Return to Part 1, Mounting Evidence Supporting Neoadjuvant ChemoIO Means Surgeons Must Adapt.
As discussed previously, even now, in the era of neoadjuvant immunotherapy and targeted therapy, surgery remains indispensable in treating many non-small cell lung cancer (NSCLC) patients. However, as we have seen from multiple clinical trials in recent years, significant improvements in long-term survival for our NSCLC patients are growing more quickly from advances in medical oncology.
Of course, we must consider the benefits that can be realized when combining the latest advances in both medical and surgical oncology. So again, here we will we discuss what lung cancer surgeons need to know to evolve in this revolutionary era.
Over- and Under-diagnosis and Treatment
Considerable data indicate that there is over-diagnosis and over-treatment for GGO-like indolent lung adenocarcinoma. Undoubtedly, the use of low-dose CT in screening high-risk populations for lung cancer has lowered lung cancer mortality by 20%.1 Still, we need to recognize that over-diagnosis, and accompanying over-treatment, have created psychological, physical, social, and economic issues. Although pathologic diagnosis is the main basis for surgical treatment of NSCLC, for GGO-like lung adenocarcinoma with indolent or even extremely indolent biological behavior, the decision to proceed with surgery should be made cautiously to avoid over-treatment. When GGO-like lung adenocarcinoma occurs in elderly and fragile patients, or in patients with severe comorbidities, it is rational to reject surgery as an option.2
Conversely, many studies have also shown that there is often insufficient pathological assessment of regional lymph nodes in lung cancer with completely solid features on imaging. The presence or absence of regional lymph node metastasis helps guide the choice of treatment strategy and the extent of resection. Failure to assess hilar and mediastinal nodes leads to incomplete staging. However, many surgeons fail to adequately assess regional nodes, relying instead on “clinical” or radiographic diagnosis instead of pathological diagnosis. To this end, preoperative ultrasound bronchoscopy (EBUS) examination and ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) for regional lymph nodes are not used sufficiently.
Insufficient diagnosis of regional lymph nodes confuses the concepts of “resectability” in surgical techniques and “curability” in oncology, resulting in inadequate treatment. As a result, patients who require systemic treatment before surgery undergo upfront surgery or even surgery with inadequate assessment of the hilum or mediastinum. Consequently, both over-diagnosis and treatment and under-diagnosis and treatment are important factors affecting the treatment outcome of NSCLC.3,4
Diagnosis and Whole-course Management
Once diagnosed, whole-course management should be offered to NSCLC patients. Firstly, because of LDCT screening programs for high-risk healthy individuals, the incidence of clinically discovered GGO-like lesions, and even multiple GGO-like lesions in the lungs, is increasing. Based on the weighted assessment of clinical risk, the following treatment strategies can be roughly proposed for these lesions:
- Periodic observation and scanning without immediate intervention;
- Observation for some GGOs and surgery or other local intervention for other GGOs;
- Staged surgeries for GGOs.
As we know, effective implementation of these strategies cannot be achieved without whole-course, inter-disciplinary management.2
Secondly, even for early-stage lung cancer determined to be resectable, a considerable number of patients may experience recurrence or metastasis after “curative resection.” The chances of recurrence or metastasis are greater after treatment of locally advanced lung cancer. Timely detection of postoperative recurrence or metastasis leads to timely intervention, which ultimately leads to improved survival. Conversely, if recurrence or metastasis is not identified in a timely manner, treatment will be delayed, and survival will be compromised. Dai et al. demonstrated that standardized follow-up and whole-course management after surgical treatment improve the long-term survival of patients.5
Third, with the emergence of more precise and more effective systemic treatment strategies, many patients with traditionally defined advanced lung cancer have survived for a long time, and the tumor burden in these long-term survivors is often reduced or relatively stable. Many patients have “oligo” metastases or induced “oligo” metastasis. Increasing attention has focused on administering local treatment for these oligo lesions. Whether to proceed with local treatment, when to adopt it, and what kind of local treatment to choose for these lesions all depends on timely diagnosis and management throughout the disease course.6
Fourth, because of the widespread use of targeted drugs and immunotherapy in postoperative patients, lung cancer, once a terminal illness at recurrence, is often becoming a chronic disease. However, we should not neglect the long-term toxicities of systemic treatment. In fact, cumulative treatment-related side effects are being experienced by patients, and thus they are receiving more attention from doctors and other care-givers. The discovery and resolution of these issues cannot be achieved without whole-course, inter-disciplinary management.
