Micrometastatic Disease
Recurrence remains a challenge in operable/resectable Stage II to III NSCLC—it often involves micrometastatic disease that may not be addressed with surgery alone1,2
42%
of patients with resectable
Stage II NSCLC experience recurrence within 3 years of surgery3
62%
of patients with resectable
Stage III NSCLC experience recurrence within 3 years of surgery3
Surgery-based Approaches
In resectable Stage II to III NSCLC,
Guidelines recommend incorporating neoadjuvant and/or adjuvant immunotherapy as needed4
National Comprehensive Cancer Network® (NCCN®) Treatment Recommendations Regarding Immunotherapy in Operable Disease
Clinical staging
Stage IIA (T2b, N0; T1, N1)
Stage IIB (T1, N2a; T2a-2b, N1; T3, N0)
Stage IIIA (T1, N2b; T2-3, N2a; T3, N1; T4 [size], N0-1)
Stage IIIB (T2-3, N2b)
Pretreatment evaluation
(including biomarker testing, eligibility for perioperative therapy, pathologic LN evaluation, etc)
Negative mediastinal LN
(if clinically indicated)
Neoadjuvant treatment (dependent on disease stage and extent of nodal involvement)
- Anti-PD-(L)1 + chemotherapy
- Targeted therapy ± chemotherapy (for patients with certain mutations)
- Chemotherapy (if ineligible for immunotherapy or targeted therapy and are likely to receive adjuvant chemotherapy)
- None
Surgical resection + LN dissection
(or systemic LN sampling)
Adjuvant treatment (dependent on disease stage and margins)
If margins are negative (R0):
- Observe
- Adjuvant systemic therapy, including:
- Anti-PD-(L)1 monotherapy (no known EGFR mutations or ALK gene fusions)
- Targeted therapy (for patients with certain mutations)
- Chemotherapy (only if neoadjuvant chemotherapy was not previously given)
- Sequential chemotherapy and consider RT
If margins are positive (R1, R2):
- Resection ± systemic therapy
- RT ± systemic therapy
- CRT (sequential or concurrent)
The NCCN NSCLC Panel recommends perioperative therapy for all histologies in eligible patients with locally advanced disease…there should be a high probability of complete resection (R0) before initiation of a neoadjuvant approach. Neoadjuvant therapy to induce resectability is an unproven approach4
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC V.7.2026
Talking to Patients About a Perioperative IO-based Regimen
Watch the lung cancer MDT at AdventHealth discuss diagnosis and staging for optimal NSCLC care.
Featuring: Dr Fortune Alabi, Pulmonologist; Dr Chung-Che (Jeff) Chang, Molecular Pathologist; Dr Charles (Wes) Hodge, Radiation Oncologist; Dr Tarek Mekhail, Medical Oncologist; Dr Mark Socinski, Medical Oncologist Brenda Rzeszutko, Nurse Navigator
Dr Sepesi:
Welcome to Beyond the Blade. I’m Dr Boris Sepesi. I’m a thoracic surgeon at Sarah Cannon Cancer Network, HCA HealthONE in Englewood, CO.
Dr Sepesi:
In this video, we’ll discuss an important role for community surgeons in early stage non-small cell lung cancer.
Dr Sepesi:
Perioperative IO-based regimens with neoadjuvant IO plus chemotherapy before surgery and adjuvant IO after surgery have recently been approved for use in early stage non-small cell lung cancer.
Dr Sepesi:
It’s increasingly important for surgeons in community practices to know that these regimens are FDA approved for resectable non-small cell lung cancer and what the implications are for their practice, including the need to refer appropriate patients to a medical oncologist to discuss this treatment option prior to surgery.
Dr Sepesi:
To discuss this, we have gathered academic and community surgeons with diverse surgical backgrounds and experiences with IO plus chemo before and IO alone after surgery.
Dr Khandhar:
I’m Sandeep Khandhar. I’m a thoracic surgeon at the Virginia Cancer Specialist Practice in Northern Virginia.
Dr Okusanya:
I’m Olugbenga Okusanya. I’m a thoracic surgeon at Thomas Jefferson Health.
Dr Sepesi:
Patients put a lot of trust in surgeons. They don’t necessarily understand the biology of cancer the way we do and therefore it is important for us to guide patients throughout the entire course of therapy rather than just through the surgical treatment.
Dr Khandhar:
When we talk to patients about lung cancer resection, we are often the last appointment. They’ve seen pulmonology, radiology, medical oncology, sometimes radiation oncology before they come to us. And tensions are always very high. They want their tumor cut out and they want it cut out right away. Sometimes just removing that tumor and cutting it out is not always the best option. We know that recurrence rates are high.
