original article

Annals of Oncology 21: 9941000, 2010

doi:10.1093/annonc/mdp426
Published online 25 October 2009

Management of occult invasive cervical cancer found

after simple hysterectomy
J.-Y. Park, D.-Y. Kim, J.-H. Kim, Y.-M. Kim, Y.-T. Kim & J.-H. Nam*
Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

Received 28 May 2009; revised 14 July 2009; accepted 29 July 2009

concurrent chemoradiation therapy (CCRT) for patients with occult invasive cervical cancer found after simple
hysterectomy.
Materials and methods: We retrospectively evaluated outcomes in 147 patients with occult invasive cervical
cancer.
Results: Forty-eight patients with IA1 lesions (IA1 group) did not receive further treatment. Of the 99 patients with
IA2IIA lesions, 26 received no definitive treatment (observation group), 44 received RT or CCRT (RT/CCRT group),
and 29 underwent RP (RP group). After a median follow-up of 116 months (range 3235 months), recurrent disease
was observed in 0%, 34.6%, 6.8%, and 0% of patients in the IA1, observation, RT/CCRT, and RP groups,
respectively. In the RT/CCRT group, treatment was delayed due to severe diarrhea in 4 patients (9%) and 12 patients
(27%) had late complications related to RT requiring further management (including two surgical interventions). Five
patients in the RP group (17%) experienced perioperative complications which were easily managed, intraoperatively
or conservatively. Late complications were not observed in the RP group.
Conclusion: Although RP and RT/CCRT had similar therapeutic efficacy, the lower rate of late complications
observed with RP makes it preferable to RT/CCRT.
Key words: concurrent chemoradiation therapy, occult cervical cancer, radiation therapy, radical parametrectomy,
simple hysterectomy

introduction
Cervical cancer is the second most common female cancer and
one of the leading causes of cancer deaths in females worldwide
[1, 2]. Widespread screening for cervical cancer has increased
the rate of early-stage diagnosis. Most patients with early-stage
cervical cancer undergo radical hysterectomy with pelvic 6
paraaortic lymphadenectomy, with 5-year survival rates of
75%90% [35]. Sometimes, however, this malignancy is
encountered after simple hysterectomy carried out for benign
gynecologic conditions or preinvasive cervical lesions. Radical
parametrectomy (RP), consisting of resection of the
parametrium, upper vaginectomy, and pelvic 6 paraaortic
lymphadenectomy may be carried out as a definite treatment in
these patients [6, 7]. However, due to technical difficulties in
carrying out RP and a lack of knowledge about the safety and
efficacy of this operation, physicians tend to administer
radiation therapy (RT) or concurrent chemoradiation therapy
(CCRT) instead.
*Correspondence to: Dr J.-H. Nam, Department of Obstetrics and Gynecology,
University of Ulsan College of Medicine, Asan Medical Center, 388-1 Poongnap-2 Dong,
Songpa-Gu, Seoul 138-736, Korea. Tel: +82-2-3010-3633; Fax: +82-2-476-7331;
E-mail: jhnam@amc.seoul.kr

The aims of this study were to estimate the feasibility, safety,

and efficacy of RP for occult invasive cervical cancer detected
after simple hysterectomy carried out for benign gynecologic
conditions or preinvasive cervical lesions and to compare the
outcomes of patients who underwent RP with those who
received RT or CCRT.

materials and methods

Following approval by the Institutional Review Board of the Asan Medical
Center (AMC, Seoul, Korea), we searched the cancer registry and
computerized database to identify patients with occult invasive cervical
cancer detected after simple hysterectomy carried out for benign
gynecologic conditions or preinvasive cervical lesions from 1989 to 2009.
Patients medical records were retrospectively reviewed, and demographic
data including age, menopausal status, parity, and body mass index were
recorded. We also reviewed patients medical records for a history of cancer,
other medical diseases, and surgery or RT of the pelvis. Clinical data
included indication for hysterectomy; results of Papanicolaou smears taken
before hysterectomy; presence of residual tumor; histologic type, size, and
grade of each tumor; presence of lymphovascular space invasion (LVSI) in
the hysterectomy specimen; presumed stage of disease, as determined using
the International Federation of Gynecology and Obstetrics (FIGO) system
for cervical cancer; the outcomes of diagnostic procedures; type and

