Gynecologic Oncology

Fallopian Tube Carcinoma: A Review

Dimitrios Pectasides, Eirini Pectasides, Theofanis Economopoulos

Second Department of Internal Medicine, Propaedeutic, Oncology Section,

University of Athens, Attikon University Hospital, Haidari, Athens, Greece

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Key Words. Primary fallopian tube carcinoma Diagnosis Staging Prognosis Treatment

Abstract
Purpose. Primary fallopian tube carcinoma (PFTC) is a
rare tumor that histologically and clinically resembles
epithelial ovarian cancer (EOC). The purpose of this
study is to review the current available literature data
on PFTC.
Patients and Results. Early clinical manifesta-
tion and prompt investigation often lead to diagnosis
at an early stage of disease. However, the diagnosis of
PFTC is rarely considered preoperatively and is usu-
ally first appreciated by the pathologist. Surgical stag-
ing/management and the use of chemotherapy follow
the concepts used in epithelial ovarian cancer (EOC).
In contrast to EOC is the importance of early lymphatic
spread in this disease. The earlier diagnosis of PFTC
leads to an apparent better survival compared with
EOC. However, as with EOC, stage and residual tumor
are the most important prognostic variables.
Conclusion. Until more extensive clinical research
has been performed, ovarian carcinoma manage-
ment principles should be used in clinical practice. The
Oncologist 2006;11:902912

