The Egyptian Journal of Radiology and Nuclear Medicine 48 (2017) 1049–1055

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The Egyptian Journal of Radiology and Nuclear Medicine

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Accuracy of 18F-FDG PET/CT in detection and restaging of recurrent

ovarian cancer
Waleed M. Hetta a,⇑, Mostafa Mahmoud Abdelkawi b, Mohammed H. Abdelbary b, Marihan A. Nasr a
a
Radiodiagnosis Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
b
Radiodiagnosis Department, Faculty of Medicine, Helwan University, Cairo, Egypt

a r t i c l e i n f o a b s t r a c t

Article history: Purpose: To estimate the accuracy of 18FDG PET/CT in detection of recurrent cancer ovary and to describe
Received 9 February 2017 the localization of metastases for restaging.
Accepted 1 June 2017 Materials and methods: 44 female patients with suspicion of ovarian cancer recurrence underwent a PET/
Available online 14 December 2017
CT scan from September 2013 to August 2015.
Results: CA-125 levels were elevated in 36 patients, 25 patients presented with alterations on imaging
Keywords: and 18 patients had clinical suspicion of recurrence. Imaging examinations were normal in 10/36 patients
Recurrent cancer ovary
with elevated CA-125. 18FDG PET/CT scan was positive in 39/44 patients, and it was negative in 5/44
PET/CT
patients, 4/5 patients continued to be disease free all over the follow-up (true negative), while PET-CT
missed recurrence in 1/5 patient (false negative). 1/39 patient was false positive. Sensitivity, specificity,
positive predictive value, negative predictive value and diagnostic accuracy of integrated PET/CT were
calculated to be 91%, 76%, 96%, 50% and 87%.
Conclusion: 18FDG PET/CT is an accurate modality for detection of recurrence of ovarian cancer. The
accuracy of PET–CT in precise localization of suspicious FDG uptake can lead to proper assessment of dis-
ease recurrence, thus allow for restaging of the disease and subsequently optimizing treatment plan for
these patients.
Ó 2017 The Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier. This
is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/
4.0/).

1. Introduction essentially play a major role to detect ovarian cancer recurrence

Ovarian cancer is responsible for about 3% of cancer cases in
female; yet, with the highest mortality among gynecological can-
cers [1]. As a result of gradual onset and few symptoms, most of
the patients are presented at advanced stage of the disease. Reduc-
tive surgery and adjuvant chemotherapy are the initial treatment
measures [1,2]. In spite of favorable response after these lines of
treatment, about 25–35% of cases with early-stage and up to 70%
with advanced disease are manifested with recurrence in two years
[2,3].
Sequential assessment of CA 125 is used to evaluate the ovarian
cancer response for treatment. Yet, normal levels of CA 125 cannot
excluded the disease, and raised CA 125 levels could not differen-
tiate localized from diffuse tumor recurrence [4–6]. Thus, imaging
Peer review under responsibility of The Egyptian Society of Radiology and Nuclear
Medicine.
⇑ Corresponding author.
E-mail address: waleedhetta@med.asu.edu.eg (W.M. Hetta).
[7–10].
Once ovarian cancer recurrence is suspected either clinically or
by elevated CA-125 level, diagnostic imaging tools; like computed
tomography, ultrasonography, and magnetic resonance imaging
must be done.
Although post contrast CT is used on a wide spectrum, its sen-
sitivity for detection of minute peritoneal and serosal implants is
limited and its ability to differentiate postoperative fibrosis from
tumor recurrence is doubtful [9–11].
Pelvic MRI is beneficial for the assessment of the local disease
recurrence, yet anatomical alterations which occurs postopera-
tively made MRI with very low specificity [12,13].
(18FDG) PET/CT has serious role in the detection of the recur-
rence of ovarian cancer depending on increased metabolic tracer
uptake of the lesion, also the coalition of the anatomical images
with the metabolic ones help in precise determination of the loca-
tion of the lesion and enable its ability for whole body scanning.
The role of PET/CTin the cases of recurrent ovarian cancer was
assessed in many studies [12,14–20].

https://doi.org/10.1016/j.ejrnm.2017.06.001
0378-603X/Ó 2017 The Egyptian Society of Radiology and Nuclear Medicine. Production and hosting by Elsevier.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1050 W.M. Hetta et al. / The Egyptian Journal of Radiology and Nuclear Medicine 48 (2017) 1049–1055

