Detection of Recurrent Cervical Cancer

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rsity Health Sciences Center, Shreveport, LA 71130-3932, USA

85.7%, a positive predictive value of 93.3%, and a negative predictive value of 100%.

Gynecologic Oncology 94 (2Conclusions. The whole-body FDG PET scan is a sensitive imaging modality for the detection of recurrent cervical carcinoma in both

symptomatic and asymptomatic women.

D 2004 Elsevier Inc. All rights reserved.

Keywords: FDG PET scan; Recurrent cervical cancer

Recurrent cervical cancer is a devastating disease for

those women unfortunate enough to suffer such an event.

Early detection of localized disease that can be treated with

either radiotherapy or pelvic exenteration often offers the

only chance for complete eradication of disease. However,

routine surveillance of women previously treated with either

radiotherapy or radical hysterectomy is usually limited to

pelvic examination, Papanicolaou smears, and chest radiog-

raphy. Much of surveillance in these women is directed at

tumor such as pain and bleeding so that further evaluation

with additional imaging studies and tissue biopsy can be

performed.

Whole-body positron emission tomography (PET) using

the glucose analog [18F]fluoro-2-deoxyglucose (FDG) has

been demonstrated to be useful in the staging of cervical

cancer and superior to either CT or MRI in the detection of

nodal disease [16]. This allows treatment to be individual-

ized especially where it concerns directing therapy to peri-Received 16 March 2004

Available online 25 May 2004

Abstract

Objective. To determine the ability of whole-body [18F]fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) scan to detect

recurrent cervical carcinoma in both symptomatic and asymptomatic women.

Materials and methods. We retrospectively reviewed the records of 44 women previously treated for cervical cancer who underwent 47

posttreatment whole-body FDG PET scans in an attempt to detect recurrent disease. Twenty-six scans were performed in asymptomatic

women, whereas 21 scans were performed in women with symptoms suggestive of recurrence.

Results. About 30.8% of asymptomatic women had recurrent disease detected by PET scan compared to 66.7% of women in the

symptomatic group. The sensitivity of PET scan for recurrent disease in asymptomatic women was 80.0%, specificity of 100%, a positive

predictive value of 100%, and a negative predictive value of 88.9%. For symptomatic women, the sensitivity of PETwas 100%, specificity ofdDivision of Hematology/Oncology, Louisiana State UniveDivision of Gynecologic Pelvic Surgery, Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center,

Shreveport, LA 71130-3932, USAbPET Imaging Center of the Biomedical Research Foundation of Northwest Louisiana, Louisiana State University Health Sciences Center,

Shreveport, LA 71130-3932, USAcDivision of Radiation Oncology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USADetection of recurrent cervical canc

asymptomatic and

James B. Unger,a,* Joseph J. Ivy,a Patrick CoFederico L. Ampil,c a

aidentifying patients with symptoms suggestive of recurrent

0090-8258/$ - see front matter D 2004 Elsevier Inc. All rights reserved.

doi:10.1016/j.ygyno.2004.04.021

* Corresponding author. Division of Pelvic Surgery, Department of

Obstetrics and Gynecology, Louisiana State University Health Sciences

Center, PO Box 33932, 1501 Kings Highway, Shreveport, LA 71130-3932.

Fax: +1-318-575-4671.

E-mail address: [email protected] (J.B. Unger).by whole-body FDG PET scan in

ptomatic women

r,a Amy Charrier,a Mohan R. Ramaswamy,b

Richard P. Monsourd

www.elsevier.com/locate/ygyno

004) 212216aortic nodal disease. More recently, other investigators have

demonstrated the ability of PET to detect recurrent cervical

cancer in symptomatic patients [79]. In addition, Grigsby et

al. [8] has demonstrated that PET can evaluate not only the

response of primary cervical cancer to therapy, but also that

detection of new abnormalities noted on PET scan after

therapy is the most significant prognostic factor for survival.

nous hydration with 250 cc of normal saline, followed by a

10-mg dose of furosemide. After a 90-min uptake period,

Results

Forty-four women previously treated for cervical cancer

underwent PET scan imaging in an attempt to detect

recurrent disease. Twenty-six of these women were asymp-

tomatic and underwent PET scan for surveillance purposes

only. Twenty-one women including three who had under-

gone a prior surveillance PET scan underwent PET scans

because of the development of symptoms suggestive of

tumor recurrence. The mean age, time from completion of

therapy to PET scan, FIGO clinical stage of disease, and

proportion of true positive PET scans between the surveil-

lance and symptomatic groups are shown in Table 1. PET

scans were positive significantly more often in symptomatic

women than women in the surveillance group.

