Recurrence Remains a Risk Even for Patients Diagnosed via Screening

With the increasing implementation of lung cancer screening during the past decade, survivors of operable early-stage lung cancer represent a growing and evolving population. While lung cancer screening has been associated with earlier detection of disease and improved survival, recurrence remains a major issue even in early-stage disease. Potter and colleagues recently published a study in the Annals of Thoracic Surgery evaluating the frequency of recurrence in patients from the National Lung Screening Trial (NLST) with pathologic stage I-II non-small cell lung cancer (NSCLC) who underwent complete resection with either lobectomy or bilobectomy. They found that the 5-year cumulative incidence of recurrence was 20.1%. While the incidence of recurrence was lowest in patients diagnosed with lung cancer detected by low-dose CT (LDCT) screening, it was still 17%, raising concerns that recurrence remains a significant risk even for patients diagnosed via screening.1

Patients with early-stage NSCLC undergo resection often with the intent to cure. However, the rates of recurrence reported in this study indicate that many patients will not achieve a cure. This brings up questions surrounding how these patients should be monitored for recurrence. Several societies and organizations have published guidelines on surveillance protocols, which are mainly based on expert panel consensus.2,3,4,5 The guidelines all agree that periodic follow-up is needed but vary in the type of imaging they recommend and surveillance intervals. For example, the commonly followed National Comprehensive Cancer Network (NCCN) guidelines recommend a chest CT with or without contrast every 6 months for the first 2 to 3 years, followed by an LDCT chest annually.2 The less aggressive guidelines by the European Society for Medical Oncology (ESMO) recommend a contrast-enhanced spiral chest CT at 12 and 24 months, followed by a chest CT annually.5 The heterogeneity between the guidelines likely reflects the varying opinions and paucity of evidence on the topic.

The current postoperative surveillance guidelines generally recommend more intensive imaging intervals for only the first 2 to 3 years.2,3,4,5 The study by Potter and colleagues found that approximately 65% of recurrences developed 1 to 4 years after resection.1 This finding raises the question of whether biannual imaging intervals should be extended beyond 2 to 3 years. A one-size-fits-all surveillance protocol may not be the best approach for a population with variable risk of recurrence. The study by Potter et al. reflects a lung cancer screening population with a heavy smoking history. An elderly patient with an extensive smoking history has a different risk profile and prognosis than a young patient with minimal tobacco exposure. Specific patient subpopulations may benefit from surveillance protocols tailored to their individualized prognostic factors. However, individualized protocols may be more challenging to implement and less likely to be adhered to than a uniform protocol.

Many questions surrounding how to perform surveillance after resection of early-stage NSCLC remain unanswered. How long patients should continue to undergo yearly imaging surveillance is still unclear. An analysis of more than 20,000 lung cancer survivors from the Surveillance, Epidemiology, and End Results (SEER) National Cancer Institute database who had survived 5 years or more found that the median 10-year risk of second primary lung cancer was 8.4%.6 Of note, this is higher than the 6.4% risk of primary lung cancer noted in the NLST at a median follow-up time of 11.3 years, suggesting that surveillance should be continued with annual LDCT to detect second primary lung cancers for as long as the patient is deemed to benefit from earlier detection.7

The survivors of early-stage NSCLC undergo annual chest CT imaging for many years after their cancer resection. Often, thoracic surgeons continue to manage the longitudinal care of these patients, especially in stage I disease, where patients are less likely to be referred to oncology. In a national survey, primary care physicians expressed low confidence and knowledge of appropriate testing for cancer recurrence.8 Additionally, primary care physicians may not feel comfortable interpreting postoperative CT findings. As more institutions establish dedicated multidisciplinary nodule management teams, perhaps survivors of early-stage NSCLC should also be followed by such groups. We know that adherence to regular imaging for screening and incidental nodules is superior in centralized lung cancer screening and nodule management programs.9,10 These programs also offer the advantage of experience with smoking cessation counseling, shared decision-making, nodule tracking systems, and an established relationship with a multidisciplinary tumor board team.

While we explore these questions and areas of need, we must remain aware that the extent of benefit from surveillance remains uncertain. Current evidence shows that surveillance detects recurrence earlier but has not demonstrated a survival benefit even in a prospective randomized trial.3,11 However, these studies were done before the era of screening, and the field continues to evolve rapidly with new indications for immunotherapy and improved novel and targeted therapies. Research evaluating the survival benefit of early recurrence detection should be continued in the context of this evolution in lung cancer evaluation and treatment.