The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
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original
article

Background: To estimate safety and efficacy of radical parametrectomy (RP) and radiation therapy (RT) or

Annals of Oncology

outcomes of definitive treatment after hysterectomy; lymph node (LN)

status after RP; adjuvant therapy after RP; recurrence; and treatment at
recurrence and death. Pathology slides were reviewed by two experienced
pathologists and clinicopathological prognostic factors and treatment
outcomes were analyzed.

surgical procedure for RP

RP surgery was carried out through a midline laparotomy in 25 patients
and through laparoscopic surgery using four trocars in 4 patients. Both
surgical approaches were basically the same with type III hysterectomy [8].
Briefly, each surgical procedure commenced with a systemic bilateral pelvic
6 paraaortic lymphadenectomy. The ureters were dissected from the
uterine artery and the cardinal ligaments and ureters were separated as
much as possible from the bladder. Cardinal ligaments were severed at their
most lateral portions and freed as much as possible from the surrounding
tissue. The uterosacral ligaments were severed near the sacrum, and the
paracolpium was resected as much as possible. An incision was made in the
vaginal cuff at least 34 cm below the fornices.

Frequency distributions were compared using the chi-square and Fishers

exact tests, and mean and median values were compared between the
groups using the Students t-test and the MannWhitney U test. Overall
survival (OS) was calculated as the number of months from the date of
simple hysterectomy to the date of death or the date censored. Disease-free
survival (DFS) was calculated as the number of months from the date of
simple hysterectomy to the date of recurrence or the date censored. Survival
curves and rates were calculated using the KaplanMeier method.
Differences in survival were assessed using the log-rank test for categorical
factors and Cox proportional hazards model for continuous factors in
univariate analysis. A P value of <0.05 in a two-sided test indicated
a significant difference. Data were analyzed using SPSS software for
Windows (version 11.0; SPSS Inc., Chicago, IL).

results
Of 2792 patients with invasive cervical cancer who were treated
and followed at AMC during the study period, 147 (5.3%) had
occult invasive cervical cancer found after simple hysterectomy
carried out for benign gynecologic conditions or preinvasive
cervical lesions. Of these 147 patients, 37 (25.2%) had
undergone simple hysterectomy at other hospitals and 110
(74.8%) had undergone simple hysterectomy at AMC. The
indications for simple hysterectomy included squamous
intraepithelial neoplasia (CIN), including carcinoma in situ
(CIS), in 102 patients (69.4%), leiomyoma in 32 patients
(21.8%), adenomyosis in 4 patients (2.7%), adenocarcinoma in
situ in 4 patients (2.7%), uterine prolapse in 3 patients (2.0%),
intractable dysfunctional uterine bleeding in 1 patient (0.7%),
and severe postpartum hemorrhage in 1 patient (0.7%). Of
102 patients who underwent inadvertent simple hysterectomy
for CIN or CIS, 31 did so due to the failure to carry out
conization or endocervical curettage and 71 did so due to the
absence of invasive lesions in conization specimens. Of the
remaining 45 patients who underwent inadvertent simple
hysterectomy due to other benign gynecologic problems, 35 did
so due to false-negative cytology and 10 did so due to the
absence of cytologic evaluation before hysterectomy. Ninetyfive patients (64.6%) underwent total abdominal hysterectomy,
47 (32.0%) underwent laparoscopic-assisted vaginal

Volume 21 | No. 5 | May 2010

hysterectomy, and 5 (3.4%) underwent vaginal hysterectomy.