Dr Okusanya:
I think it’s really important to talk to our patients about what their available options are. The last thing you would ever want is a patient to leave your clinic, see a commercial, and then come back to you and say, “Hey, what about this option? Is that something I’m a candidate for?”
Dr Okusanya:
So, engaging your patients in a conversation about any particular option, I think is reasonable, even if you don’t think that’s the option that they should take. But maybe in the case of a perioperative IO-based regimen, that’s the one they should take. So, I think making sure to take the time to have an open discussion and build a relationship with your patient is really critical in order to move forward.
Dr Sepesi:
Here are key ways to talk to your patients about a perioperative IO-based regimen.
Dr Khandhar:
Number one. Immunotherapy plus chemotherapy before surgery works in two ways. In preclinical models, it activates your body’s own immune system to find and attack those cancer cells and destroys rapidly growing cancer cells. Additionally, giving immunotherapy after surgery may help remove any remaining cancer cells. IO may also affect normal, healthy cells.
Dr Okusanya:
Number two. Perioperative regimens are one of the latest advances in lung cancer treatment for early-stage non-small cell lung cancer and have been studied in several major clinical trials.
Dr Khandhar:
Number three. A perioperative IO-based regimen requires a team of specialists, instead of just one physician, to focus on you and your lung cancer. This ensures that your situation and all treatment options are discussed by all relevant specialties so you can receive the best possible care.
Dr Okusanya:
Number four. With a perioperative IO-based regimen, as with all cancer treatments, you, as the patient, are the most important member of your care team. You should feel free to ask all the questions you have of the other members of the care team so that you’re confident in the treatment you’re receiving.
Dr Khandhar:
Number five. A perioperative IO-based regimen provides the opportunity before surgery to make important lifestyle changes such as quitting smoking, exercising, and other activities that might improve how you do with surgery.
Dr Okusanya:
Number six. Perioperative IO-based regimens are recommended by lung cancer experts and treatment guidelines for appropriate patients with resectable non-small cell lung cancer.
Dr Khandhar:
Number seven. With surgery, our goal is curative intent. Perioperative IO-based regimens are the latest advance in the curative intent setting of resectable non-small cell lung cancer.
Dr Sepesi:
Doctors, thank you for sharing this helpful information for community surgeons to share with appropriate patients. I think it’s important to emphasize that perioperative IO-based regimens are FDA approved and becoming a standard of care for resectable non-small cell lung cancer. They’re also recommended by thoracic surgery guidelines as well as other treatment guidelines.
Dr Sepesi:
It is critical that all community surgeons have open conversations with their patients and refer them to medical oncologists prior to surgery to ensure patients can make informed decisions on what treatment is best for them.
Dr Sepesi:
Thanks for watching. Be sure to “like” the video and subscribe to this channel for more expert insights.
5 Reasons for Using a
Perioperative IO-based Regimen
Watch the lung cancer MDT at AdventHealth discuss diagnosis and staging for optimal NSCLC care.
Featuring: Dr Fortune Alabi, Pulmonologist; Dr Chung-Che (Jeff) Chang, Molecular Pathologist; Dr Charles (Wes) Hodge, Radiation Oncologist; Dr Tarek Mekhail, Medical Oncologist; Dr Mark Socinski, Medical Oncologist Brenda Rzeszutko, Nurse Navigator
Dr Sepesi:
Welcome to Beyond the Blade. I’m Dr Boris Sepesi. I’m a thoracic surgeon at Sarah Cannon Cancer Network, HCA HealthONE in Englewood, CO.
Dr Sepesi:
Perioperative IO-based regimens with neoadjuvant IO plus chemotherapy before surgery and adjuvant IO after surgery have recently been approved for use or are being studied in early-stage non-small cell lung cancer.
Dr Sepesi:
It is important for all community thoracic surgeons to know about these regimens and what we are going to discuss today are reasons for the use of these perioperative IO-based regimens.
Dr Sepesi:
To discuss this, we have gathered academic and community surgeons with diverse surgical backgrounds and experiences with IO plus chemo before and IO alone after surgery.
Dr Khandhar:
I’m Sandeep Khandhar. I’m a thoracic surgeon at the Virginia Cancer Specialist Practice in Northern Virginia.
Dr Okusanya:
I’m Olugbenga Okusanya. I’m a thoracic surgeon at Thomas Jefferson Health.
Dr Sepesi:
There are known risks with a perioperative regimen from the potential for surgical delays, patient attrition, complications from the systemic treatment, etc.
