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Abstract

Opinion statement: Cervical cancer (CC) is the fourth most frequent tumor and the fourth most common cause of cancer death among women worldwide. Furthermore, more than 40 % of women with early CC are affected during reproductive age and wish to remain fertile. Thus, many patients demand a more conservative policy for managing these lesions in order to have an uneventful pregnancy in the near future. For this reason, interest in fertility preservation strategies has been increasing, and the number of published studies on this topic has grown significantly. Conization was the first fertility-sparing surgical procedure tested in stage IA1 CC. However, in recent decades, other strategies have been tested, particularly for more advanced tumors. The aim of this review is to analyze the main techniques performed in patients with CC who are eligible for fertility-sparing surgery, with particular attention paid to open questions and controversies.
Curr. Treat. Options in Oncol. (2016) 17: 5
DOI 10.1007/s11864-015-0386-9
Fertility-Sparing Options
in Young Women with Cervical
Cancer
Federica Tomao, MD, PhD
1,2,*
Giacomo Corrado, MD, PhD
3
Fedro Alessandro Peccatori, MD, PhD
1
Sara Boveri, MD, PhD
1
Eleonora Petra Preti, MD, PhD
1
Nicoletta Colombo, MD, PhD
1
Fabio Landoni, MD, PhD
1
Address
*,1
European Institute of Oncology BIEO,^, Via Giuseppe Ripamonti 435, 20141,
Milan, Italy
Email: federica.tomao@ieo.it
2
University BSapienza^, Sapienza, Rome
3
National Cancer Institute BRegina Elena^,ReginaElena,Rome
Published online: 25 January 2016
*Springer Science+Business Media New York 2016
This article is part of the Topical Collection on Gynecologic CancersFederica
Tomao and Giacomo Corrado contributed equally to this work.
Keywords Fertility sparing ICervical cancer IConization ITrachelectomy INeoadjuvant chemotherapy IUterus
transplantation
Opinion Statement
Cervical cancer (CC) is the fourth most frequent tumor and the fourth most
common cause of cancer death among women worldwide. Furthermore, more than
40 % of women with early CC are affected during reproductive age and wish to
remain fertile. Thus, many patients demand a more conservative policy for
managing these lesions in order to have an uneventful pregnancy in the near
future. For this reason, interest in fertility preservation strategies has been
increasing, and the number of published studies on this topic has grown signif-
icantly. Conization was the first fertility-sparing surgical procedure tested in
stage IA1 CC. However, in recent decades, other strategies have been tested,
particularly for more advanced tumors. The aim of this review is to analyze the
main techniques performed in patients with CC who are eligible for fertility-
sparing surgery, with particular attention paid to open questions and
controversies.
Gynecologic Cancers (RJ Morgan, Section Editor)
Introduction
Cervical cancer (CC) accounts for 6.7 million new cancer
cases and 3.5 million cancer deaths among the female
population worldwide [1]. According to most interna-
tional guidelines, standard treatment of CC consists of
surgery for early tumors and concomitant chemoradia-
tion for locally advanced disease. Because the risk of
lymph node involvement is very low (G1%)inpatients
with stage IA1 tumors in the absence of
lymphovascular space invasion (LVSI), conization
represents a reasonable option for preserving fertil-
ity [2]. On the contrary, the management of IA1
tumors with LVSI and early disease, defined by the
International Federation of Gynecology and Obstet-
rics (FIGO) as stage IA2IB1 CC, should be more
aggressive, including radical hysterectomy with pel-
vic lymphadenectomy, thus significantly affecting
reproductive capability. More than 42 % of patients
affected by CC are younger than 45 years, and up
to 40 % of early tumors are diagnosed in women
of reproductive age [3]. For these reasons, conser-
vative strategies have gained increasing interest in
the past decades, especially for patients affected by
early disease. The most investigated surgical proce-
dures aimed toward preserving fertility consist of
organ-sparing surgery, such as conization or trach-
electomy associated with laparoscopic pelvic
lymphadenectomy. Other investigators proposed
neoadjuvant chemotherapy (NACT) in patients
with larger tumors to reduce tumor size so that
fertility may be preserved. However, only a few
centers perform these procedures; thus, such alter-
natives remain largely in the experimental stage.
One of the most futuristic approaches for fertility
preservation in women without a uterus consists of
uterine transplantation. Recent studies analyzed
this potential preservation option, which until
now has been applied mainly for benign condi-
tions [4,5,6••]. In this report, we provide a
review of the existing literature data on the
fertility-conserving strategies available for CC, ana-
lyzing the results from studies published in the
past 10 years.
Standard Treatment by Disease Stage
Stage IA1
According to most international guidelines, the first diagnostic and curative step
for microscopic tumors is conization [4]. In the presence of negative
margins and the absence of clinical contraindications to surgery, the
cone biopsy may represent definitive treatment. However, for patients
not interested in future pregnancy, the standard treatment is radical
surgery consisting of extrafascial or radical hysterectomy with or without
pelvic lymphadenectomy, depending on margin status. Thus, conization
was the first fertility-sparing surgical method used in CC and has been a
valid and safe procedure for patients with IA1 tumors without LVSI who
want to preserve their fertility. For patients with LVSI, who have an
increased risk of lymph node involvement, pelvic lymph node dissection
or sentinel node biopsy should be considered [7]. Moreover, for these
patients, some authors suggest trachelectomy, a surgical procedure in
which the uterine cervix and adjacent tissues are removed.
Stage IA2
The standard treatment for IA2 tumors consists of radical hysterectomy with
pelvic lymphadenectomy. However, for patients desiring to preserve fertility,
cone biopsy or radical trachelectomy with pelvic lymph node dissection (or
sentinel node biopsy) with or without para-aortic lymph node sampling also
may be considered [8].
5Page 2 of 18 Curr. Treat. Options in Oncol. (2016) 17: 5
Stage IB1
Radical surgery also is the first therapeutic choice for IB1 tumors. Scientific
evidence shows that trachelectomy with pelvic lymphadenectomy is the most
appropriate surgical treatment for fertility sparing in patients with these tumors.
However, tumors larger than 2 cm clearly are associated with a higher risk of
recurrence (3 % for lesions 2 cm vs 17 % for lesions 92cm)[9••]; thus,
international guidelines stress that this procedure is valid mostly for tumors
measuring 2cmindiameter[4]. Finally, some authors have suggested
conization in this tumor setting as well [10••,1116].
More Advanced Tumors
For higher-stage tumors, the standard treatment consists of pelvic radiotherapy
with concurrent cisplatin-based chemotherapy with or without para-aortic
lymph node radiotherapy followed by final brachytherapy. Some authors
advocate NACT followed by radical surgery [17]. However, all these approaches
lead to the loss of reproductive capability. Some authors propose a neoadjuvant
approach followed by conservative surgery to avoid the destruction of genital
organs.