Sixty-five patients underwent unilateral (n = 11) or bilateral
(n = 51) salpingo-oophorectomy or ovarian cystectomy
(n = 3) during hysterectomy. After simple hysterectomy,
presumed FIGO stage was IA1 in 48 patients (32.7%), IA2 in
7 patients (4.8%), IB1 in 85 patients (57.8%), IB2 in 4 patients
(2.7%), and IIA in 3 patients (2.0%). The characteristics of the
147 patients are shown in Table 1.

patients with IA1 lesions

The hysterectomy specimens from all 48 patients with IA1
lesions had negative resection margins. All patients had
squamous lesions. After simple hysterectomy, none underwent
further imaging. Six patients (12.5%) had positive LVSI. None
of these patients underwent further treatment after simple
hysterectomy. After a median follow-up time of 158 months
(range 34235 months), none of these patients had recurrent
disease (Figure 1).
patients with IA2IIA lesions
Of the 99 patients with IA2IIA lesions, 26 received no further
definitive treatment, including RT, CCRT, or RP (observation/
chemotherapy group), and 44 patients received RT or CCRT
(RT/CCRT group) and 29 underwent RP (RP group) as
definitive treatments after simple hysterectomy.
observation/chemotherapy group. Of the 26 patients who did not
receive RT, CCRT, or RP, 20 refused further treatment, whereas
6 received adjuvant chemotherapy; two patients received
paclitaxel/cisplatin, three received 5-fluorouracil/cisplatin, and
one received vincristine/ifosfamide/cisplatin. The mean
number of chemotherapy cycles was 4 (range 36). All six
patients who received adjuvant chemotherapy had IB1 lesions;
of these, three had squamous cell carcinoma and three had
adenocarcinoma. Of the 26 patients in this group, 2 underwent
computed tomography (CT) of the abdomen and pelvis, 3
underwent magnetic resonance imaging (MRI) of the abdomen
and pelvis, and 2 underwent whole-body positron emission
tomographycomputed tomography (PETCT) after simple
hysterectomy. None showed evidence of a pelvic lesion or
lymphadenopathy. After a median follow-up time of 104
months (range 7232 months), nine patients (34.6%) had
recurrent disease. The median time to recurrence was 46
months (range 4137 months). Recurrent sites were the vaginal
stump (n = 2), the pelvis (n = 4), the pelvis and pelvic LNs
(n = 1), and the pelvis and paraaortic LNs (n = 2). Four
patients received RT and five patients received CCRT at
recurrence, with four dying of disease. The 10-year DFS and OS
rates were 63% and 84%, respectively (Figure 1). Of the six
patients who received adjuvant chemotherapy, one (17%) had
recurrent disease and died of disease. Of the remaining 20
patients who did not receive adjuvant chemotherapy, 8 (40%)
had recurrent disease and 3 (15%) died of disease. There were
no differences in DFS and OS between the two groups
(P = 0.315 and 0.935, respectively).
RT/CCRT group. Thirty-two patients received RT and 12
received CCRT. The chemotherapeutic regimen was weekly

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statistical analysis

original article

original article

Annals of Oncology

Table 1. Characteristics of patients (N = 147)

Characteristics

147 (100.0)
48 (2875)
78 (53.1)
69 (46.9)

IA2IIA lesiona
Obs or CTx

P valueb
RT or CCRT

RP

26 (17.7)
45 (2863)

44 (29.9)
52 (3475)

29 (19.7)
51 (3374)

15 (57.7)
11 (42.3)

18 (40.9)
26 (59.1)

14 (48.3)
15 (51.7)

0.776b
0.535b

0.008b
78 (53.1)
69 (46.9)

15 (57.7)
11 (42.3)

15 (34.1)
29 (65.9)

19 (65.5)
10 (34.5)

48
7
85
4
3

0 (0.0)
5 (19.2)
21 (80.8)
0 (0.0)
0 (0.0)

0 (0.0)
5 (4.5)
37 (84.1)
9 (9.1)
1 (2.3)

0 (0.0)
0 (0.0)
27 (93.1)
0 (0.0)
2 (6.9)

