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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

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

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: Received March 11, 2006; accepted June 22, 2006. AlphaMed Press 1083-7159/2006/$20.00/0 doi: 10.1634/
The Oncologist 2006;11:902912
Pectasides, Pectasides, Economopoulos 903

a fivefold higher bilateral occurrence in infertile patients bleeding or spotting with negative diagnostic curettage. Pap
than in fertile patients, and Hanton et al. [18] reported a bet- smear positivity occurs in 10%36% of cases [34]. The Pap
ter prognosis in nulliparous women. smear shows abnormal, suspicious, or poorly differentiated
PFTC has been described in high-risk breastovarian cells or glands alternating with negative smear [34]. Also,
cancer families with germ-line BRCA-1 and BRCA-2 muta- psammoma bodies found in the Pap smear are suggestive of
tions [1922]. Some studies suggested that the frequency gynecologic malignancy, and more detailed examination is
and structure of the chromosomal changes (BRCA-1 or required [51].
BRCA-2 mutations) observed in PFTC had similarities with
those found in breast, serous ovarian, and uterine carcino- Imaging
mas, and consequently, a common molecular pathogenesis Imaging routinely carried out for suspected gynecologic
was claimed [2226]. Some cases of occult PFTC have been malignancies includes ultrasound, computed tomography
detected at prophylactic salpingo-oophorectomy in BRCA- (CT) scan and magnetic resonance imaging (MRI) of the
1 mutation carriers [27]. Therefore, the risk for this malig- abdomen. Of course, imaging techniques do not safely rule
nancy should be considered when prophylactic surgery is out the presence of malignancy or conversely rule in that

