22
Gynecologic Tumors

Eugene C. Lin and Abass Alavi

Cervical Cancer1,2

The primary value of positron emission tomography (PET) in cervical cancer is in diagnosis of extrapelvic disease in initial staging and in detection of recurrence.

Primary Tumor

Clinical Indication: D

PET will detect the majority of primary tumors (Figs. 22.1 and 22.2), but is not as accurate as magnetic resonance imaging (MRI) for assessing locoregional involvement.³ The degree of uptake in the primary tumor at diagnosis negatively correlates with treatment response and prognosis.⁴

Staging

Clinical Indication: B

PET is useful in staging locally advanced untreated cervical carcinoma. There are conflicting data on the value of PET in early-stage resectable cervical cancer.5

1. PET is more accurate than conventional imaging for evaluating lymph node metastases (Figs. 22.1 and 22.2).⁶
   
2. PET is particularly useful for evaluating disease in paraaortic nodes when computed tomography (CT) and MRI do not demonstrate adenopathy.⁷
   
3. Prognosis. Standardized uptake value (SUV) ≥ 3.3 in para-aortic lymph nodes is a negative prognostic factor.⁸
   
4. Radiation planning. When nodal radiotherapy is planned, the radiation field can be determined based on PET results.⁹ There are also potential applications of PET in planning intracavitary brachytherapy.
   
   
   
   
   

   
   

   Fig. 22.1 Metastatic cervical cancer. Coronal positron emission tomography/computed tomography scan demonstrates uptake in a primary cervical carcinoma (arrow) with multiple pelvic and retroperitoneal nodal metastases.

   
   
   
   

   
   

   Fig. 22.2 Primary cervical cancer with pelvic nodal metastases. Coronal positron emission tomography/computed tomography scan demonstrates intense uptake in a primary cervical cancer with pelvic nodal metastases (arrows). Given the location of these nodal metastases, ureteral activity if present could potentially decrease sensitivity. (Courtesy of Bruce Higginbotham, Little Rock, AR.)

   
   
   
   
   • PET is particularly useful for detecting para-aortic nodal disease when only pelvic nodal enlargement is seen on CT and MRI. This results in changing the appropriate treatment field accordingly.
   
   
5. Positive PET. The positive predictive value of PET for pelvic and para-aortic nodes is high (90%+), and a positive PET study is sufficient to justify treatment by radiation or surgery.10
   
6. Negative PET. However, a negative PET does not preclude histologic lymph node sampling, as microscopic disease cannot be not excluded.

Accuracy and Comparison with Other Modalities

1. Body region (PET). Table 22.1¹¹
   
2. MRI. PET is more accurate than MRI for pelvic nodal metastases.¹¹ PET/CT is more sensitive than MRI for pelvic nodal metastases, but there is no difference in specificity (Table 22.2).¹²
   
3. CT. PET detects more abnormal pelvic lymph nodes than CT (79% vs 47%).¹¹ Increased uptake in lymph nodes on PET even when CT is negative is associated with poor prognosis.¹³
   

   
   

   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   

   Table 22.1 Sensitivity and Specificity of Positron Emission Tomography in the Detection of Nodal Metastases

   Body Region	Sensitivity %	Specificity %
   Aortic nodes	84	95
   Pelvic nodes	79	99

   
   
4. Early-stage cervical cancer. PET and PET/CT have low to moderate sensitivity but high specificity for the lymph nodes metastases in early-stage cervical cancer. PET has a sensitivity of 53% and specificity of 90% for pelvic lymph node metastases in early-stage (IA to IIA) cervical cancer. The sensitivity for para-aortic nodes is even lower (25%).¹⁴ Therefore, PET may have limited value in early-stage cervical cancer if MRI is negative.¹⁵ PET/CT performs considerably better in early cervical cancer staging, with a sensitivity of 73% and specificity of 97%.¹⁶

Pearls

1. Urinary activity. Minimizing the effects of radioactive urine in the bladder and ureters is important in cervical cancer, as the specific areas of concern are the pelvic and para-aortic nodes (Fig. 22.2).
   
2. Dual time point imaging. Dual time point imaging (an additional delayed 3-hour scan) increases accuracy in para-aortic lymph nodes, particularly inferior para-aortic nodes.¹⁷

Pitfalls

1. In patients with early-stage disease, most of the false-negative results will be seen in the pelvis.
   

   
   

   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   

   Table 22.2 Sensitivity and Specificity of Positron Emission Tomography (PET) versus Magnetic Resonance Imaging (MRI) in the Detection of Pelvic Nodal Metastases

   	Sensitivity %	Specificity %
   PET	79	99
   MRI	72	96

   
   
2. In patients’ advanced stages of disease, more false-negative results will be noted in para-aortic nodes.
   
3. Lymphangiography can cause false-positive nodal uptake.18
   
4. A short axis diameter > 0.5 cm is the size threshold for accurate identification of metastatic lymph nodes from cervical cancer by PET/CT.¹⁶