0.170b
(32.7)
(4.8)
(57.8)
(2.7)
(2.0)

0.003b
121 (82.3)
23 (15.6)
3 (2.0)

21 (80.8)
5 (19.2)
0 (0.0)

36 (81.8)
5 (11.4)
3 (6.8)

16 (55.2)
13 (44.8)
0 (0.0)
0.056b

28
110
9
1.1

(19.0)
(74.8)
(6.1)
(0.15.0)

7
16
3
1.1

(26.9)
(61.5)
(11.5)
(0.52.5)

6
34
4
1.7

(13.6)
(77.3)
(9.1)
(0.55.0)

11
16
2
1.7

(37.9)
(55.2)
(6.9)
(0.63.5)

98 (66.7)
25 (17.0)
24 (16.3)

21 (80.8)
2 (7.7)
3 (11.5)

23 (52.3)
11 (25.0)
10 (22.7)

6 (20.7)
12 (41.4)
11 (37.9)

137 (93.2)
10 (6.8)

26 (100.0)
0 (0.0)

40 (90.9)
4 (9.1)

28 (96.6)
1 (3.4)

25 (96.2)
1 (3.8)
104 (7232)
9 (34.6)
4 (15.4)
63
84

34 (77.3)
10 (22.7)
100 (9232)
3 (6.8)
2 (4.5)
93
94

27 (93.1)
2 (6.9)
73 (3220)
0 (0.0)
0 (0.0)
100
100

0.969b
0.026b

0.642b

0.108b
128 (87.1)
19 (12.9)
116 (3235)
12 (8.2)
6 (4.1)
91
96

0.068b
0.272b
0.514b
0.199b
0.276b

The details of patients with IA1 lesion are not shown here.
Comparison between the RT/CCRT and RP groups.
Obs, observation; CTx, chemotherapy; RT, radiation therapy; CCRT, concurrent chemoradiation therapy; RP, radical parametrectomy; FIGO, International
Federation of Gynecology and Obstetrics; LVSI, lymphovascular space invasion; DFS, disease-free survival; OS, overall survival.

cisplatin in one patient, paclitaxel/cisplatin in two patients, and

5-fluorouracil/cisplatin in nine patients. The mean number of
chemotherapy cycles was 3.3 (range 16). The mean time from
hysterectomy to the commencement of RT or CCRT was 29
days (range 8124 days). Twenty-three patients received wholepelvic radiation therapy (WPRT) only, 3 patients received
intracavitary radiation therapy (ICR) only, and 18 patients
received both. The mean radiation dose for WPRT was 5006
cGy (range 40005080 cGy), and the mean radiation dose for
ICR was 2162 cGy (range 15003000 cGy). The mean duration
of RT or CCRT was 49 days (range 1367 days). In four
patients, RT or CCRT was delayed due to severe diarrhea. RT

996 | Park et al.

or CCRT were well tolerated in other patients. Of the 44

patients in this group, 7 underwent CT, 12 underwent MRI,
and 2 underwent PETCT after simple hysterectomy. Only
two MRI scans revealed suspected residual tumors in the
vaginal stump. After a median follow-up time of 116 months
(range 9232 months), three patients (6.8%) had recurrent
disease. The median time to recurrence was 9 months (range
619 months). Recurrent sites were the pelvis in one patient;
the pelvis, paraaortic, and cervical LNs in one patient; and
bone and lung in one patient. One patient received
chemotherapy consisting of three cycles of paclitaxel/cisplatin,
and two patients received CCRT (one received three cycles of

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Number of patients, n (%)

Age (years), mean (range)
Menopause, n (%)
No
Yes
Parity, n (%)
2
>2
FIGO stage, n (%)
IA1
IA2
IB1
IB2
IIA
Histology, n (%)
Squamous cell carcinoma
Adenocarcinoma
Adenosquamous cell carcinoma
Grade, n (%)
Well differentiated
Moderately differentiated
Poorly differentiated
Size of tumor (cm), mean (range)
Depth of invasion, n (%)
<1/3
1/3 to 2/3
2/3
Resection margin, n (%)
Negative
Positive
LVSI, n (%)
Negative
Positive
Follow-up time (months), median (range)
Recurrence, n (%)
Death, n (%)
10-year DFS (%)
10-year OS (%)

