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Fallopian Tube Cancer

Read review article here and below. Survival stats are here, here and below.

The first descriptions of a primary malignancy of the fallopian tube are attributed to Renaud and Ricci in 1845. Since that time, there have been fewer than 1500 cases reported. This is the rarest of the female genital tract malignancies, making up only 0.15% to 1.8% of all gynecologic malignancies,   with an average of 0.3%.  The theoretic incidence is 3 to 3.6 cases per million women per year.There is a reported 14% higher incidence in whites than in blacks.  

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 The age range of this disease has been reported to be from 18 to 87years, with most occurrences in the fifth and sixth decades of life. In a review of the literature of 393 patients, a mean age of 55 years was described.  This is consistent with the mean age of 56.7years in a metaanalysis of 577 patients more recently computed.The clinical profile of these patients reveals a relative low parity rate,  with a mean parity of 1 to 1.7.By virtue of the mean age of incidence, most patients are postmenopausal.

Pelvic inflammatory disease and tuberculous salpingitis were once believed to be causative factors in the development of fallopian tube malignancies. If this were the case, one would expect a higher incidence of tubal malignancies given the prevalence of pelvic inflammatory disease. No study to date has proven this theory.

Natural History

The primary spread of disease is similar to that of ovarian cancers in that there is local extension of tumor to adjacent structures to involve the peritoneum, omentum, bowel, and ovaries.However, 70% of patients with fallopian tube tumors have disease confined to the pelvis at presentation, compared with 48% of patients with ovarian malignancies, and up to 50% of patients are diagnosed with stage I disease.This is probably a result of the early presentation of abnormal bleeding and pain with distention of a small tubal lumen, which is absent in the anatomy of the ovary. Many authors believe that local extension is followed in frequency by lymphatic or hematogenous spread.However, in view of inconsistent staging and the advent of improved surgical resection with exploration and lymph node sampling, early lymphatic and vascular invasion may play a more prominent role in disease progression than previously thought -- that is, periaortic spread may precede intraabdominal dissemination. Lymph node positivity has been found to be 75% at autopsy. In a review of 67 patients, Sedlis reported that tubal musculature was rarely involved when lymphatic metastases were present. Far less common in fallopian tube cancer are distant metastases toliver and lung, which occur most often by local extension outside the peritoneal cavity by means of nodal versus transdiaphragmatic and hematogenous spread.  Distant metastases are more important as a site of treatment failure in ovarian cancer, in which more than 50% of recurrences occur outside the peritoneal cavity along with intraperitoneal disease. With this difference between ovarian and fallopian tube cancer, one could argue for aggressive postsurgical adjuvant treatment in fallopian tube carcinoma.

Clinical Presentation

Unlike ovarian malignancies, tumors of the fallopian tube cause early clinical signs and symptoms. Although the triads of pelvic pain, pelvic mass, and leukorrhea or vaginal bleeding, vaginal discharge, and lower abdominal pain have been described as pathognomonic, the highest percentage of patients presenting with such a triad of symptoms has been only 11%. Another classic sign, hydrops tubae profluens, which is a sudden emptying of accumulated fluid in the distended fallopian tube that causes profuse, watery, serosanguinous discharge to be released from the vagina, accompanied by a decrease in pelvic mass size on physical examination, was attributed to only 9% in a metaanalysis of 122 patients.In many other series it was been specifically reported that neither a triad nor hydrops tubae profluens was present in any of the patients reviewed.  Despite these inconsistencies in symptoms, the most common presenting sign is metrorrhagia, followed by pain and vaginal discharge. The most common physical sign is a pelvic mass, which occurs in 12% to 66% of patients.

Pathologic Classification

The most common histopathology of fallopian tube malignancies is serous papillary adenocarcinoma, similar to that found in the ovary. Benign tumors are found even less frequently than malignant neoplasms. Rare histologic subtypes are found: endometrioid, clear cell, transitional cell, squamous cell, malignant mixed mullerian tumors, and leiomyosarcomas. Tumors previously graded as papillary (pure), papillary-alveolar, and alveolar-medullary  are now routinely classified as well, moderately, and poorly differentiated (grades I, II, and III, respectively). Disease is bilateral in approximately 5% to 30% of patients at the time of initial diagnosis. This is considered to be a multicentric primary. Malignancies are distributed equally between the left and right fallopian tubes.