Introduction [11, 12]. A study from Finland reported that the incidence of
Primary fallopian tube carcinoma (PFTC) is an uncommon PFTC is increasing, with an age-adjusted incidence of 1.2
tumor accounting for approximately 0.14%1.8% of female per million for 19531957 to 5.4 per million for 19931997
genital malignancies [17]. It is estimated, based on the [7]. About 1,200 cases of PFTC have been reported in the
data obtained from nine population-based cancer registries literature until now [13, 14].
in the U.S., that the average annual incidence of PFTC is 3.6
per million women per year [8]. In England and Wales, 40 Etiology
cases of PFTC and 4,500 cases of epithelial ovarian cancer The etiology of this cancer is unknown. Hormonal, repro-
(EOC) are registered annually [9]. Furthermore, data from ductive, and possibly genetic factors thought to increase
an ovarian cancer screening study that followed up a cohort EOC risk might also increase PFTC risk. High parity has
of 22,000 postmenopausal women revealed a higher than been reported to be protective [7], and a history of preg-
expected ratio of PFTC to EOC among these volunteers nancy and the use of oral contraceptives decreases the PFTC
[10]. It is also possible that the true incidence of PFTC has risk significantly [15]. It has been reported that there is no
been underestimated [9] because PFTC may have been mis- statistically significant correlation between PFTC and age,
takenly identified as ovarian tumors during initial surgery race, weight, education level, pelvic inflammatory disease,
and/or during microscopic examination by a pathologist, infertility, previous hysterectomy, endometriosis, lactose
as the histological appearance of these tumors are identical intolerance, or smoking [11, 15, 16]. Meng et al. [17] found
Correspondence: D. Pectasides, M.D., Second Department of Internal Medicine, Propaedeutic, Oncology Section, Attikon Univer-
sity Hospital, Rimini 1, Haidari, Athens, Greece. Telephone: 210-5831691, 210-6008610; Fax: 210-5831690, 210-6008610; e-mail:
pectasid@otenet.gr Received March 11, 2006; accepted June 22, 2006. AlphaMed Press 1083-7159/2006/$20.00/0 doi: 10.1634/
theoncologist.11-8-902
The Oncologist 2006;11:902912 www.TheOncologist.com
Pectasides, Pectasides, Economopoulos
a fivefold higher bilateral occurrence in infertile patients
than in fertile patients, and Hanton et al. [18] reported a bet-
ter prognosis in nulliparous women.
PFTC has been described in high-risk breastovarian
cancer families with germ-line BRCA-1 and BRCA-2 muta-
tions [1922]. Some studies suggested that the frequency
and structure of the chromosomal changes (BRCA-1 or
BRCA-2 mutations) observed in PFTC had similarities with
those found in breast, serous ovarian, and uterine carcino-
mas, and consequently, a common molecular pathogenesis
was claimed [2226]. Some cases of occult PFTC have been
detected at prophylactic salpingo-oophorectomy in BRCA-
1 mutation carriers [27]. Therefore, the risk for this malig-
nancy should be considered when prophylactic surgery is
performed in such high-risk women [28]. In the case of pro-
phylactic surgery, the uterus and the intrauterine portion of
the fallopian tube should be removed.
Clinical Manifestations
PFTC most frequently occurs between the fourth and sixth
decades of life [29, 30], with a median age of occurrence
of 55 years (range, 1788 years). However, PFTC has been
reported in young girls aged 1719 [3134]. Patients with
PFTC appear to have a shorter history of symptoms than
those with EOC [35]. The clinical symptoms and signs of
PFTC are shown in Table 1 [11, 30, 36 41]. These symptoms
are not specific. Latzkos triad of symptoms, consisting of
intermittent profuse serosanguinous vaginal discharge,
colicky pain relieved by discharge, and abdominal or pelvic
mass has been reported in 15% of cases [34]. Hydrops tubae
profluens, a pathognomonic feature, implies intermittent
discharge of clear or blood-tinged fluid spontaneously or
on pressure followed by shrinkage of an adnexal mass and
occurs in 5% of patients. PFTC is rarely asymptomatic, in
contrast to EOC. In many cases, the preoperative diagnosis
of PFTC is extremely rare [26, 29, 42, 43].
The rate of preoperative diagnosis was in the range of
0%10% [6, 44, 45]. Vaughan et al. [46] reported a rate
of 21% of preoperative diagnosis, Baekelandt et al. [28]
reported a rate of only 2%, and Meng et al. [17] reported
that an intraoperative diagnosis is missed in up to 50% of
patients. Some patients have been found to have extensive
pelvic tumor, perhaps manifested by a tubo-ovarian mass.
Even when such disease is resected, it is often impossible
on histopathologic examination to determine the origin
of the tumor. These cases are almost always classified as
ovarian in origin because ovarian cancer is more common
than PFTC [9]. When compared with EOC, PFTC is often
diagnosed at an earlier stage because of abdominal pain
secondary to tubal distention [4750]. However, a diagno-
sis of PFTC may be suspected in cases of postmenopausal
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903
bleeding or spotting with negative diagnostic curettage. Pap
smear positivity occurs in 10%36% of cases [34]. The Pap
smear shows abnormal, suspicious, or poorly differentiated
cells or glands alternating with negative smear [34]. Also,
psammoma bodies found in the Pap smear are suggestive of
gynecologic malignancy, and more detailed examination is
required [51].
Imaging
Imaging routinely carried out for suspected gynecologic
malignancies includes ultrasound, computed tomography
(CT) scan and magnetic resonance imaging (MRI) of the
abdomen. Of course, imaging techniques do not safely rule
out the presence of malignancy or conversely rule in that
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possibility, and their findings cannot change the manage-
ment of PFTC. Transvaginal and transabdominal ultra-
sound is an essential imaging technique in the diagnostic
workup of patients with possible tubal pathology [52, 53].
Timor-Tritsch and Rottem [54] demonstrated the benefits
of transvaginal over transabdominal ultrasound in the
imaging of fallopian tubes. The echographic appearance
of fallopian tubes is nonspecific, mimicking other pelvic
diseases, such as tubo-ovarian abscess, ovarian tumor,
and ectopic pregnancy. Echogram shows a cystic mass
with spaces and mural nodules, a sausage-shaped mass,
or a multilobular mass with a cog-and-wheel appearance
[5557]. Low-impedance vascular flow within the solid
components has been reported [58]. In addition, it was
demonstrated that transvaginal ultrasound examination
with color Doppler can detect areas of neovascularization
within the fallopian tube and thus may aid in the preopera-
tive diagnosis of PFTC. Three-dimensional Doppler can
show tubal wall irregularities such as papillary protru-
sions and pseudosepta and depictions of vascular abnor-
malities (arteriovenous shunts, microaneurysms, tumor
lakes, blind ends, and dichotomous branching typical of
malignant tumor vessels) [59].
The lesion can have the appearance of a small, solid,
lobulated mass on CT scan or on MRI. On CT scan, the
lesion has an attenuation equal to that of other soft tissue
masses and enhances less than the myometrium. On T1-
weighted MR images, the tumor is usually hypointense;
on T2-weighted MR images the tumor is often homoge-
neously hyperintense. Imaging can most often detect solid
and cystic components with papillary projections, which on
MRI can be remarkably enhanced by the administration of
gadolinium [60]. Associated findings include peritumoral
ascites, intrauterine fluid collection, and hydrosalpinx
[61]. MRI seems to be better than CT scan or ultrasound in
detecting tumor infiltration of the bladder, vagina, pelvic
sidewalls, pelvic fat, and rectum.
904 Fallopian Tube Carcinoma

