Why everyone is talking about it
On October 13, 2026, the Vatican announced that Pope Leo XIV had undergone a minimally invasive (video-assisted) operation in Rome to remove the lower lobe of his right lung for a nodule. The pathology confirmed a lung adenocarcinoma.1 He is reported never to have smoked.2 No details of stage or molecular testing have been released, and I have no involvement in his care, so I won’t comment on his individual situation. His story does reflect something I see more and more in my own practice: lung cancer in people who never smoked.
Lung cancer in never-smokers is not rare
Smoking still causes most lung cancer, but about 1 in 4 lung cancers worldwide is not attributable to tobacco.3 These cancers are more common in women and in people of East Asian background. They behave so differently from smoking-related cancers that researchers describe them as almost a separate disease.3 Other risk factors include radon, second-hand smoke, air pollution, occupational exposures and family history. I cover these in What causes lung cancer?
Adenocarcinoma and EGFR: the connection
Almost all lung cancers in never-smokers are adenocarcinomas, the type that starts in the mucus-producing glands of the lung. This is the type the Pope was diagnosed with. What makes these tumours different is what drives them. Smoking-related cancers carry hundreds of mutations caused by tobacco damage. Never-smoker adenocarcinomas are usually driven by one key genetic switch stuck in the “on” position.
In a large genomic study, 78–92% of never-smoker lung adenocarcinomas had a driver alteration that could be targeted with treatment, compared with about half of adenocarcinomas in smokers.4 The most common is a mutation in the EGFR (epidermal growth factor receptor) gene. In a French national program that tested more than 17,000 patients, most of whom had smoked, EGFR mutations were found in 11%.5 In an Asian study of advanced adenocarcinoma, where about half the patients had never smoked, EGFR mutations were found in 51%, and they were more common still in never-smokers.6
The driver mutations, and how often each is found
Every patient with lung adenocarcinoma should have their tumour tested for these drivers, because the result can change treatment completely. These are the main ones:
| Driver | How often (non-small cell lung cancer) | Who it tends to affect | Examples of targeted drugs |
|---|---|---|---|
| EGFR | ~11% in Western patients; ~50% in Asian patients with adenocarcinoma5,6 | Never-smokers, women, East Asian background | Osimertinib |
| ALK | ~5%5 | Younger patients, never-smokers | Alectinib, lorlatinib |
| KRAS | ~29% (G12C is one subtype)5 | Mostly current or former smokers | Sotorasib, adagrasib (G12C) |
| MET exon 14 | ~3%8 | Often older patients | Capmatinib, tepotinib |
| BRAF V600E | ~2%5 | Smokers and never-smokers | Dabrafenib plus trametinib |
| ROS1 | ~1–2%8 | Younger never-smokers | Crizotinib, entrectinib |
| RET | ~1–2%8 | Younger never-smokers | Selpercatinib |
| HER2 | ~1%5 | Never-smokers, women | Trastuzumab deruxtecan |
| NTRK | <1%8 | Rare, any age | Larotrectinib, entrectinib |
Frequencies are approximate and vary with ethnicity and smoking history. Drug availability and funding in Ontario depend on the indication.
Why EGFR and ALK cancers can spread to the brain
One feature I discuss with every patient who has an EGFR or ALK cancer is the brain. In one study, about 1 in 4 patients with advanced EGFR- or ALK-driven lung cancer already had brain metastases when they were diagnosed. For those living with advanced EGFR cancer, the proportion rose to about half by five years.7 That is why a brain MRI is part of staging, and why it matters that the newer targeted drugs are designed to reach the brain.
Targeted therapy: osimertinib and others
Targeted drugs are tablets that switch off the specific driver. Osimertinib is the one I use most often for EGFR-mutated cancer.
- Advanced disease: in the FLAURA trial, osimertinib kept cancer controlled for a median of 18.9 months vs 10.2 months with older EGFR drugs,9 and patients lived longer (median 38.6 vs 31.8 months).10
- After surgery: for patients whose EGFR-mutated cancer has been removed (stage IB–IIIA), adding osimertinib after the operation reduced the risk of death by about half in the ADAURA trial.11
- ALK: alectinib controlled ALK-positive cancer for longer than the older drug crizotinib, with 68% vs 49% of patients free of progression at one year,12 and it works well in the brain.
This is why testing matters even in early-stage cancer that I remove surgically: the result can decide whether a patient benefits from a targeted drug afterwards. You can see where each treatment fits in Lung cancer treatment by stage.
Where surgery fits
When a never-smoker’s lung cancer is found early, as a small nodule, surgery remains the treatment that offers the best chance of cure. In most patients I do this by keyhole (VATS) or robotic (RATS) lobectomy, the same kind of operation reported for the Pope. The tumour and its lymph nodes are then tested for driver mutations, which guides any further treatment.
One challenge is that Ontario’s lung screening program is aimed at people with a significant smoking history, so many never-smokers are found only when they develop symptoms or when a nodule shows up on a scan done for another reason. Read more in Lung cancer screening in Ontario.
Have a lung nodule or a new diagnosis? Read about lung cancer surgery or see the referral information.
Common questions
Can you get lung cancer if you never smoked?
What is an EGFR mutation in lung cancer?
What is the difference between EGFR and ALK lung cancer?
Does EGFR lung cancer spread to the brain?
What type of lung cancer did Pope Leo have?
References
- CBS News. Pope Leo recovering “as expected” after surgery and lung cancer diagnosis, Vatican says. October 14, 2026.
- Fox News. Pope’s diagnosis shines light on surprising lung cancer risks for never-smokers. October 2026.
- Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers — a different disease. Nat Rev Cancer. 2007;7:778–790.
- Devarakonda S, Li Y, Martins Rodrigues F, et al. Genomic profiling of lung adenocarcinoma in never-smokers. J Clin Oncol. 2021;39:3747–3758.
- Barlesi F, Mazieres J, Merlio JP, et al. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet. 2016;387:1415–1426.
- Shi Y, Au JS, Thongprasert S, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol. 2014;9:154–162.
- Rangachari D, Yamaguchi N, VanderLaan PA, et al. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung Cancer. 2015;88:108–111.
- Tan AC, Tan DSW. Targeted therapies for lung cancer patients with oncogenic driver molecular alterations. J Clin Oncol. 2022;40:611–625.
- Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378:113–125.
- Ramalingam SS, Vansteenkiste J, Planchard D, et al. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020;382:41–50.
- Tsuboi M, Herbst RS, John T, et al. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389:137–147.
- Peters S, Camidge DR, Shaw AT, et al. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017;377:829–838.