Adenocarcinomas and Other Histotypes
Adenocarcinomas of the uterine cervix account for approximately 25 % of all
newly diagnosed CC cases [18]. Other histotypes represent a very small per-
centage, with the remaining 75 % consisting of the squamous variant. In
general, adenocarcinomas are more likely to have lymph node involvement and
hematogenous metastasis [18]. Eifel et al. [19,20] reported significantly higher
rates of distant metastasis for FIGO stage IB1-III adenocarcinomas than for
squamous CC. Furthermore, numerous retrospective studies, including two
large reviews by Chen et al. [21] and Hopkins and Morley [22], reported poorer
overall survival (OS) in women with adenocarcinomas than in those with
squamous tumors. Moreover, there still is no consensus regarding ovary pres-
ervation in young patients with early-stage CC. In general, the rate of ovarian
metastasis in early-stage squamous CC is approximately 0 to 1.3 %. A recent
meta-analysis found that adenocarcinoma is associated with a higher risk for
ovarian metastasis compared with squamous CC [23]. Thus, some studies
concluded that young women with squamous CC who are planning to undergo
radical hysterectomy may opt to preserve their ovaries; whereas, simultaneous
bilateral salpingo-oophorectomy is recommended for patients with adenocar-
cinoma, regardless of their age. However, a recent study by Lyu et al. [24]
showed that ovarian preservation might be oncologically safe for young women
with stage I cervical adenocarcinoma.This study included women aged 45 years
and younger with stage I cervical adenocarcinoma and adenosquamous carci-
noma. A total of 1062 women (64.8 %) underwent oophorectomy, and 577
(35.2 %) had their ovaries preserved during hysterectomy. The authors dem-
onstrated that ovarian preservation had no effect on cancer-specific survival
based on the Cox proportional hazards model. Although some evidence shows
that IA1 adenocarcinomas with negative margins may be treated conservatively
with no risk of recurrence [25], few data exist regarding the safety of fertility-
sparing surgery in larger tumors of these histotypes. Mangler et al. [26]found
Curr. Treat. Options in Oncol. (2016) 17: 5 Page 3 of 18 5
that among tumors recurring after vaginal radical trachelectomy (VRT), adeno-
carcinomas were overrepresented, accounting for 40 % of cases, compared with
29 % at first diagnosis. Although it remains unclear whether adenocarcinomas
are associated with a high incidence of recurrence, a study by Nishio et al. [27]
suggests that patients treated by abdominal radical trachelectomy (ART) may
have a higher risk of recurrence if they have a tumor 20 mm in diameter, severe
LVSI, and adenocarcinoma, which exhibits skip lesions in some cases.
Fertility Strategies
Nodal Staging
CC usually spreads locally into the vagina, parametrium, and lymphatic system.
Predictors of tumor dissemination include tumor size, LVSI, histopathologic
grade of differentiation, and stromal invasion [28]. Furthermore, pelvic lymph
node status is related strictly to parametrial involvement [2931]. Based on
these findings, it appears that pelvic lymphadenectomy and conization provide
all the important prognostic factors for fertility-sparing surgery; thus, nodal
status assessment is the first step in determining whether a conservative surgical
approach for CCis warranted. This step can be skipped only in patients with IA1
tumors without LVSI, because in these cases, the risk of lymph node involve-
ment is negligible (G1 %). However, in the presence of LVSI, most guidelines
recommend performing a pelvic lymph node study [7], even though scientific
evidence shows no correlation between LVSI and lymph node metastasis [32,
33]. In IA2 squamous CC, the risk of pelvic lymph node involvement is
approximately 8 %. In more advanced stages, the incidence of nodal metastasis
increases to 15 to 20 % for stage IB1 tumors and around 30 % for locally
advanced neoplasia [34].
The standard approach for pelvic lymphadenectomy in fertility-sparing
surgery usually is via laparoscopy, except for abdominal trachelectomy. How-
ever, some authors suggest the use of sentinel lymph node (SLN) biopsy, a
technique generally associated with fewer complications and morbidities, such
as lymphedema, lymphocele formation, or prolonged surgical time. A recent
meta-analysis showed that SLN mapping is an accurate method for assessing
lymph node involvement in uterine CC, with a detection rate of 89.2 % [35].
However, in patients with tumors larger than 2 cm and with stage IB2 or more
advanced disease, the detection rate and sensitivity are lower. Moreover, the
diagnostic efficacy of this procedure varies depending on the mapping method
(blue dye, radiotracer, or both) and whether the patient has a history of
preoperative NACT. Thus, most international guidelines consider SLN mapping
in fertility-sparing surgery to be a feasible procedure but stress that the best
detection rates and mapping results are in tumors with a maximum diameter of
less than 2 cm [7]. In general, SLN still is considered an experimental procedure.
Conization
In a cone biopsy, a nonfragmented specimen is obtained with at least 3 mm of
negative margins. Moreover, if the margins of resection are positive, a repeat
cone biopsy and eventual trachelectomy will be necessary. As previously re-
ported, simple conization, with or without lymphadenectomy, represents a
reasonable treatment option for stage IA12 tumors in patients who wish to
5Page 4 of 18 Curr. Treat. Options in Oncol. (2016) 17: 5
become pregnant [36]. For these lesions, the most debated question is which
technique to use for excision. Several studies hypothesized that cold-knife
conization (CKC) is more likely than the loop electrosurgical excision proce-
dure (LEEP) to yield negative margins in precancerous lesions and in situ
carcinomas [37,38]. First, there is a perception that LEEP is associated with
incomplete excision, because the depth of resected tissue and the overall di-
mensions of the specimen tend to be smaller compared with CKC. It also is
argued that the tissue margins in a LEEP biopsy sample may show significant
thermal artifact, which might interfere with the pathologic assessment of biopsy
margins [39,40]. However, recent evidence shows that no significant differ-
ences exist between the two procedures with regard to the incidence of persis-
tent and/or recurrent endocervical neoplasia in patients with adenocarcinoma
histotypes [41]. In terms of obstetric outcomes, a meta-analysis published in
Lancet Oncology in 2006 showed that all the excisional procedures used to treat
cervical intraepithelial neoplasia result in similar pregnancy-related morbidity,
with no apparent neonatal morbidity [42]. Successively, another meta-analysis
showed more preterm deliveries among patients treated with CKC (OR, 2.8)
than those treated with with loop conization (1.7) [43]. However, insufficient
data exist regarding the best option for excising intraepithelial and microscopic
invasive cervical cancer; therefore, randomized clinical trials are needed to
identify the most appropriate therapeutic procedure.
The curative potential of conization has not been widely exploited in stage
IB1 lesions. Recent studies suggest that in certain circumstances, patients with
stage IB1 disease undergoing radical hysterectomy might have been safely cured
by simple hysterectomy or even by cervical conization [4449]. Covens et al.
[44] suggested that the incidence of parametrial involvement is only 0.6 % in
patients with tumors smaller than 2 cm, negative pelvic lymph nodes, and
depth of invasion less than 10 mm. Similar data were reported by Steed et al.
[45] and Wright et al. [46]. In particular, Wright et al. [46]retrospectively
analyzed the pathologic characteristics of 594 specimens from patients who
underwent radical hysterectomy for invasive cervical cancer and found that 64
cases, or 10.8 %, had parametrial involvement. Moreover, they showed that in
women with negative lymph nodes, without LVSI, and with tumors smaller
than 2 cm, the incidence of parametrial disease was only 0.4 %. In this
perspective, an analysis of 28 recurrences reported among 548 patients (5 %)
treated by radical trachelectomy confirmed that the risk factors for recurrence
were lesions 92 cm, LVSI, and stromal invasion deeper than 10 mm [50]. These
data suggest that a less radical surgical approach might be used in this patient
setting. Therefore, some authors have proposed the use of conization, or
eventually simple trachelectomy (ST), to preserve fertility in patients with IB1
cervical tumors. Thus, conization might represent a safe treatment option in
select cases and may in turn improve the obstetric as well as the surgical
outcome in terms of reduced risk of urologic morbidity. One of the many
reports on the use of laparoscopic lymphadenectomy with conization in IB1
cervical cancers was published by Maneo et al. [11] This study included 36
patients from three different institutions. The authors reported only one pelvic
lymph nodal relapse after a median follow-up of 66 months (range, 6168).
With regard to obstetric outcomes, 21 pregnancies occurred in 17 patients and
14 live babies were born (two preterm at 27 and 32 weeks), with one pregnancy
ongoing at the time of manuscript preparation. Finally, three first-trimester
Curr. Treat. Options in Oncol. (2016) 17: 5 Page 5 of 18 5
miscarriages, one second-trimester fetal loss, an ectopic pregnancy, and a ter-
mination of pregnancy were recorded. Furthermore, a recent study by Ditto
et al. [16]showedthatthisprocedureisassociatedwitha53%rateof
spontaneous pregnancies. Thus, these data suggest that conization
should be a valid therapeutic option for young patients who have IB1
tumors and want to preserve fertility. Table 1lists most of the important
studies regarding the use of conization in early CC, including FIGO
stage IB1 tumors.
