Key takeaways

  • The likelihood of EGFR-positive lung cancer returning is largely tied to how advanced it is when first diagnosed, with lower chances in early stages and higher odds in later stages.
  • Newer targeted therapies have significantly improved outcomes by reducing recurrence risk and extending the length of time people live without the disease coming back.
  • While recurrence is a serious concern, the availability of effective targeted treatments means many people can still achieve meaningful survival and maintain a good quality of life.

Lung cancer is broadly categorized into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC includes several subtypes, most commonly adenocarcinoma and squamous cell carcinoma. EGFR-positive lung cancer is a subtype of NSCLC that occurs almost overwhelmingly in adenocarcinoma and rarely in squamous cell carcinoma.

Recurrence rates for any lung cancer depends heavily on the stage at diagnosis and the treatment that’s given. In EGFR-positive lung cancer, recurrence risk follows the same pattern seen across overall NSCLC: It tends to be lower in early-stage disease and higher in more advanced stages.

Estimates suggest the risk of recurrence may be around 15% in early-stage EGFR-positive lung cancer and up to 93% in advanced-stage disease. By comparison, in NSCLC overall, early-stage recurrence rates estimated to be around 29% and rise to nearly 57% in more advanced stages.

That said, outcomes for EGFR-positive lung cancer have improved significantly in recent years. Adjuvant targeted therapy has helped lower the recurrence risk for many people with EGFR-positive lung cancer.

Recurrence of EGFR-positive lung cancer usually happens within the first 2 years after curative surgery.

However, the overall recurrence risk of any lung cancer is mostly dependent on the stage at diagnosis, and EGFR-positive lung cancer is no different. The overall recurrence rate of EGFR-positive lung cancer is around 40% when all stages are lumped together. In early stages, the recurrence rate can be as low as 15%, but as it becomes more advanced, there can be nearly a 93% chance of recurrence.

Adjuvant therapies, such as osimertinib (Tagrisso), have decreased the chances of recurrence over a 4-year period. For example, one trial showed that those receiving adjuvant osimertinib had a 70% chance of no disease recurrence at the 4-year mark, compared to only a 29% chance for the placebo group.

Generally, treatment for early-stage EGFR-positive lung cancer involves surgical resection, and then adjuvant osimertinib is recommended for up to 3 years. If the disease is more advanced, then chemotherapy plus radiation are used to treat the cancer instead of surgery, and the duration of adjuvant osimertinib continues until there is recurrence of the disease.

Recurrence risk in NSCLC, including EGFR-positive lung cancer, is most strongly influenced by staging, pathologic (tumor) features at the time of resection, and certain molecular features.

Tumor features linked with a higher recurrence risk include:

  • more advanced the pathologic stage
  • lymph node involvement
  • larger tumor size
  • lymphatic invasion (cancer cells are seen in lymphatic or blood vessels)
  • pleural invasion (tumor involvement in the pleura)
  • high-risk histology patterns, such as micropapillary features

Molecular features linked with a higher risk of recurrence include:

  • TP53 mutation
  • non-terminal respiratory unit (non-TRU) RNA subtype
  • certain EGFR mutation patterns (for example, EGFR exon 19 deletion mutation compared to exon 21 L858R mutation)

How often you should schedule check-ups depends on your stage at diagnosis, your treatment, and how recently treatment ended. In general, follow-up visits may be recommended:

  • every 6 months after surgery for early-stage lung cancer
  • every 3 months if the cancer is more advanced or you’re receiving ongoing treatment

There are two ways recurrence may be detected, either by surveillance scans done by your doctor or through certain symptoms:

  • local (respiratory) symptoms such as new or worsening cough, wheezing, chest discomfort, blood in sputum
  • distant (spread to other areas) symptoms such as fatigue, weight loss, loss of appetite, bone pain, headaches, back pain, jaundice (yellowing of the skin or eyes)

If you experience any of these symptoms, be sure to tell your oncology team.

First line treatment for EGFR-positive lung cancer is usually osimertinib by itself or combined with chemotherapy.

If osimertinib has already been used, then your doctor may consider amivantamab (Rybrevant) plus lazertinib (Lazcluze).

You’ll work with your oncology team to determine the best approach for you.

People with EGFR-positive lung cancer generally have a better long-term outlook than those who have lung cancer without an EGFR mutation. After recurrence, long-term survival is approximately 33 to 49 months when treated with a targeted therapy.

While recurrence is serious, the availability of elective targeted treatments means that many people can still achieve meaningful survival while maintaining quality of life.

The risk of recurrence in EGFR-positive lung cancer is largely determined by the features of the cancer itself, including tumor size, staging, and molecular features.

However, choosing adjuvant treatment with osimertinib after surgery significantly reduces the risk of recurrence compared to opting for post-surgical surveillance. You and your doctor can work together to make a plan for next steps after surgery, taking into account your overall health, tolerance for side effects, and personal preferences.

Even though recurrence can’t be completely prevented, targeted adjuvant therapy helps improve your chances of staying recurrence-free for longer.

Sheel Patel, MD, is an ABMS board certified physician in hematology, oncology, and internal medicine. Dr. Patel is a practicing physician at the Orlando VA Medical Center in Florida.