Total

original article

Annals of Oncology

paclitaxel/cisplatin and the other received three cycles of

5-fluorouracil/cisplatin); of these three patients, two died of
disease. The characteristics of the three patients who had
recurrent disease after RT or CCRT are shown in Table 2. The
10-year DFS and OS rates were 93% and 94%, respectively
(Figure 1). During follow-up after RT or CCRT, 12 patients
(27%) suffered late complications related to RT requiring
further management; these complications included radiation
cystitis (n = 4), radiation proctitis or colitis (n = 6), radiation
vaginitis (n = 4), rectovaginal fistula (n = 1), and ureteral
stricture (n = 1). Two patients required surgical management.
Of the 12 patients with late complications, 8 (67%) had
received WPRT and ICR, with a total dose of >6540 cGy, and 4
(33%) had received WPRT only, with a total dose of 5040 cGy.
Of the 44 patients who received RT or CCRT, four had positive
resection margins on simple hysterectomy specimens. Of these,
three patients with FIGO stage IB1 lesions received RT, one
patient with a FIGO stage IB2 lesion received CCRT with three
cycles of 5-fluorouracil and cisplatin, and one patient with
a FIGO stage 1B1 lesion underwent RP. None showed evidence
of recurrent disease after treatment.
RP group. Twenty-nine patients underwent RP with pelvic
lymphadenectomy. Nineteen patients underwent paraaortic
lymphadenectomy, 11 underwent unilateral or bilateral
salpingo-oophorectomy, and 3 underwent ovarian
transposition during RP. Four patients underwent laparoscopic
RP. Of the 29 patients who underwent RP, one patient with
a IB1 lesion had positive resection margins on simple
hysterectomy specimen. One patient underwent CT, 10
underwent MRI, and 7 underwent PETCT after simple
hysterectomy. Only one MRI scan revealed a residual tumor in
the vaginal stump. The mean time from simple hysterectomy to
RP was 34 days (range 13114 days). The mean operating time
was 297 min (range 172433 min), and the mean estimated
blood loss during surgery was 538 ml (range 2001000 ml).
Seventeen patients (59%) required perioperative transfusions,
with a mean transfusion volume of 2.4 pints (range 15 pints).
The mean preoperative and postoperative hemoglobin (Hb)

Volume 21 | No. 5 | May 2010

concentrations and perioperative Hb change were 13.1 gm/dl

(range 11.914.3), 11.0 gm/dl (range 9.113.6), and 2.1 gm/dl
(range 0.55.6), respectively. Three intraoperative
complications were recorded, including one bladder
perforation and two rectal serosa lacerations, all of which were
managed with intraoperative suturing. After surgery, two
patients experienced complications, including one with
mechanical ileus that was managed conservatively and one with
urethrocutaneous fistula that was managed surgically. The
mean time to return of bowel movements was 2.8 days (range
1.04.0 days). The mean postoperative hospital stay was 17 days
(range 743 days). In three patients, residual disease was found
on the vaginal stump after RP, measuring 0.4, 0.5, and 0.5 cm,
respectively. No RP specimen showed involvement of the
parametrium or resection margin. The mean number of total,
paraaortic, and pelvic LNs retrieved were 36.8 (range 1357),
4.3 (range 37), and 33.4 (1353), respectively. Four patients
had LN metastasis; the mean number of LNs involved was 1.8
(range 13). Two patients had right obturator LN metastasis,
one had right internal iliac LN metastasis, and one had
involvement of both external iliac LNs. The characteristics of
the four patients with LN metastasis are shown in Table 3. Four
patients with LN metastasis and one with two intermediate risk
factors (positive LVSI and stromal invasion >2/3) received
adjuvant therapy after RP; one received RT, one received five
cycles of paclitaxel/cisplatin, one received three cycles of 5fluorouracil/cisplatin, and two received CCRT, consisting of
three cycles of 5-fluorouracil/cisplatin or six cycles of weekly
cisplatin. After a median follow-up of 73 months (range 3220
months), no patient showed evidence of disease recurrence
(Figure 1) or late complications related to RP that required
further management.