Dr Sepesi:
In my practice, I really try to communicate with medical oncologists, and we also utilize nurse navigators to really follow these patients even while they’re getting their neoadjuvant therapy to make sure that they are going through the process safely, to really learn about how they’re tolerating the regimen as we plan the operations.
Dr Okusanya:
I think it’s really important for thoracic surgeons to know this because I personally remember seeing a patient with an early-stage lung cancer who was going to be a candidate for these strategies that could help her in her pathway. And I think it’s really important for all surgeons, all community surgeons, academic surgeons to be able to have these options to present to their patients.
Dr Sepesi:
Here’s our list of our reasons for using perioperative IO-based regimens. Dr Okusanya, please get us started.
Dr Okusanya:
Number five. Like to be at the forefront of treatment advances? Perioperative IO-based regimens are one of the latest treatment advances and are becoming a standard-of-care for appropriate patients in the curative-intent setting of resectable non-small cell lung cancer.
Dr Khandhar:
Number four. Resectable non-small cell lung cancer is heterogeneous and often involves micrometastatic disease. Cancer cells that spread beyond the tumor may lead to recurrence after surgery. It is hypothesized that an IO regimen before surgery may reduce tumor burden prior to definitive therapy and may target circulating cancer cells, while IO after surgery may target any remaining cancer cells.
Dr Okusanya:
Number three. Many of the patients who have heard about perioperative regimens as a treatment option may appreciate learning from us how an IO regimen works with their body’s own immune system to activate T cells before surgery to fight the cancer and how it works after surgery to continue to destroy cancer cells. It is also important to tell them that an IO may also affect healthy cells.
Dr Khandhar:
Number two. My reasons for treating patients with an IO-based regimen before surgery are that performance status should be ideal and compliance rates with systemic therapy may be higher. The time before surgery also provides the opportunity for patients to incorporate lifestyles modifications, such as short-term smoking cessation and pre-surgery exercise, that may help improve performance status and outcomes.
Dr Okusanya:
Number one. Despite our best efforts with R0 resections, only about a third of patients with resectable non-small cell lung cancer are alive at 5 years. Patients with resectable non-small cell lung cancer may require a multimodal approach that’s inclusive of surgery and systemic therapy, such as with an IO-based regimen before and after surgery. Referring these patients to a medical oncologist and collaborating with them is key for helping them make an informed treatment decision.
Dr Sepesi:
Doctors, thank you for sharing this list. I think it’s important to emphasize that perioperative IO-based regimens are becoming a standard-of-care for resectable non-small cell lung cancer and recommended by surgical societies and various treatment guidelines.
Dr Sepesi:
Surgeons should refer all appropriate patients to medical oncologists and truly collaborate with them, communicate with them even on treatment decisions.
Dr Sepesi:
Thanks for watching. Be sure to “like” the video and subscribe to this channel for more expert insights.
KEY POINTS
A multimodal approach to the treatment of Stage II to III NSCLC can help optimize outcomes where appropriate
- Recurrence remains a challenge in operable/resectable Stage II to III NSCLC—it often involves micrometastatic disease that may not be addressed with surgery alone1,2
- Guidelines recommend incorporating immunotherapy into the neoadjuvant, perioperative, or adjuvant setting4
- There should be a high probability of complete resection (R0) before initiation of a neoadjuvant approach—guidelines do NOT recommend using neoadjuvant therapy to induce resectability4
ALK=anaplastic lymphoma kinase; CRT=chemoradiotherapy; EGFR=epidermal growth factor receptor; IO=immuno-oncology; LN=lymph node; NCCN=National Comprehensive Cancer Network® (NCCN®); PD-(L)1=programmed cell death protein 1 or programmed death-ligand 1; RT=radiation therapy.
References: 1. Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Transl Lung Cancer Res. 2014;3(4):242-249. 2. Hüyük M, Fiocco M, Postmus PE, Cohen D, von der Thüsen JH. Systematic review and meta-analysis of the prognostic impact of lymph node micrometastasis and isolated tumour cells in patients with stage I-IIIA non-small cell lung cancer. Histopathology. 2023;82(5):650-663. 3. Rajaram R, Huang Q, Li RZ, et al. Recurrence-free survival in patients with surgically resected non-small cell lung cancer: a systematic literature review and meta-analysis. Chest. 2024;165(5):1260-1270. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed August 7, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
This information is intended for US Healthcare Professionals only.
©2026 AstraZeneca. All rights reserved. US-108160 Last Updated 7/26