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performed in such high-risk women [28]. In the case of pro- possibility, and their findings cannot change the manage-
phylactic surgery, the uterus and the intrauterine portion of ment of PFTC. Transvaginal and transabdominal ultra-
the fallopian tube should be removed. sound is an essential imaging technique in the diagnostic
workup of patients with possible tubal pathology [52, 53].
Clinical Manifestations Timor-Tritsch and Rottem [54] demonstrated the benefits
PFTC most frequently occurs between the fourth and sixth of transvaginal over transabdominal ultrasound in the
decades of life [29, 30], with a median age of occurrence imaging of fallopian tubes. The echographic appearance
of 55 years (range, 1788 years). However, PFTC has been of fallopian tubes is nonspecific, mimicking other pelvic
reported in young girls aged 1719 [3134]. Patients with diseases, such as tubo-ovarian abscess, ovarian tumor,
PFTC appear to have a shorter history of symptoms than and ectopic pregnancy. Echogram shows a cystic mass
those with EOC [35]. The clinical symptoms and signs of with spaces and mural nodules, a sausage-shaped mass,
PFTC are shown in Table 1 [11, 30, 36 41]. These symptoms or a multilobular mass with a cog-and-wheel appearance
are not specific. Latzkos triad of symptoms, consisting of [5557]. Low-impedance vascular flow within the solid
intermittent profuse serosanguinous vaginal discharge, components has been reported [58]. In addition, it was
colicky pain relieved by discharge, and abdominal or pelvic demonstrated that transvaginal ultrasound examination
mass has been reported in 15% of cases [34]. Hydrops tubae with color Doppler can detect areas of neovascularization
profluens, a pathognomonic feature, implies intermittent within the fallopian tube and thus may aid in the preopera-
discharge of clear or blood-tinged fluid spontaneously or tive diagnosis of PFTC. Three-dimensional Doppler can
on pressure followed by shrinkage of an adnexal mass and show tubal wall irregularities such as papillary protru-
occurs in 5% of patients. PFTC is rarely asymptomatic, in sions and pseudosepta and depictions of vascular abnor-
contrast to EOC. In many cases, the preoperative diagnosis malities (arteriovenous shunts, microaneurysms, tumor
of PFTC is extremely rare [26, 29, 42, 43]. lakes, blind ends, and dichotomous branching typical of
The rate of preoperative diagnosis was in the range of malignant tumor vessels) [59].
0%10% [6, 44, 45]. Vaughan et al. [46] reported a rate The lesion can have the appearance of a small, solid,
of 21% of preoperative diagnosis, Baekelandt et al. [28] lobulated mass on CT scan or on MRI. On CT scan, the
reported a rate of only 2%, and Meng et al. [17] reported lesion has an attenuation equal to that of other soft tissue
that an intraoperative diagnosis is missed in up to 50% of masses and enhances less than the myometrium. On T1-
patients. Some patients have been found to have extensive weighted MR images, the tumor is usually hypointense;
pelvic tumor, perhaps manifested by a tubo-ovarian mass. on T2-weighted MR images the tumor is often homoge-
Even when such disease is resected, it is often impossible neously hyperintense. Imaging can most often detect solid
on histopathologic examination to determine the origin and cystic components with papillary projections, which on
of the tumor. These cases are almost always classified as MRI can be remarkably enhanced by the administration of
ovarian in origin because ovarian cancer is more common gadolinium [60]. Associated findings include peritumoral
than PFTC [9]. When compared with EOC, PFTC is often ascites, intrauterine fluid collection, and hydrosalpinx
diagnosed at an earlier stage because of abdominal pain [61]. MRI seems to be better than CT scan or ultrasound in
secondary to tubal distention [4750]. However, a diagno- detecting tumor infiltration of the bladder, vagina, pelvic
sis of PFTC may be suspected in cases of postmenopausal 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 should be demonstrable; and (d) The ovaries and endome-
diagnostic for PFTC, >80% of patients have elevated pre- trium are either normal or contain less tumor than the tube.
treatment serum CA-125 levels [34, 49]. Elevated serum CA- Molecular biology studies have shown that PFTC is
125 levels have been detected more frequently in advanced characterized by an extremely unstable phenotype with
or recurrent disease [10, 49, 6264]. Gadducci et al. [48] highly scattered DNA ploidy patterns and frequent p53
reported that preoperative serum CA-125 levels were >35 U/ gene alterations [7579].
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- Pattern of Spread and Staging
dent prognostic factor of disease-free survival and overall Tubal carcinoma spreads in much the same manner as
survival (OS) in patients with PFTC [10, 34]. Serum CA-125 EOC, principally by the transcelomic exfoliation of cells
levels postsurgery have also been associated with response to that implant throughout the peritoneal cavity. In approxi-
chemotherapy [19, 64, 65]. CA-125 is also a useful marker for mately 80% of patients with advanced disease, metas-
post-treatment follow-up. It is an early and sensitive marker tases are confined to the peritoneal cavity [41]. Tumor
for tumor progression during follow-up [6366]. It has been spread can also occur by means of contiguous invasion,
reported that the lead time (elevated serum CA-125 levels transluminal migration, and hematogenous dissemina-
prior to clinical or radiological diagnosis of recurrence) is 3 tion [80]. Bilateral tubal involvement has been reported in
months (range, 0.57 months) [34]. 10%27% of cases [10, 47, 48, 67, 71, 81]. Gadducci et al.

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
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-
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%

Pectasides, Pectasides, Economopoulos 905

[48] reported that both tubes were involved in 31.8% of 88 to achieve optimal debulking despite maximum effort, sur-
cases (23.8% of stage III cases and 39.1% of stage IIIIV gery should be attempted again after a few courses of che-
cases) and Schiller and Silverberg [81] reported bilateral motherapy. Very aggressive forms of surgery should only be
involvement in 9.1% of 11 cases (5.3% of stage III cases considered in highly individualized patients [88]. Consid-
and 30.4% of stage IIIIV cases). ering the strong tendency for lymphatic spread of the tumor,
Penetration of the serosa is an ominous sign associated a systematic pelvic and para-aortic lymphadenectomy is
with a poor prognosis [44, 50, 80, 81]. In the latter stages of the preferred to lymph node sampling [48, 89, 90]. Klein et al.
disease, the natural course is more parallel to that of EOC. [89] reported that the median survival times were 43 and
Data from the literature indicate that patients with 21 months, respectively, in patients with and without lymph
PFTC have a higher rate of retroperitoneal and distant node dissection. In advanced disease, the bulk of extra-
metastases than those with EOC [12, 4850, 70, 80, tubal disease and postoperative residual disease >2 cm are
8284]. Metastases to the para-aortic lymph nodes have adverse prognostic factors [13, 46]. In young patients who
been documented in 33% of the patients with all stages want to retain fertility, limited surgery can be considered
of disease [85]. The PFTC is richly permeated with lym- for patients with an in situ carcinoma and in those women