Table 1. Clinical features of primary fallopian tube carcinoma

Clinical Features Percentage
Vaginal bleeding or spotting 50%60%
Abdominal pain, colicky or dull 30%49%
Abdominal or pelvic mass 60% (range, 12%84%)
Ascites 15%
Rare presentations (acute abdomen, palpable inguinal node, umbilical-bone cerebral
metastases, cerebellar degeneration) [3841]
Postmenopausal bleeding or spotting with negative Pap smear

CA-125 Level the tube and arises from the endosalpinx; (b) Histologically,
CA-125 is a useful tumor marker for the diagnosis, assess- the pattern reproduces the epithelium of the mucosa and
ment of response to treatment, and detection of tumor often shows a papillary pattern; (c) If the wall is involved,
recurrence during follow-up. The CA-125 antigen is often the transition between benign and malignant epithelium

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expressed by PFTC [62]. Although CA-125 per se is not
diagnostic for PFTC, >80% of patients have elevated pre-
treatment serum CA-125 levels [34, 49]. Elevated serum CA-
125 levels have been detected more frequently in advanced
or recurrent disease [10, 49, 6264]. Gadducci et al. [48]
reported that preoperative serum CA-125 levels were >35 U/
ml in 85.3% of cases (68.7% for stage III and 94.7% for stage
IIIIV). The pretreatment serum CA-125 level is an indepen-
dent prognostic factor of disease-free survival and overall
survival (OS) in patients with PFTC [10, 34]. Serum CA-125
levels postsurgery have also been associated with response to
chemotherapy [19, 64, 65]. CA-125 is also a useful marker for
post-treatment follow-up. It is an early and sensitive marker
for tumor progression during follow-up [6366]. It has been
reported that the lead time (elevated serum CA-125 levels
prior to clinical or radiological diagnosis of recurrence) is 3
months (range, 0.57 months) [34].
should be demonstrable; and (d) The ovaries and endome-
trium are either normal or contain less tumor than the tube.
Molecular biology studies have shown that PFTC is
characterized by an extremely unstable phenotype with
highly scattered DNA ploidy patterns and frequent p53
gene alterations [7579].
Pattern of Spread and Staging
Tubal carcinoma spreads in much the same manner as
EOC, principally by the transcelomic exfoliation of cells
that implant throughout the peritoneal cavity. In approxi-
mately 80% of patients with advanced disease, metas-
tases are confined to the peritoneal cavity [41]. Tumor
spread can also occur by means of contiguous invasion,
transluminal migration, and hematogenous dissemina-
tion [80]. Bilateral tubal involvement has been reported in
10%27% of cases [10, 47, 48, 67, 71, 81]. Gadducci et al.

Cytology
Several authors state that the cervicovaginal smear is an Table 2. Frequency of different histologic subtypes in
inadequate diagnostic tool and no one would consider using primary fallopian tube carcinoma (PFTC) and epithelial
ovarian cancer (EOC)
it for the diagnosis of PFTC. Positive Pap smears have been
PFTC EOC
reported in only 0%23% of cases [6, 51, 6770]. The dis-
Serous 49.5%83.3% 75% (60%80%)
crepancy between an abnormal Pap smear and negative
Endometrioid 8.3%50% 20% (15%24%)
findings on colposcopy, cervical biopsy, and endometrial
curettage should be considered suspicious for PFTC. Mixed 3.9%16.7% 3%
Undifferentiated 7.8%11.3% 1%2%
Pathology Clear cell 1.9% 5% (3.7%12.1%)
The diagnosis of PFTC is usually first made by a patholo- Transitional 11.7% 1%2%
gist on histopathological examination. The most common Mucinous 3%7.6% 2.4%19.9%
histological types are shown in Table 2 [50, 7175]. Serous
tumors are graded with respect to their differentiation and Table 3. Grading in primary fallopian tube carcinoma
(PFTC) and epithelial ovarian cancer (EOC)
extent of solid components: most tumors are poorly differ-
PFTC EOC
entiated [48, 50, 71] (Table 3).
Grade 1 15%20% 20%
Because it is difficult to differentiate PFTC from EOC,
patients with at least one of the following criteria should Grade 2 20%30% 30%
have the diagnosis of PFTC [72]: (a) The main tumor is in Grade 3 50%65% 50%