Recurrent disease was confirmed by biopsy or CT in all

eight women in the surveillance group with positive PET

scans (Table 2). In addition, one woman who had received

extended field radiation and chemotherapy for stage IB2 had

J.B. Unger et al. / Gynecologic Oncology 94 (2004) 212216 213positron emission and transmission scanning was per-

formed from the skull base to the proximal thighs on a

GE Advance PET scanner (General Electric, Milwaukee,

WI). The typical scan time was 60 min. Tomographic

images were reconstructed in three orthogonal planes

(using an iterative algorithm) and viewed on a computer

workstation. Images were interpreted by qualitative visual

analysis; lesions were identified as areas of FDG uptake

considered by the reader to be notably above surrounding

or expected background activity. All studies were inter-

preted by an experienced nuclear medicine physician orIn the present study, we evaluated the clinical usefulness

of whole-body FDG-PET scans in detecting recurrent cer-

vical cancer in women with symptoms suggestive of recur-

rent tumor such as pain and bleeding. We also performed

PET scans in women without symptoms of recurrence for

surveillance purposes only. In addition to studying the

ability of PET to detect recurrent disease in these women,

a secondary objective was to evaluate the potential of this

imaging modality in detecting disease earlier in asymptom-

atic patients compared to women with symptoms suggestive

of recurrent tumor.

Materials and methods

Patients

The charts of 45 patients receiving care at our institu-

tion for cervical cancer and who had undergone PET scan

imaging in an attempt to detect cancer recurrence between

2000 and 2003 were reviewed. A minimum of 6 months

follow-up after the posttreatment PET scan was required

to be included in this study. This study was approved by

the Institutional Review Board at Louisiana State Univer-

sity Health Sciences Center in Shreveport.

Recurrent disease was confirmed in all cases with

either tissue biopsy or the demonstration of progressive

disease by CT. Clinical proof of no recurrent disease

consisted of a negative tissue biopsy, negative CT, or a

lack of clinical evidence of recurrence within 6 months of

the PET scan. The International Federation of Gynecology

and Obstetrics (FIGO) classification was used for clinical

staging [10]. Statistical analysis was performed using

independent t test for continuous variables and chi-square

for categorical variables. P < 0.05 was considered statis-

tically significant.

FDG-PET

All patients fasted for at least 4 h before the intravenous

administration of 550 MBq (15 mCi) of 2-[18F]-fluoro-2-

deoxy-D-glucose (FDG). Patients then underwent intrave-nuclear radiologist.a cervical biopsy demonstrating persistent disease at 3

months in spite of a negative surveillance PET scan done

at the same time. This patient plus another woman who

developed a recurrence 4 months after a negative surveil-

lance scan were considered as having false negative PET

scans. A third woman developed a recurrence 13 months

after her negative surveillance scan and this was not

considered a false negative since it occurred more than 6

months since her last PET scan. Follow-up for women with

negative PET scans in this group averaged 16.4 F 9.9months (range 633). The sensitivity of the PET scan for

recurrent disease in the surveillance group was 80.0%,

specificity of 100%, positive predictive value of 100%,

and negative predictive value of 88.9%. The mean age of

women with recurrent disease in the surveillance group was

42.1 F 9.3 years compared to 42.8 F 10.6 years for womenwithout disease (P = 0.88). Women with negative PET scans

Table 1

Age, months to posttreatment PET, proportion of true positive PET scans

and stage

Surveillance

group (N = 26)

Symptomatic

group (N = 21)

P value

Age (years)* 42.6 F 10.1(2864)

43.4 F 8.6(2762)

0.76

Months to

posttreatment

PET scan*

7.8 F 8.4(240)

18.6 F 20.3(380)

0.02

Proportion of

women with true

positive PET scan

8 (30.8%) 14 (66.7%) 0.01

FIGO stage 0.63

IB1 3 (11.5%) 5 (23.8%)