The sensitivity of FDG PET/CT in detection of recurrence of ovar- and 75%; estimated specificity 84% and 78%) for CT and MRI
ian cancer is 85–100% [21]. The spatial resolution of PET is about respectively.
5–10 mm which increase its ability to detect lesion less than 1 A prospective multicenter Australian study of 90 patients [20]
cm [22]. to measure the effect of 18FDG PET/CT in the treatment of cases
Gu et al. [12] hold a study to estimate the ability of CA-125 with query recurrence of cancer ovary and estimated the data
levels, PET alone, PET/CT, MRI and CT to diagnose ovarian cancer given by 18FDG PET/CT. According to data given by PET/CT, man-
recurrence. Highest specificity was detected in CA-125 levels agement was changed in 58.9% of patients (53 patients) as a result
(92%), yet highest sensitivity with PET/CT (90%). CT and MRI man- of additional 168 sites detected by PET/CT at unsuspected loca-
ifested comparable diagnostic capability (estimated sensitivity 79% tions. PET/CT is better than to CT alone in detection of peritoneal
nodules as well as nodal metastases and suspecting the patients
with high probability of disease progression within 12 months.
Table 1 The study preferred PET/CT to be the examination of choice with
Indications of PET-CT in suspected recurrent cancer ovary. suspected recurrence ovarian cancer.
Indications of PET-CT Number %
The goal of our study was to asses the accuracy of 18FDG PET/CT
in cases of clinically suspected recurrent ovarian carcinoma and to
CA-125 >35 l/ml 36 81.8
CT 13 29.5 56.8
detect the suspected and unsuspected sites of metastatic deposits.
US 6 13.6
MRI 6 13.6
Clinical 18 40.9 2. Patients and methods

The study included 44 female patients (with age of 42–65 years;

mean age of 50.5) with suspected recurrence of cancer ovary in ret-
Table 2 rospective study. The patients had a PET/CT scan done at Misr Radi-
Diagnostic accuracy of PET-CT.
ology Centre [MRC] private practice group in Cairo, Egypt, during
Final result the period from September 2013 to August 2015. The study was
True positive (n) 38 under the approval of local Ethics committee.
False positive (n) 1 Patient’s clinical data, as well as, laboratory results and recent
True negative (n) 4 imaging are available. The indications of PET/CT scan: any doubt
False negative (n) 1
of disease recurrence; either clinically (like ascites, pain or deteri-
Sensitivity (%) 91%
Specificity (%) 76% oration of general conditions), laboratory [raised serum CA-125
Positive predictive value (%) 96% over >35 U/ml] or abnormal imaging findings by contrast enhanced
Negative predictive value (%) 50% CT, ultra-sonography or MRI. PET scan is avoided with raised blood
Diagnostic accuracy (%) 87% glucose level above 150 mg/dl and recent post-operative condition.

A B C
Case No 1
Fig. 1. 58-years old female patient, having history of ovarian carcinoma submitted for TAH and BSO seven years ago. She was presented after routine abdominal
ultrasonography revealed splenic focal lesions yet with normal tumor marker so PET/CT is ordered to delineate the underlying etiology. (A) MIP PET CT image revealed three
abnormal foci of hyper metabolism [arrows]. The corresponding fused corrected PET images revealed a couple of hypermetabolic splenic focal lesions; achieving 8.2 and 9.7
SUV max and small tiny 7 mm nodule resting on the falciform ligament of minimal activity. The patient underwent splenectomy and excision of the nodule [all are
pathologically proven to be metastatic in nature].
 W.M. Hetta et al. / The Egyptian Journal of Radiology and Nuclear Medicine 48 (2017) 1049–1055 1051

Table 3 18
4. FDG PET/CT interpretation
Distribution of metastasis by PET CT.