Radical Trachelectomy
In 1957, Eugen Aburel was the first to report a new technique for fertility-
sparing surgery in CC that consisted of pelvic lymphadenectomy with removal
of the cervix and parametria (ART). However, none of the women he treated
with this procedure achieved a successful pregnancy. The international group of
Ungar et al. [51] later revived the use of this surgical approach, publishing their
initial experience in 1997. The extent of radicality of ART is the nearest to our
oncogynecologic representation of a radical surgical procedure in invasive CC
that supposes extirpation of paracervical tissues to the extent of Querleu-
Morrow types C1 and C2.
At the annual meeting of the Society of Gynecologic Oncology in 1994,
Daniel Dargent and his group presented their experience with laparoscopic
pelvic lymphadenectomy and VRT as a fertility-sparing therapy for CC; subse-
quently, they published a study performed with 47 patients [52]. Shortly
thereafter, several groups reported studies that raised as many questions as they
answered [5255]. Because the cervix is readily accessible through the vagina,
VRT is the most Bnatural^approach. With regard to the oncologic outcomes
associated with VRT, the recurrence rate reported in most studies is less than
5 %, with a death rate around 2 % [9••,50,5661,62••,6366]. In particular,
Plante et al. [62••] reported on 125 patients treated by VRT, showing that
tumors 92 cm were statistically associated with a higher risk of recurrence
(P= 0.001). Other authors, however, showed that the oncologic outcomes
appear to be comparable between radical hysterectomy and radical trachelec-
tomy for similarly sized lesions [50,58].
In general, VRT requires specialized skills in the vaginal approach; therefore,
some surgeons prefer an abdominal route. In 1997, Smith et al. [55]werethe
first to describe the ART procedure, which provides the advantage of a more
radical resection of the parametria. Einstein et al. [54] compared a series of 28
VRTs and 15 ARTs, showing that the average parametrial length obtained
abdominally was nearly twice as wide as that obtained vaginally (3.97 vs.
1.45 cm), suggesting that ART should be reserved for patients with larger
lesions. However, it must be noted that approximately 65 % of patients do not
show any residual cancer in the trachelectomy specimen after a diagnostic cone
biopsy [56,67]. This issue was raised previously in cases with stage IA2 tumors
as well and highlights the question as to whether less aggressive surgery is as
effective as radical trachelectomy [68]. Based on the studies of ART, the recur-
rence rate appears to be higher [27,69]. However, the tumors reported in those
studies were significantly larger, and 20 % of the patients showed nodal
involvement. Moreover, several studies showed that ART is significantly asso-
ciated with a higher rate of cervical stenosis and cerclage erosions.
5Page 6 of 18 Curr. Treat. Options in Oncol. (2016) 17: 5
Table 1. Conization in early-stage CC (including FIGO stage IB1 tumors)
Study Patients,
n
Median
age, y
Histotype Stage Type of
treatment
Oncologic
results
Obstetric
results
DFS,
%
OS,
%
Pregnancies,
n
Live
births, n
Landoni et al.
(2007)
[10••]
11 32 5 SCC 6
AdenoCa
3IA28IB1 LPSPLF+CON
a
100 100 3 3
Maneo et al.
(2011)
[11]
36 31 24 SCC 12
AdenoCa
36 IB1 PLF + CON 97.2 97.2 21 14
Fagotti et al.
(2011)
[12]
17 33 12 SCC 4
AdenoCa
1GC
4IA213
IB1
LPS PLF + CON 100 100 2 2
Fanfani et al.
(2014)
[13]
23 30 11 SCC 11
AdenoCa
1GC
7IA116
IB1
LPS PLF + CON 100 100 7 6
Choi et al.
(2013)
[14]
21 31 17 SCC 2
AdenoCa
2GC
10IA11IA2
9IB11
IIA
11 CON + PDT;
5 LPS PLF +
CON + PDT
95 100 9 5
Andikyan
(2014)
et al. [15]
10 28 8 SCC 1
AdenoCa
1GC
7IA13
IB1
LPS SNB + CON 100 100 3 3
Ditto et al.
(2015)
[16]
22 31 10 SCC 11
AdenoCa
1 Adenosq
6IA216
IB1
18 LPS
b
PLF +
CON
86 94 8 3
Adenosq adenosquamous, AdenoCa adenocarcinoma, CON conization, DFS disease-free survival, GC glassy cell, LPS laparoscopic, OS overall survival, PDT photodynamic therapy, PLF
pelvic lymphadenectomy, SCC squamous cell carcinoma, SNB sentinel node biopsy
a
Two patients underwent neoadjuvant chemotherapy; one patient received adjuvant chemotherapy
b
Three patients with metastatic lymph nodes and one who did not comply with follow-up underwent radical hysterectomy
Curr. Treat. Options in Oncol. (2016) 17: 5 Page 7 of 18 5
Recently, laparoscopic radical trachelectomy was introduced [70]. This pro-
cedure has the innate advantages of laparoscopic surgery over laparotomy,
resulting in less blood loss and a shorter hospital stay. Vieira et al. [71]
published a recent retrospective analysis of the use of radical trachelectomy,
comparing open with minimally invasive surgery (MIS) for early-stage CC. A
total of 100 patients from four different institutions were included in the
analysis; 58 patients underwent open radical trachelectomy, whereas the other
42 underwent MIS. The pregnancy rate was higher in the open-surgery group
(51 vs. 28 %, P=0.018), although the median follow-up was shorter in the MIS
group (25 vs. 66 months). Unfortunately, data regarding oncologic outcomes
were not reported.
Finally, some authors have suggested the use of robotics to obtain a radical
trachelectomy such as that provided by ART but with the benefits of a mini-
mally invasive approach [7277]. However, the available data are too incon-
sistent to determine the obstetric and oncologic outcomes of this approach.
With regard to the obstetric outcome from radical trachelectomy, abdominal
or full laparoscopic radical procedures do not result in good pregnancy rates
[51,78••,7981]. Poor pregnancy results probably are a result of the complete
discontinuation of important nerves from the pelvic plexus for tubal motility
during an abdominal or full laparoscopic radical trachelectomy. The crucial
factor in second-trimester abortion or premature labor is the amount of stromal
tissue remaining; however, safe margins must be the same in abdominal and in
vaginal procedures [51,78••,7981]. Regarding complications related to the
procedure, the most frequent are bladder dysfunction, vulvar edema/hemato-
ma, and lymphocele. Other problems specifically related to trachelectomy are
dyspareunia, dysmenorrhea, cervical stenosis, menstrual abnormalities, and
chronic discharge. Moreover, after radical trachelectomy, most women need to
undergo assistive reproductive procedures to conceive, because the cervix also is
fundamental for conception.
Simple Trachelectomy
Some studies have reported the absence of residual disease in trachelectomy
specimens in the range of 60 to 65 %, questioning the necessity for radical surgery
in patients with low-risk tumors [67]. Lanowska et al. [9••] performed step
sectioning of all the parametrial tissues from 112 VRT cases and identified only one
micrometastasis. Rob et al. [78••] conducted a pilot study testing the use of a large-
cone biopsy or ST in patients with node-negative disease who previously
underwent lymphadenectomy [78••] and reported one isthmic recurrence and one
carcinoma in situ. Other authors reported similar results with ST [67,82,83]. In
particular, Raju et al. [83] compared 15 STs with 51 radical
trachelectomies and reported no recurrences in the former group.
Table 2lists most of the important studies on ART, VRT, and ST.
Neoadjuvant Chemotherapy and Fertility-Sparing Surgery
For tumors larger than 2 cm, NACT followed by conization or trachelectomy
may be a valid choice. One of the most important studies on this topic was
published by Maneo et al. [90••], who reported that 39 % of their study
patients had either no residual disease or in situ disease only, and 39 % had
microscopic residual disease (G3 mm) in the cone specimen. Subsequently, as
5Page 8 of 18 Curr. Treat. Options in Oncol. (2016) 17: 5
Table 2. Trachelectomy: ART, VRT, and ST
Study Patients,
n
Median
age, y
Histotype Stage Type of
treatment
Oncologic
results
Obstetric
results
DFS,
%
OS,
%
Pregnancies,
n
Live
births,
n
Ungar et al.