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Pectasides, Pectasides, Economopoulos
[48] reported that both tubes were involved in 31.8% of 88
cases (23.8% of stage III cases and 39.1% of stage IIIIV
cases) and Schiller and Silverberg [81] reported bilateral
involvement in 9.1% of 11 cases (5.3% of stage III cases
and 30.4% of stage IIIIV cases).
Penetration of the serosa is an ominous sign associated
with a poor prognosis [44, 50, 80, 81]. In the latter stages of the
disease, the natural course is more parallel to that of EOC.
Data from the literature indicate that patients with
PFTC have a higher rate of retroperitoneal and distant
metastases than those with EOC [12, 4850, 70, 80,
8284]. Metastases to the para-aortic lymph nodes have
been documented in 33% of the patients with all stages
of disease [85]. The PFTC is richly permeated with lym-
phatic channels that drain into the para-aortic lymph
nodes through infundibulopelvic lymphatics. An intrapel-
vic course with drainage into the superior gluteal lymph
nodes is also possible. The existence of anastomoses
with lymphatics of the uterus in the round ligament may
explain the development of inguinal node metastases [85].
Semrad et al. [2] reported that a large number of patients
with an unknown nodal status at the initial staging who
later developed recurrence probably had persistent dis-
ease in their lymphatics. On routine lymphadenectomy,
42%59% of patients show lymph node metastases, with
almost equal involvement of the para-aortic and pelvic
lymph nodes [34]. Compared with EOC, nodal spread is
more common in PFTC, and therefore these observations
provide the basis for recommending lymph node sampling
as a mandatory procedure of surgical staging [28, 48]. Sur-
gical understaging, as in the case of EOC, was common
in older series. Therefore, many of the stage III patients
were probably understaged because of the lack of surgical
retroperitoneal assessment.
The staging of PFTC is based on the surgical findings
at laparotomy. The International Federation of Gynecol-
ogy and Obstetrics (FIGO) EOC staging system has been
adapted to apply to PFTC (Table 4) [19, 86, 87]. PFTC is
often diagnosed at an earlier stage than EOC. In general,
20%25% of patients have stage I, 20% have stage II, 45%
50% have stage III, and 5%10% have stage IV [34].
Treatment
Surgery
Surgery is the treatment of choice for PFTC. Surgical prin-
ciples are the same as those used for ovarian cancer. The
majority of patients in the literature had clearly suboptimal
staging by todays standards [46]. Aggressive cytoreductive
surgery with removal of as much tumor as possible is war-
ranted in patients with advanced disease. If it is impossible
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905
to achieve optimal debulking despite maximum effort, sur-
gery should be attempted again after a few courses of che-
motherapy. Very aggressive forms of surgery should only be
considered in highly individualized patients [88]. Consid-
ering the strong tendency for lymphatic spread of the tumor,
a systematic pelvic and para-aortic lymphadenectomy is
preferred to lymph node sampling [48, 89, 90]. Klein et al.
[89] reported that the median survival times were 43 and
21 months, respectively, in patients with and without lymph
node dissection. In advanced disease, the bulk of extra-
tubal disease and postoperative residual disease >2 cm are
adverse prognostic factors [13, 46]. In young patients who
want to retain fertility, limited surgery can be considered
for patients with an in situ carcinoma and in those women
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with stage I and grade I carcinoma [34].
Second-Look Laparotomy
As in the case of EOC, second-look laparotomy does not
have a role in the management of PFTC [91]. In EOC, sec-
ond-look laparotomy has not been proven to be beneficial
since 50% of patients with a surgical complete response still
go on to relapse. In addition, there is no curative second-line
therapy for those patients with positive findings at second-
look laparotomy. A review of 310 patients included in 13
literature series revealed that 32 (62.7%) of the 51 patients
submitted to second-look operation were found to be in
pathologic complete remission (pCR) [92]. Recurrence was
recorded for 22% of these 32 patients. A negative second-
look laparotomy is associated with longer survival. Second-
look laparotomy should currently be reserved for patients
enrolled in clinical trials.
Radiotherapy
Radiotherapy could possibly be considered either as adju-
vant therapy for early-stage patients [2, 5, 28, 45, 46, 73,
85, 9396], for stage III residual negative patients, or in the
relapse setting. Although radiotherapy has been used tradi-
tionally in the past as an adjuvant therapy for PFTC, its role
in the era of effective chemotherapy is less well defined and
controversial. In view of its low efficacy and high rate of
serious complications, the use of postoperative radiother-
apy in the treatment of patients with PFTC is no longer rec-
ommended. Intraperitoneal instillation of radioisotopes did
not seem to reduce the recurrence risk in early-stage disease
[12, 47].
Adjuvant Chemotherapy
Based on the propensity for microscopic distant spread and
the relatively high risk for recurrence despite complete surgi-
cal resection, chemotherapy seems to have a strong rationale
as adjuvant treatment for patients with early-stage disease;
906 Fallopian Tube Carcinoma