General Management

Primary treatment of adenocarcinoma of the fallopian tube is surgical resection at the time of initial diagnosis. Extensive surgical resection and staging should be performed (total abdominal hysterectomy, omentectomy, and bilateral salpingectomy), as well as sampling of ascitic fluid or peritoneal washings and peritoneal sampling of diaphragm, bladder, and bowel. Recent reports advocate lymph node sampling, because nodal involvement may occur early in the course of disease spread, even earlier than the extent of pelvic spread may indicate.  Numerous authors have observed that the amount of residual tumor left behind at primary resection (> 2 cm) has major prognostic implications. Some investigators have reported satisfactory results with conservative surgical treatment (unilateral salpingectomy only) if tumor has not invaded beyond the mucosa. Most patients, however, require some form of adjuvant treatment postoperatively to combat bulky residual disease or to treat assumed microscopic involvement.

More recently, combination chemotherapeutic regimens have been used in response to the poor results obtained with single agents. However, it has been suggested that these initial poor responses were caused by their use for recurrence after primary treatment failure. Deppe and colleagues  reported a surgically documented response by second-look laparotomy for the use of cisplatin-based combination chemotherapy. A later study retrospectively compared results in patients treated with and without cisplatin in combination and with single agent therapy. Peters and co-workers observed an overall response rate of 81% in 12 of 14 patients who received the cisplatin-based regimen. However, more patients with recurrence and failure received the less-aggressive treatment. Of patients who were free of disease at second-look laparotomy, 33% subsequently had relapses. In the only prospective trial, 18 patients receiving at least 6 to 12 cycles of cisplatin, doxorubicin, and cyclophosphamide achieved response rates of 53%, similar to the results seen in ovarian carcinoma.
Radiation Therapy

Postoperative radiation therapy has been a traditional form of therapy for fallopian tube carcinoma dissemination and recurrence. It has been recommended by some authors and questioned by others. It is also difficult to evaluate results in the past literature because of variability in staging, surgical staging techniques, treatment volume, dose fractionation, and type of radiation used. All reported studies are retrospective and usually involve small numbers of patients treated over long periods.

Several early, small studies observed promising results with techniques similar to those used in treatment of ovarian carcinoma These authors suggested that use of whole-abdomen external beam irradiation or intraperitoneal administration of radioactive colloids (**32P, **198Au) results in better survival rates than does surgery alone. Some investigators observed that there are too few data to support the use of radioactive colloids and that there is no role in patients with bulky disease. The best results were achieved when total dose greater than 50 Gy in 5 to 6 weeks was used with megavoltage as opposed to orthovoltage therapy. McMurray and Brown  stated that recurrence of early-stage disease (I and II) was likely to be in the upper abdomen if only pelvic irradiation was performed and that areas at risk, such as the abdomen and paraaortics, should be included within the initial treatment volume. Other studies noted a 50% relapse rate when early-stage disease was treated with surgery alone or with surgery plus pelvic irradiation, compared with a greater than 50% 5-year survival rate when the abdomen and paraaortic areas were treated.

Wolfson and associates  reported on 72 patients with carcinoma of the fallopian tube (24 stage I, 20 stage II, 24 stage III, and 4 stage IV) treated at six medical centers. Adjuvant chemotherapy was administered to 54 and postoperative irradiation to 22 patients. Of the latter group, 14 received whole-pelvis external irradiation, 5 whole-abdomen irradiation, 2 **32P instillation, and 1 vaginal brachytherapy only. The 5-, 8-, and 15-year survival rates were 44%, 24%, and 19%, respectively, for patients treated with chemotherapy and 27%, 17%, and 14% for those treated with irradiation. Significant prognostic factors included stage I versus more advanced stage and age at diagnosis (younger or older than 60 years). Patterns of failure included 2 vaginal, 5 pelvic, 24 abdominal, and 15 distant metastases. Abdominal failures were 21% in patients with stage I disease versus 79% in stages II, III, and IV. Patients experiencing abdominal relapse were more likely to die (83%) than those without abdominal relapse (39%).

A recent study using the new FIGO staging system for fallopian tube carcinoma compared the outcome in carcinoma in situ versus stage I with use of either irradiation or cisplatin-based chemotherapy  tumor penetration through the basement membrane (invasive carcinoma) reduced survival by 50%. Stage I patients treated by irradiation showed a significantly better prognosis than patients treated by chemotherapy. A few studies reported disappointing results with the use of radiation therapy to treat early-stage fallopian tube carcinoma. However, these studies contained small numbers, used treatment to the pelvis only,  and had inconsistent or incomplete surgical resection and staging.Many series that showed no benefit with irradiation used orthovoltage therapy, which is unable to deliver high doses to the deeper pelvic structures.

Little information exists regarding combination or concomitant use of chemotherapy and irradiation as postoperative treatment. In most studies, a single modality was used, and the other approach was attempted after failure occurred. Because both modalities have shown response when used together or separately, randomized, prospective study might be of help in this regard.