As part of Oncofeed, we continue our review of important aspects of lung cancer. In the previous article, we focused on the relationship between tobacco use and lung cancer based on real-world data from Georgia. However, modern oncology has highlighted another important fact about lung cancer: the same diagnosis does not always mean the same disease.
Today, we know that two patients may have the same histological diagnosis of lung cancer and a similar disease stage, yet have completely different tumor biology – and therefore completely different treatment needs. This is why, particularly in non-small cell lung cancer (NSCLC), histological diagnosis alone is often no longer sufficient. The molecular profile of the tumor plays an increasingly important role in treatment selection.
One Diagnosis – Different Biology
Lung cancer treatment has undergone a radical transformation over the past two decades. In the past, particularly during the 1990s, systemic treatment of advanced NSCLC was based mainly on chemotherapy, and different molecular subtypes often did not significantly influence treatment selection.
The subsequent discovery of epidermal growth factor receptor (EGFR) mutations and EGFR inhibitors, followed by the recognition of the clinical significance of anaplastic lymphoma kinase (ALK), ROS1, BRAF, MET, RET, NTRK, and other molecular alterations, made lung cancer one of the clearest examples of how personalized medicine can transform the treatment paradigm.
If one patient has an activating EGFR mutation, while another has an ALK rearrangement, both may have lung adenocarcinoma, but their optimal systemic treatments may be completely different. Therefore, in modern oncology, the question is no longer simply: “What is the patient’s diagnosis?”, but rather: “What molecular characteristics does their specific tumor have?”
“Smart Drugs” – When Treatment Targets a Specific Molecular Alteration
Targeted therapies are often referred to by the public as “smart drugs.” This is, of course, not a scientific term, but it describes the concept quite well.
Unlike traditional cytotoxic chemotherapy, targeted drugs are directed against specific molecular alterations or signaling pathways. For example, when tumor growth is driven by a specific driver alteration, the corresponding drug is designed to block that particular mechanism.
In many cases, these treatments are administered orally as daily tablets, which can also change the practical experience of treatment for patients – with fewer hospital visits for infusions and the possibility of continuing part of the treatment at home.
There is also another, less visible but important benefit – the psychological aspect. Being able to receive treatment at home can reduce the stress associated with frequent hospital visits, while allowing patients to maintain greater independence and a sense of control in their daily lives. Cancer treatment can itself disrupt a patient’s normal routine; therefore, when an appropriate targeted therapy can be taken at home, treatment may become less disruptive and psychologically easier to integrate into everyday life.
This raises the key question: how do we determine whether a particular patient needs a specific targeted drug?
The answer is simple – through molecular testing.
Today, molecular testing should no longer be viewed as merely an additional laboratory investigation. Identification of the appropriate biomarker can directly influence the choice of first-line treatment.
In NSCLC, the testing panel may include clinically important alterations such as EGFR, ALK, ROS1, BRAF, MET, RET, NTRK, KRAS, and HER2, while PD-L1 expression is particularly important when planning immunotherapy.
Current recommendations support broad, multigene molecular profiling. The 2026 American Society of Clinical Oncology (ASCO) guidelines recommend that broad tissue- and/or blood-based multigene panels be accessible for patients with NSCLC, together with assessment of PD-L1 and, where appropriate, HER2/MET by immunohistochemistry (IHC). Comprehensive next-generation sequencing (NGS), including RNA-based approaches, is preferred, particularly for better detection of gene rearrangements.
This is important because testing a single gene individually may miss other clinically relevant molecular alterations.
What Do We See in Georgia?
This is where international recommendations become particularly interesting when considered alongside real-world data from Georgia.
In our study, “Clinicopathological and molecular profile of lung cancer: real-world data from Georgia,” the clinical, pathological, and molecular characteristics of 270 patients diagnosed at the Caucasus Medical Centre between 2023 and 2025 were analyzed. The study showed that 83% of patients had NSCLC, including 52% with adenocarcinoma and 38% with squamous cell carcinoma.
One of the most interesting findings of our study concerned the molecular data.
Although molecular testing was not performed in all patients, clinically relevant biomarkers were identified at a considerable frequency among those who were tested:
- EGFR mutation – 15.6%
- ALK rearrangement -10%
- PD-L1 ≥50% – 28%
Importantly, only 64 patients were tested for EGFR, 59 for ALK, and 81 for PD-L1.
In these patients, good treatment responses and effective disease control further demonstrate that molecular profiling is not merely a diagnostic step – it can directly guide treatment selection and influence clinical outcomes.
Current recommendations emphasize having biomarker results available at the time treatment decisions are made. Comprehensive molecular profiling before treatment initiation is associated with better treatment planning and, in some datasets, improved overall survival.
When the amount of available tissue is insufficient, liquid biopsy and circulating tumor DNA (ctDNA) may also be used in appropriate situations. However, a negative blood-based test does not always exclude the presence of a molecular alteration, as liquid biopsy has a risk of false-negative results. Therefore, whenever feasible, tissue-based testing remains important.
Molecular testing can also become important when the disease progresses, when it is necessary to identify mechanisms of acquired resistance and select subsequent treatment.
The clinical significance of molecular testing is clearly illustrated by EGFR-mutated lung cancer.
The FLAURA trial demonstrated that, in patients with previously untreated, EGFR-mutated metastatic NSCLC, treatment with osimertinib, a third-generation EGFR TKI, significantly improved overall survival, reaching 38.6 months, compared with 31.8 months in the control group receiving standard EGFR-targeted agents – gefitinib or erlotinib (Ramalingam et al., 2020).
Similarly, in ALK-positive disease, the ALEX trial demonstrated a significant advantage of alectinib, a second-generation ALK TKI, over crizotinib, a first-generation ALK TKI. At 12 months, 68.4% of patients receiving alectinib had not experienced disease progression, compared with 48.7% in the crizotinib group. Alectinib also significantly reduced the risk of disease progression in the brain (Peters et al., 2017).
Ultimately, a lung cancer diagnosis today does not mean that every patient will follow the same treatment pathway or have a predetermined outcome. Molecular testing gives us the opportunity to understand the tumor more precisely and tailor treatment to its specific characteristics.
Our Georgian real-world data demonstrate that this is not merely a theoretical concept derived from international clinical trials. Georgian patients harbor EGFR, ALK, and other potentially targetable molecular alterations.
For a patient, targeted therapy can mean the possibility of long-term disease control and preservation of quality of life.
One diagnosis, Different biology, Different treatment – and today, more opportunities to extend survival and preserve quality of life.
Author: Ana Tsereteli, MD, Caucasus Medical Centre