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phatic channels that drain into the para-aortic lymph with stage I and grade I carcinoma [34].
nodes through infundibulopelvic lymphatics. An intrapel-
vic course with drainage into the superior gluteal lymph Second-Look Laparotomy
nodes is also possible. The existence of anastomoses As in the case of EOC, second-look laparotomy does not
with lymphatics of the uterus in the round ligament may have a role in the management of PFTC [91]. In EOC, sec-
explain the development of inguinal node metastases [85]. ond-look laparotomy has not been proven to be beneficial
Semrad et al. [2] reported that a large number of patients since 50% of patients with a surgical complete response still
with an unknown nodal status at the initial staging who go on to relapse. In addition, there is no curative second-line
later developed recurrence probably had persistent dis- therapy for those patients with positive findings at second-
ease in their lymphatics. On routine lymphadenectomy, look laparotomy. A review of 310 patients included in 13
42%59% of patients show lymph node metastases, with literature series revealed that 32 (62.7%) of the 51 patients
almost equal involvement of the para-aortic and pelvic submitted to second-look operation were found to be in
lymph nodes [34]. Compared with EOC, nodal spread is pathologic complete remission (pCR) [92]. Recurrence was
more common in PFTC, and therefore these observations recorded for 22% of these 32 patients. A negative second-
provide the basis for recommending lymph node sampling look laparotomy is associated with longer survival. Second-
as a mandatory procedure of surgical staging [28, 48]. Sur- look laparotomy should currently be reserved for patients
gical understaging, as in the case of EOC, was common enrolled in clinical trials.
in older series. Therefore, many of the stage III patients
were probably understaged because of the lack of surgical Radiotherapy
retroperitoneal assessment. Radiotherapy could possibly be considered either as adju-
The staging of PFTC is based on the surgical findings vant therapy for early-stage patients [2, 5, 28, 45, 46, 73,
at laparotomy. The International Federation of Gynecol- 85, 9396], for stage III residual negative patients, or in the
ogy and Obstetrics (FIGO) EOC staging system has been relapse setting. Although radiotherapy has been used tradi-
adapted to apply to PFTC (Table 4) [19, 86, 87]. PFTC is tionally in the past as an adjuvant therapy for PFTC, its role
often diagnosed at an earlier stage than EOC. In general, in the era of effective chemotherapy is less well defined and
20%25% of patients have stage I, 20% have stage II, 45% controversial. In view of its low efficacy and high rate of
50% have stage III, and 5%10% have stage IV [34]. serious complications, the use of postoperative radiother-
apy in the treatment of patients with PFTC is no longer rec-
Treatment ommended. Intraperitoneal instillation of radioisotopes did
not seem to reduce the recurrence risk in early-stage disease
Surgery [12, 47].
Surgery is the treatment of choice for PFTC. Surgical prin-
ciples are the same as those used for ovarian cancer. The Adjuvant Chemotherapy
majority of patients in the literature had clearly suboptimal Based on the propensity for microscopic distant spread and
staging by todays standards [46]. Aggressive cytoreductive the relatively high risk for recurrence despite complete surgi-
surgery with removal of as much tumor as possible is war- cal resection, chemotherapy seems to have a strong rationale
ranted in patients with advanced disease. If it is impossible as adjuvant treatment for patients with early-stage disease;
906 Fallopian Tube Carcinoma

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

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
Abbreviations: FIGO, International Federation of Gynecology and Obstetrics; TNM, TumorNodesMetastasis.

