osimertinib for EGFR T790M)
  • SCLC second-line: lurbinectedin or topotecan
  • Palliative: external beam radiation for symptomatic bone metastases, SVC syndrome, brain mets (whole-brain or stereotactic)
  • SVC syndrome management: head elevation, steroids, diuretics, radiation, endovascular stent
  • Malignant pleural effusion: indwelling tunneled catheter or pleurodesis
  • Pain control, palliative care integration early (Temel NEJM 2010)

Complications

  • Metastases to brain, bone, liver, adrenal
  • SVC syndrome, malignant pleural effusion, pericardial effusion/tamponade
  • Post-obstructive pneumonia
  • Paraneoplastic syndromes: SIADH, Cushing, Lambert-Eaton, HPOA, hypercalcemia (PTHrP), digital clubbing
  • Treatment toxicities: pneumonitis (radiation, immune checkpoint inhibitors), neutropenia, neuropathy

PANCE pearls

  • USPSTF 2021 expanded LDCT screening to 50-80 years with ≥20 pack-years, current or quit within 15 — broader than prior 2013 criteria.
  • Pancoast (superior sulcus) tumor: shoulder/arm pain + Horner syndrome + T1 nerve root involvement — usually NSCLC.
  • Squamous cell — hypercalcemia from PTHrP, central location. Adenocarcinoma — peripheral location, most common in never-smokers, drives molecular testing.
  • SCLC — central, paraneoplastic SIADH/Cushing/LEMS, rapidly progressive; stage as limited vs extensive (not TNM in everyday practice).
  • Always send NSCLC adenocarcinoma for molecular markers AND PD-L1 — drives first-line therapy choice.

References

  • USPSTF 2021 — Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement (USPSTF, JAMA 2021)
  • NLST — Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening (NLST Research Team, NEJM 2011)
  • PACIFIC — Durvalumab after Chemoradiotherapy in Stage III NSCLC (Antonia et al., NEJM 2017)
  • KEYNOTE-189 — Pembrolizumab + Pemetrexed-Platinum for Metastatic Nonsquamous NSCLC (Gandhi et al., NEJM 2018)
  • IMpower133 — First-Line Atezolizumab + Chemotherapy in Extensive-Stage SCLC (Horn et al., NEJM 2018)

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Related Pulmonary diagnoses

AsthmaChronic Obstructive Pulmonary Disease (COPD)Community-Acquired Pneumonia (CAP)Hospital-Acquired and Ventilator-Associated Pneumonia (HAP/VAP)Aspiration Pneumonia and PneumonitisTuberculosis (Active and Latent)Pulmonary Embolism (PE)Pulmonary HypertensionPneumothorax (Spontaneous and Tension)Pleural EffusionAcute Respiratory Distress Syndrome (ARDS)BronchiectasisCystic FibrosisSarcoidosis

Differentials & related conditions

Carcinoid Syndrome

Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.