(2005) [51]
30 31 26 SCC 1
Adk 1 Adenosq
2Other
10 IA2
15 IB1
5IB2
ART NA NA 3 2
Shepherd et al.
(2006) [56]
123 31 83 SCC
33 Adk
3 Adenosq
4Other
2IA2
121 IB1
VRT NA NA 88 47
Hertel et al.
(2006) [57]
108 32 75 SCC
33 Adk
18 IA1 + LVSI
21 IA2
69 IB1
VRT 96 98 16 12
Marchiole et al.
(2007) [58]
257: 118 FSS,
139 RH
32 vs. 47 90 SCC
25 Adk
3Other
10 IA1 + LVSI
19 IA2
83 IB1
6 IIA
118 LAVRT 96 95 NA NA
Pareja et al.
(2008) [84]
15 30 11 SCC
4Adk
3IA2
12 IB1
ART NA NA 3 3
Beiner and
Covens
(2007) [50]
180 31 39 SCC
44 Adk
6 Adenosq
1GC
NA 90 VRT 95 99 NA NA
Sonoda et al.
(2008) [59]
43 31 8 IA1
7IA2
28 IB1
24 SCC
16 Adk
3 Adenosq
VRT 98 100 11 4
Rob et al.
(2008) [78••]
40 NA 3 IA1
10 IA2
27 IB1
32 SCC
7Adk
1 Adenosq
ST 98 100 23 12
Diaz et al.
(2008) [60]
150: 40 FSS,
110 RH
32 20 SCC
20 Other
40 IB1 28 VRT
12 ART
96 92 9 4
Chen et al.
(2008) [61]
16 28 14 SCC
2Adk
3IA1
7IA2
6IB1
LAVRT 100 100 5 1
Nishio et al.
(2009) [27]
61 33 58 SCC
2Adenok
1 Adenosq
4IA1
8IA2
ART NA NA 4/29 (13.8 %)
who were
NA
Curr. Treat. Options in Oncol. (2016) 17: 5 Page 9 of 18 5
Table 2. (Continued)
Study Patients,
n
Median
age, y
Histotype Stage Type of
treatment
Oncologic
results
Obstetric
results
DFS,
%
OS,
%
Pregnancies,
n
Live
births,
n
21 Other 49 IB1 (13
with tumors
92cm)
trying to
conceive
Lanowska et al.
(2011) [9••]
212 32 154 SCC
55 Adenok
3 Adenosq
34 IA1+LVSI
47 IA2
131 IB1
VRT 92 98 NA NA
Cibula et al.
(2009) [85]
24 33 14 SCC
10 Adk
2IA2
22 IB1
ART NA NA 6 5
Du et al. (2011)
[86]
68 28 NA 3 IA1
28 IA2
37 IB1
ART + SLN 97 100 8 5
Plante et al.
(2011) [62••]
125 31 69 SCC
48 Adk
8 Adenosq
7IA1+LVSI
29 IA2
85 IB1
2IB2
2IIA
VRT 96 98 106 77
Nick et al. (2011) [72]37 29 12SCC
22 Adk
3 Adenosq
5IA1
11 IA2
21 IB1
ART NA NA 4 3
Wethington
et al. (2012)
[87]
101 31 40 SCC
6Adk
6 Adenosq
1 Clear cell
3IA1
8IA2
88 IB1
1IB2
1IIA
70 ART NA NA 16 31
Kim et al.
(2012) [63]
105 32 45 SCC
50 Adk
8 Adenosq
2Others
14 IA1
12 IA2
79 IB1
51 VRT
49 ART
5RT
NA NA 27 20
Saso et al.
(2012) [69]
30 32.5 15 SCC
10 Adk
4 Adenosq
1GC
2IA2
25 IB1
2IB2
1IIA
ART 90 98 3 2
Palaia et al.
(2012) [82]
14 32 11 SCC
3Adk
5IA2
9IB1
ST 100 100 NA NA
5Page 10 of 18 Curr. Treat. Options in Oncol. (2016) 17: 5
Table 2. (Continued)
Study Patients,
n
Median
age, y
Histotype Stage Type of
treatment
Oncologic
results
Obstetric
results
DFS,
%
OS,
%
Pregnancies,
n
Live
births,
n
Raju et al.
(2012) [83]
66 28 34 SCC
30 Adk
2 Adenosq
7IA2
59 IB1
51 VRT
15 ST
98 100 21 18
Wethington
et al. (2013)
[64]
29 31 13 SCC
12 Adk
4 Adenosq
IB1 22 ART
6VRT
1RT
97 100 0 0
Plante et al.
(2013) [67]
16 30 10 SCC
6Adk
4IA1+LVSI
6IA2
6IB1
ST 100 100 8 4
Li et al. (2013)
[88]
62 30 50 SCC
5Adk
7 Adenosq
IB1 ART NA NA 3 1
Cao et al. (2013)
[65]
150 30 135 SCC
15 Adk
18 IA1+LVSI
19 IA2
113 IB1
77 VRT
73 ART
NA NA 24 14
Hauerberg et al.
(2015) [66]
120 30 82 SCC
36 Adk
2 Adenosq
2 CIS, persistent
dysplasia
7IA1
8IA2
103 IB1
VRT 88 95 77 NA
Tokunaga et al.
(2015) [89]
42 32 1 IA1
4IA2
37 IB1
42 SCC ART 93 NA 5 3
Adenosq adenosquamous, Adk,adenocarcinoma,ART abdominal radical trachelectomy, CIS carcinoma in situ, DFS disease-free survival, FSS fertility-sparing surgery, GC glassy cell,
LAVRT laparoscopic-assisted vaginal radical trachelectomy, LVSI lymphovascular space invasion, NA not available, OS overall survival, RH radical hysterectomy, RT robotic
trachelectomy, SCC squamous cell carcinoma, SLN sentinel lymph node mapping, ST simple trachelectomy, VRT vaginal radical trachelectomy
Curr. Treat. Options in Oncol. (2016) 17: 5 Page 11 of 18 5
showninTable3, other authors investigated the use of the neoadjuvant
approach. In particular, Robova et al. [91], in their study on the use of
NACT followed by pelvic lymphadenectomy and ST, reported no resid-
ual disease in six women (21.4 %), microscopic disease in 11 women
(39.3 %), and macroscopic tumor in 11 women (39.3 %). Finally,
Lanowska et al. [92] performed lymphadenectomy before NACT to
identify patients with nodal disease and offered this procedure to node-
negative patients only, showing a notably worse prognosis [92]. How-
ever, this interesting concept should be validated further. In conclusion,
down-staging by NACT in IB1 and IB2 CC before fertility-sparing surgery
is still an experimental procedure, although it shows some promise.
Future Developments
As previously described, fertility-sparing surgery usually is indicated in patients with
tumors smaller than 2 cm in diameter, whereas for patients with larger tumors who
have a strong desire to preserve their fertility, NACT may offer the chance for
conservative surgery. However, for more locally advanced stages, the need for
radical hysterectomy, which may be followed by adjuvant chemoradia-
tion or exclusive chemoradiation, does not allow for conservative man-
agement. Ovarian transposition outside the radiation field is a valid
approach to preserve ovarian function both for endocrine reasons and
for fertility functions, thus allowing embryo transfer to a surrogate
mother. In fact, the available motherhood options for women without a
uterus are adoption (to acquire legal motherhood) or pregnancy in a
gestational surrogate carrier to acquire genetic motherhood, followed by
adoption to achieve legal motherhood.