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

Pectasides, Pectasides, Economopoulos 907

on small series showed the possible value of cyclophos- possibly be recommended for the management of optimally
phamide, doxorubicin, and cisplatin (the CAP regimen) debulked PFTC.
and paclitaxel-containing regimens [49, 70, 94, 100, 101]. Another taxane, docetaxel, at a dose of 75100 mg/m 2,
Pectasides et al. [94] treated 14 patients with a CAP com- was administered in 30 assessable for response patients
bination (10 patients) or carboplatin plus cyclophospha- with EOC, PFTC, and peritoneal carcinomatosis who
mide (four patients). Eight of these patients had a complete failed paclitaxel-based chemotherapy [103]. The overall
clinical response, and two had partial responses. Among response rate was 23% (one complete response and six par-
the eight complete responders, five patients underwent a tial responses), with a median survival time of 44 weeks
second-look operation, and pCR was confirmed in four of (9.5 months). Nine patients had stable disease, and 14 had
five of them. disease progression. Among the 19 patients who progressed
Very few data exist on the activity of paclitaxel as first- during prior paclitaxel treatment, two (11%) responded to
line chemotherapy in patients with PFTC [100, 102, 103]. docetaxel, compared with five (45%) of the 11 patients in
Gemignani et al. [104] reported their experience on the use other paclitaxel-resistance categories. Recently, the com-
of paclitaxel-based chemotherapy after initial surgery in bination of carboplatin (AUC 6) and docetaxel (60 mg/m2)

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24 patients with PFTC, of whom 17 had stage IIIIV dis- delivered every 3 weeks for six courses showed activity
ease. Twenty-three patients received paclitaxel at a dose of (objective responses for 32 of 42 [81%] assessable patients)
135175 mg/m2 with carboplatin or cisplatin; the majority, in the treatment of patients with EOC, PFTC, and perito-
17 of 23 (74%), received carboplatin. One patient received neal carcinomatosis who had either received no prior che-
paclitaxel alone. The median disease progression-free motherapy or had experienced a treatment-free interval of
survival rate at 3 years was 67% in the optimally debulked >2 years before developing disease recurrence [108]. The
group, compared with 45% in the suboptimally debulked major toxicity was bone marrow suppression.
group. They concluded that optimally cytoreduced patients The same treatment strategy should be followed in the
with PFTC treated with a paclitaxel-based chemotherapy case of second-line chemotherapy for recurrent PFTC. Plat-
regimen have an excellent possibility of survival. Simi- inum-sensitive patients (relapse after 6 months) should be
larly, Baekelandt et al. [105] administered the combination retreated with a platinum with or without paclitaxel, while
of carboplatin (area under the concentrationtime curve platinum-refractory (progression during platinum-based
[AUC] 6) plus paclitaxel (175 mg/m2) to eight patients with therapy) or platinum-resistant (relapse within 6 months)
PFTC, of whom four were chemotherapy-nave and four had patients should be treated with nonplatinum agents such
recurred after a platinum-free interval of at least 6 months. as topotecan or liposomal doxorubicin. However, response
Three (37.5%) patients achieved a complete response and rates of platinum analogues in the less than 6 months
four (50%) had a partial response, for an overall response group are still in the 10%15% range, and therefore one
rate of 87.5%. could argue that in all but truly platinum-refractory dis-
With regard to relapse therapy, all the information ease there is a role for using platinum analogues, given that
comes from EOC. Paclitaxel has been shown to have activ- the other agents in this scenario have similar low response
ity in platinum-pretreated patients with PFTC [104107]. rates. Topotecan has been investigated as salvage chemo-
Tresukosol et al. [106] reported that paclitaxel at a dose of therapy in patients who failed platinum- and paclitaxel-
200 mg/m2 produced a complete response in a patient with based chemotherapy [109, 110]. Dunton and Neufeld [111]
recurrent platinum-resistant disease, and Ichikawa et al. used topotecan to treat a patient with PFTC who failed car-
[107] reported that the combination of carboplatin (AUC 6) boplatin and paclitaxel chemotherapy. That patient demon-
plus paclitaxel (180 mg/m 2) achieved a complete response strated a complete clinical response to topotecan. Because
in a patient with a platinum-pretreated tumor. In EOC, there myelosuppression is the dose-limiting toxicity (DLT) of
is evidence that using intraperitoneal therapy as one com- topotecan when given at a dose of 1.5 mg/m2 for 5 days, new
ponent may be more effective than i.v. chemotherapy for schedules of topotecan administration are currently being
stage III, residual <1 cm, patients. Armstrong et al. [101] investigated for recurrent EOC, PFTC, and peritoneal
reported a statistically significant prolongation of progres- carcinomatosis [112, 113]. Brown et al. [112] conducted a
sion-free survival and OS in the intraperitoneal arm, asso- trial to determine the DLT and maximum tolerated dose
ciated with a 25% lower risk for death compared with i.v. (MTD) of topotecan administered for 3 days every 21 days.
chemotherapy for patients with newly diagnosed stage III Twenty patients with recurrent EOC, PFTC, or peritoneal
ovarian carcinoma or primary peritoneal carcinoma, opti- carcinoma were treated with escalating doses of topotecan
mally debulked. [101]. Although data from intraperitoneal beginning at 2.50 mg/m 2 on an outpatient basis. Colony-
therapy do not exist for PFTC, this type of treatment could stimulating factors were not employed prophylactically but
908 Fallopian Tube Carcinoma