discussion
Our findings indicate that occult IA1 cervical cancer found after
simple hysterectomy can be followed safely without further
management, regardless of the status of LVSI. In patients with

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Figure 1. Disease-free survival (left) and overall survival (right) by stage and treatment modality in 147 patients with occult invasive cervical cancer. IA1
observation (Obs), 48 patients with IA1 lesions who did not receive further management; Obs/chemotherapy (CTx), 26 patients with IA2IIA lesions who
did not receive further management or who received adjuvant chemotherapy; radiation therapy (RT)/concurrent chemoradiation therapy (CCRT), 44
patients with IA2IIA lesions who received RT or CCRT; radical parametrectomy (RP), 29 patients with IA2IIA lesions who underwent RP.

Patient

Age
(years)

FIGO
stage

Histology

Grade

Tumor
size (cm)

LVSI

DSI

RM

Treatment

RT type

RT dose
(cGy)

RFS
(months)

OS
(months)

Status

1
2
3

46
45
47

IB1
IB2
IB1

SCCa
SCCa
SCCa

2
3
2

1.1
4.0
1.5

Positive
Positive
Negative

1/3 to 2/3
>2/3
1/3

Negative
Negative
Negative

CCRT wP 6 cycles
CCRT FP 6 cycles
RT

WPRT + ICR
WPRT + ICR
WPRT

6540
7440
5040

19
6
9

56
9
36

DOD
DOD
AWD

RT, radiation therapy; CCRT, concurrent chemoradiation therapy; FIGO, International Federation of Gynecology and Obstetrics; LVSI, lymphovascular space invasion; DSI, depth of cervical stromal invasion;
RM, resection margin on simple hysterectomy specimen; RFS, recurrence-free survival; OS, overall survival; SCCa, squamous cell carcinoma; wP, weekly cisplatin; WPRT, whole-pelvic radiation therapy; ICR,
intracavitary radiation therapy; DOD, die of disease; FP, 5-fluorouracil + cisplatin; AWD, alive with disease.

original article

998 | Park et al.

Table 2. The characteristics of patients who had recurrence after RT or CCRT

Table 3. The characteristics of patients with pelvic LN metastasis after RP

Patient

Age (years)

FIGO
stage

Histology

Grade

Tumor size
(cm)

LVSI

DSI

RM

Site of LN
metastasis

No. of LN
metastases

Adjuvant treatment
after RP

Recurrence

OS (months)

Status

1
2
3
4

45
66
48
66

IB1
IIA
IB1
IIA

AdCa
SCCa
AdCa
SCCa

2
1
2
1

2.5
2.7
3.5
2.0

Negative
Negative
Positive
Negative

>2/3
>2/3
>2/3
>2/3

Negative
Negative
Negative
Negative

Both external iliac

Right internal iliac
Right obturator
Right obturator

3
1
2
1

CCRT FP 3 cycles
CCRT wP 6 cycles
TP 5 cycles
RT

None
None
None
None

123
3
63
93

NED
NED
NED
NED

Annals of Oncology

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Volume 21 | No. 5 | May 2010

LN, lymph node; RP, radical parametrectomy; FIGO, International Federation of Gynecology and Obstetrics; LVSI, lymphovascular space invasion; DSI, depth of cervical stromal invasion; RM, resection margin
on simple hysterectomy specimen; OS, overall survival; AdCa, adenocarcinoma; CCRT, concurrent chemoradiation therapy; FP, 5-fluorouracil + cisplatin; NED, no evidence of disease; SCCa, squamous cell
carcinoma; wP, weekly cisplatin; TP, paclitaxel + cisplatin; RT, radiation therapy.