Recently, Brännström et al. [4]reportedtheresults of the first clinical
trial on uterine transplantation, in nine patients, from live donors. Most
of these patients had congenital absence of the uterus; only one had
previously undergone radical hysterectomy for CC of an unspecified
stage. All the women received immunosuppression to prevent rejection
of the transplant. The authors subsequently reported the outcomes in
the seven patients with a viable uterus after transplantation during a
follow-up of 12 months [5]. All the patients had regular menses, and
their uterine artery blood flow was unchanged. Four women showed
mild inflammation on biopsy after mycophenolate mofetil withdrawal;
all were treated with corticosteroids and azathioprine for the remainder
of the 12 months. Subclinical rejection was observed on ectocervical
biopsy in five recipients; however, all these rejection episodes were
treated successfully with corticosteroids or dose increments of tacroli-
mus. Moreover, the same group reported the first live birth after uterus
transplantation, in a patient with Rokitansky syndrome, after in vitro
fertilization treatment of both the patient and her partner [6••]. Al-
though these interesting results show that uterus transplantation is fea-
sible, the use of high doses of immunosuppressive agents, the risk of
cancer recurrence in immunocompromised patients, and the possible
vascular abnormalities after pelvic radiation must be considered with
caution before taking this approach in the vast majority of young
women with a previous diagnosis of CC. Thus, only improvements in
5Page 12 of 18 Curr. Treat. Options in Oncol. (2016) 17: 5
Table 3. Neoadjuvant chemotherapy and fertility-sparing surgery
Study Patients,
n
Median
age, y
Histotype Stage CT regimen Type of
treatment
Oncologic
results
Obstetric
results
DFS,
%
OS,
%
Pregnancies,
n
Live
births,
n
NACT + Conization
Maneo et
al. (2008)
[90••]
21 30 9 SCC
12 Adk
21 IB1 9 TIP
12 TEP
LPS PLF +
CON
100 100 10 9
Salihi et al.
(2015) [93]
11 32 6 SCC
4Adk
1Adenosq
10 IB1
1IB2
2TIP
9TC
LPS PLF +
CON
100 100 6 7
NACT +
Trachelectomy
Marchiole
et al. (2011)
[94]
7284SCC
3Adk
2IB1
92cm
3IB2
2 IIA1
5TIP
2TEP
LPS PLF +
VRT
100 100 1 0
Lanowska
et al.
(2014)
[92]
20 32 11 SCC
8Adk
1Adenosq
14 IB1
92cm
5IB2
1 IIA
TIP LPS PLF +
VRT
95 100 7 4
Robova et
al. (2014)
[91]
28 29 15 SCC
13 Adk
21 IB1
7IB2
IP (cisplatin
doxorubicin
for Adk)
LPS PLF +
ST
80 90 13 11
Adenosq adenosquamous, Adk adenocarcinoma, CON conization, CT chemotherapy, DFS disease-free survival, IP ifosfamide, and cisplatin, LPS laparoscopic, NA not available, NACT
neoadjuvant chemotherapy, OS overall survival, PLF pelvic lymphadenectomy, SCC squamous cell carcinoma, SLN sentinel lymph node mapping, ST simple trachelectomy, TC paclitaxel
and carboplatin, TEP paclitaxel, epirubicin, and cisplatin, TIP paclitaxel, ifosfamide, and cisplatin, VRT vaginal radical trachelectomy
Curr. Treat. Options in Oncol. (2016) 17: 5 Page 13 of 18 5
immunosuppressive therapy and very thorough patient selection will
transform this futuristic procedure into a reproductive option for young
cancer survivors without a uterus.
Conclusions
Results from the studies reported in this review show that radical hysterectomy no
longer is the standard treatment for small lesions in young women. For patients
with IA1-2 tumors, conization with or without nodal staging is a valid option for
fertility preservation. Currently, as documented by most international guidelines,
trachelectomy is considered a standard fertility-sparing procedure in patients with
early CC and tumors smaller than 2 cm. However, the low incidence of parametrial
involvement reported in patients with tumors smaller than 2 cm and no nodal
disease or LVSI suggest that conization and ST may be valid choices for fertility
sparing in these lesions as well. Moreover, for women with tumors larger than 2 cm
who seek parenthood, downsizing of the tumor to 2cmbyNACT,followedby
uterus-sparing surgery, may be considered in order to avoid radical surgery. On the
basis of its capability in terms of surgical radicality, ART might be effective in these
cases. However, the high percentage of nodal disease in larger tumors has led to the
use of adjuvant treatment in nearly half of patients, with the consequent damage of
reproductive surgery. For this reason, consideration should be given to offering
these patients NACT. In effect, interesting results have been obtained with the use of
NACT approaches followed by conization or trachelectomy. However, these
procedures are experimental and should be investigated further in future stud-
ies. For patients with more advanced disease, uterus transplantation may be a
viable option, although it currently is regarded as a futuristic approach.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no competing interests.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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... The 2020 NCCN guidelines recommend conization for patients in IA1 without lymphatic vascular invasion (LVSI), RT suggested for patients in IA2 ~ IB1 and selective IB2 [6]. It has been reported that conization combined with neoadjuvant chemotherapy (NACT) is used in IB1 patients without medium and high risk [7,8]. Morice P et al. [9] found that the oncological results were remarkably similar in patients with stage IB1 cevical cancer treated by different surgical modalities (conization, simple trachelectomy and RT). ...
... NACT could reduce the tumor volume and may effectively inhibit the micrometastases of paracervical tissue and pelvic lymph nodes [26,27]. Therefore, it has been reported that NACT combined with conization is used for early-stage cervical cancer patients with tumors less than 2 cm in diameter [7,28] and NACT combined with RT surgery for early-stage cervical cancer patients whose tumors larger than 2 cm in diameter [10,11,29]. Viveros-Carreno D et al. [11] even reported the fertility-sparing surgery combined with NACT was used in early-stage cervical cancer women with tumors larger than 4 cm in diameter, and the 4.5-year disease-free survival was 92.3% and the 4.5-year overall survival rate was 100%. ...
Article
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Background Radical trachelectomy is an acceptable alternative to radical hysterectomy for patients with early-stage cervical cancer who wish to preserve reproductive function. This study is designed to compare the laparoscopic versus abdominal radical trachelectomy and provide oncological and obstetric outcome data on patients who have undergone fertility-sparing surgery. Methods We retrospectively analyzed all early-stage cervical cancer patients who underwent abdominal radical trachelectomy (ART) or laparoscopic radical trachelectomy (LRT) between January 2005 and June 2017 in West China Second University Hospital, Sichuan University. Patients' clinical details and follow-up were obtained from hospital records. Results A total of 33 patients (5 with IA1, 2 with IA2, and 26 with 1B1) were included, including 18 patients treated with ART and 15 patients treated with LRT. The median age at initial diagnosis was 30.00 ± 4.30 years (range 22–39). The mean follow-up time was 74.67 months. Among the 33 patients, 2 patients (6.06%, 1 abdominal/1 laparoscopic) developed recurrence, and there are no evidence of disease for the remaining 31 patients till now. The overall survival rate 96.99% (32/33). The LRT group had a shorter hospital stay (P = 0.01) and less blood loss (P < 0.01) than the ART group. There is no significant difference in the length of operative time (P = 0.48) between the two surgical routes. Overall, 15/33 patients (45.45%) have tried to conceive. 6 (40.00%) patients were pregnant and 6 (40.00%) patients were infertility. The ART group had a higher clinical pregnancy rate (P = 0.03) than the LRT group. Conclusions There is no statistically significant difference in oncological outcome between the two surgical approaches. The clinical pregnancy rate in the ART group was significant higher than that in the LRT group. However, LRT resulted in less blood loss and decreased length of hospital stay.
... Accordingly, the analysis has included multiple treatments for cervical cancer, which include surgery, radiotherapy and chemotherapy. 29,30 There is a paucity of published evidence surrounding patients transitioning between the different diagnosed and undiagnosed FIGO stages of cervical cancer. Hence, inclusion of these health states may have increased inherent uncertainty within the model. ...
