FDG PET–CT Versus CT for Lung Cancer Surveillance: The "Con" Side

Lung cancer remains the leading cause of cancer-related deaths.¹ Advances in early detection of lung cancer following the implementation of screening programs and the availability of newer therapies have increased the number of patients treated with curative intent. Proportionally, lung cancer surveillance after curative therapy is also growing. It is imperative now more than ever to detect relapsed, recurrent, or new primary lung cancer early, during surveillance, so that early treatment can be initiated. Although recommendations of the timing of imaging surveillance vary, all national and international society guidelines, including those issued by the National Comprehensive Cancer Network, the European Society for Medical Oncology, and more recently the American Society of Clinical Oncology, recommend CT chest with or without contrast as the imaging modality of choice.^2-4 Imaging surveillance recommendations range from every 3 to 6 months for the first 2 to 3 years, and stipulate every 6 months for the next 2 years and annually after that. Despite the ability of fluorodeoxyglucose (FDG) PET–CT to provide functional and anatomical information, no society has recommended its use for routine surveillance. Currently, its role is limited to problem-solving when CT or clinical findings indicate new or recurrent disease.

Post-Treatment Surveillance

CT chest done with contrast and with the inclusion of the adrenal gland has a high negative predictive value of 99% for recurrence on post-treatment surveillance.⁵ Lou et al.⁶ showed that almost all second primary cancers and the majority of recurrences were detected by post-therapeutic surveillance CT scans. A more recent, large retrospective analysis of site and timing for lung cancer recurrence showed that overall, distant metastases occur more frequently than local or regional recurrence, and the brain was the single most common site of metastases.⁷ Surveillance PET–CT does not include the brain, because of its limited sensitivity in this region. The authors concluded that chest CT provides an adequate assessment of most other sites of recurrent disease, including lung, thoracic lymph nodes, adrenal glands, much of the liver, and the thoracic spine (the most common site of bone metastases).⁷ 
The evidence supporting surveillance following the treatment of lung cancer is limited to subgroups of the different stages and types of lung cancer and their initial therapies. There are even fewer studies comparing the effectiveness of chest CT versus FDG PET–CT for surveillance following treatment. Choi et al.,⁸ in their prospective study for resected NSCLC, incorporated annual PET–CT in addition to surveillance chest CT. They concluded that although PET–CT detected recurrence earlier than CT alone, there was no statistically significant survival difference between the two imaging modalities. Mansueti et al.,⁹ in their retrospective study, evaluated PET–CT versus CT on OS in stage I–III NSCLC and concluded that there was no statistical difference in OS. Reddy et al.,¹⁰ in their retrospective study, compared the surveillance efficacy of PET–CT versus CT for stage III NSCLC treated with definitive radiation. They found that PET–CT surveillance did not result in decreased time to detection of locoregional or distant recurrence or in improved survival. The most recent randomized prospective pilot trial, by Gambazzi et al.,¹¹ compared FDG PET–CT and CE–CT surveillance for patients with NSCLC after treatment with curative intent over a period of 2 years. This study found similar sensitivity, specificity, and positive predictive value between the two imaging modalities and concluded that PET–CT did not demonstrate an added benefit for routine surveillance. The number of potentially curable recurrences was similar in the two groups. 

Dose, Cost, and Confounding Factors

Whereas some argue that PET–CT is more sensitive for the detection of regional and distant recurrences, the factors that prevent its incorporation into the surveillance algorithm include the radiation dose and the cost. There is a much higher radiation dose associated with PET–CT, approximately 32 mSv as compared to 3–7 mSv for a standard chest CT.⁴ Similarly, consider that PET–CT costs approximately $3,000, whereas CT chest can be $190 to $230, depending on the use of contrast.⁴ Work-up of incidental findings in the abdomen and pelvis can also add to the costs.

False-positive PET–CT examinations are known to occur after radiation therapy, precluding its use for at least 3 months after radiotherapy. It has also been shown that there may be persistent FDG uptake at the treatment site for up to 2 years, especially after stereotactic body radiation therapy.¹² Brown fat, infections, inflammatory conditions such as sarcoid-like reaction to chemotherapy, and increased bone marrow uptake for patients on marrow-stimulating agents, are some factors that can also confound PET–CT interpretation. Gambazzi et al.,¹¹ in their pilot study, found a 22% false-positive rate in PET–CT examinations as compared to a 17% false-positive rate in CTs. False-negative PET–CT examinations include nodules < 8 mm in size, growing small nodules, and subsolid nodules. Lower lobe nodules may not be easily detected because of motion artifact, given the longer length of PET–CT examination, which precludes breath-holding.¹³ The variable physiologic uptake of FDG by normal tissues and the altered biodistribution of FDG related to hyperglycemia or hyperinsulinemia may also be confounding factors. Other challenges with PET–CT include longer examination times and preprocedure patient preparation, such as limitations for diet and physical activity. A chest CT can be obtained with minimal or no patient preparation and CT chest scanners are more universally available compared to the more expensive PET–CT scanners.

In summary, although there is a paucity of prospective trials and high-quality population-based data for appropriate surveillance strategy following definitive treatment of lung cancer, currently chest CT continues to be the imaging modality of choice. Surveillance guidelines will, however, need continual reassessment, especially with the evolution of novel approaches such as blood-based biomarkers, newer radiotracers, and molecular imaging strategies, in conjunction with the improving local and systemic salvage options. The future is likely to hold a personalized and more integrated approach to lung cancer surveillance.

References:

1. Key statistics for lung cancer. Cancer.org. Accessed August 31, 2020. https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html
2. Clinical practice guidelines in oncology, non small cell cancer. Small cell cancer Version 6.2020. National Comprehensive Cancer Network. Accessed August 31, 2020. https://www.nccn.org/professionals/physician_gls/pdf/nscl_blocks.pdf
3. ESMO clinical practice guidelines: lung and chest tumours. European Society for Medical Oncology. Accessed August 31, 2020. https://www.esmo.org/guidelines/lung-and-chest-tumours
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