IB2 12 (46.1%) 9 (42.8%)

IIA 2 (7.7%) 2 (9.5%)

IIB 6 (23.1%) 3 (14.3%)

IIIA 0 (0%) 1 (4.8%)

IIIB 3 (11.5%) 1 (4.8%)*Mean F SD, range.

from 6 to 23 months. The sensitivity of PET scans in this

symptomatic group was 100%, specificity of 85.7%, posi-

tive predictive value of 93.3%, and negative predictive

value of 100%. Two of the three women in the symptomatic

group who had negative PET scans earlier for surveillance

later developed positive PET scans as noted above. Recur-

rent disease was confirmed by biopsy in both cases. The

mean age of women in the symptomatic group with positive

PET scans was 42.5 F 6.8 years compared to 44.3. F 12.4years for women with negative PET scans (P = 0.77).

Women with positive PET scans were imaged 13.1 F 13.8months post-therapy compared to 34.1 F 29.2 months forthose with negative PET scans (P = 0.03).

The mean time post-therapy to PET scan confirmation of

recurrent disease in the surveillance group of 8.1 F 6.2months (range 218) was not significantly different from

the 13.1 F 13.8 months (range 358) of the symptomaticgroup (P = 0.34). The mean age of women with positive

J.B. Unger et al. / Gynecologic Oncology 94 (2004) 212216214Table 2

PET scan findings in asymptomatic women

Positive PET

scan findings

Confirmation Result

1 periaortic and

supraclavicular nodes

biopsy true positive

2 negative negative exams true negative

3 pelvic nodes biopsy true positive

4 negative negative CT,

negative exams

true negative


negative exam

true negative

6 local pelvic biopsy true positive



9 periaortic nodes progressive

disease on CT

true positive



12 pelvic nodes progressive

disease on CT

true positivewere imaged 7.7 F 9.3 months post-therapy compared to8.1 F 6.2 months for women with disease (P = 0.91).

Fifteen of the twenty-one women in the symptomatic

group had positive PET scans. Disease was confirmed by

biopsy or CT in all but one case (Table 3). This patient had a

PET scan suggesting vaginal recurrence 13 months after

radical hysterectomy for Stage IB1 adenocarcinoma of the

cervix. However, clinical examination was negative for

disease and a repeat scan 4 months later showed spontane-

ous resolution of the area of concern. No women in this

group with negative PET scans were found to have concur-

rent or subsequent disease by clinical examination, biopsy,

or CT. One woman had a pelvic mass discovered on both

PET and CT. The FDG uptake of this mass was not

considered to significantly exceed that of the surrounding

areas and therefore it was not considered to be a positive

scan. At laparotomy, only adherent bowel was noted and no

tumor was found. Follow-up for women with negative PET

scans in this group averaged 12.6F 8.3 months with a range

PET scans in the surveillance group of 42 0.1 F 9.3 years(range 3161) was not significantly different from the 42.5

F 6.9 years (range 3258) of women in the symptomatic








20 periaortic and


progressive

disease on CT

true positive


22 periaortic nodes

and mediastinum

progressive

disease on CT

true positive


24 pulmonary and

peritoneal implants

progressive

disease on CT

true positive

25 negative positive biopsy of

cervical lesion at

time of negative PET

false negative

26 negative positive biopsy of

pelvic nodes 4 months

after negative PET

false negative

Table 3

PET scan findings in symptomatic women

Positive PET

scan findings

Confirmation Result


disease on CT

true positive

2 vaginal recurrence biopsy true positive

3 peritoneal implants progressive

disease on CT

true positive

4 local pelvic biopsy true positive

5 vaginal recurrence noneno disease false positive


disease on CT

true positive7 negative negative CT,

negative exam

true negative

8 pelvic and periaortic

nodes, peritoneal implants

progressive

disease on CT

true positive

9 periaortic and


progressive

disease on CT

true positive

10 negative negative exam true negative


negative exam

true negative

12 local pelvic and

inguinal nodes


13 local pelvic,

liver metastasis


14 local pelvic,

periaortic nodes

progressive

disease on CT

true positive

15 local pelvic,

periaortic nodes


16 local pelvic,

periaortic nodes

progressive

disease on CT

true positive


18 pelvic nodes biopsy true positive


20 pelvic and

periaortic nodes


21 negative negative true negativelaparotomy

symptomatic early in their post-therapy course than those

who develop symptoms later.

