LungÕ 2026: Integrating Care and Advancing Treatment for Locally Advanced Lung Cancer

From multidisciplinary treatment planning and modern radiotherapy to biomarker-guided consolidation and perioperative immunotherapy, locally advanced lung cancer is entering a new era of personalized care. At LungÕ 2026 – Virtual Global Congress on Lung Oncology, the theme “Integrating Care: Advances in Locally Advanced Disease” highlights one of the most important challenges in thoracic oncology: how to bring increasingly sophisticated treatments together into a coordinated, evidence-based strategy that improves long-term survival.

Organized by OncoDaily as part of its O Series of global oncology congresses, LungÕ 2026 will take place virtually on November 5, 2026, bringing together international specialists to examine contemporary developments across the lung cancer continuum.

The congress is designed to connect advances in early diagnosis, molecular profiling, systemic therapy, radiotherapy, surgical management, and multidisciplinary care with the practical realities of treatment delivery.

Locally advanced lung cancer is a particularly relevant setting for this discussion. The population includes patients with potentially resectable stage III non-small cell lung cancer (NSCLC), patients with unresectable stage III disease requiring definitive chemoradiotherapy, and those with limited-stage small cell lung cancer (SCLC).

Although these clinical situations differ substantially, they share a common principle: successful treatment requires more than choosing an effective systemic agent. It depends on accurate staging, appropriate local treatment, timely sequencing, biomarker assessment, toxicity management, and coordination among multiple specialties.

Recent evidence from PACIFIC, LAURA, KEYNOTE-671, PACIFIC-5, and ADRIATIC has reshaped several aspects of care, establishing new opportunities to improve disease control and survival.

However, these advances have also created new questions about treatment selection, optimal sequencing, pulmonary toxicity, molecular residual disease, and equitable access to complex multimodality strategies.

Locally Advanced Lung Cancer: A Multidisciplinary Challenge

Stage III NSCLC represents one of the most heterogeneous categories in lung oncology. Patients may present with a potentially resectable primary tumor and limited nodal involvement, extensive multistation mediastinal disease, locally invasive tumors, or disease requiring definitive chemoradiotherapy because surgery is not technically or oncologically appropriate.

Determining resectability is therefore not simply an anatomical decision. It requires integration of tumor extent, nodal distribution, cardiopulmonary function, anticipated surgical morbidity, likelihood of complete resection, and the availability of effective nonoperative alternatives.

A central objective of modern multidisciplinary care is to establish the optimal treatment strategy before initiating therapy. Thoracic surgeons, medical oncologists, radiation oncologists, radiologists, pathologists, pulmonologists, and supportive care teams each contribute essential information.

PET/CT and appropriate brain imaging help clarify disease extent, while invasive mediastinal nodal staging may be necessary when nodal status will influence treatment. Molecular profiling is increasingly important even when treatment is delivered with curative intent.

The presence of EGFR mutations, ALK rearrangements, and other actionable alterations may influence systemic treatment selection, particularly after chemoradiotherapy.

In 2026, the goal is no longer to categorize every stage III NSCLC patient within a single treatment pathway. It is to define the most appropriate multimodality strategy for each clinical and molecular disease context.

The PACIFIC Standard: A Foundation for Unresectable Stage III NSCLC

The PACIFIC trial established one of the most important advances in the management of unresectable stage III NSCLC.

For patients without disease progression following concurrent platinum-based chemoradiotherapy, consolidation durvalumab significantly improved progression-free survival (PFS) and overall survival (OS) compared with placebo.

At five years, estimated OS was 42.9% with durvalumab versus 33.4% with placebo. Median OS reached 47.5 versus 29.1 months, corresponding to a hazard ratio (HR) of 0.72. The estimated five-year PFS rates were 33.1% versus 19.0%.

These findings demonstrated that immunotherapy administered after definitive chemoradiotherapy could provide durable survival benefit in a population historically associated with high rates of recurrence.

For patients with unresectable stage III NSCLC without an EGFR sensitizing mutation, concurrent chemoradiotherapy followed by consolidation durvalumab remains a foundational treatment strategy when clinically appropriate.

However, eligibility depends on completion of definitive treatment without progression and adequate recovery from treatment-related toxicity. The timing of consolidation, functional status, pulmonary complications, and local regulatory indications also influence treatment delivery.

In the European Union, durvalumab’s stage III indication includes a requirement for PD-L1 expression in at least 1% of tumor cells, whereas the United States does not apply the same PD-L1 restriction. These differences illustrate an important aspect of integrated oncology care: treatment decisions must consider both scientific evidence and the local regulatory environment.