Table 4. Staging of primary fallopian tube carcinoma (PFTC)

FIGO TNM
0 Primary tumor cannot be assessed Tx
No evidence of primary tumor TO
Carcinoma in situ (pre-invasive carcinoma) Tis
I Carcinoma confined to fallopian tubes T1
IA Tumor confined to 1 tube without infiltrating the serosal surface: no ascites T1a
IB Tumor confined to both tubes without infiltrating the serosal surface: no ascites T1b
IC Tumor confined to 1 or both tubes with extension onto/through the tubal serosa or with positive T1c
malignant cells in the ascites or positive peritoneal washings
II Tumor involving both tubes with pelvic extension T2
IIA Extension and/or metastases to uterus and/or ovaries T2a
IIB Extension to other pelvic organs T2b
IIC Stage IIA or IIB with positive malignant cells in the ascites or positive peritoneal washings T2c

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III Tumor involving 1 or both tubes with peritoneal implants outside the pelvis and/or positive regional T3 and/or N1
lymph nodes
IIIA Microscopic peritoneal metastases outside the pelvis T3a
IIIB Macroscopic peritoneal metastases outside the pelvis 2 cm in greatest dimension T3b and/or N1
IIIC Peritoneal metastases more than >2 cm in greatest dimension and/or positive regional lymph nodes T3c and/or N1
IV Distant metastases beyond the peritoneal cavity. Positive pleural cytology and/or parenchymal liver M1
metastases
Abbreviations: FIGO, International Federation of Gynecology and Obstetrics; TNM, TumorNodesMetastasis.

however, very few data for this malignancy are currently
available in the literature [6, 12, 47, 50, 67, 70, 97]. Single-
agent chemotherapy does not seem to be effective, while
platinum-based combination chemotherapy is the most
commonly used adjuvant therapy for these patients, identi-
cal to EOC patients [41, 44, 68, 98]. Patients with stage IA
and IB may not require adjuvant therapy, as for patients with
EOC. All other patients are treated with platinum-based
combinations. In addition, early-stage patients with tumors
infiltrating the serosa or with pre- or intra-operatively rup-
tured tumors should receive chemotherapy. Peters et al. [50]
reported no statistically significant difference in survival
with the addition of single-agent chemotherapy in patients
with disease limited to the tubes. Similarly, Gadducci et al.
[48] reported no significant difference in the recurrence
rate between patients with stage I disease who were treated
with platinum-based combination chemotherapy and those
who were not. However, the International Collaborative
Ovarian Neoplasm (ICON)-1 and Adjuvant ChemoTherapy
In Ovarian Neoplasm (ACTION) studies have shown that
chemotherapy for early-stage patients with ovarian cancer
did confer a survival benefit [98]. Nine hundred twenty-five
patients (477 in ICON-1 and 448 in ACTION) who had sur-
gery for early-stage ovarian cancer were randomly assigned
to receive either platinum-based adjuvant chemotherapy
(n = 465) or observation (n = 460) until chemotherapy was
indicated. The OS rates at 5 years were 82% in the chemo-
therapy arm and 74% in the observation arm (difference,
8%; hazard ratio [HR], 0.67; p = .008). The recurrence-free
survival rate at 5 years was also better in the adjuvant che-
motherapy arm than in the observation arm (76% vs. 65%;
difference, 11%; HR, 0.64; p = .001). The same treatment
strategy for early-stage disease could also be of benefit for
patients with early-stage, high-risk PFTC.
Combination Chemotherapy for
Advanced Disease
The current gold standard chemotherapy for EOC in
North America is a platinumtaxane combination, and
in Britain, it is platinum followed on relapse by a taxane.
There are very few data that are extractable from the lit-
erature with regard to PFTC. Several authors using cis-
platin-based chemotherapy in patients with advanced
PFTC reported overall responses rates of 53%92% [4,
49, 50, 68, 70, 92, 94, 96, 99]. Peters et al. [50] reported a
75% complete response rate in a study of 46 patients with
advanced or recurrent PFTC. Similarly, Gadducci et al.
[48], among the 45 patients with advanced disease treated
with cisplatin-based chemotherapy, reported complete
and partial responses in 64.4% and 17.8% of patients,
respectively. The 5-year survival rate was 56% for the
complete responders, whereas all the partial responders
died within 56 months and all patients with stable or pro-
gressive disease died within 21 months. Literature data

