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Cancer of the Ovary - Treatment
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Contents
Surgical PhilosophyAdvanced Stage Disease - Cytoreductive Surgery.Aim to surgically remove all, or as much macroscopically visible tumour as possible. This will entail no less than TAHBSO + Infra-colic omentectomy + washings (or aspiration of ascitic fluid). Often surgery will entail retroperitoneal approach to pelvic mass, with en block TAHBSO + resection of rectosigmoid. Every attempt will be made to perform a primary colorectal anastomosis (+/- covering ileostomy). Total omentectomy will be frequently required +/- sacrifice of gastro-epiploic vessels. A systematic search will be conducted throughout the peritoneal cavity as well as palpation of retro-peritoneal lymph nodes. If there is macroscopic disease at any of these sites, an attempt will be made at cytoreduction. Procedures occasionally required to obtain optimal cytoreduction include: splenectomy, hepatic mobilization and stripping of under surface of diaphragm, resection of segments GIT, partial urinary cystectomy, retroperitoneal lymph node debulking, ureterolysis. Early Disease - Surgical Staging.The philosophy of the management of clinically early stage disease, is to remove all evident disease, and to surgico-pathologically determine the true extent of disease. Occult advanced stage disease will be found in up to 25% of patients with clinical stage I disease, usually in the omentum and retroperitoneal lymph nodes (2). It is crucial to identify these patients because with aggressive surgical and chemotherapeutic intervention, the chance of cure or sustained remission is maximized. Technique:
Outside ReferralsPatients suspected of having ovarian cancer are strongly advised to be referred and managed by staff at the Qld Centre for Gynaecological Cancer (QCGC). If there is any doubt, discussion with QCGC staff is recommended. There is evidence from retrospective series that patients with ovarian cancer managed in a dedicated gynaecological oncology unit by certified gynaecologic oncologists, have a statistically significantly longer median survival, overall survival and disease-free interval than patients managed by gynaecologists on their own, or in conjunction with general surgeons (3). Unless there is strict adherence to the above surgical principles, patients operated upon at outside centres will require re-laparotomy. From experience to date and in recognition the above principles, most patients with ovarian malignancy operated upon at outside centres will require reoperation. This allows optimization of cytoreduction for patients with advanced disease or determination of true stage for patients with early stage disease (often allowing chemotherapy to be withheld). Interval Cytoreduction.Interval cytoreduction is a surgical attempt at cytoreduction after a limited course of chemotherapy, usually 2-4 cycles. There are 2 clinical circumstances where interval cyto-reduction is utilized.
Second Look LaparotomySecond look laparotomy is a comprehensive staging procedure in a patient who has no clinical, radiographic or tumour marker evidence of disease at the completion of first line surgery and adjuvant chemotherapy. There are no quality randomized prospective trials that adequately address this issue. The best available data are retrospective series which have conflicting recommendations. The place of second look surgery is individualized after discussion between the surgeon and the patient. Second look laparotomy strongly recommended as part of any experimental protocols evaluating first and second line chemotherapy agents. Secondary CytoreductionSecondary cytoreduction is defined as a surgical attempt to debulk malignancy after a disease-free status has been attained following primary treatment. On the basis of retrospective data, the following variables are associated with an increased likelihood of attaining optimal secondary cytoreduction and improving survival:
