Comprehensive Genomic Profiling in NSCLC: Lab Processing Improves, but Biopsy-to-Order Delays Persist
核心洞察
Median overall turnaround time for tissue-based CGP in NSCLC improved from 36.6 days in 2018 to 27.0 days in 2024, driven largely by faster molecular laboratory processing.
The time from biopsy to CGP ordering remained stagnant at approximately 14 days and is now the largest contributor to overall delay.
Ordering turnaround time varied dramatically between clinical sites, with the slowest quintile taking 23.8 days versus 8.0 days in the fastest quintile.
A large national analysis published in JCO Oncology Practice reveals that while molecular laboratories have dramatically accelerated comprehensive genomic profiling (CGP), the clinical workflow between biopsy and test ordering remains the dominant bottleneck—and it has not improved in seven years.
The study, led by Adam H. Fox, MD, MS, a lung cancer pulmonologist at Medical University of South Carolina's Hollings Cancer Center, examined tissue-based CGP turnaround time across 271,574 solid tumor samples from 5,497 U.S. clinical sites between 2018 and 2024. The findings paint a nuanced picture: overall turnaround time is improving, but the gains are almost entirely attributable to faster sequencing, not faster clinical decision-making.
NSCLC Turnaround Time: The Numbers
For non-small cell lung cancer (搜索) (NSCLC), the median overall turnaround time—from specimen collection to CGP result reporting—declined from 36.6 days (IQR, 27.9–51.6) in 2018 to 27.0 days (IQR, 19.5–39.9) in 2024. This improvement was driven by molecular laboratory processing, which fell from a median of 15.2 days (IQR, 13.5–17.3) to 7.1 days (IQR, 6.2–8.1) over the same period (P = .009).
However, the ordering turnaround time—the interval from specimen collection to the CGP order being placed—was 13.0 days in 2018 and 14.0 days in 2024. "To see no real improvement over time in that area was really frustrating," Fox told Healio.
The remaining component, specimen transfer time from order to laboratory receipt, accounted for a median of 4.4 days.
Wide Variation Between Clinical Sites
The study documented striking disparities between the fastest and slowest clinical sites. Among sites with at least 10 NSCLC orders in 2024, the shortest quintile achieved a median overall turnaround time of 19.5 days (IQR, 16.7–20.6), while the longest quintile required 38.9 days (IQR, 35.3–41.8; P < .001).
The ordering step drove this gap. Median ordering turnaround time ranged from 8.0 days (IQR, 6.8–9.1) in the fastest quintile to 23.8 days (IQR, 21–28.3) in the slowest quintile (P < .001). For a patient with newly diagnosed advanced lung cancer, this represents more than two additional weeks of uncertainty—and potentially the difference between receiving biomarker-informed therapy and starting empiric treatment.
"This is the longest component of the process but, the good news is, it also is the most modifiable," Fox said.
Factors Associated with Faster Testing
Several factors correlated with shorter turnaround time in the NSCLC cohort. Younger patient age, nonsquamous histology, testing of unstained slides, higher clinical site ordering volume, and electronic ordering methods were all associated with reduced overall turnaround time. Ordering through an electronic health record, online portal, or paper form was faster than fax orders, while fax and email or other manual processes were linked to longer delays.
The NSCLC cohort comprised 62,650 samples: 61.5% lung adenocarcinoma, 21.3% squamous cell carcinoma, and 14.5% NSCLC not otherwise specified. NSCLC turnaround times were faster than those for other solid tumors, which had a median overall turnaround time of 33.5 days and a median ordering turnaround time of 20.0 days in 2024.
Why Speed Matters
In advanced NSCLC, first-line treatment decisions frequently depend on biomarkers including EGFR (搜索), ALK (搜索), ROS1 (搜索), BRAF (搜索), MET, RET, NTRK, KRAS (搜索), HER2, PD-L1 (搜索), and tumor mutational burden. The same principle increasingly applies in earlier-stage disease, where biomarkers can influence choices between adjuvant targeted therapy, neoadjuvant chemoimmunotherapy, perioperative approaches, and post-chemoradiotherapy strategies.
"We know selecting the right treatment first can improve outcomes, but there is a pressure to start therapy on the part of both oncologists and patients," Fox said. "There is a limit to how long they are willing to wait, and it varies from person to person. We cannot simply ask, 'Is testing getting done?' We also need to ask, 'How long is it taking?'"
When results are delayed, clinicians may face pressure to initiate treatment before the complete molecular picture is available—potentially leading to missed targeted therapy opportunities, less precise treatment selection, avoidable toxicity, and worse outcomes.
Reflex Testing and Other Solutions
Reflex testing—where molecular testing is automatically initiated based on predefined clinical and pathology criteria—has shown promise in single-center studies, yielding shorter turnaround times and higher rates of biomarker-informed care. However, implementation barriers include cost, the need for institutional consensus on which tumor types and stages should trigger testing, and coordination across pulmonology, interventional radiology, pathology, oncology, surgery, and administrative teams.
Fox highlighted the central role of pathologists: "A primary care physician, a pulmonologist, an interventional radiologist, a surgeon or any number of other people might acquire a biopsy through some means, but they all go through a pathologist. Anything that can be done to empower them and help them identify patients who need testing, and make sure processes are coordinated with the oncology group, will eliminate some of the downstream bottlenecks."
Study Limitations
The analysis drew data from a single commercial laboratory (FoundationOne CDx (搜索), which interrogates 324 cancer-associated genes along with microsatellite instability and tumor mutational burden), so findings may not fully generalize to other laboratories or in-house testing platforms. Only completed tissue-based CGP tests were included; plasma-based testing was not analyzed. The study lacked granular institutional details—including whether sites used reflex testing—and did not capture patient-centered timing such as time from imaging detection to biopsy or from diagnosis to treatment initiation. It also does not directly demonstrate that longer turnaround time caused worse outcomes.
A Call to Action
"I would urge anyone working as part of a multidisciplinary team in oncology care to not assume that this testing is happening as quickly as they would hope," Fox said. "It is very important for them to look at internal data to see how long this process is taking, talk to corresponding specialists—from the ones helping to obtain biopsies to the ones who are using molecular testing results—and identify ways to streamline the process and ensure patients receive optimal care."
The message is clear: precision oncology cannot depend only on better tests. It needs better systems. For patients with lung cancer, the clock starts before the sequencing run begins.