original article

Annals of Oncology

Volume 21 | No. 5 | May 2010

Table 4. The outcomes by treatment modality in patients with occult

cervical cancer found after simple hysterectomy
Author

Year

Treatment
modality

5-year OS
rate (%)

Cosbie [16]
Barber et al. [15]
Green et al. [32]

1963
1968
1969

Andras et al. [17]

Davy et al. [18]
Papavasiliou et al. [19]
Heller et al. [20]
Orr et al. [33]
Kinney et al. [34]
Chapman et al. [35]
Roman et al. [21]
Fang et al. [22]
Choi et al. [23]
Crane et al. [24]
Huerta Bahena et al. [25]
Chen et al. [26]
Munstedt et al. [9]
Leath et al. [6]
Ayhan et al. [7]
Present study

1973
1977
1980
1986
1986
1992
1992
1993
1993
1997
1999
2003
2003
2004
2004
2006
2009

86
115
30
21
118
72
36
35
23
27
18
122
73
64
18
59
29
80
23
27
44
29

RT
RP
RT
RP
RT
RT
RT
RT
RP
RP
RP
RT
RT
RT
RT
RT
RT
RT
RP
RP
RT or CCRT
RP

54
32
30
61
89
77
89
67
NR
82
89
65
67
76
93
59
8295
83
96
89
94a
100a

a
10-year OS rate.
OS, overall survival; RT, radiation therapy; RP, radical parametrectomy;
NR, not reported; CCRT, concurrent chemoradiation therapy.

months. Surgical intervention was required in 4.5% of patients,

similar to previously reported rates of 6%7% [3, 21, 24]. In
agreement with previous results, most of our patients with late
complications received WPRT and ICR, with total dose >6540
cGy [3, 21, 24]. Although the role of brachytherapy in
combination with WPRT is not yet clear, most patients treated
with WPRT alone in our series did well. Considering the higher
rate of complications, ICR may be safely omitted in selected
patients.
Five-year survival rates after RP have been reported to range
from 67% to 96% [6, 7, 3235] (Table 4). We observed 10-year
DFS and OS rates after RP of 100%, providing further evidence
of the safety of RP in patients with: (i) FIGO stage IA2IIA
tumors; (ii) squamous cell carcinoma, adenocarcinoma, or
adenosquamous cell carcinoma; and (iii) tumors <4 cm in
diameter, regardless of grade of tumor, depth of invasion, or
LVSI. Although previous studies have indicated that all patients
with positive surgical margins on simple hysterectomy
specimens are poor candidates for RP [6], our results indicate
that if there is no parametrial involvement, RP can be carried
out safely in patients with small residual disease on the vaginal
stump after simple hysterectomy. However, if there is a high
probability that a patient will receive adjuvant RT or CCRT
after RP, then RT or CCRT should be carried out instead of RP
because the combination of radical surgery and RT is associated
with a particularly high morbidity rate with no further survival
benefit [5]. Indeed, large prospective trials are required to fully
establish the patient eligibility criteria for RP.

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more advanced early-stage lesions (stage IA2IIA), however,

