Decentralized NGS: Transforming Cancer Care in Rural Settings

Abstract:

Prof. Dr. Bence Sipos discusses how decentralized next-generation sequencing (NGS) is reshaping cancer care, particularly in rural and underserved regions. He explains that faster, on-site genomic testing shortens turnaround times, reduces reliance on bridging therapies, and enables quicker, genomically guided treatment decisions. Sipos outlines the clinical, technical, and operational requirements for implementation—including regional laboratory networks, structured training, and reimbursement reform—and highlights liquid biopsy and digital connectivity as key innovations for expanding equitable, global access to precision oncology.

What are the most pressing consequences of delayed genomic testing in cancer care, particularly for patients in rural or underserved regions?

When we talk about delayed genomic testing in cancer care—especially for patients in rural or underserved regions—the consequences can be quite serious. Lung cancer patients are a helpful example of this as these patients often present with advanced disease and very severe symptoms. If we can start either conventional systemic therapy or a targeted treatment quickly, based on the tumor’s genomic profile, we can often relieve symptoms within days, induce a rapid tumor response and, for some patients, significantly prolong survival. Every week we lose waiting for results can mean missed opportunities for symptom control and better outcomes.

How does decentralized next-generation sequencing (NGS) fundamentally shift the limitations of traditional centralized testing models?

Decentralized next-generation sequencing (NGS) fundamentally changes the old, centralized testing model we all relied on a few years ago. Between 2015 and 2018, centralized NGS centers were essential. There simply wasn’t enough sequencing capacity and expertise in local laboratories. Since around 2020, however, we’ve seen substantial progress in molecular pathology labs across Germany. Many of them can now perform high-quality NGS on-site. This development has made true near-patient molecular testing possible for essentially all tumor types, not just a few selected indications. In other words, we’ve moved from “send everything to a distant center” to “test locally, integrate directly into clinical care.”

From a clinician’s standpoint, how does rapid access to genomic data reshape treatment decisions and timelines in oncology?

From a clinician’s standpoint, rapid access to genomic data really reshapes treatment decisions and timelines. If we receive molecular pathology results within just a few days, the management of metastatic patients changes dramatically. We no longer need to start “bridging” therapies while waiting for results. This is critical because bridging therapies, while often necessary when patients can’t wait for results, could delay or even preclude the optimal genomically guided treatment. Instead, we can stratify treatment very quickly—sometimes even between two weekly molecular tumor boards. That shortens decision pathways, reduces uncertainty, and helps us initiate the best possible, genomically guided therapy without delay.

What are the essential clinical, technical, and operational requirements for implementing on-site genomic testing in a hospital setting?

To implement on-site genomic testing in a hospital, several clinical, technical, and operational elements need to be in place. From a clinical standpoint, the process usually starts once the histological diagnosis is established, often within a multidisciplinary tumor board. In that setting, the oncologist and pathologist discuss the case and the relevant molecular tests can immediately be requested. If pre-analytics are well organized, tissue processing and DNA/RNA extraction can start the same day. With an efficient setup, sequencing can be done within 1–2 working days for urgent cases, and within about 5 working days for routine ones. Overall, it’s about having clear workflows, appropriate infrastructure and close collaboration between clinical and laboratory teams.

What key barriers do institutions face when adopting decentralized NGS, and what strategies can help overcome them?

Of course, institutions face some barriers when they try to adopt decentralized NGS. The key challenges are: first, limited molecular expertise among pathologists; second, the need for a suitable sequencing platform; and third, a minimum sample volume—typically at least 4 to 6 cases per week—to ensure consistent workflows and economic viability. Our approach to overcoming these barriers has been through building local networks.

By creating regional collaborations between pathology institutes and hospitals, we can share expertise, pool samples and jointly invest in technology. This way, we reach the required case numbers and create a sustainable, cost-effective structure. Thankfully, the German Society of Pathology has introduced a structured training program for scientists working in molecular pathology. This initiative helps increase the number of appropriately trained scientific professionals and is particularly valuable for smaller molecular pathology laboratories, where building and maintaining specialized expertise can otherwise be challenging. In this way, structured professional training complements local network formation and supports the sustainable implementation of decentralized NGS testing.

