When should a Positron Emission Tomography (PET) scan be performed in patients with suspected cancer, neurological disorders, or cardiovascular disease?

When to Perform PET Scans: Evidence-Based Indications

PET scans should be performed when functional metabolic information will change clinical management in cancer staging, suspected recurrence with equivocal conventional imaging, or when differentiating benign from malignant lesions—not for routine screening or surveillance in asymptomatic patients.

Cancer-Specific Indications

Lung Cancer

• Order PET/CT for solid indeterminate pulmonary nodules ≥0.8 cm when pre-test probability of malignancy is 5-65%, as it demonstrates 88-96% sensitivity and 77-88% specificity for differentiating benign from malignant nodules 1
• Perform PET/CT for initial staging of confirmed lung cancer to assess locoregional involvement and detect distant metastases, particularly adrenal gland involvement 2
• Use PET/CT for suspected recurrence when patients are candidates for salvage treatment 1
• Do not order PET/CT for ground-glass nodules, part-solid nodules with small solid components, or routine surveillance in asymptomatic patients 1

Colorectal Cancer

• Order PET/CT to assess operability of recurrent disease and liver metastases when CT or MRI is equivocal, or to rule out distant metastases that would obviate curative intervention 2
• PET/CT is the first-choice modality for suspected recurrence when serum carcinoembryonic antigen is elevated but CT is negative 2
• Use PET/CT for preoperative staging of local and metastatic recurrence 2

Gynecological Cancers

• Perform PET/CT for response evaluation in cervical cancer, as it is superior for evaluating treatment efficacy and predicts event-free and overall survival 2
• Order PET/CT for assessment of nodal involvement in cervical cancer patients 2
• Use PET/CT in suspected ovarian cancer recurrence when cancer antigen 125 is elevated but CT and MRI are negative 2
• Do not order PET/CT for endometrial or vaginal cancer outside clinical trials 2

Head and Neck Cancer

• Perform PET/CT for initial metastatic screening in pharyngeal cancer patients 2
• Use PET/CT when biopsy has been inconclusive for differentiating benign from malignant tumors 2
• Order PET/CT to identify primary tumors in patients with metastatic cervical lymphadenopathy of unknown origin, as it identifies at least 30% of primary tumors not detected by conventional means 2

Melanoma

• Order PET/CT for initial metastatic screening in high-risk melanoma (Stage III AJCC) 2
• Use PET/CT for suspected local or metastatic recurrence 2
• Do not use PET/CT for detecting nodal micrometastases 2

Breast Cancer

• Perform PET/CT for locoregional and distant metastatic screening in patients with invasive tumors 2
• Use PET/CT when suspecting local or metastatic recurrence 2
• Do not order PET/CT for detecting nodal micrometastases 2

Gastrointestinal Cancers

• Order PET/CT for pretreatment evaluation of nodal and metastatic status in esophageal cancer to complement endoscopic ultrasound 2
• Use PET/CT for differential diagnosis and staging of pancreatic cancer in patients with normal serum glucose 2
• Do not order PET/CT for gastric carcinoma outside clinical trials 2

Hepatobiliary Cancers

• Perform PET/CT for differential diagnosis of hepatic metastases, cholangiocarcinomas, and benign tumors in patients with solitary hepatic lesions 2
• Consider PET/CT for early diagnosis of cholangiocarcinoma in patients with sclerosing cholangitis 2

Thyroid Cancer

• Order PET/CT for well-differentiated thyroid cancer when suspecting residual disease or recurrence and standard imaging (including radioactive iodine scans) is not conclusive 2
• Use PET/CT for preoperative staging of medullary thyroid cancer when further surgery is indicated for persistent or recurrent disease 2
• Do not use PET/CT for diagnosis of thyroid nodules 2

Testicular Cancer

• Perform PET/CT for detection of malignancy in post-treatment residual masses 2
• Use PET/CT when tumor markers are elevated at follow-up suggesting recurrent disease 2
• Do not use PET/CT to differentiate fibrous masses from mature teratomas 2

Neuroendocrine Tumors

• Order PET/CT for diagnosis and staging only when octreotide scan is normal 2
• Do not use PET/CT as first-line imaging 2

Renal Cell Carcinoma

• Do not routinely obtain PET scans in follow-up after renal cell carcinoma treatment 2
• PET scan may be considered selectively but should not be obtained routinely 2

Cancers Where PET is NOT Indicated

• Bladder cancer: no indication outside clinical trials 2
• Prostate carcinoma: limited utility for initial staging or recurrence detection 2

Critical Timing Considerations

Post-Treatment Intervals

• Wait at least 1 month after radiotherapy or surgery before performing PET/CT to reduce false-positive results from inflammation 1, 3
• Perform PET/CT within 60 days of planned resection and within 30 days before radiation therapy for staging purposes 1

Important Caveats and Pitfalls

False-Negative Results

• Certain malignancies show low FDG uptake: carcinoid tumors, adenocarcinomas with predominant ground-glass components, mucinous adenocarcinomas, and bronchioloalveolar carcinoma 1
• PET/CT has limited sensitivity for lesions <1 cm 2

False-Positive Results

• Inflammatory and infectious processes are the primary cause of false-positive PET/CT results 1
• Do not order PET/CT in regions with high prevalence of endemic infections without understanding the high false-positive rate 1
• Always correlate PET findings with clinical context and consider biopsy confirmation for FDG-avid lesions 1

Site-Specific Limitations

• PET/CT cannot evaluate brain metastases; brain MRI with contrast is required 1
• For adrenal nodules, lack of FDG uptake indicates benign adenoma with 94% sensitivity and 82% specificity 1
• PET/CT has high accuracy (>90%) for detecting bone metastases, superior to bone scintigraphy 1

When NOT to Order PET Scans

Screening

• Do not use PET/CT for whole-body cancer screening in asymptomatic populations, as it frequently yields equivocal findings requiring further evaluation with associated costs and potential complications 4
• The clinical relevance of occasionally detected cancers is too low to justify population-wide screening 4

Routine Surveillance

• Do not order PET/CT for routine surveillance of treated cancer in asymptomatic patients without clinical suspicion of recurrence 1
• Do not use PET/CT for routine follow-up of confirmed diffuse lung disease 1

Specific Clinical Scenarios

• Do not order PET/CT for evaluation of diffuse lung disease or acute exacerbation of interstitial lung disease 1
• Bone scan should only be performed if bone pain, elevated alkaline phosphatase, or radiographic findings suggest bony neoplasm are present 2

Non-Oncologic Indications

Emerging Applications

• PET/CT is increasingly used for infections of unknown origin 2
• PET/CT has applications in inflammatory conditions 2
• PET/CT is being investigated for neurological disorders including dementias, epilepsy, and movement disorders 2, 5
• PET/CT may replace myocardial scintigraphy for cardiovascular disease evaluation 2