Article
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Objective: To assess the health economic impact of cervical screening with liquid based cytology (LBC) compared with conventional cytology (CC) in Germany. Methods: An economic model was constructed depicting the management of a hypothetical cohort of women aged ≥20 years who undergo cervical screening in Germany. The model estimated the cost-effectiveness and cost-benefit of LBC compared with CC at 2017/18 prices over a time-horizon of 70 years. Results: Performing cervical screens with LBC instead of CC is expected to increase the probability of detecting a true positive over a subject's lifetime by 73% (0.038 versus 0.022) and of diagnosing a subject with stage 3 cervical intraepithelial neoplasia (CIN3) (0.019 versus 0.011). Women screened with LBC instead of CC are expected to have a 57% reduction in the probability of having undetected CIN3 (0.006 versus 0.014) and to experience a 44% reduction in the probability of transitioning into disease progression (from 0.018 to 0.010). The mean discounted lifetime cost of healthcare resource use associated with performing cervical screens with LBC and CC was estimated at €4852 and €7523 per subject respectively. For every Euro invested in cervical screening with LBC instead of CC, the German healthcare system could potentially save ~€170 over a subject's lifetime. Conclusion: Within the study's limitations, the analysis showed that LBC affords a cost-effective cervical screening test compared with CC in Germany, since it improves detection rates and has the potential to lead to a reduction in disease progression for less cost.
... (2) Sin embargo, para llegar al estadio de cáncer invasor las mujeres pasan por un espectro continuo de lesiones, entre las que se encuentran las neoplasias intraepiteliales cervicales grado I (lesión intraepitelial de bajo grado), grado II, y grado III y el carcinoma in situ (lesiones intraepiteliales de alto grado las tres anteriores), que generalmente aparecen después de una infección mantenida por el virus del papiloma humano (3,4) y de la presencia de otros cofactores tales como: inmunodepresión, infección por otros agentes virales, bacterianos y durante el embarazo. (5,6) Todo este proceso puede demorar hasta 15 -20 años. (7) Entre las lesiones precursoras del cáncer del cuello uterino se conoce que la de más alta probabilidad de progresar a estadios invasores son las de alto grado de malignidad. ...
Article
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Introduction: the trend of grade-III cervical intraepithelial neoplasm and its impact on patients is unknown. Objectives: to estimate the trend and evolution of grade-III cervical intraepithelial neoplasia (CIN III) in Pinar del Río during the period 2004-2014. Method: two-stage study. First: observational, retrospective, cross-sectional to determine the annual incidence of injuries (CIN III) and second: the temporal trend of them, as well as the evolution of patients. Results: the average annual incidence rate in women aged 15 years and over was 64.6x100 000 women, while in women involve in the screening program was 83.5x100 000. The difference between the concluding moment and the preliminary moment, it reported a annual increase of 27.6%. The average age for the diagnosis of CIN III-CIS was: 37.87 ± 10.6 years (range 15-81 years). Guane and Mantua were the municipalities with the highest incidence. More than 50% showed histological signs of HPV infection. The assessment of the edges involved in conization did not report cases of micro-invasive or invasive carcinoma. The lethality reported in these women was zero percent. Conclusions: there is an increase in the detection of NIC III-CIS lesions. Guane and Mantua were the municipalities with the highest rates of incidence. The number of sexual partners and human papillomavirus infection are risk factors for the disease, not the age of cohabitation. The correct implementation of procedures has allowed no invasion or death to occur.
... 7 Therefore, the oncological safety of FSS remains questionable because in larger tumors a high percentage of nodal disease has led to the use of adjuvant treatment with the obvious consequences in fertility. 47 We acknowledge that both obstetric and oncological outcomes are important for patient selection with this promising strategy. They should balance the best chance for cure with optimum fertility results. ...
Article
Full-text available
Objective: It is difficult to critically outline the optimal treatment for women with early-stage cervical cancer (eCC) wishing fertility preservation. Neoadjuvant chemotherapy (NAC) to downstage "bulky" eCC could potentially lead to fertility-sparing surgery (FSS) in a wider patient population. The rationale is to provide oncological safety balanced with maximal fertility effort. We aimed to obtain the most accurate fertility outcomes for eCC women treated with NAC followed by FSS and identify potential factors favoring fertility. Methods: A systematic search of MEDLINE, EMBASE, Web of Science, and Cochrane Database was performed. Studies that reported obstetric outcomes of eCC women treated with NAC followed by FSS were located. For the meta-analysis, we calculated the proportions of women who had the outcomes per total number of women who were considered for FSS. For the meta-regression, we extracted the relative risk of the outcome variables to enable comparison of the results across the studies. Results: Seven studies enrolling 86 patients were included in the meta-analysis. Pooling of results from seven studies rendered summary proportions of 0.49 (95% confidence interval [CI], 0.32-0.66) and 0.42 (95% CI, 0.32-0.53) for the outcomes of pregnancies and live births, respectively. The outcome of first- and second-trimester losses by pooling seven studies rendered a summary proportion of 0.16 (95% CI, 0.09-0.27). For the outcome of premature deliveries, pooling of results from five studies rendered a summary proportion of 0.06 (95% CI, 0.02-0.16). This reached 0.29 (95% CI, 0.15-0.48) in women who achieved live births. In multivariate meta-regression, the more radical surgical approach resulted in a less favorable pregnancy rate compared with the less radical surgical approach (P = 0.015). Conclusions: This strategy achieves live births in four of 10 eCC women who desire fertility, whereas their risk of miscarriage is low. Three of 10 live births will be premature.
Article
Fertility preservation in women with cervical cancer is a demanding but evolving issue. Some remarkable achievements have been reached, in particular the improvement of primary and secondary prevention and the broadening of the indications for conservative surgery up to FIGO 2018 stage IB2. Natural pregnancy rate and the rate of obstetrics complications following conservative approach is satisfactory even if not optimal. On the other hand, the use of classic strategies for fertility preservation such as oocytes or ovarian cortex freezing is extremely limited, being the uterus compromised by treatment in a high proportion of cases. In fact, the availability of uterine surrogacy can play a role in the counseling and the decision-making process. The recent advent of uterus transplantation is fascinating but, at present, cannot be viewed as a realistic solution.
Article
PurposeTo explore the value of histogram analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) quantitative parameters and apparent diffusion coefficient (ADC) values in predicting the neoadjuvant chemotherapy (NACT) response for cervical cancers.Methods Sixty-three patients with pathologically proved stage IB2–IIA2 cervical cancer from March 2013 to January 2017 were retrospectively analyzed. They were divided into two groups on the basis of therapeutic response: the significant response (SR) group, which contains complete response patients and partial response patients, and nonsignificant response (non-SR) group, which contains progressive diseases and stable diseases. Clinical characteristics, DCE-MRI parameters (Ktrans, Kep, Ve), and ADC values before NACT were analyzed and compared between the two groups.ResultsSR group and non-SR group were documented in 35 and 28 patients. The mean Ktrans value, 90th percentile Ktrans value, maximal Ktrans value, and 90th percentile ADC value of tumors in SR were significantly higher than those in non-SR group (P = 0.012, P = 0.022, P = 0.005, P = 0.033, respectively), and the mean Ve value and 10th percentile Ve value of tumors were significantly lower in SR group (P = 0.041, P = 0.033, respectively). Kep values did not significantly differ between SR and non-SR. The 90th percentile Ktrans value combined with the 90th percentile ADC value had the highest area under the curve at 0.740 (P = 0.003) to predict NACT effectiveness.Conclusion Histogram analysis of DCE-MRI multi-parameters combined with ADC values may serve as sensitive indicators for predicting NACT effectiveness in cervical cancers.
Chapter
Cervical cancer is the second most common gynecological cancer, and approximately 45% are diagnosed in women younger than 40 years. In Western societies, in which women tend to delay childbearing and cervical cancer incidence peaks within the third decade of life, fertility-sparing treatment options have become a major issue.