Location Number % The images were revised by two radiologists long practiced
Local recurrence 17 44.7 with CT and PET CT. The two readers were oriented about the
Pelvic lymphadenopathy 7 18.4 patients’ history with cancer ovary but not aware other imaging
Para-aortic lymph nodes 18 47.3 results as well as serum CA-125 levels. CT scans, PET images and
Distant lymphadenopathy 4 10.5
fused PET-CT images were presented simultaneously. Abnormally
Peritoneal implants 27 71
increased FDG uptake and its location was indicated on the CT
Distant metastasis Liver 12 5 31 13.1
was diagnosed as positive [or hypermetabolic] for recurrence.
Spleen 1 2.6
Bone 2 5.2 Any abnormality detected on CT but with not FDG uptake on PET
Lung 3 7.8 scan was diagnosed as negative finding. Semi-quantitative analysis
Pleura 1 2.6 to measure a standardized uptake value (SUV) to help in differen-
tiation benign from malignant uptake, was also performed. The
lesions with increased uptake are classified by location as follows:
18
local recurrence, pelvic lymphadenopathy, abdominal lym-
3. FDG PET/CT imaging phadenopathy, peritoneal lesions, distant lymphadenopathy and
distant metastasis.
All patients were instructed to fast for at least 6 h with avoid- Results of 18FDG PET/CT scan were correlated with the results of
ance of high protein diet and vigorous activity for 24 h before the patients’ follow-up that were done for minimum six months after
exam. After physical examination and taking history, blood sugar the initial scan. Disease relapse was established surgically, clini-
test was done maintaining blood glucose levels <150 mg/dl. The cally, by persistently raised CA-25 levels, abnormalities at other
patient rests at least 20 min to reduce muscular activity which imaging modality or by response to chemotherapy.
may interfere with tracer uptake. IV injection of 5–10 mCi [approx-
imate dose to the patient; 1 mCi/10 kg] was the usual dose admin-
5. Results
istered to each patent 60 min before the exam. The patients were
asked to lie supine for about 40–60 min post injection in quite
The total of 44 patients, with suspected recurrent ovarian can-
room. The examination was started with low dose non-enhanced
cer, were subjected to PET/CT. The mean age of patients was 50.
routine CT scan from the skull base to the mid-thigh preformed
5 ± 7.3 years. The serum CA 125 levels was 15–810 U/ml, with a
for attenuation correction. Then PET study was done on an inte-
mean level of 118 ± 120 U/ml. The level for normal CA-125 was
grated PET CT scanner ingenuity-TF 128 multislice PhilipsÒ. The
maximally 35 U/ml.
images were taken in 6–8 sequential table positions in a 3D tech-
Among the 44 patients, CA-125 serum levels were raised in 36
nique [3 min per each table position]. Following this, enhanced
patients, 25patients were presented with abnormal US, CT or MRI
diagnostic CT scanning using 60–100 ml nonionic IV contrast.
findings (6 presented by alteration in US, 6 in MRI and 13 in CT),
Parameters of diagnostic CT component: were 150 kV, 200–220
and 18 patients had clinical suspicion of recurrence (like ascites,
mAs, slice thickness of 3.5 mm and pitch = 0.9.
abdominal pain, deterioration of the general condition) (Table 1).
Attenuation correction was done by integration of corrected
10 patients were having elevated serum levels of CA-125 yet with
reconstructed PET images with volume data of CT with contrast.
normal imaging examinations.
The images were obtained using an advanced workstation unit, 18
FDG PET/CT scan was positive in 39/44 patients, and it was
using a specialized software, obtaining a suitable layout having
negative in 5/44 patients, 4/5 proved to be disease free during
the PET, CT and the fused PET-CT images. On trans axial, coronal
follow-up time (true negative), they were having normal CA-125
and sagittal displays.
serum levels and there was no disease recurrence on any further

A B C D
• Case No 2

Fig. 2. 65 yrs. old female having old history of ovarian cancer submitted for TAH and BSO 2 yrs ago. Post-operative PET CT was completely normal. Then elevated CA 125. PET/
CT rescanning revealed aggressive form of metastatic relapsed disease as shown in the PET/MIP [images A] with multiple variable sized hypermetabolic peritoneal nodules
unevenly distributed in the peritoneal cavity; achieving very high metabolic activity; achieving 12.5 up to 36.4 SUV max [ coronal fused PET/CT; image D]. Few of them are
seen in the pelvic operative site achieving 22.1 SUV max [image C]. Associated small cutaneous metastatic nodule in the lower inner quadrant of the left breast achieving 11.5
SUV max and two metastatic LNs in the left axillary and right anterior epiphrenic regions achieving 6.8 and 10.4 SUV max [images B and A].
1052 W.M. Hetta et al. / The Egyptian Journal of Radiology and Nuclear Medicine 48 (2017) 1049–1055