LAURA Introduces Molecular Precision After Chemoradiotherapy

The phase III LAURA trial demonstrated that molecular selection can fundamentally change post-chemoradiotherapy treatment.

The study evaluated osimertinib following definitive chemoradiotherapy in patients with unresectable stage III NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations. Among 216 randomized patients, median PFS was 39.1 months with osimertinib compared with 5.6 months with placebo.

The HR was 0.16 (95% CI 0.10–0.24; p<0.001), representing an 84% reduction in the hazard of progression or death. These results established a substantial disease-control benefit and supported regulatory approval of osimertinib following definitive chemoradiotherapy in this molecularly defined population.

Updated analyses have also demonstrated favorable outcomes beyond first progression. At the second interim OS analysis, the HR for death was 0.67 (95% CI 0.40–1.14), although survival data remained immature and did not establish a statistically significant OS benefit.

The clinical implications extend beyond the efficacy of one drug. LAURA demonstrates why molecular testing should be integrated into the diagnostic assessment of stage III disease rather than deferred until metastatic recurrence.

For patients with EGFR-mutated unresectable stage III NSCLC, post-chemoradiotherapy treatment now follows a different evidence-based pathway from the conventional durvalumab strategy. The distinction also raises important questions about treatment duration, acquired resistance, CNS surveillance, and the potential use of circulating tumor DNA to monitor residual disease.

As other molecularly targeted treatments continue to expand in metastatic NSCLC, determining which alterations can guide curative-intent consolidation strategies will remain an important research priority.

PACIFIC-5 Extends Evidence to Patients Receiving Sequential Chemoradiotherapy

Although concurrent chemoradiotherapy is generally preferred for medically suitable patients with unresectable stage III NSCLC, not everyone can tolerate this approach.

Older adults, patients with significant comorbidities, and those with impaired functional reserve may receive sequential chemotherapy and radiotherapy. This creates an important evidence gap because the original PACIFIC population had completed concurrent chemoradiotherapy.

The phase III PACIFIC-5 study evaluated consolidation durvalumab after concurrent or sequential chemoradiotherapy. Among 381 patients in the modified intention-to-treat population, median PFS reached 14.0 months with durvalumab versus 6.5 months with placebo.

The HR was 0.75 (95% CI 0.58–0.99; p=0.038). Interim OS numerically favored durvalumab, but the difference was not statistically significant. These findings extend the randomized evidence supporting consolidation durvalumab to a broader population that includes patients treated with sequential chemoradiotherapy.

However, eligibility and benefit should still be assessed according to patient fitness, treatment-related toxicity, and applicable regional guidance. From an integrated-care perspective, PACIFIC-5 reinforces the importance of providing effective treatment pathways for patients who cannot receive the most intensive standard regimen.

More Immunotherapy Is Not Necessarily Better

The success of consolidation durvalumab led investigators to explore whether introducing immunotherapy earlier, during chemoradiotherapy itself, might further improve outcomes.

However, the phase III PACIFIC-2 trial did not demonstrate this benefit. The study randomized 328 patients to receive durvalumab or placebo concurrently with chemoradiotherapy, followed by the corresponding consolidation treatment.

The primary PFS endpoint was not met (HR 0.85; 95% CI 0.65–1.12; p=0.247). There was also no significant OS improvement (HR 1.03; 95% CI 0.78–1.39; p=0.823). Treatment discontinuation due to adverse events was more frequent in the durvalumab group.

These findings emphasize that the clinical effectiveness of immunotherapy depends not only on the agent but also on its timing within the treatment sequence. Combining immune checkpoint blockade with thoracic radiotherapy may increase treatment complexity without necessarily improving survival.

Other strategies evaluating intensified consolidation immunotherapy and novel combinations remain under investigation, including approaches targeting additional immune checkpoints and the tumor microenvironment.

However, these approaches should not displace established treatment pathways before randomized evidence demonstrates a favorable benefit-risk balance.

Resectable Locally Advanced NSCLC: Perioperative Therapy Changes the Treatment Paradigm

For selected patients with resectable stage III disease, the treatment landscape has evolved through the introduction of neoadjuvant chemoimmunotherapy and perioperative immune checkpoint inhibition. The phase III KEYNOTE-671 trial demonstrated the durability of this approach.