Article
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Today, the patient who is diagnosed with early cervical cancer is offered a variety of treatments apart from standard therapy. Patients can be treated with a less radical hysterectomy (RH) regarding parametrectomy, a trachelectomy either vaginal or abdominal, and this can be performed through a minimal invasive or open procedure. All this in combination with nerve sparing and/or sentinel node technique. Level 1 evidence for the oncological safety of all these modifications is only available from 3 randomized controlled trials (RCTs). Two RCTs on more or less radical parametrectomy both showed that oncological safety was not compromised by doing less radical surgery. Because of the heterogeneity of the patient population and the high frequency of adjuvant radiotherapy, the true impact of surgical radicality cannot be assessed. Regarding the issue of oncological safety of fertility sparing treatments, case-control and retrospective case series suggest that trachelectomy is safe as long as the tumor diameter does not exceed 2 cm. Recently, both a RCT and 2 case-control studies showed a survival benefit for open surgery compared to minimally invasive surgery, whereas many previous case-control and retrospective case series on this subject did not show impaired oncological safety. In a case-control study the survival benefit for open surgery was restricted to the group of patients with a tumor diameter more than 2 cm. Although modifications of the traditional open RH seem safe for tumors with a diameter less than 2 cm, ongoing prospective RCTs and observational studies should give the final answer. Copyright © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.
Article
Objective: This study aimed to evaluate oncologic outcomes of women with stage IB1 cervical cancer treated with uterine-preserving surgery (UPS) (defined as conization or trachelectomy) versus non-UPS (defined as hysterectomy of any type). Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women younger than 45 years diagnosed with stage IB1 cervical cancer from 1998 to 2012. Only those who underwent lymph node (LN) assessment were included. Outcomes of UPS versus non-UPS were analyzed. Results: Among 2717 patients, 125 were treated with UPS and 2592 were treated with non-UPS. Those in the UPS group were younger (median age 33 vs 37 years, P < 0.001), less commonly had tumor size greater than 2 cm (27% vs 45%, P < 0.001), and less commonly received adjuvant radiation therapy (18% vs 29%, P = 0.006). There was no difference in distribution of tumor grade, histology, or rate of LN positivity. Median follow-up was 79 months (range, 0-179). There was no difference in 5-year disease-specific survival (DSS) between the UPS versus non-UPS groups (93% vs 94%, respectively, P = 0.755). When stratified by tumor size, DSS for UPS versus non-UPS was as follows: tumors 2 cm or less, 96.8% versus 96.3% (P = 0.683); tumors greater than 2 cm, 82.4% versus 90.4% (P = 0.112). Factors independently associated with worsened survival included adenosquamous histology (hazard ratio [HR] 2.29, 95% confidence interval [CI]1.51-3.47), G3 disease (HR 2.44, 95% CI 1.01-5.89), tumor size greater than 2 cm (HR 1.93, 95% CI 1.36-2.75) and LN positivity (HR 2.29, 95% CI 1.64-3.22). The UPS was not associated with a higher risk of death. Conclusions: The UPS does not seem to compromise oncologic outcomes in a select group of young women with stage IB1 cervical cancer, especially in the setting of tumors 2 cm or less. Further studies are needed to clarify the role of UPS in tumors greater than 2 cm.
Article
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Radical trachelectomy is considered standard of care in patients with early-stage cervical cancer interested in future fertility. The goal of this study was to compare operative, oncologic, and fertility outcomes in patients with early-stage cervical cancer undergoing open vs. minimally invasive radical trachelectomy. A retrospective review was performed of patients from four institutions who underwent radical trachelectomy for early-stage cervical cancer from June 2002 to July 2013. Perioperative, oncologic, and fertility outcomes were compared between patients undergoing open vs. minimally invasive surgery. A total of 100 patients were included in the analysis. Fifty-eight patients underwent open radical trachelectomy and 42 patients underwent minimally invasive surgery (MIS=laparoscopic or robotic). There were no differences in patient age, body mass index, race, histology, lymph vascular space invasion, or stage between the two groups. The median surgical time for MIS was 272minutes [range, 130-441 minutes] compared with 270minutes [range, 150-373 minutes] for open surgery (P=0.78). Blood loss was significantly lower for MIS vs. laparotomy (50mL [range, 10-225mL] vs. 300mL [50-1,100mL]) (p<0.0001). Nine patients required blood transfusion, all in the open surgery group (p=0.010). Length of hospitalization was shorter for MIS than for laparotomy (1day [1-3 days] vs. 4days [1-9 days]) (P<0.0001). Three intraoperative complications occurred (3%): 1 bladder injury, and 1 fallopian tube injury requiring unilateral salpingectomy in the MIS group and 1 vascular injury in the open surgery group. The median lymph node count was 17 (range, 5-47) for MIS vs. 22 (range, 7-48) for open surgery (p=0.03). There were no differences in the rate of postoperative complications (30% MIS vs. 31% open surgery). Among 83 patients who preserved their fertility (33 MIS vs. 50 open surgery), 34 (41%) patients attempted to get pregnant. Sixteen (47%) patients were able to do so (MIS: 2 vs. laparotomy: 14, p=0.01). The pregnancy rate was higher in the open surgery group when compared to the MIS group (51% vs. 28%, p=0.018). However, median follow-up was shorter is the MIS group compared with open surgery group (25months [range, 10-69] vs. 66months [range, 11-147]). To date, there has been one recurrence in the laparotomy group and none in MIS group. Our results suggest that radical trachelectomy via MIS results in less blood loss and a shorter hospital stay. Fertility rates appear higher in patients undergoing open radical trachelectomy. Copyright © 2015. Published by Elsevier Inc.
Article
Although vaginal radical trachelectomy is an effective treatment for early stage cervical cancer and has an acceptable live birth rate, there are concerns over its oncological safety and possible surgical injury with this radical procedure. Moreover, most gynecologists have difficulty performing this unfamiliar procedure and require special training. Many of these problems can be overcome with the use of abdominal radical trachelectomy. The abdominal approach provides adequate resection of the parametrial and vaginal tissue and does not require special training. Only a few case studies have investigated abdominal radical trachelectomy. This retrospective study presents follow-up data and reviews a series of cases conducted in Japanese women with early stage cervical cancer who had undergone elective abdominal radical trachelectomy and pelvic lymphadenectomy between 2002 and 2008. The aim of the study was to assess the effectiveness and safety of the abdominal approach in this population. A total of 61 patients at a median age of 33 years (range, 26-44 years) were followed up for a median 27 months (range, 1-67 months). There were 6 recurrences (9.8%, 6/61); 1 occurred in a patient with adenocarcinoma. None of the other 5 recurrences were found in cases with a primary tumor diameter of <20 mm. Twenty-nine (47.5%) of the 61 patients attempted to conceive and 4 (13.8%) were successful. Of the 4 live births, 2 were preterm, the remaining 2 were full term. The rates of serious intraoperative and postoperative complications were similar to those reported in the literature for standard radical hysterectomy and lymphadenectomy. The investigators conclude from these findings that an abdominal radical trachelectomy is an effective and relatively safe procedure in selected patients and may be an acceptable treatment option for young women with early stage cervical cancer.