The decision to perform secondary cytoreduction is individualized after consideration of the above factors and the availability of further active chemotherapeutic agents. Epithelial Ovarian CancerAdjuvant TreatmentPatients who have undergone a comprehensive surgical staging procedure and are found to have Stage IA and IB, grade I or grade II disease do not require adjuvant chemotherapy. All other patients require adjuvant chemotherapy. There is strong evidence that the most effective combination chemotherapy regimen in treating epithelial ovarian cancer is Cisplatinum and Paclitaxel (5). First Line Chemotherapy:-Cisplatinum 70 mg/m2 and Paclitaxel 135mg/m2 over 24 hours q3weekly x 6cycles or Carboplatinum AUC 5 and Paclitaxel 135mg/m2 q3(-4)weekly for 6 cycles, (where Cisplatinum not tolerated or contraindicated) Secondary Chemotherapy (Where Taxol Not Tolerated)Cisplatinum 75 mg/m2 and Cyclophosphamide 750 mg/m2 q3weeky for 6 cycles Note: Where hospital/government authorities enforce Cisplatinum/Cyclophosphamide given as first line treatment, careful attention is given to adequacy of response to treatment with view to early change to Cisplatinum/Pacitaxel if response considered inadequate. Other Active Agents:-Adriamycin, Hexamethylmelamine, Etoposide, Ifosfamide, Chlorambucil, Melphalan, Topotecan, Gemcytibine, Tamoxifen Role of RadiotherapyRadiotherapy is utilized in a palliative setting for symptomatic relief of symptoms caused by localized disease. Low Malignant Potential (Borderline) Epithelial Ovarian TumoursSurgical principles for the management of Low Malignant Potential
Tumours are identical to those in the management of frankly invasive
disease. As patients with LMP tumours present at a younger mean age and
have a higher incidence of early stage of disease, the need for correct
staging is highlighted. There is a role for fertility-conserving surgery
for patients who wish to maintain reproductive potential and who have
stage I disease. Pelvic clearance at the completion of child-bearing is
advised. Germ Cell TumoursAll germ cell tumours except mature cystic teratomas (and monodermal derivatives such as struma ovarii and carcinoid tumours) and gonadoblastomas, are considered malignant. Germ cell tumours occur more frequently in younger women (< 30 years of age) and tend to present at an earlier stage. The principles of surgery with respect to staging of early stage disease are unchanged from those used in the management of epithelial ovarian carcinoma. Particular attention should be directed to fertility preservation where this is desired, as conservative surgery + adjuvant chemotherapy has a proven role. Precise staging is of particular importance in treating dysgerminomas and immature teratomas, as this will determine the need for adjuvant chemotherapy. All malignant germ cell tumours except Stage IA dysgerminomas and Stage IA grade I teratomas require adjuvant treatment. The imperative for surgically debulking advanced malignant germ cell tumours is not proven. These tumours are very chemosensitive, potentially reducing the necessity for optimal cytoreduction. If optimal cytoreduction of advanced disease is easily obtained, this is recommended. However, the surgeon should be mindful that the extent of surgery should not compromise the timely administration of chemotherapy as this is the most important modality in treating these tumours. Adjuvant Treatment: Cisplatin 100 mg/m2 IV day 1 Repeat every 3 weeks for 3 cycles, or 3 cycles beyond a complete clinical or tumour marker response. The role of second-look laparotomy (SLL) is also unproven. Consideration for this procedure should be individualized. The strongest case for SLL is following the treatment of incompletely debulked, germ cell tumours containing elements of immature teratoma. This tumour has a low incidence of positive tumour markers and value has been found in identification of persistent malignant disease and in removal of areas of residual mature cystic teratoma often found at sites of previously active disease (7). Salvage regimens:
Stromal Cell TumoursSimilar principles employed in the management of Stromal Cell tumours as with Germ Cell Tumours. These tumours occur at any age, so consideration to conservative treatment of stage I disease in young, reproductive-aged patients. There is a 30-60% incidence of significant hormonal activity by these tumours. This will often precipitate clinical symptoms. Furthermore, these hormones can be used as tumour markers, including:
Stage IA tumours, well and moderately differentiated, < 10cm in size, < 2 mitoses per 10 high power fields: do not require adjuvant chemotherapy. Stage IB - IV : for adjuvant chemotherapy with Bleomycin, Etoposide and
Platinum (BEP) using same regimen as for Germ Cell Tumours Other MalignanciesThe commonest malignancies of this category include metastatic disease most commonly from the GIT and breast. Prognosis is poor. Management of all patients in this category must be individualized. References
Dr James L. Nicklin
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