References:

• 1. Potter, Alexandra L., Christina L. Costantino, Raiya A. Suliman, Chinmay S. Haridas, Priyanka Senthil, Arvind Kumar, Nicholas R. Mayne, Nikhil Panda, Linda W. Martin, and Chi-Fu Jeffrey Yang. “Recurrence After Complete Resection for Non-Small Cell Lung Cancer in the National Lung Screening Trial.” The Annals of Thoracic Surgery 116, no. 4 (October 2023): 684–92. https://doi.org/10.1016/j.athoracsur.2023.06.004.
• 2. National Comprehensive Cancer Network. Non-Small Cell Lung Cancer (Version 1.2024). https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed January 8, 2024.
• 3. Schneider, Bryan J., Nofisat Ismaila, Joachim Aerts, Caroline Chiles, Megan E. Daly, Frank C. Detterbeck, Jason W.D. Hearn, et al. “Lung Cancer Surveillance After Definitive Curative-Intent Therapy: ASCO Guideline.” Journal of Clinical Oncology 38, no. 7 (March 1, 2020): 753–66. https://doi.org/10.1200/JCO.19.02748.
• 4. Colt, Henri G., Septimiu D. Murgu, Robert J. Korst, Christopher G. Slatore, Michael Unger, and Silvia Quadrelli. “Follow-up and Surveillance of the Patient With Lung Cancer After Curative-Intent Therapy.” Chest 143, no. 5 (May 2013): e437S-e454S. https://doi.org/10.1378/chest.12-2365.
• 5. Vansteenkiste, J., L. Crinò, C. Dooms, J.Y. Douillard, C. Faivre-Finn, E. Lim, G. Rocco, et al. “2nd ESMO Consensus Conference on Lung Cancer: Early-Stage Non-Small-Cell Lung Cancer Consensus on Diagnosis, Treatment and Follow-Up.” Annals of Oncology 25, no. 8 (August 2014): 1462–74. https://doi.org/10.1093/annonc/mdu089.
• 6. Han, Summer S., Gabriel A. Rivera, Martin C. Tammemägi, Sylvia K. Plevritis, Scarlett L. Gomez, Iona Cheng, and Heather A. Wakelee. “Risk Stratification for Second Primary Lung Cancer.” Journal of Clinical Oncology 35, no. 25 (September 1, 2017): 2893–99. https://doi.org/10.1200/JCO.2017.72.4203.
• 7. “Lung Cancer Incidence and Mortality with Extended Follow-up in the National Lung Screening Trial.” Journal of Thoracic Oncology 14, no. 10 (October 2019): 1732–42. https://doi.org/10.1016/j.jtho.2019.05.044.
• 8. Potosky, Arnold L., Paul K. J. Han, Julia Rowland, Carrie N. Klabunde, Tenbroeck Smith, Noreen Aziz, Craig Earle, John Z. Ayanian, Patricia A. Ganz, and Michael Stefanek. “Differences Between Primary Care Physicians’ and Oncologists’ Knowledge, Attitudes and Practices Regarding the Care of Cancer Survivors.” Journal of General Internal Medicine 26, no. 12 (December 2011): 1403–10. https://doi.org/10.1007/s11606-011-1808-4.
• 9. Smith, Harrison B., Ralph Ward, Cassie Frazier, Jonathan Angotti, and Nichole T. Tanner. “Guideline-Recommended Lung Cancer Screening Adherence Is Superior With a Centralized Approach.” Chest 161, no. 3 (March 2022): 818–25. https://doi.org/10.1016/j.chest.2021.09.002.
• 10. Osarogiagbon, Raymond U., Wei Liao, Nicholas R. Faris, Meghan Meadows-Taylor, Carrie Fehnel, Jordan Lane, Sara C. Williams, et al. “Lung Cancer Diagnosed Through Screening, Lung Nodule, and Neither Program: A Prospective Observational Study of the Detecting Early Lung Cancer (DELUGE) in the Mississippi Delta Cohort.” Journal of Clinical Oncology 40, no. 19 (July 1, 2022): 2094–2105. https://doi.org/10.1200/JCO.21.02496.
• 11. Westeel, Virginie, Pascal Foucher, Arnaud Scherpereel, Jean Domas, Philippe Girard, Jean Trédaniel, Marie Wislez, et al. “Chest CT Scan plus X-Ray versus Chest x-Ray for the Follow-up of Completely Resected Non-Small-Cell Lung Cancer (IFCT-0302): A Multicentre, Open-Label, Randomised, Phase 3 Trial.” The Lancet Oncology 23, no. 9 (September 2022): 1180–88. https://doi.org/10.1016/S1470-2045(22)00451-X.