a definitive treatment, such as RT, CCRT, or RP, is necessary
because these patients are at increased risk of recurrence and
death, although they received adjuvant chemotherapy after
simple hysterectomy. Although similar survival outcomes were
obtained in the RT/CCRT and RP groups, the lower rate of late
complications after RP makes the latter preferable compared
with RT/CCRT in this patient population. RP was feasible in all
patients in our series and the operative parameters and
complications were acceptable.
Cervical cancer may be found incidentally after simple
hysterectomy carried out for benign gynecologic conditions or
preinvasive cervical lesions. The incidence of occult invasive
cervical cancer, however, is not clear, although in the present
study it comprised 5.3% of all cervical cancers. Occult invasive
cervical cancer after simple hysterectomy can occur due to several
causes. We found that the absence of invasive lesions in the
conization specimens from patients with CIN or CIS and falsenegative cytology were the most common causes of inadvertent
simple hysterectomy. Other studies have found that the most
common causes of inadvertent simple hysterectomy were the lack
of preoperative Pap smear, negative cytology, and no clinical
evidence of cancer, followed by inadequate evaluation of an
abnormal Pap smear or cervical biopsy and failure to carry out
conization or endocervical curettage [7, 9, 10].
If a lesion is found to be IA1 cervical cancer, further
management is not required, regardless of the status of LVSI
[11, 12]. However, if the lesion is larger, definitive RT, CCRT,
or RP is required because higher recurrence and death rates
have been observed in patients who did not receive further
management or who received adjuvant chemotherapy only.
Although we found that patients who did not receive definitive
treatment had smaller tumors and a greater incidence of
superficial (<1/3) stromal invasion than those in the RT/CCRT
and RP groups, 34.6% of patients had recurrent disease. All of
these patients had pelvic failure and some also had distant
failure. Using RT or CCRT for recurrent disease, five patients
were successfully re-treated, but four patients died of disease.
These results are in agreement with previous findings indicating
that simple hysterectomy is not sufficient for patients with
more than microinvasive cervical carcinoma (stage IA1 disease)
due to high recurrence and mediocre survival rates [1315].
Five-year survival rates after RT for occult cervical cancer
have been found to range from 54% to 93% [9, 1627]
(Table 4). In our series, 10-year DFS and OS rates after RT or
CCRT were 93% and 94%, respectively. Factors associated with
poor outcome after RT or CCRT may include residual disease
after simple hysterectomy [17, 18, 21, 24], positive resection
margins in hysterectomy specimens [18], deeper cervical
stromal invasion [3, 20], long time interval from hysterectomy
to RT (>6 months) due to delayed RT [18, 27], and histologic
type of adenocarcinoma [3].
In general, late complications of RT for cervical cancer have
been reported in 5%15% of patients [28]. Most early studies,
however, included relatively short follow-up periods. In more
recent studies, with longer follow-up, significant late
complication rates of 10%16% [29, 30] and 16%21% have
been reported [31]. In our series, late complications were
observed in 27% of patients after a median follow-up of 100

original article

disclosure
There is no conflict of interest to declare.

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Most physicians are reluctant to carry out RP in patients with

IA2IIA occult invasive cervical cancer because they consider the
RP procedure to be quite difficult, require an experienced
surgeon, and be associated with a high rate of surgery-related
morbidity. Therefore, most patients with IA2IIA occult
invasive cervical cancer undergo RT or CCRT [9, 1627], with
few undergoing RP [6, 7, 3235]. This is in contrast to the
current treatment of patients with early-stage cervical cancer,
most of whom undergo radical hysterectomy as primary
treatment. RP has been found to be feasible for most patients and
not particularly technically difficult, as assessed by objective
measures such as operating time, estimated blood loss,
transfusion requirement, and postoperative hospital stay [6, 7,
3235]. We found that the perioperative complication rate was
17%, which is within the previously reported range of 8.7%30%
[6, 7, 3235]. In the present study, most complications were
easily managed, either intraoperatively or conservatively. The
occurrence of long-term morbidity after RP is rare.
In conclusion, we have shown that the survival outcome after
RP was similar to that after RT or CCRT in patient populations
with similar disease stage, tumor size, positive resection margin,
positive LVSI, grade of tumor, and depth of stromal invasion.
In addition, RP was feasible in all patients. The immediate
surgical parameters were acceptable, the rate of perioperative
complications was very low, and there was no late morbidity.
Due to the high rates of long-term morbidity after RT or
CCRT, RP may be preferable for selected patients with IA2IIA
occult invasive cervical cancer. We think that RP may be of
greatest benefit in young patients who want to preserve their
ovarian and sexual function.

Annals of Oncology