imaging while PET-CT missed recurrence in 1/5 patient (false neg-
ative) because of small size of lesion which was detected in follow
up imaging when it became larger enough to be identifiable. 1/39
patient was false positive as detected hypermetabolic nodes were
just due to inflammation. The recurrence was confirmed in the true
positive cases histologically by biopsy or with second look surgery
in 17/39, whereas 21/39 were confirmed on clinical/radiological
follow up (ranging from 3 to 6 months) or by response to
chemotherapy on subsequent imaging.
Specificity, sensitivity, negative predictive value as well as pos-
itive predictive value and diagnostic accuracy of integrated PET/CT
were found to be 91%, 76%, 96%, 50% and 87% (Table 2).

A B C

D E

F G
• Case No 3
Fig. 3. 50-years old female patient with history of right ovarian carcinoma underwent surgical excision Post-operative PET/CT was negative for any avid metastatic lesions.
The Patient then was referred due to clinical suspicion after detected of lower neck swelling proved by ultrasonography to be cervical lymph nodes with elevated tumor
marker. MIP PET image revealed multifocal avid lesions [arrows; image A]. Corresponding fused PET CT images revealed multiple newly developed hypermetabolic lower
deep cervical, supraclavicular and left posterior triangle lymph nodes having intense avidity for FDG uptake; achieving 11.5–25.6 SUV max. The largest and most active one is
seen in the left supraclavicular group [images B and C]. Also, there are multiple newly developed hypermetabolic bilateral hilar and mediastinal [retrocaval, pre-carinal,
aortopulmonary, subcarinal] lymph nodal groups achieving 4.9 up to 17.7 SUV max [images D and E]. Moreover, multiple retroperitoneal abdominal metastatic adenopathies
involving the right retrocrural, precaval, coeliac, aortocaval, retrocaval and left para aortic groups achieving SUV max 8.8 up to 20.8 [images F and G].
 W.M. Hetta et al. / The Egyptian Journal of Radiology and Nuclear Medicine 48 (2017) 1049–1055 1053

In the 10 patients with normal findings on conventional imag-
ing and high CA-125 level, PET/CT was found to be significantly
positive in all of them, whereas from the 8 patients with CA-125
showing normal levels, 5 were presented with a clearly positive
PET/CT scan (Fig. 1).
As regarding detection at regional level, six regions were
identified (Table 3); local recurrence (Fig. 2) (detected in 17
patients), pelvic lymphadenopathy (7 patients), para-aortic
lymph nodes (Figs. 3 and 4) (in 18 patients), distant lym-
phadenopathy (Figs. 3 and 4) (in 4 patients), peritoneal implants
(Fig. 5) (in 27 patients) and distant metastasis (Fig. 2) (in 12
patients) including 5 organs; liver (in 5 patients), lung (in 2
patients), pleura (in 1 patient), spleen (in 2 patients), and bone
(in 2 patients).
The most common site of metastasis overall were the lymph
nodes (76.3%) (Figs. 2 and 3) yet the peritoneal implants were
the most common in patients with normal conventional imaging
(n = 7/10).

Case No 4
Fig. 4. 56 years old female patient, presented with history of ovarian cancer treated with surgery followed by post-operative chemotherapy currently presented with elevated
tumor markers. PET/CT revealed multiple small hypermetabolic lymph nodes at the porta hepatis, achieving SUV max up to 6.35 and much smaller solitary node in the left
para-aortic region achieving SUV max up to 3.9. The patient received chemotherapy with progressive improvement by reduction of tumor markers and reduction of activity at
follow up studies.