could be added for grade 4 marrow toxicity. They concluded figures have not changed significantly with time, indicating
that topotecan can be safely administered on schedule as an the need for further research. Stage of disease at the time of
outpatient on days 13 every 21 days. The MTD was 3.75 diagnosis is the most important factor affecting prognosis.
mg/m2. Generally, the reported 5-year survival rate is about 65% or
Liposomal doxorubicin has been reported to achieve higher [15, 30, 99]. Benedet and Miller [118] collected 278
response rates in the range of 17%26% in patients with patients with PFTC from six literature series and calculated
recurrent EOC after treatment with platinum-based che- the 5-year survival rates in relation to stages: 62% for stage
motherapy [114, 115]. Eighty-two patients with EOC that I, 36% for stage II, 17% for stage III, and 0% for stage IV.
either progressed on or recurred within 6 months of comple- Similarly, Rosen et al. [119], in a retrospective analysis of
tion of platinum and paclitaxel chemotherapy were treated 115 patients, found 5-year survival rates of 50.8% for stages
with liposomal doxorubicin at a dose of 50 mg/m 2 every 4 I and II and 13.6% for stages III and IV. In a large popula-
weeks [115]. All patients had measurable disease. There tion-based tumor registry study of 416 women with PFTC,
was one complete response and 14 partial responses, for a the reported 5-year survival rate by stage was as follows:
total response rate of 16.9%. For platinum- and paclitaxel- stage I (n = 102), 95%; stage II (n = 29), 75%; stage III (n

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refractory patients, the response rate was 18.3%. Markman = 52), 69%; and stage IV (n = 151), 45% [120]. Compared
et al. [116] demonstrated that liposomal doxorubicin at a with 9,032 women treated for EOC during the same study
dose of 40 mg/m 2 every 4 weeks had limited activity (9%) period, patients with PFTC showed better survival stage by
in 49 platinum- and paclitaxel-refractory ovarian cancer stage. The 5-year survival rates are influenced by the qual-
patients but was associated with less toxicity than the stan- ity of surgical staging and the different therapeutic regi-
dard dose. mens used in these studies [120].
The recommended treatment for PFTC is demonstrated As in EOC, residual disease after initial surgery is also
in Table 5. a significant prognostic factor [13, 44, 48, 50]. Patients with
stage IIIIV disease had a 5-year survival rate of 55% if the
Hormonotherapy residual tumor was <1 cm in diameter, compared with 21%
Hormonal agents increasingly have been used in PFTC. The for those with larger residual tumor (p = .0169) [48].
rationale is that tubal epithelia undergo changes with hor- With disease limited to the fallopian tube, the depth
monal fluctuation during the menstrual cycle. Embryologi- of invasion of the tubal wall was correlated with the risk
cally and histologically the tubal epithelium is derived from for treatment failure [50]. The depth of invasion in stage I
the same source as the endometrial epithelium. Progesta- disease and intraoperative tumor rupture are independent
tional agents have been used because of the known cyclic prognostic factors [28, 46]. The presence or absence of
response of the normal tube to hormonal changes during invasion of the tubal wall, the depth of invasion when pres-
the menstrual cycle [5, 85, 95]. Because no randomized tri- ent, and the location of the tumor within the tube (fimbrial
als exist and nearly all patients treated with progestational or nonfimbrial) appeared to be prognostically significant
agents are also treated with combination chemotherapy, no [71, 121].
firm conclusions can be drawn with regard to their useful- The majority of studies looking at the degree of histo-
ness. Steroid receptors have been found in a few cases, but logical differentiation of the tumor as a prognostic factor
their clinical role is unclear [28]. have found this to be unhelpful [43, 44, 46, 47, 95, 117, 119].
However, Vaughan et al. [46] reported that grade signifi-
Prognostic Factors and Survival cantly correlated with survival, and Gadducci et al. [48]
Most recurrences are extrapelvic, and half or more of them found a correlation on univariate, but not multivariate,
are extraperitoneal, usually in combination with intraper- analysis. Supporting this is the recent finding that grade is
itoneal recurrence [2, 44, 49, 50]. Most recurrences have correlated with lymphogenous metastases, with anaplastic
been reported in the first 23 years [3, 91] but have also tumors metastasizing early [122]. The presence of lympho-
occurred many years later [50]. Because there is no effec- cytic infiltration has also been suggested to be associated
tive second-line or salvage chemotherapy, recurrent disease with a more favorable outcome [119]. Although there was
is associated with a very poor prognosis. a difference in the median and 5-year survival according to
The OS rate for patients with PFTC is approximately lymphocytic infiltration in the study of Vaughan et al. [46],
30%50%, compared with 40% for patients with EOC [13, this was not significant.
28, 71, 87, 92, 117]. This figure is somewhat higher than that Other reported prognostic factors include advanced
for patients with EOC and possibly reflects the higher pro- age [48, 71, 75, 105], serous versus endometrioid, bilater-
portion of patients with early-stage disease. However, these ality, positive peritoneal cytology, site of tumor within the