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Pectasides, Pectasides, Economopoulos
on small series showed the possible value of cyclophos-
phamide, doxorubicin, and cisplatin (the CAP regimen)
and paclitaxel-containing regimens [49, 70, 94, 100, 101].
Pectasides et al. [94] treated 14 patients with a CAP com-
bination (10 patients) or carboplatin plus cyclophospha-
mide (four patients). Eight of these patients had a complete
clinical response, and two had partial responses. Among
the eight complete responders, five patients underwent a
second-look operation, and pCR was confirmed in four of
five of them.
Very few data exist on the activity of paclitaxel as first-
line chemotherapy in patients with PFTC [100, 102, 103].
Gemignani et al. [104] reported their experience on the use
of paclitaxel-based chemotherapy after initial surgery in
24 patients with PFTC, of whom 17 had stage IIIIV dis-
ease. Twenty-three patients received paclitaxel at a dose of
135175 mg/m2 with carboplatin or cisplatin; the majority,
17 of 23 (74%), received carboplatin. One patient received
paclitaxel alone. The median disease progression-free
survival rate at 3 years was 67% in the optimally debulked
group, compared with 45% in the suboptimally debulked
group. They concluded that optimally cytoreduced patients
with PFTC treated with a paclitaxel-based chemotherapy
regimen have an excellent possibility of survival. Simi-
larly, Baekelandt et al. [105] administered the combination
of carboplatin (area under the concentrationtime curve
[AUC] 6) plus paclitaxel (175 mg/m2) to eight patients with
PFTC, of whom four were chemotherapy-nave and four had
recurred after a platinum-free interval of at least 6 months.
Three (37.5%) patients achieved a complete response and
four (50%) had a partial response, for an overall response
rate of 87.5%.
With regard to relapse therapy, all the information
comes from EOC. Paclitaxel has been shown to have activ-
ity in platinum-pretreated patients with PFTC [104107].
Tresukosol et al. [106] reported that paclitaxel at a dose of
200 mg/m2 produced a complete response in a patient with
recurrent platinum-resistant disease, and Ichikawa et al.
[107] reported that the combination of carboplatin (AUC 6)
plus paclitaxel (180 mg/m 2) achieved a complete response
in a patient with a platinum-pretreated tumor. In EOC, there
is evidence that using intraperitoneal therapy as one com-
ponent may be more effective than i.v. chemotherapy for
stage III, residual <1 cm, patients. Armstrong et al. [101]
reported a statistically significant prolongation of progres-
sion-free survival and OS in the intraperitoneal arm, asso-
ciated with a 25% lower risk for death compared with i.v.
chemotherapy for patients with newly diagnosed stage III
ovarian carcinoma or primary peritoneal carcinoma, opti-
mally debulked. [101]. Although data from intraperitoneal
therapy do not exist for PFTC, this type of treatment could
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907
possibly be recommended for the management of optimally
debulked PFTC.
Another taxane, docetaxel, at a dose of 75100 mg/m 2,
was administered in 30 assessable for response patients
with EOC, PFTC, and peritoneal carcinomatosis who
failed paclitaxel-based chemotherapy [103]. The overall
response rate was 23% (one complete response and six par-
tial responses), with a median survival time of 44 weeks
(9.5 months). Nine patients had stable disease, and 14 had
disease progression. Among the 19 patients who progressed
during prior paclitaxel treatment, two (11%) responded to
docetaxel, compared with five (45%) of the 11 patients in
other paclitaxel-resistance categories. Recently, the com-
bination of carboplatin (AUC 6) and docetaxel (60 mg/m2)
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delivered every 3 weeks for six courses showed activity
(objective responses for 32 of 42 [81%] assessable patients)
in the treatment of patients with EOC, PFTC, and perito-
neal carcinomatosis who had either received no prior che-
motherapy or had experienced a treatment-free interval of
>2 years before developing disease recurrence [108]. The
major toxicity was bone marrow suppression.
The same treatment strategy should be followed in the
case of second-line chemotherapy for recurrent PFTC. Plat-
inum-sensitive patients (relapse after 6 months) should be
retreated with a platinum with or without paclitaxel, while
platinum-refractory (progression during platinum-based
therapy) or platinum-resistant (relapse within 6 months)