in predicting prognosis in asymptomatic women following

an average of 5 months earlier in asymptomatic women as

opposed to symptomatic women, this was not statistically

J.B. Unger et al. / Gynecologic Oncology 94 (2004) 212216 215Surveillance of asymptomatic women previously treated

for cervical cancer is problematic. Standard follow-up

typically consists of frequent clinical examinations, Papani-

colaou smears, and chest radiography. Routine surveillance

cervical cytology in these women has not been shown to be

helpful for detecting recurrent disease [12]. Most surveil-

lance is directed at identifying women with symptoms so

that further evaluation with imaging studies and biopsies

can be performed. In cases where localized disease is found,group (P = 0.90). There was no significant difference in the

clinical FIGO stage between women with positive PET

scans in the surveillance group compared to those in the

symptomatic group (P = 0.63). Four of the eight women

(50%) in the surveillance group with recurrent disease and a

positive PET scan had disease limited to the original

treatment field, compared to only 4 of the 14 women

(28.6%) in the symptomatic group with positive PET scan

and confirmed disease (P = 0.22).

Discussion

The purpose of this retrospective study was to investigate

the usefulness of PET scan imaging in the detection of

recurrent disease in asymptomatic and symptomatic women

previously treated for cervical cancer. A secondary objective

was to look at the potential of surveillance PET scans in

asymptomatic women to detect recurrent disease earlier than

in women with symptoms suggestive of recurrent tumor.

Unfortunately, women with symptomatic recurrent cervical

cancer have limited treatment options and often do not

survive their disease. Earlier detection of recurrent disease

has the potential to improve survival for these women,

although this remains unproven to this point. However,

Bodurka-Bevers [11] has shown that for women with

recurrent Stage IB disease, survival is better for asymptom-

atic women compared to symptomatic women.

Symptoms of recurrent disease such as pain and bleeding

are ominous signs in women previously treated for cervical

cancer. As reported by Havrilesky et al. [9] and confirmed in

our report, there is a high likelihood that recurrent cancer

will be found with PET scan imaging in symptomatic

women. Havrilesky et al. [9] reported finding recurrent

disease in 12 of 20 patients with a sensitivity for PET scan

of 86%. We found recurrent disease with PET scan in 14 of

21 such women with a PET scan sensitivity of 100%. Sun et

al. [7] reviewed the PET scan results of 20 women with

known recurrent disease and reported a sensitivity of 90%.

Clearly, PET scans are useful in detecting recurrent disease

in symptomatic women. Unfortunately, as shown in our

study, the majority of these women have disease that is no

longer localized to the pelvis. In addition, we found that

PET scans are more likely to be positive in women who areradiotherapy or pelvic exenteration may be lifesaving.significant. This may be due to any number of factors. This

is a small series and therefore may lack adequate power to

detect such a small difference. Also, this is a retrospective

study and surveillance PET scans were performed at varying

intervals after treatment was completed. Finally, our patients

with symptoms with recurrent cancer presented relatively

early in their posttreatment course, an average of 13 months,

which may make the usefulness of routine surveillance with

PET problematic.

In conclusion, it is clear that PET scan imaging is useful

in the detection of recurrent cervical cancer in symptomatic

patients. PET scans post-therapy in asymptomatic patients

for surveillance purposes appear promising, but must await

further study with prospective, standardized protocols be-

fore it can be recommended for routine use. Only with data

from this type of study will one be able to address the

ultimate question of whether routine surveillance with PET

scan imaging can lead to improved survival in women with

recurrent cervical cancer.

Acknowledgments

The authors would like to thank the Biomedical Research

Center of Northwest Louisiana for funding PET Scans for

many of our patients.

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J.B. Unger et al. / Gynecologic Oncology 94 (2004) 212216216

Detection of recurrent cervical cancer by whole-body FDG PET scan in asymptomatic and symptomatic womenMaterials and methodsPatientsFDG-PET

ResultsDiscussionAcknowledgementsReferences

Detection of Recurrent Cervical Cancer

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