Recurrence

Clinical Indication: C

Limited data suggest that PET is more sensitive than conventional imaging for recurrent cervical cancer. PET might be best employed in patients with better prognoses (e.g., determined by squamous cell carcinoma antigen levels and symptoms) and possibility of salvage therapies. In these patients, accurate determination of recurrence location can help decide between salvage therapy and chemoradiation.19,20

Accuracy and Comparison with Other Modalities

1. PET. Sensitivity 96%, specificity 81%11
   
2. Body region. The sensitivity for recurrence is poor in the lung, retrovesical, and para-aortic lymph nodes.²¹
   
3. CT/MRI. PET is more sensitive than CT/MRI, but there is no difference in specificity.
   
   
   
   
   • PET is more sensitive than CT/MRI for metastases (89% vs 39%), but there is no difference in local lesion detection.²⁰

Pearls

1. Symptoms. PET is useful in both symptomatic and asymptomatic women.22
   
2. Squamous carcinoma antigen. PET is useful in detecting recurrence if serum squamous carcinoma antigen is elevated.²³

Pitfalls

Therapy Response and Prognosis

Clinical Indication: C

1. Therapy response. There are limited data on the utility of PET for evaluation of therapy response in cervical carcinoma.
   
   
   
   
   1. Radiotherapy effect.24 Following irradiation, increased fluorodeoxyglucose (FDG) activity is common from inflammation; therefore, increased FDG activity is sensitive but nonspecific for active tumor.
      
   2. Neoadjuvant chemotherapy.²⁵ Decrease in SUV correlates better with histological response than MRI in patients undergoing neoadjuvant therapy prior to radical hysterectomy.
   
   
2. Prognosis
   
   
   
   
   1. Pretherapy. A visual grading system, which incorporates the primary tumor size, its shape, the degree of nonuniformity of FDG uptake, and the level of pelvic or para-aortic nodal involvement by PET, can estimate prognosis.²⁶
      
   2. Posttherapy. Persistent FDG uptake following therapy, particularly in para-aortic nodes, is a strong predictor of poor prognosis.²⁷

Ovarian Cancer: Ovarian Masses1,2

Clinical Indication: C

1. PET employed alone results in a substantial number of false-positive and -negative results.
   
2. However, PET can complement the results of ultrasound and/or MRI findings and improve the overall accuracy of diagnostic imaging in patients with ovarian masses (as seen in Fig. 6.38).²⁸

Accuracy and Comparison with Other Modalities

1. PET. Sensitivity 58 to 86%, specificity 54 to 86%28
   
2. Comparison: Table 22.3²⁸
   

   
   

   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   

   Table 22.3 Sensitivity and Specificity of Positron Emission Tomography versus Other Imaging Modalities in the Evaluation of Primary Ovarian Masses

   	Sensitivity %	Specificity %
   PET	58	76
   US	92	60
   MRI	83	84
   Combined	92	85

   
   

   Abbreviations: MRI, magnetic resonance imaging; PET, positron emission tomography; US, ultrasound.

Pearls

1. Standardized uptake value. There is no established SUV threshold for distinguishing malignant from benign ovarian lesions: published values range from 3.25 to 7.9.29,30
   
2. Visual threshold. One arbitrary visual threshold for malignancy includes any uptake equal to or greater than that of the liver.²⁸
   
3. Postmenopausal uptake. Ovarian uptake in the postmenopausal woman is much more worrisome than in a premenopausal woman, and malignancy should be strongly suspected.³⁰

Pitfalls

1. False-negatives. Low-grade tumors, early-stage ovarian carcinomas
   
2. False-positives
   
   
   
   
   1. Inflammatory processes, endometriomas, benign cystic lesions (e.g., corpus luteum cyst, dermoid cyst, serous cyst), thecoma, physiologic uptake
      
   2. In premenopausal women, physiologic ovarian uptake is most common around ovulation and during the early luteal phase of the menstrual cycle.31 Physiologic ovarian uptake can be minimized by scheduling PET just after menstruation.
      
   3. Bowel or iliac node activity on PET can be difficult to differentiate from ovarian activity (as seen in Fig. 10.13, p. 111).

Recurrence

Clinical Indication: B

1. PET is most useful when conventional imaging is inconclusive and cancer antigen (CA-) 125 is elevated.
   
2. Second look laparotomy. Although PET is accurate in the diagnosis of ovarian cancer recurrence (particularly if used in conjunction with conventional imaging techniques), it is still limited because a second-look laparotomy is still necessary if recurrence is strongly suspected. The sensitivity of PET for small volume disease (< 1 cm) is low compared with second-look laparotomy.32 Despite this, PET can change management due to its high positive predictive value.^33,34
   
   
   
   
   1. A positive PET scan can preclude the need for invasive surgical assessment.
      
   2. Tumor deposits large enough to be identified by PET may be considered for surgical resection because these lesions may not respond to chemotherapy.
      
      
      
      
      

      
      

      Fig. 22.3 Metastatic ovarian cancer. Coronal positron emission tomography/computed tomography (PET/CT) scan demonstrates both nodal (arrowheads) and peritoneal (arrows) metastases from ovarian cancer. PET has better sensitivity for nodal metastases than peritoneal metastases in ovarian cancer. (Courtesy of Carolyn Meltzer, MD, Atlanta, GA).

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