patients should be treated with nonplatinum agents such
as topotecan or liposomal doxorubicin. However, response
rates of platinum analogues in the less than 6 months
group are still in the 10%15% range, and therefore one
could argue that in all but truly platinum-refractory dis-
ease there is a role for using platinum analogues, given that
the other agents in this scenario have similar low response
rates. Topotecan has been investigated as salvage chemo-
therapy in patients who failed platinum- and paclitaxel-
based chemotherapy [109, 110]. Dunton and Neufeld [111]
used topotecan to treat a patient with PFTC who failed car-
boplatin and paclitaxel chemotherapy. That patient demon-
strated a complete clinical response to topotecan. Because
myelosuppression is the dose-limiting toxicity (DLT) of
topotecan when given at a dose of 1.5 mg/m2 for 5 days, new
schedules of topotecan administration are currently being
investigated for recurrent EOC, PFTC, and peritoneal
carcinomatosis [112, 113]. Brown et al. [112] conducted a
trial to determine the DLT and maximum tolerated dose
(MTD) of topotecan administered for 3 days every 21 days.
Twenty patients with recurrent EOC, PFTC, or peritoneal
carcinoma were treated with escalating doses of topotecan
beginning at 2.50 mg/m 2 on an outpatient basis. Colony-
stimulating factors were not employed prophylactically but
908
could be added for grade 4 marrow toxicity. They concluded
that topotecan can be safely administered on schedule as an
outpatient on days 13 every 21 days. The MTD was 3.75
mg/m2.
Liposomal doxorubicin has been reported to achieve
response rates in the range of 17%26% in patients with
recurrent EOC after treatment with platinum-based che-
motherapy [114, 115]. Eighty-two patients with EOC that
either progressed on or recurred within 6 months of comple-
tion of platinum and paclitaxel chemotherapy were treated
with liposomal doxorubicin at a dose of 50 mg/m 2 every 4
weeks [115]. All patients had measurable disease. There
was one complete response and 14 partial responses, for a
total response rate of 16.9%. For platinum- and paclitaxel-
refractory patients, the response rate was 18.3%. Markman
et al. [116] demonstrated that liposomal doxorubicin at a
dose of 40 mg/m 2 every 4 weeks had limited activity (9%)
in 49 platinum- and paclitaxel-refractory ovarian cancer
patients but was associated with less toxicity than the stan-
dard dose.
The recommended treatment for PFTC is demonstrated
in Table 5.
Hormonotherapy
Hormonal agents increasingly have been used in PFTC. The
rationale is that tubal epithelia undergo changes with hor-
monal fluctuation during the menstrual cycle. Embryologi-
cally and histologically the tubal epithelium is derived from
the same source as the endometrial epithelium. Progesta-
tional agents have been used because of the known cyclic
response of the normal tube to hormonal changes during
the menstrual cycle [5, 85, 95]. Because no randomized tri-
als exist and nearly all patients treated with progestational
agents are also treated with combination chemotherapy, no
firm conclusions can be drawn with regard to their useful-
ness. Steroid receptors have been found in a few cases, but
their clinical role is unclear [28].
Prognostic Factors and Survival
Most recurrences are extrapelvic, and half or more of them
are extraperitoneal, usually in combination with intraper-
itoneal recurrence [2, 44, 49, 50]. Most recurrences have
been reported in the first 23 years [3, 91] but have also
occurred many years later [50]. Because there is no effec-
tive second-line or salvage chemotherapy, recurrent disease
is associated with a very poor prognosis.
The OS rate for patients with PFTC is approximately
30%50%, compared with 40% for patients with EOC [13,
28, 71, 87, 92, 117]. This figure is somewhat higher than that
for patients with EOC and possibly reflects the higher pro-
portion of patients with early-stage disease. However, these
Fallopian Tube Carcinoma
figures have not changed significantly with time, indicating
the need for further research. Stage of disease at the time of
diagnosis is the most important factor affecting prognosis.
Generally, the reported 5-year survival rate is about 65% or
higher [15, 30, 99]. Benedet and Miller [118] collected 278
patients with PFTC from six literature series and calculated
the 5-year survival rates in relation to stages: 62% for stage
I, 36% for stage II, 17% for stage III, and 0% for stage IV.