Article
Background: The aim of this study was to identify the independent histopathologic prognostic factors for patients with cervical carcinoma treated with radical hysterectomy including paraaortic lymphadenectomy. Methods: A total of 187 patients with stage IB to IIB cervical carcinomas treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy were retrospectively analyzed. The median follow-up period was 83 months. Cox regression analysis was used to select independent prognostic factors. Results: Using multivariate Cox regression analysis, lymph node (LN) status (negative vs. metastasis to pelvic nodes except for common iliac nodes vs. common iliac/paraaortic node metastasis), histopathologic parametrial invasion, lymph-vascular space invasion (LVSI), and histology of pure adenocarcinoma were found to be independently related to patients' poor survival. For patients who had a tumor histologically confined to the uterus and have neither parametrial invasion nor lymph node metastasis, LVSI was the most important prognostic factor, and histologic type, depth of cervical stromal invasion, and tumor size were not related to survival. The survival of patients with a tumor extending to parametrium or pelvic lymph node(s) was adversely affected by histology of pure adenocarcinoma. When the tumor extended to common iliac or paraaortic nodes, patients' survival became quite poor irrespective of LVSI or histologic type of pure adenocarcinoma. Patients' prognosis could be stratified into low risk (patients with a tumor confined to the uterus not associated with LVSI: n = 80), intermediate risk (patients with a tumor confined to the uterus associated with positive LVSI, and patients with squamous/adenosquamous carcinoma associated with pelvic lymph node metastasis or parametrial invasion: n = 86), and high risk (patients with pure adenocarcinoma associated with pelvic lymph node metastasis or parametrial invasion, and patients with common iliac/paraaortic node metastasis: n = 21) with an estimated 5-year survival rate of 100 +/- 0 (mean +/- SE)%, 85.5 +/- 3.9%, and 25.1 +/- 9.7%, respectively. Conclusions: LN status, parametrial invasion, LVSI, and histology of pure adenocarcinoma are important histopathologic prognostic factors of cervical carcinoma treated with radical hysterectomy and systematic retroperitoneal lymphadenectomy. Prognosis for patients with cervical carcinoma may be stratified by combined analysis of these histopathologic prognostic factors. Postoperative therapy needs to be individualized according to these prognostic factors and validated for its efficacy using randomized clinical trials.
Article
Standard treatment of cervical cancer FIGO stage IB1 is a radical hysterectomy with pelvic lymphadenectomy. As the number of patients with a preserved fertility wish has increased, the need for fertility sparing surgery emerges. In this study we discuss 11 patients with cervical carcinoma stage IB treated with neoadjuvant chemotherapy followed by large cone resection. In this retrospective study we included 10 patients with FIGO stage IB1 and 1 patient with IB2 cervical cancer, who first received a pelvic lymphadenectomy followed by neoadjuvant chemotherapy and conization. Paclitaxel-ifosfamide-cisplatinum or a combination of paclitaxel-carboplatin was used as neoadjuvant chemotherapy. Complete response after chemotherapy was observed in 64%, partial response in 27% and 9% had progressive disease. All patients with response underwent a conization, with no residual disease on pathology in 80%. Patients with residual disease were treated by radical hysterectomy. In 9 patients fertility sparing surgery could be performed and 6 (67%) got pregnant. Five patients had 7 children and two patients had four missed abortions. Two premature deliveries at 32 and 33weeks were described, both in the same patient. Recurrence was observed in one patient that was treated with simple hysterectomy followed by radiochemotherapy. Median follow up time is 58months with all patients alive and no evidence of disease until now. Neoadjuvant chemotherapy followed by conization seems to be a promising new fertility sparing treatment modality in patients with cervical carcinoma stage IB1, but further studies with larger populations should confirm these data. Copyright © 2015. Published by Elsevier Inc.
Article
To present and evaluate an unselected national single center strategy with fertility preserving trachelectomy in cervical cancer. In 2003 nationwide single-center referral of women for trachelectomies was agreed upon between all Danish departments performing cervical cancer surgery with the purpose of increasing volume, to increase surgical safety and facilitate follow-up. Prospective data were recorded in the Danish Gynecological Cancer Database of all Vaginal Radical Trachelectomies (VRT) performed in Denmark between 2002 and 2013. Oncologic, fertility and obstetrical outcomes of 120 unselected consecutive VRTs were assessed. To obtain complete follow-up about fertility treatment, pregnancy and obstetric outcome the women filled out an electronic questionnaire. Median follow-up: 55.7months. 85.8% of the patients had stage IB1 disease, 68.3% squamous cell carcinomas, 30.0% adenocarcinomas and 1.7% adenosquamous carcinomas. Six recurrences (5.1%) and 2 deaths (1.7%) occurred. Four women with adenocarcinomas (10.5%) had recurrences, compared to two women with squamous cell carcinomas (2.5%). Seventy-two women (60.0%) desired to conceive and 55 women obtained a total of 77 pregnancies. Of the 72 women 40 were referred to fertility treatment. First and second trimester miscarriage rates were 21.6% and 2.7%, respectively. A total of 53 children were born of which 41 were delivered after gestational week 34. This unselected national single center referral study confirms the oncological safety of Vaginal Radical Trachelectomy. The complete follow-up regarding reproductive data, reveals a surprisingly extensive need of fertility treatment and due to the rate of prematurity, these pregnancies must be regarded as high-risk pregnancies. Copyright © 2015. Published by Elsevier Inc.
Article
PURPOSE: Neoadjuvant chemotherapy (NACT) and radical surgery (RS) have emerged as a possible alternative to conventional radiation therapy (RT) in locally advanced cervical carcinoma. In 1990, a phase III trial was undertaken to verify such a hypothesis in terms of survival and treatment-related morbidity. PATIENTS AND METHODS: Patients with squamous cell, International Federation of Gynecology and Obstetrics stage IB2 to III cervical cancer were eligible for the study. They received cisplatin-based NACT followed by RS (type III to V radical hysterectomy plus systematic pelvic lymphadenectomy) (arm A) or external-beam RT (45 to 50 Gy) followed by brachyradiotherapy (20 to 30 Gy) (arm B). RESULTS: Of 441 patients randomly assigned to NACT+RS or RT, eligibility was confirmed in 210 and 199 patients, respectively. Treatment was administered according to protocol in 76% of arm A patients and 72% of arm B patients. Adjuvant treatment was delivered in 48 operated patients (29%). There was no evidence for any significant excess of severe morbidity in one of the two arms. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 58.9% and 55.4% for arm A and 44.5% and 41.3% for arm B (P = .007 and P = .02), respectively. Subgroup survival analysis shows OS and PFS rates of 64.7% and 59.7% (stage IB2-IIB, NACT+RS), 46.4% and 46.7% (stage IB2-IIB, RT) (P = .005 andP = .02), 41.6% and 41.9% (stage III, NCAT+RS), 36.7% and 36.4% (stage III, RT) (P = .36 and P = .29), respectively. Treatment had a significant impact on OS and PFS. CONCLUSION: Although significant only for the stage IB2 to IIB group, a survival benefit seems to be associated with the NACT+RS compared with conventional RT.
Article
To evaluate pathologic features with implications on surgical radicality in women treated with radical hysterectomy and pelvic lymphadenectomy for cervical cancer stage IA1 with lymph vascular space invasion (LVSI) and stage IA2 by correlating findings in conization and hysterectomy specimens. Women with cervical cancer stage IA1 with LVSI and stage IA2 diagnosed by loop electrosurgical excisional procedure or cold knife conization were treated with radical hysterectomy and pelvic lymphadenectomy from January 1999 to December 2011 in 2 institutions. Fifty patients were enrolled: 40 with stage IA2 and 10 with stage IA1 with LVSI. Median age was 43 (30-67) years. All patients underwent cervical conization for diagnosis (45 loop electrosurgical excisional procedure, 5 cold knife). Lymph vascular space invasion was detected in 15 patients (30%). Two patients had positive pelvic nodes. No parametrial involvement was detected in the entire cohort. Positive margins were present in 35 patients, and residual disease was detected in 22 patients (44%). Positive margins predicted residual disease at radical hysterectomy (P = 0.02). Medium follow-up time was 51 months. One patient developed a pelvic recurrence, and there were no disease-related deaths. Patients with positive margins in cone biopsy specimens have an increased risk of residual disease at radical hysterectomy and require careful evaluation before conservative surgery. Pelvic lymph node evaluation is essential because lymph node metastasis may occur even in early stages. The lack of parametrial invasion in this study reinforces the knowledge that the select group of patients with microinvasive cervical carcinoma stages IA1 LVSI and stage IA2 have a very low risk of parametrial infiltration. Less radical surgery can be carefully considered for these patients.