Key takeaways
- Biomarker testing should be built into the diagnostic pathway so results are available before first-line treatment decisions are made.
- Tissue and plasma ctDNA should be used as complementary tools rather than treating liquid biopsy as a complete substitute for tissue profiling.
- Preserving biopsy material is critical because excessive IHC can exhaust tissue needed for comprehensive genomic profiling, and repeat biopsy may not be feasible.
- Molecular results only help if they can be interpreted, which makes access to RNA-based fusion testing and molecular tumor boards increasingly important.
- Treatment should not get ahead of the biology: when molecular testing is still pending and the patient is clinically stable, Sood argued that clinicians should wait for the results before committing to therapy.
At the Community Oncology Global Congress (COGC 2026), organized by OncoDaily, Karan Sood, Medical Oncologist in the Department of Medical Oncology at the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, focused on a persistent problem in lung cancer: having a targeted therapy available means little if the patient never receives the molecular test that identifies them as a candidate.
Lung cancer remains the most commonly diagnosed cancer worldwide and the leading cause of cancer death, with approximately 2.5 million new cases and 1.8 million deaths estimated in 2022.
Meanwhile, treatment has become increasingly dependent on biology. EGFR, ALK, ROS1, RET, MET, BRAF, KRAS, NTRK and other alterations can redirect therapy, while PD-L1 expression helps guide immunotherapy decisions.
Yet Sood’s presentation centered on the gap between what precision oncology can offer and what patients actually receive.
“Two-thirds of the patients never reach the right drug. Even if you do the biomarker testing, you don’t have the accessibility to the drug. Almost 65 percent are lost somewhere in the precision medicine pathway.”
The First Decision Starts With the Biomarker Result
Sood distilled his approach into three words:
“Test right, test once, and test fast.”
Timing matters because the treatment decision often cannot wait indefinitely for molecular results.
He described a rapid NGS pathway at Tata Memorial Hospital with turnaround times of approximately two days, allowing clinicians to make molecularly informed decisions within days of receiving the biopsy.
“The patient comes in with a tissue biopsy. You send the liquid biopsy or tissue biopsy and you get the reports in two days. By the end of the third day you have the ability to tell the patient what treatment they are a candidate for. This is something in the direction which the community center also needs to go in.”
Not every community practice can reproduce the infrastructure of a high-volume tertiary center. Sood acknowledged that directly.
His larger point was that testing should begin as soon as tissue becomes available rather than after a treatment plan has already been chosen.
“As soon as the patient is biopsied, the requisition for sending the tissue NGS or biomarker testing should be done.”
That becomes increasingly important as biomarker-directed therapy moves beyond metastatic disease and into earlier stages of NSCLC.
Tissue and Plasma Should Not Compete
Liquid biopsy can make molecular testing easier, particularly when tissue is scarce or difficult to obtain.
But Sood cautioned against treating plasma testing as a replacement for tissue profiling.
“Plasma ctDNA should be a complementary test. It should not be the only testing.”
His preferred model is a parallel approach when clinically and financially feasible: tissue-based comprehensive genomic profiling alongside plasma ctDNA.
“It’s not a fallback. It’s a parallel track.”
That distinction matters because a negative plasma result does not necessarily exclude an actionable alteration. Tissue can still provide information that circulating DNA testing misses, while plasma can help when tissue is inadequate and may provide additional insight into emerging resistance.
The details of the assay matter as well.
Sood emphasized the importance of confirming whether a platform adequately detects gene fusions. RNA-based testing can improve detection of alterations involving genes such as ALK, ROS1, RET, NTRK and NRG1 that may be missed by some DNA-only approaches.
“Even if we have the test reports and we can’t interpret them, then there is no point getting these NGS tests done.”
That is where molecular tumor boards and accessible specialist interpretation become particularly important for community practices.
Use the Biopsy Wisely
Precision oncology also depends on something much less sophisticated than sequencing technology: having enough tissue left to sequence.
Sood warned against exhausting small biopsy specimens with unnecessary immunohistochemistry before molecular testing has been considered.
A lung biopsy may be difficult, invasive, and sometimes impossible to repeat. Every section therefore matters.
“Multiple times you see you cannot get a repeat tissue biopsy from patients, and patients are hesitant to give another biopsy, especially when it is from the primary lung. It is very inconvenient because these are mostly CT-guided and very cumbersome.”
His proposed pathway was more deliberate: establish the diagnosis with a focused IHC approach, preserve tissue, proceed reflexively to molecular profiling, incorporate plasma testing when appropriate, and then bring complex findings to a molecular tumor board.
“Reflex testing is important. It removes the decision that is getting missed.”
The goal is to prevent biomarker testing from becoming something clinicians remember only after tissue has been exhausted or treatment has already begun.
Do Not Let Immunotherapy Get Ahead of the Biomarker Result
The expansion of immunotherapy has made waiting for molecular results even more important.
Sood reviewed the impact of trials including KEYNOTE-024, KEYNOTE-189 and KEYNOTE-407, which established major roles for immunotherapy and chemoimmunotherapy across metastatic NSCLC.
But PD-L1 is only one part of the treatment decision.
In NSCLC, PD-L1 is generally reported using the tumor proportion score (TPS), not the combined positive score used in some other cancers. FDA documentation for pembrolizumab in NSCLC similarly defines PD-L1 expression by TPS.
And a high PD-L1 result should not encourage clinicians to skip molecular testing.
For patients with actionable oncogenic drivers such as EGFR or ALK, the presence of a targeted treatment can fundamentally change the preferred first-line strategy.
Sood’s practical message was therefore to resist starting immunotherapy simply because the PD-L1 result arrives before comprehensive molecular testing.
“If the molecular testing is pending, one should wait.”
There will be exceptions when the patient is clinically deteriorating and treatment cannot safely be delayed. But when the situation allows, the biomarker result should arrive before the treatment choice is locked in.
Before the First Treatment
The value of biomarker testing is ultimately determined by timing.
For Sood, the priority is to make molecular profiling part of the diagnostic pathway rather than something added after treatment planning has already begun. That means preserving tissue, sending comprehensive testing early, using plasma ctDNA when appropriate, and making sure complex findings can be interpreted.
This becomes especially important when immunotherapy is being considered before the full molecular profile is available.
“If the molecular testing is pending, one should wait.”
In precision oncology, the crucial result is not simply the one that comes back.
It is the one that comes back in time to change the first decision.
Written by Eliz Baloyan, MD, Features Writer and Editor at OncoDaily and CancerWorld