Fifth, an increasing number of early to advanced stage NSCLC patients require on-going multidisciplinary discussions to continuously revise treatment strategies during their treatment, a requirement that is particularly evident in large-volume cancer hospitals. This is both the reason for, and the result of, whole-course management. Regular tumor boards with all disciplines involved helps address this concern.
Sixth, after surgical treatment of primary lung cancer, the number of patients with metachronous or second primary lung cancer is also increasing. These new primary cancers also mandate timely treatment, highlighting once again the importance of whole-course management.
Multidisciplinary Discussions
Multidisciplinary management in oncology includes broad and narrow specialties. Most multidisciplinary tumor boards (MTBs) will include surgical, medical and radiation thoracic oncology, interventional pulmonary and interventional radiology, as well as individuals with expertise in radiologic and pathologic diagnostics, not to mention nursing, social service, and oncology pharmacy.
First, cancer is the result of long-term effects of many factors, including genetic susceptibility and exposure to cancer-causing agents. Aging also plays a role. Thanks to modern medicine, human life expectancy has increased significantly, bringing more and more cancer patients to our clinics with a wide range of comorbidities. For clinicians, the knowledge required to manage cancer while considering a patient’s other unique health concerns is becoming increasingly complex. There is an urgent need for interdisciplinary teams to communicate and work together in this arena.
Indeed, traditional medical education—from basic science to clinical skill, from surgery to internal medicine, and from system to organ—is fragmented and not highly integrated. Except for select cancer hospitals, oncological surgery is generally taught and performed by general surgeons, making it difficult to enforce strict guidelines for oncological surgery.
Finally, oncology is the most active research field globally. constantly evolving treatment methods are constantly evolving, and there has been a rapid expansion in new drugs with diverse targets and mechanisms of action. In short, it is almost impossible for a general oncologist to master all the knowledge and techniques related to cancer treatment. In fact, data indicate that patients who undergo treatment under the aegis of a multidisciplinary framework survive longer.7,8,9
In summary, because of significant progress in oncological research for NSCLC, and because surgery is an early and critical intervention during the whole-course management of NSCLC, lung cancer surgeons need to adjust accordingly to continue to improve survival and quality of life of NSCLC patients.
References:
- 1. Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. New England Journal of Medicine. Aug 4 2011;365(5):395-409. doi:10.1056/NEJMoa1102873
- 2. Chen KN. The diagnosis and treatment of lung cancer presented as ground-glass nodule. General thoracic and cardiovascular surgery. Jul 2020;68(7):697-702. doi:10.1007/s11748-019-01267-4
- 3. Saji H, Okada M, Tsuboi M, et al. Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): a multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial. The Lancet. 2022/04/23/ 2022;399(10335):1607-1617. doi:https://doi.org/10.1016/S0140-6736(21)02333-3
- 4. Altorki N, Wang X, Kozono D, et al. Lobar or Sublobar Resection for Peripheral Stage IA Non–Small-Cell Lung Cancer. New England Journal of Medicine. 2023;388(6):489-498. doi:doi:10.1056/NEJMoa2212083
- 5. Dai L, Yan W, Kang X, et al. Exploration of Postoperative Follow-up Strategies for Early Staged NSCLC Patients on the Basis of Follow-up Result of 416 Stage I NSCLC Patients after Lobectomy. Zhongguo fei ai za zhi = Chinese journal of lung cancer. Mar 20 2018;21(3):199-203. doi:10.3779/j.issn.1009-3419.2018.03.15
- 6. Chen KN. Factors to Consider in Surgical Resection of Pulmonary Metastatic Carcinoma. Annals of surgical oncology. Mar 2023;30(3):1297-1298. doi:10.1245/s10434-022-13059-x
- 7. Zeng Y, Zhu S, Wang Z, et al. Multidisciplinary Team (MDT) Discussion Improves Overall Survival Outcomes for Metastatic Renal Cell Carcinoma Patients. Journal of multidisciplinary healthcare. 2023;16:503-513. doi:10.2147/jmdh.s393457
- 8. Gaudioso C, Sykes A, Whalen PE, et al. Impact of a Thoracic Multidisciplinary Conference on Lung Cancer Outcomes. The Annals of thoracic surgery. Feb 2022;113(2):392-398. doi:10.1016/j.athoracsur.2021.03.017
- 9. Bilfinger TV, Albano D, Perwaiz M, Keresztes R, Nemesure B. Survival Outcomes Among Lung Cancer Patients Treated Using a Multidisciplinary Team Approach. Clinical lung cancer. Jul 2018;19(4):346-351. doi:10.1016/j.cllc.2018.01.006