A B
• Case No 5
Fig. 5. 64 yrs. female having history of cancer ovary submitted for TAH and BSO. On routine work up, she had discovered elevated CA125 after 6 months of the operation.
Conventional diagnostic CT images [A and B; bottom images] revealed minimal pelviabdominal ascites and subtle omental nodularity. Fused PET CT images [A and B; middle
images] revealed intensely avid tiny confluent peritoneal nodules/infiltrate, achieving 6.8 up to 10.1 SUV max, confirmed occult peritoneal carcinomatosis].
1054 W.M. Hetta et al. / The Egyptian Journal of Radiology and Nuclear Medicine 48 (2017) 1049–1055
6. Discussion
The cancer ovary contributes for 3.5% of cases of cancer in
female; it is usually associated with high mortality (4%) as a result
of presentation and diagnosis at late stage of the disease [23]. It has
been previously described that measurement serum CA-125 level
has an important role in management and assessment of treatment
response of cancer ovary. Preoperatively, serum CA-125 level is
closely correlated with disease severity in patients with raised
CA-125 level [24]. It was also emphasized that normal CA-125 level
didn’t provide an evidence to deny tumor recurrence and that is
also proved in our study.
In a study by Forstner et al. [25] they found that the accuracy of
MRI in assessment of tumor recurrence is about 60%. Even though
CT scan is the most commonly used imaging modality, its sensitiv-
ity for small deposits was found to be quiet low, particularly when
their enhancement is comparable to adjacent structures [26]. Ovar-
ian cancer metastases primarily involve the peritoneum rather
than parenchymal structures; accordingly, it is a real challenge to
interpret small sized metastatic deposits on the visceral surfaces
using CT and MR imaging [27,28].
PET/CT accurately detected all cases with suspected ovarian
cancer recurrence. Positive PET/CT scan were found in all cases
with raised CA-125 values and unremarkable conventional imag-
ing. However, in this series, most patients with normal CA-125
levels were found to have positive PET/CT scan. The most frequent
site of disease recurrence were the lymph nodes, most of the
involved groups were in the pelviabdominal region as well as in
the thoracic cavity either in the form of mediastinal lym-
phadenopathies or isolated lung nodules. Peritoneal implants pre-
sented in 71% of cases. Distant organ metastases involved the liver,
spleen, lung, bone and pleura. PET/CT was able to detect unsus-
pected active foci, most of which were lymph node metastases at
a supradiaphragmatic location.
PET/CT has a unique superior value in patients with elevated
CA-125 values and non-conclusive other imaging modalities while
still suspecting ovarian cancer recurrence [29].
When comparing imaging with CT and MR with FDG PET imag-
ing, the later depends on functional instead of morphological data
depending on elevated glucose metabolism by malignant tumors
[30].
Most of our results are concurrent with other multiple studies
that discusses the role of PET/CT in patients with cancer ovary.
These studies stated that accuracy, sensitivity, and specificity were
65%–100%, 75%–100%, and 43%–100%, respectively, [31–40] which
was compatible with our study that revealed sensitivity, specificity
an accuracy of 91, 76 and 89% respectively.
In another recent study, Gu et al. [41] stated accuracy of 95%,
sensitivity of 92%, and specificity of 89%, for PET/CT which is rela-
tively higher in specificity and accuracy than ours.
Torizuka et al. [42] evaluated the role of FDG PET in detection of
recurrence of cancer ovary in 25 patients. They reported that FDG
PET revealed sensitivity and accuracy of 80% and 84% respectively,
compared to lower sensitivity and accuracy (56 and 65%, respec-
tively) for conventional CT imaging, yet in our study the sensitivity
and accuracy were slightly higher (being 91 and 89% respectively).
Torizuka et al. [42] also stated that recurrence could be detected
easily by PET/CT due to its metabolic activity. Flamen and Schelling
et al. [43,44] reported the ability of FDG PET in detection of viable
tumor tissue after treatment which can be missed by conventional
imaging like CT.
Simcock et al. [45], emphasized the influence of PET/CT on the
treatment of patients with recurrent ovarian cancer. They reported
that PET/CT resulted in a major change of treatment plan in 58%
patients.
In our study, it has been clear that PET/CT has a high positive
predictive value (96%). This would suggest a strong proof of its reli-
ably in identifying patients with macroscopic disease and for
whom the appropriate management plan would be performed.
On the other hand, in our study PET/CT obtained a low negative
predictive value (50%) and is concordant with prior studies
[42,46]. This refers to limited ability of PET/CT in detecting micro-
scopic or smaller lesions.
In conclusion, 18FDG PET/CT is a precise tool with unique value
in detection of ovarian cancer recurrence. The accuracy of PET–CT
in precise localization of suspicious FDG uptake can lead to proper
assessment of disease recurrence, thus allow for restaging of the
disease and subsequently optimizing treatment plan for these
patients.
Conflict of interest
The authors declared that there is no conflict of interest.
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