One important challenge in Germany specifically is the funding of molecular pathology services for hospitalized patients. Hospitals are reimbursed through the Diagnosis-Related Groups (DRG) system, which often covers only a small proportion—or, in some cases, none—of the actual costs of comprehensive molecular pathology testing. This creates a significant financial disincentive and can slow the further expansion of local molecular pathology laboratories. If we want near-patient genomic testing to become broadly available, reimbursement structures need to reflect its clinical value and the real costs of delivering high-quality testing.

How does integrating rapid genomic testing influence collaboration between oncologists, pathologists, and laboratory teams?

When rapid genomic testing is integrated into routine care, it strengthens collaboration between oncologists, pathologists and laboratory teams. Short communication channels and clearly defined logistics are crucial. In challenging cases, for example, when we only have very small biopsy specimens, it’s essential that the treating physicians and the lab team can speak quickly and directly to one another. That allows us to optimize pre-analytical handling, avoid sample loss and still achieve reliable sequencing results. In day-to-day practice, this kind of close interaction improves trust, speeds up decision-making and = benefits the patient.

In what ways does decentralized testing impact sample integrity, success rates, and diagnostic reliability?

Decentralized testing also has a direct impact on sample integrity, success rates and diagnostic reliability. Once local pathology institutes are actively involved in molecular testing, they can better control critical pre-analytic steps, such as fixation, processing and embedding of samples. The integration of daily workflows increases surgical pathologists’ awareness for the needs of molecular diagnostics. It also means that molecular results can be directly incorporated into the final pathology report, which improves diagnostic precision. A good example is a metastatic pancreatobiliary carcinoma with an IDH1 mutation or an FGFR2 fusion. This pattern strongly suggests cholangiocarcinoma with specific targeted therapy options, rather than pancreatic carcinoma. Often, histology alone cannot make this distinction as clearly as the combination of morphology and genomics can.

Can you share a real-world example that illustrates the clinical impact of faster genomic turnaround times?

An example that highlights the clinical impact of fast genomic turnaround is when I had a 71-year-old woman, a former smoker who quit 40 years ago, presenting with multiple lung tumors, lymph node involvement and brain metastases. A transbronchial biopsy showed pulmonary adenocarcinoma. PD-L1 testing revealed a TPS of 80% and ICS of 3%. Based on PD-L1 alone, one might immediately consider chemo-immunotherapy. However, NGS identified an EML4 (exon 13)::ALK (exon 20) fusion and we had this result on the third business day. With that information, the oncologist could start ALK-targeted therapy instead of chemo-immunotherapy. Had we not had the NGS result so quickly, the patient would likely have received a suboptimal regimen that could have significantly worsened the prognosis of an ALK-rearranged lung cancer.

How can regional or smaller healthcare centers maintain quality standards and regulatory compliance with on-site NGS?

Smaller regional centers often ask how they can maintain quality standards and regulatory compliance with on-site NGS. One practical solution is to use integrated sequencing systems, such as Thermo Fisher Scientific’s Ion Torrent Genexus System. These instruments are designed to reduce hands-on time for laboratory technologists, which is very helpful in settings with limited staff. But technology alone is not enough. Pre-analytic steps must be standardized and the entire process needs to be covered by certification and accreditation frameworks. The advantage of integrated systems is that they combine multiple steps in a controlled pipeline, which makes quality management and regulatory compliance more achievable, even in smaller institutions.

What role does clinician education play in ensuring the effective use of decentralized genomic insights?

Clinician education also plays a major role in making decentralized genomic insights truly effective. Oncologists and other clinicians need to understand what integrated genomic sequencing can and cannot offer and when it is most relevant. Effective clinician education ensures genomic insights translate into clinical action. This helps clinicians identify the right patients for testing, order tests at the right time, interpret the findings appropriately, and use the findings to guide treatment decisions.  In many hospitals that have local molecular pathology, this education happens quite naturally in regular tumor boards, where cases are discussed and new genomic findings are reviewed. Through this ongoing dialogue, oncologists become more alert to the indications for testing and more confident in interpreting results. Once the workflow is established and reliable, we typically see high satisfaction among oncology teams because they get actionable results within timelines that match clinical needs.