Patients with resectable stage II, IIIA, or selected stage IIIB (N2) NSCLC received neoadjuvant pembrolizumab plus chemotherapy followed by surgery and adjuvant pembrolizumab, or the corresponding placebo-containing strategy.

At five years, event-free survival was 49.9% with pembrolizumab versus 26.5% with placebo. Five-year OS was 64.6% versus 53.6%, corresponding to an HR for death of 0.74. These findings confirm that perioperative immunotherapy can provide durable survival improvements in appropriately selected patients.

Other randomized trials, including CheckMate 816, CheckMate 77T, and AEGEAN, have further strengthened the evidence supporting immunotherapy-based strategies in resectable NSCLC. However, surgical eligibility and the optimal use of neoadjuvant therapy require careful multidisciplinary evaluation.

Patients with extensive mediastinal disease or a low likelihood of complete resection may be better served by definitive chemoradiotherapy and consolidation treatment. Conversely, selected patients with technically resectable disease may benefit from a perioperative treatment strategy.

The most important consideration is not whether surgery or radiotherapy is universally superior, but whether the chosen pathway provides the greatest likelihood of durable disease control with acceptable morbidity.

Radiotherapy Advances: Precision, Safety, and Treatment Completion

Modern radiotherapy remains central to locally advanced lung cancer management. Intensity-modulated radiotherapy, image guidance, improved target delineation, and adaptive planning approaches have expanded opportunities to deliver effective treatment while reducing unnecessary radiation exposure to normal tissues.

For unresectable stage III NSCLC, a conventional radiation dose of approximately 60 Gy delivered with platinum-based concurrent chemotherapy remains a standard approach. However, treatment intensification through higher radiation doses has not consistently improved outcomes and may increase toxicity.

The challenge is therefore to optimize treatment quality rather than simply escalate radiation intensity. Radiation planning must carefully account for lung dose, esophageal exposure, cardiac structures, tumor motion, and baseline pulmonary function.

These considerations become particularly important when radiotherapy is followed by immunotherapy or targeted therapy associated with pneumonitis. Patients receiving durvalumab or osimertinib after chemoradiotherapy require careful evaluation for respiratory symptoms and radiographic abnormalities.

Distinguishing radiation pneumonitis, immune-mediated pneumonitis, drug-associated interstitial lung disease, infection, and cancer progression can be clinically challenging.

Early communication between radiation oncology, medical oncology, radiology, and pulmonary specialists is essential. The broader principle is that successful multimodality therapy depends not only on treatment efficacy but also on the patient’s ability to complete the intended sequence safely.

Limited-Stage SCLC: ADRIATIC Establishes a New Consolidation Strategy

The integration of immunotherapy after chemoradiotherapy has also transformed limited-stage SCLC. Historically, concurrent platinum–etoposide chemotherapy and thoracic radiotherapy formed the principal curative-intent treatment strategy.

The phase III ADRIATIC trial demonstrated that consolidation durvalumab following chemoradiotherapy significantly improves survival in patients without disease progression. Median OS was 55.9 months with durvalumab compared with 33.4 months with placebo (HR 0.73; p=0.01).

Median PFS reached 16.6 versus 9.2 months (HR 0.76; p=0.02). These results supported regulatory approval of durvalumab for limited-stage SCLC after concurrent platinum-based chemoradiotherapy. ADRIATIC demonstrates that effective integration of local treatment and systemic immunotherapy can extend beyond NSCLC.

However, important questions remain concerning optimal radiotherapy fractionation, prophylactic cranial irradiation, brain MRI surveillance, long-term toxicity, and selection of patients most likely to benefit.

The findings reinforce the importance of managing limited-stage SCLC through coordinated multidisciplinary care rather than viewing systemic treatment and radiotherapy as independent components.

Circulating Tumor DNA Could Enable More Personalized Consolidation

One of the most promising future directions in locally advanced lung cancer is circulating tumor DNA-based minimal residual disease assessment. Following definitive chemoradiotherapy or surgery, patients may have no radiologically measurable disease but remain at risk of recurrence from microscopic residual cancer.

Detection of tumor-derived DNA in plasma may provide an additional method of estimating recurrence risk. Studies in stage III NSCLC have demonstrated associations between persistent ctDNA positivity and unfavorable outcomes, while ctDNA clearance may identify patients with better prognosis.

However, these findings have not yet established a validated approach for changing consolidation therapy. It remains uncertain whether ctDNA-negative patients can safely receive shorter or less intensive treatment, or whether ctDNA-positive patients benefit from additional treatment escalation.