Similarly, Rosen et al. [119], in a retrospective analysis of
115 patients, found 5-year survival rates of 50.8% for stages
I and II and 13.6% for stages III and IV. In a large popula-
tion-based tumor registry study of 416 women with PFTC,
the reported 5-year survival rate by stage was as follows:
stage I (n = 102), 95%; stage II (n = 29), 75%; stage III (n
Downloaded from http://theoncologist.alphamedpress.org/ by guest on June 18, 2017
= 52), 69%; and stage IV (n = 151), 45% [120]. Compared
with 9,032 women treated for EOC during the same study
period, patients with PFTC showed better survival stage by
stage. The 5-year survival rates are influenced by the qual-
ity of surgical staging and the different therapeutic regi-
mens used in these studies [120].
As in EOC, residual disease after initial surgery is also
a significant prognostic factor [13, 44, 48, 50]. Patients with
stage IIIIV disease had a 5-year survival rate of 55% if the
residual tumor was <1 cm in diameter, compared with 21%
for those with larger residual tumor (p = .0169) [48].
With disease limited to the fallopian tube, the depth
of invasion of the tubal wall was correlated with the risk
for treatment failure [50]. The depth of invasion in stage I
disease and intraoperative tumor rupture are independent
prognostic factors [28, 46]. The presence or absence of
invasion of the tubal wall, the depth of invasion when pres-
ent, and the location of the tumor within the tube (fimbrial
or nonfimbrial) appeared to be prognostically significant
[71, 121].
The majority of studies looking at the degree of histo-
logical differentiation of the tumor as a prognostic factor
have found this to be unhelpful [43, 44, 46, 47, 95, 117, 119].
However, Vaughan et al. [46] reported that grade signifi-
cantly correlated with survival, and Gadducci et al. [48]
found a correlation on univariate, but not multivariate,
analysis. Supporting this is the recent finding that grade is
correlated with lymphogenous metastases, with anaplastic
tumors metastasizing early [122]. The presence of lympho-
cytic infiltration has also been suggested to be associated
with a more favorable outcome [119]. Although there was
a difference in the median and 5-year survival according to
lymphocytic infiltration in the study of Vaughan et al. [46],
this was not significant.
Other reported prognostic factors include advanced
age [48, 71, 75, 105], serous versus endometrioid, bilater-
ality, positive peritoneal cytology, site of tumor within the
OTncologist
he
Pectasides, Pectasides, Economopoulos
Table 5. Current postoperative treatment in primary fallopian tube carcinoma
Stage Treatment
IAB, optimal surgical staging, No further treatment
no pre- or intraoperative rupture
IAB, suboptimal surgical staging, Carboplatin (AUC 6) plus paclitaxel (175 mg/m2) every 3 weeks for 36 cycles
pre- or intraoperative rupture
ICIIA Carboplatin (AUC 6) plus paclitaxel (175 mg/m2) every 3 weeks for 6 cycles
IIBIV Carboplatin (AUC 56) plus paclitaxel (175 mg/m2) every 3 weeks for 6 cycles
Abbreviation: AUC, area under the concentrationtime curve.
tube (fimbrial versus nonfimbrial), HER-2/neu expres-
sion, p53 alteration [76, 77], and elevated pretreatment
CA-125 level [28, 34, 48, 71, 117]. The importance of an
occlusion of the abdominal tubal ostium that could possi-
bly prevent or delay local spread is not clear [123]. The role
of DNA-ploidy is negligible [124]. PFTC shares several
biologic and clinical features with EOC. However, when
compared with EOC, PFTC more often tends to recur in
retroperitoneal nodes and distant sites. Stage, patient age,
and among patients with advanced disease, residual tumor
after initial surgery are the most important prognostic fac-
tors for survival [124, 125].
Conclusion
PFTC is a rare tumor accounting for <1% of all female geni-
tal tract cancers. Histologically and clinically, it resembles
EOC. The diagnosis of PFTC is rarely considered preopera-
tively and is usually first appreciated at the time of opera-
tion or by a pathologist. Both carcinomas have a similar age
distribution, are more common among nulliparous women,
and are often of serous papillary histology. Surgery should
consist of total abdominal hysterectomy, bilateral salpingo-
oophorectomy, omentectomy, and lymph node dissection
from the pelvic and para-aortic regions. Aggressive debulk-
ing surgery should be attempted in patients with advanced
disease. PFTC is similar to EOC in surgical staging, surgi-
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