Lung Cancer Diagnosis and Staging During COVID-19

By Brendon Stiles, MD

A remarkable publication in early August described the progress we have made in reducing lung cancer mortality during the past several years.¹  This has been due to a combination of factors including decreased incidence, earlier detection, better staging, and introduction of targeted therapy. These advances have led to dramatic increases in 2-year relative survival after a diagnosis of lung cancer for both men and women. However, that progress has the potential to be significantly reversed by the COVID-19 pandemic, which has disrupted the entire spectrum of cancer care. This may be particularly true of lung cancer, a disease with respiratory symptoms that may mimic those of COVID-19. 

During the pandemic, lung cancer screening (LCS) programs were largely suspended, and symptomatic patients potentially postponed seeking medical treatment or were misdiagnosed. Additionally, the invasive procedures required for appropriate diagnosis and staging are often potentially aerosol-generating procedures—a fact that may introduce further delays or even lead to elimination of some standard diagnostic procedures due to the potential for health-care provider exposure to COVID-19. As a result, the nation has seen plummeting rates of new lung cancer diagnoses, approaching a 50% decline in the most severely impacted states. Clearly a need exists to channel resources to lung cancer screening programs, radiologists, pulmonologists, and thoracic surgeons in order to anticipate the increased efforts required to diagnosis and stage the thousands of patients who have likely gone undiagnosed during the COVID-19 pandemic. Without such an effort, further delays in diagnosis may lead to an excess in lung cancer deaths that, in turn, might very well erase the gains we have made during the past decade.

Returning to Best Practices

The pathway back is relatively straightforward.  In the areas where COVID-19 infection rates are low or decreasing, we must get screening and nodule-detection programs back up to speed. Because LCS rates of eligible patients were already markedly lower than those of other cancer screening programs, we must do more than just “reopen” screening programs. The fear of increased progression of respiratory failure in smokers with COVID-19 and the uncertainty about the effects of nicotine on infection rates make this a critical time to fund and focus on tobacco cessation programs. In addition, a concerted effort must be made to increase LCS referrals at the primary care level by discussing the benefits of screening and by fairly explaining the associated risks, which are quite low. Telemedicine may also allow some LCS programs to decrease the burden on primary care physicians, to ultimately have a broader geographic reach, and to facilitate the shared decision-making visit. Similarly, programs for incidentally detected suspicious lung nodules may be better able to contact and follow patients through telemedicine.  Investments in infrastructure or in teams to track these patients will be critical, particularly in areas where high volumes of CT scans were performed for patients with COVID-19.

Fear of COVID-19 exposure exists on both the patient and physician side of invasive procedures, such as those aerosol-generating procedures involved in the investigation of suspicious nodules: bronchoscopy, navigational bronchoscopy, and endobronchial ultrasound. Clearly we must choose carefully which types of nodules require invasive workups. For LCS, adherence to the Lung-RADS classification system should generally establish the correct diagnostic pathway.² Incidentally detected nodules are perhaps more challenging. Certainly the workup of non-solid nodules and of some-part-solid nodules can be delayed in areas with high active COVID-19 infection rates. However, patients with solid nodules, symptomatic patients, or those with apparent higher-stage clinical disease deserve a timely and efficient definitive diagnosis and stage. Clearly hospitals and clinics need to establish procedures for pre-visit screening to query patients about COVID-19 symptoms and risk factors. Even more important is the establishment of and adherence to a process for rapid pre-procedure COVID-19 PCR testing. Scheduling should be facilitated in order to group tests and procedures around the COVID-19 testing in order to avoid the need for several rounds of testing.  Similarly, PET scans should be obtained early in the workup process, before tissue biopsy when insurance allows, to complete clinical staging in order to optimize targeted invasive staging. Liquid biopsy for patients with an apparent high burden of disease is an effective adjunct to invasive biopsy for molecular diagnosis and may be appropriate in many cases. When a tissue diagnosis is required, percutaneous biopsy done under local anesthesia carries a low risk of aerosolization and may in many cases be preferable to other procedures, such as navigational bronchoscopy and EBUS for diagnosis. However, when bronchoscopic biopsy or mediastinal staging is necessary, it can be done safely when effective testing protocols exist. This does not obviate the need for personal protective equipment.  Aerosol-generating procedures should ideally be done in negative-pressure rooms where available. Although procedures should be performed expeditiously, obtaining an accurate diagnosis and enough tissue for molecular studies remain critical. Staging procedures should, therefore, generally be performed by experienced operators with rapid on-site pathology. Our preference is for patients to be under general endotracheal anesthesia in order to minimize coughing and to maintain a closed respiratory circuit. The Society for Advanced Bronchoscopy has written a consensus statement and guidelines for bronchoscopy during the COVID-19 pandemic, which provide a helpful and practical framework for such procedures.³

Finally, where resources allow, some situations may arise in which it is advantageous to forego attempts at percutaneous or bronchoscopic biopsy and proceed straight to surgical excisional biopsy and staging for highly suspicious nodules. However, this practice should generally be minimized given the potential for increased respiratory complications in patients who are at higher risk for COVID-19 and should be limited to peripheral nodules, which can easily be removed with minimally invasive sublobar resections for diagnosis. Surgical OR availability obviously depends on local resources and on the phase of COVID-19 infections in the individual hospital. In a rapidly escalating phase in which OR supplies and hospital beds are limited, consideration may need to be given to alternative treatment approaches, such as stereotactic ablative radiotherapy for stage I tumors or to neoadjuvant therapy for patients with clinical stage IB-III disease, for diagnosed cancers.  

In conclusion, the stakes are high for patients with lung cancer during the COVID-19 pandemic. There has already been a remarkable decrease in new diagnoses of lung cancer patients. It would seem unlikely that the true incidence of lung cancer is decreasing, but rather that many patients are simply going undiagnosed either because they are avoiding the medical system or because that system is failing to get the patients’ workups done in a timely fashion.  Such delays in diagnosis may have disastrous consequences regarding survival rates.⁴  It is beholden on us to accurately and efficiently diagnose, stage, and molecularly classify new patients with lung cancer, even in the COVID-19 era. 

References

1. Howlander N, Forjaz G, Mooradian MJ, Meza R, et al.  The effect of advances in lung-cancer treatment on population mortality. N Engl J Med. 2020;383:640-649. 
2. American College of Radiology. Lung CT Screening Reporting & Data System (Lung-RADS). https://www.acr.org/Clinical-Resources/Reporting-and-Data-Systems/Lung-…. Accessed September 3, 2020.
3. Pritchett MA, Oberg CL, Belanger A, et al.  Society for Advanced Bronchoscopy Consensus Statement and Guidelines for bronchoscopy and airway management amid the COVID-19 pandemic.  J Thor Dis. 2020;12(5):1781-1798.
4. Maringe C, Spicer J, Morris M, Purushotham A, et al.  The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modeling study.  Lancet Onc. 2020;21:1023-1034.