Molecular Profiling must become a Reflex test for every Lung Cancer Patient
By Arunima Rajan
In an interview with Arunima Rajan, Dr Kunjal Patel, molecular oncopathologist at Neuberg Centre for Genomic Medicine, explains why comprehensive genomic testing should come before the first line of lung cancer treatment, and what still stands in the way.
Most patients think of a lung cancer diagnosis as a scan and a biopsy. Can you help us understand what actually happens once that tissue sample lands on your desk, and why molecular testing has become such a critical extra step?
A lung cancer diagnosis only begins with confirming the presence of cancer cells under the microscope. In an era of multiple targeted therapy options, molecular analysis is no longer optional but a necessary next step in lung cancer management. Once a biopsy reaches the molecular pathology laboratory, we assess its quality and the percentage of tumour cells present, then run next-generation sequencing (NGS) to determine which genetic changes, or driver mutations, are present in the tumour tissue. Many lung cancer patients now receive targeted treatment based on the results of their molecular testing, because this therapy has shown better response and lower toxicity than conventional chemotherapy. By applying molecular testing to a lung cancer biopsy, oncologists are able to map a patient's treatment journey.
Genomic profiling and NGS sound intimidating to a layperson. In plain terms, what are you actually looking for in a patient's tumour DNA, and how does that change what treatment they are offered?
All cancers result from mutations, or changes in the DNA of cells, that lead to uncontrolled growth. With next-generation sequencing, we study the building blocks of many cancer-associated genes at the same time and look for alterations that can cause cancer. What we focus on are actionable or targetable mutations, meaning mutations against which there are approved targeted therapies available, or which are being investigated in clinical trials. If such a mutation is detected, the oncologist can select an available targeted therapy to attack the cancer cells. Even when no directly actionable mutation is found, NGS can give clues about how well other therapies, such as immunotherapy or chemotherapy, are likely to work in that patient.
You have worked across government hospitals in Delhi, the University of Minnesota in the United States and Neuberg Diagnostics over the past decade. How has the accessibility of NGS testing for lung cancer patients changed in recent years, and where are the gaps?
In the past decade, there has been substantial progress in the availability of molecular diagnostics in India. Earlier, DNA sequencing services were available only at a select few tertiary cancer centres, many of which shipped samples abroad for sequencing and interpretation, delaying reporting significantly. There are now many accredited laboratories with in-house NGS facilities, at a better cost to patients and with faster turnaround times. Growing awareness among oncologists about the utility of NGS in lung cancer has led to wider use of targeted therapy. That said, patients from small towns and non-urban areas continue to face poor access, affordability barriers, delayed referrals and a lack of insurance reimbursement for NGS testing and targeted therapies.
Precision oncology promises a treatment matched to a patient's specific mutation type. How often does that promise actually play out for lung cancer patients here, compared with developed countries?
Precision oncology is now a real option for many lung cancer patients in India, given the improved availability of NGS testing domestically. A sizable number of lung cancer patients in the Indian population have genetic alterations in the EGFR, KRAS, ALK, ROS1, MET or RET genes, making them good candidates for targeted therapies, with a marked improvement in prognosis. However, realising the full benefit of precision oncology also depends on timely testing of tumour tissue, the availability and affordability of specialised drugs, and appropriate follow-up testing to detect early relapse or resistance. Most high-income countries have systems in place that treat comprehensive molecular testing as the standard of care, along with better insurance coverage, which allows most eligible patients to undergo personalised treatment. India is steadily catching up through a growing number of diagnostic facilities, improved availability of targeted therapies and more insurance companies covering cancer treatment.
Is there a moment in your lab work where a molecular finding completely changed the direction of a patient's treatment plan, something a clinician or pathologist may never have known without your report?
We see multiple instances in our daily practice where molecular analysis alone directs the appropriate treatment course for a patient. In one case, comprehensive NGS found an unusual but actionable mutation that had been missed on a standard, smaller gene panel. This patient, who would otherwise have been given conventional chemotherapy, was instead recommended a targeted treatment option. It underlines why comprehensive genomic testing matters, because it can prove decisive in cases where standard testing is negative.
Biomarkers such as EGFR, ALK and PD-L1 keep coming up in conversations about lung cancer therapy. Could you explain, in a way patients' families could understand, what these terms actually mean and why they matter?
Biomarkers are indicators that tell us something about how a cancer behaves, as well as the types of therapy that might work best on it. EGFR and ALK are examples of mutations and fusions found in lung cancer that have been established as driver mutations for cancer development and can be treated with targeted therapy. PD-L1, on the other hand, is a surface protein present on some tumours and is used as an indicator of whether the tumour will respond to immunotherapy. Identifying these biomarkers allows oncologists to move past conventional chemotherapy and tailor treatment to the molecular profile of the tumour.
What are the biggest hurdles you face, whether cost, awareness among clinicians or something else, in getting more Indian lung cancer patients tested for actionable mutations before they start treatment?
There are still many challenges. Although the cost of molecular testing has fallen considerably over the past decade, many Indian patients still consider it expensive, especially in the absence of health insurance or reimbursement. Oncologist awareness has improved, but variability remains in the timing, type and scope of molecular testing across healthcare facilities and practitioners. Another issue is inadequate tissue for NGS, particularly in cytology cell blocks, where liquid biopsy is emerging as a promising alternative. Delays in referrals, problems with shipping samples on time and the absence of specialised molecular laboratories in many non-urban regions add to the difficulty.
If you could change one thing about how molecular pathology is integrated into everyday lung cancer care in India, what would it be, and why?
By far the most significant single improvement would be making comprehensive NGS testing the standard of care for every patient diagnosed with lung cancer, before any therapy begins. Just as histopathology and PD-L1 biomarker testing have become routine for lung cancer patients in India, molecular profiling must become a reflex test for every diagnosed patient rather than an optional or supplementary one. Early testing allows actionable mutations to be detected before treatment starts, saving precious time and improving clinical outcomes. Lung cancer molecular testing programmes at the hospital level, better financial coverage and reimbursement for NGS testing, and greater collaboration among healthcare professionals will deliver the consistent, specialised and timely care that lung cancer patients in India deserve.
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