Assay sensitivity, sampling intervals, low tumor DNA shedding, and the interpretation of negative findings are important limitations. Prospective interventional studies will be needed to determine whether ctDNA-guided treatment improves outcomes compared with established approaches.

For now, ctDNA should be considered an emerging risk-stratification tool rather than a routine substitute for molecular profiling, imaging, or standard consolidation therapy.

Integrating Supportive Care and Improving Global Access

While novel drugs and radiation technologies continue to improve outcomes, access to coordinated care remains a major determinant of treatment success. Patients with locally advanced lung cancer often require multiple appointments, complex diagnostic investigations, prolonged treatment courses, and close monitoring for toxicity.

Delays in molecular testing, incomplete staging, interruptions in radiotherapy, and limited access to multidisciplinary assessment may compromise the ability to deliver curative-intent treatment. Effective supportive care should therefore begin at diagnosis rather than after treatment-related complications occur.

Nutritional assessment, smoking cessation, pulmonary rehabilitation, symptom management, psychosocial support, and assessment of comorbidities can contribute to treatment tolerance and quality of life.

Patient navigation and communication between specialties are particularly important when treatment involves sequential surgery, chemotherapy, radiotherapy, immunotherapy, or targeted therapy. These challenges are even more pronounced in resource-limited settings, where access to molecular diagnostics, advanced radiation technology, and newer systemic treatments may vary considerably.

A truly integrated approach must therefore combine evidence-based treatment selection with practical strategies for equitable delivery. The global format of LungÕ 2026 offers an opportunity to bring these discussions to clinicians working across different healthcare environments.

What Should Change in Clinical Practice?

The key development in locally advanced lung cancer is the movement from largely stage-based treatment decisions toward biologically informed, multidisciplinary pathways.

For patients with potentially resectable disease, the decision between surgery-containing and definitive nonsurgical treatment should be established through careful evaluation of tumor extent, mediastinal involvement, functional status, and the anticipated benefits and risks of each strategy.

For unresectable stage III NSCLC without a sensitizing EGFR mutation, definitive chemoradiotherapy followed by consolidation durvalumab remains a central evidence-based approach. For unresectable EGFR exon 19 deletion- or L858R-mutated disease, osimertinib after chemoradiotherapy provides a distinct molecularly guided consolidation pathway.

For limited-stage SCLC, consolidation durvalumab after concurrent chemoradiotherapy has become an important standard supported by an overall survival benefit. Across these settings, advances in radiation delivery, toxicity monitoring, and multidisciplinary coordination are essential to maximizing the benefit of systemic treatment.

However, substantial unmet needs persist. Many patients experience recurrence, develop treatment-limiting toxicity, or are unable to access the complete recommended treatment sequence. Research into molecular residual disease, novel immunotherapy combinations, targeted treatment, and adaptive radiotherapy may help address these gaps.

OncoDaily Takeaway

Locally advanced lung cancer is entering an era in which treatment outcomes depend increasingly on the integration of surgery, radiotherapy, systemic therapy, molecular profiling, and supportive care.

PACIFIC established durable survival benefit with consolidation durvalumab after chemoradiotherapy in unresectable stage III NSCLC, while LAURA demonstrated the transformative potential of EGFR-directed consolidation with osimertinib.

KEYNOTE-671 and other perioperative studies have expanded treatment opportunities for selected resectable patients, and ADRIATIC has introduced a survival-improving consolidation strategy for limited-stage SCLC.

At the same time, negative studies such as PACIFIC-2 emphasize that treatment intensification must be supported by randomized evidence rather than biological rationale alone.

Future advances will increasingly depend on accurate molecular characterization, improved selection between resectable and unresectable treatment pathways, better management of pulmonary toxicity, and prospective validation of response-adapted strategies.

The central message of “Integrating Care: Advances in Locally Advanced Disease” is that the future of lung oncology lies not simply in adding more treatments, but in combining the right treatments in the right sequence for the right patient.

As LungÕ 2026 brings the international thoracic oncology community together, translating these advances into coordinated, accessible, and patient-centered care remains one of the most important priorities for improving long-term outcomes.

About LungÕ 2026

LungÕ 2026 – Virtual Global Congress on Lung Oncology

Date: November 5, 2026
Format: Virtual international congress
Organizer: OncoDaily
Series: OncoDaily O Series

Congress information and registration: https://oncodaily.com/lungo-2026-virtual-global-congress-on-lung-oncology

Scientific Sources

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