Non-Small Cell Lung Cancer Recurrent

Recurrent non-small cell lung cancer means the cancer has returned after treatment. Even after successful treatment that achieves remission, between 30% and 55% of patients develop recurrence, though modern treatments offer hope and new options for managing the disease when it returns.

Table of contents

• What Is Recurrent Non-Small Cell Lung Cancer?
• Why Does Cancer Come Back After Treatment?
• When and Where Cancer Returns
• How Likely Is Recurrence?
• Treatment Options for Recurrent Cancer
• The Importance of Follow-Up Care

What Is Recurrent Non-Small Cell Lung Cancer?

Recurrent non-small cell lung cancer means that the cancer has come back after it has been treated^[1]. When cancer goes into remission (a state where there are no detectable signs of cancer), it’s certainly a cause for celebration. However, remission is not the same as a cure. Cancer cells in the body can remain inactive and undetectable for months or years before growing again^[2].

Lung cancer recurrence happens when your cancer returns after you’ve been in remission for at least one year^[3]. While some patients never experience a recurrence of lung cancer, others may see the cancer return after several months or even several years. The type and stage of lung cancer when first diagnosed are important factors that influence the likelihood of the cancer coming back^[4].

Why Does Cancer Come Back After Treatment?

Even when doctors achieve what appears to be complete removal of cancer during treatment, recurrence can still happen. The reasons are complex. Right from the start, there are often hidden cancer cells that cannot be detected by standard methods such as modern diagnostic imaging. These occult micro-metastatic cancer cells (tiny cancer cells spread throughout the body) may already be present at the time of surgery, suggesting an underestimation of the true tumor stage^[5].

Another possibility is that handling the tumor during surgery itself might lead to the spread of cancer cells. Some studies have found evidence of disseminated tumor cells (cancer cells that have spread from the original tumor) or circulating tumor cells (cancer cells moving through the bloodstream) in patients, which may contribute to later recurrence^[6].

When and Where Cancer Returns

If non-small cell lung cancer recurs, it usually happens within five years after the initial treatments^[7]. Most recurrences occur within the first two to three years, though some patients may experience a return of cancer even later.

Lung cancer can recur in three primary ways, depending on where the cancer returns^[8]:

• Local recurrence is when cancer returns to the lung close to where it was initially found
• Regional recurrence happens when cancer grows in the lymph nodes near the initial site
• Distant recurrence occurs when lung cancer is found in a new site far from where it was initially located, such as in the brain, bones, liver, or adrenal glands^[9]

How Likely Is Recurrence?

Despite curative treatment, between 30% and 55% of patients with non-small cell lung cancer develop recurrence and die of their disease^[10]. The likelihood of recurrence depends heavily on the stage of cancer at initial diagnosis.

The stage of non-small cell lung cancer at diagnosis significantly impacts the likelihood that it will recur^[11]:

• Stage I: Recurrences occur in 5% to 19% of patients
• Stage II: Recurrence rates range from 11% to 27%
• Stage III: Recurrences occur in 24% to 40% of patients

Patients who received a diagnosis of non-small cell lung cancer are generally less likely to experience recurrence than those with small cell lung cancer, which is a more aggressive form of the disease^[12].

Treatment Options for Recurrent Cancer

The following are treatment options for recurrent non-small cell lung cancer. Your healthcare team will suggest treatments based on your needs and work with you to develop a treatment plan. Treatment decisions are based on where the cancer has come back, what treatments have already been given, any side effects you have from previous treatment, whether the cancer has certain gene changes, and your overall health^[13].

Chemotherapy

Chemotherapy (treatment using drugs that kill cancer cells) may be used to treat recurrent non-small cell lung cancer if you are well enough to have it. It is the treatment offered if there are no genetic changes that can be identified in the lung cancer tumors^[14].

If chemotherapy was not previously used as a treatment, combination chemotherapy may be used. The most common chemotherapy drug combination used to treat recurrent non-small cell lung cancer is cisplatin or carboplatin with gemcitabine. Other combinations may include cisplatin or carboplatin with docetaxel, carboplatin and paclitaxel, gemcitabine and docetaxel, gemcitabine and vinorelbine, or cisplatin and pemetrexed for adenocarcinoma types of non-small cell lung cancer^[15].

Single drugs may be offered if you are in poor health. A single chemotherapy drug may also be offered if cisplatin can’t be used anymore because of side effects. The drugs that may be used include gemcitabine, paclitaxel, or docetaxel^[16].

Targeted Therapy

Targeted therapy (treatment that targets specific genes or proteins in cancer cells) is usually offered for non-small cell lung cancer that has come back after treatment. The type of targeted therapy given will depend on the type of genetic change found during diagnosis^[17].

For cancers with EGFR mutations (changes in a gene called epidermal growth factor receptor), drugs like erlotinib may be used after other chemotherapy has been tried. Erlotinib may be used whether the cancer is EGFR positive or not. Other drugs like gefitinib or afatinib may be used for EGFR-positive non-small cell lung cancer if targeted therapy has not been used before. Osimertinib may be offered for recurrent EGFR-positive non-small cell lung cancer that has developed a mutation to the T790M gene^[18].

Radiation Therapy and Surgery

Locoregional relapse (cancer that returns near the original site) can be treated the same way as initial lung cancer, including surgery, radiotherapy (treatment using high-energy rays to kill cancer cells), and chemotherapy, or combined treatment. Approximately 1% to 2% of all recurrent lung cancer is treated with curative reoperation. External beam radiation therapy has been particularly effective in isolated cases where cancer returns at the surgical site^[19].

The Importance of Follow-Up Care

It’s critical that you keep follow-up appointments with your cancer specialist. These will be every few months shortly after you’ve gone into remission. As time goes and based on your health, follow-up appointments may be spread further apart^[20].

During the first two years after remission, your doctor will typically order a chest CT scan every six months, but this could be every three months depending on your case. After two years, a low-dose CT scan once a year, sometimes twice, is common. Ongoing blood work can help watch for tumor markers that could indicate that cancer cells are starting to grow again^[21].

These occasional appointments are a good time for cancer survivors to ask questions and talk about anything that seems abnormal. Symptoms and changes you experience may or may not be related to cancer coming back. They could be signs of another health condition that you’ll want to catch early, or they could be related to lung cancer. Note that new side effects from cancer treatment can appear weeks, months, or even years after treatment is complete^[22].