To what extent can decentralized NGS help bridge disparities and advance equity in precision oncology?

Decentralized NGS can make a real difference in terms of equity in precision oncology. If high-quality genomic testing is available locally, then smaller and medium-sized hospitals, as well as private oncologists, can offer their patients state-of-the-art tumor profiling. Samples do not have to be sent to larger NGS facilities, rather, they can be profiled locally and then either treated on-site or referred to a specialized center with all necessary information already available. This reduces regional disparities, speeds up access to advanced therapies and clinical trials and helps ensure that precision oncology is not limited to a few large university hospitals, but becomes accessible across the healthcare system.

What are the broader economic and operational implications for health systems adopting near-patient genomic testing?

Near-patient genomic testing requires an initial investment in technology, staff training, quality management, accreditation and digital infrastructure. However, the economic discussion should not focus only on the price of the sequencing run. We also have to consider the cost of delays. This may include prolonged hospital stays, repeated appointments, inefficient use of tissue and treatments that may be started before the relevant molecular information is available.

From an operational perspective, decentralized testing can shorten transport times, reduce administrative interfaces and make the entire diagnostic pathway more predictable. If a local network pools cases from several hospitals and pathology practices, it can achieve sufficient sample volume to operate efficiently while maintaining short turnaround times.

The best model is not necessarily that every small hospital runs a complete molecular laboratory independently. In many regions, the most sustainable solution will be a network model. This means local pathology and oncology teams manage tissue selection, pre-analytics and clinical communication, while a regional molecular pathology hub provides validated testing, bioinformatics, quality assurance and interpretation. That creates both clinical proximity and economic sustainability. Molecular testing budgets, trained personnel, and robust external quality assurance are recognized barriers to wider adoption of precision oncology.

How is the oncology diagnostics landscape evolving with the emergence of rapid and decentralized technologies?

Oncology diagnostics is moving from a sequential, test-by-test approach toward integrated and parallel molecular profiling. In the past, we often tested one biomarker after another, which used time and precious tissue. Today, targeted NGS panels can assess multiple clinically relevant alterations from a single specimen and support a more complete therapeutic strategy from the beginning.

At the same time, diagnostics is becoming faster and more closely connected to clinical decision-making. Rapid sequencing platforms, improved automated extraction and library-preparation systems and structured molecular reporting are allowing pathology laboratories to provide actionable results within clinically meaningful timelines. This means molecular results are no longer an additional piece of information delivered late in the pathway. Instead, they are becoming an integral part of the primary diagnostic report and of the initial treatment plan.

The landscape is also becoming more networked. Local laboratories can provide fast, patient-near testing and direct communication with treating physicians, while complex variants, rare tumor types and difficult therapeutic decisions can be discussed in regional or virtual molecular tumor boards. Current European Society for Medical Oncology (ESMO) recommendations emphasize interdisciplinary expertise, structured reporting, follow-up of recommendations and turnaround time as relevant quality indicators for molecular tumor boards.

Looking ahead, what innovations will be most critical in expanding access to genomic testing globally?

The most important innovation will not be a single new sequencing device. Instead, it will be the combination of simpler technology, robust workflows, digital connectivity, and international quality networks. We need sequencing platforms that are easier to operate, require less hands-on time, work reliably with small or challenging samples and can be maintained at sustainable cost. Integrated workflows will be particularly important for regional hospitals and resource-limited settings.

Digital solutions will be equally important. Cloud-based bioinformatics, standardized reporting and virtual molecular tumor boards can connect local healthcare providers with molecular expertise.

We will also see a growing role for liquid biopsy, particularly when tumor tissue is limited or repeated profiling is needed during treatment. Liquid biopsy is not a universal replacement for tissue pathology, but it can complement conventional tissue-based testing and may reduce barriers in selected clinical situations.

Ultimately, global access will depend on making high-quality testing not only technically available, but also clinically useful: results must be rapid, reliable, affordable, linked to treatment access, and interpreted within an appropriate clinical framework. Otherwise, genomic information alone will not translate into better outcomes.