Pectasides, Pectasides, Economopoulos 909

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- cal management, and indications for adjuvant chemother-
sion, p53 alteration [76, 77], and elevated pretreatment apy. Both carcinomas have a poor prognosis with stage and
CA-125 level [28, 34, 48, 71, 117]. The importance of an residual tumor size and respond to platinum-based chemo-
occlusion of the abdominal tubal ostium that could possi- therapy. However, there are two differences between the two

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bly prevent or delay local spread is not clear [123]. The role diseases: PFTC is more often diagnosed at an earlier stage,
of DNA-ploidy is negligible [124]. PFTC shares several and the role of routine lymphadenectomy is well established
biologic and clinical features with EOC. However, when and is mandatory in PFTC. Stage and residual tumor are the
compared with EOC, PFTC more often tends to recur in most important prognostic factors for outcome. Patients
retroperitoneal nodes and distant sites. Stage, patient age, with stage I low-risk disease submitted to optimal surgical
and among patients with advanced disease, residual tumor staging may not receive postoperative treatment. In con-
after initial surgery are the most important prognostic fac- trast, patients with stage I low-risk disease not submitted
tors for survival [124, 125]. to complete surgical staging, as well as those with stage I
high-risk disease or stage IIA disease, should receive 36
Conclusion cycles of adjuvant carboplatin plus paclitaxel. Patients with
PFTC is a rare tumor accounting for <1% of all female geni- advanced disease should be treated with a combination of
tal tract cancers. Histologically and clinically, it resembles carboplatin plus paclitaxel, as with EOC. Second-line treat-
EOC. The diagnosis of PFTC is rarely considered preopera- ment for persistent/recurrent disease should be based on the
tively and is usually first appreciated at the time of opera- platinum-free interval, whereas secondary cytoreduction
tion or by a pathologist. Both carcinomas have a similar age should be considered only for highly selected patients with
distribution, are more common among nulliparous women, localized late relapse. More extensive clinical research must
and are often of serous papillary histology. Surgery should be performed in order to have definite etiologic, diagnostic,
consist of total abdominal hysterectomy, bilateral salpingo- and management modalities, and prognostic markers.
oophorectomy, omentectomy, and lymph node dissection
from the pelvic and para-aortic regions. Aggressive debulk- Disclosure of Potential Conflicts
ing surgery should be attempted in patients with advanced of Interest
disease. PFTC is similar to EOC in surgical staging, surgi- The authors indicate no potential conflicts of interest.

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