Ovarian

Cancer

JoAnn H. Eriksson and Janet Ruth Walczak

I

T IS ESTIMATED that in 1990 there will be 20,500 new cases of ovarian cancer and 12,400 deaths from ovarian cancer in the United States. The virulent behavior of ovarian cancer is demonstratedby the fact that it is the leading cause of death due to gynecologic cancer (47%) while accounting for only 23% of all gynecologic malignancies. It is the fifth leading causeof cancerdeath among women in the United States’ and a leading causeof death in women in all industrialized countries except Japan. One out of every 71 women in the United Stateswill develop ovarian cancer.’ Malignant neoplasmsof the ovary can occur at any age. Throughout childhood and adolescence, germ cell tumors of the ovary are a leading cause of cancer death. Epithelial ovarian cancer occurs most commonly in women more than 50 years of age, with the peak incidence between the agesof 55 and 59 years.3 Despite advancesin the staging and treatmentof ovarian cancer, most women will not be cured by initial standard therapy. A woman with progressive ovarian cancer will have repeatedepisodesof intestinal obstruction asthe tumor spreadsthroughout the abdominal cavity and over the surface of the bowel, resulting in inanition, malnutrition, and death. The inability to determine the causeof the disease,to detect the diseaseearly, to reduce mortality rates through effective therapy, and to eliminate suffering from advanceddiseasemakesovarian cancer a major challenge to all health professionals. A majority of ovarian cancers are epithelial in origin, yet the nonepithelial cancers, particularly From the Rush Presbyterian, St Lukes Medical Center and Rush University, Chicago, IL; and The Johns Hopkins Oncology Center, Baltimore, MD. JoAnn H. Eriksson, RN, MS: Clinical Nurse Specialist, Gynecologic Oncology, Rush Presbyterian, St Lukes Medical Center, and Assistant Professor, College of Nursing, Rush University, Chicago, IL; Janet Ruth Walczak, RN, MSN: Clinical Nurse Specialist, Gynecologic Oncology, The Johns Hopkins Oncology Center, Baltimore, MD. Address reprint requests to Janet Ruth Walczak, RN, MSN, The Johns Hopkins Oncology Center, Room 163, 600 N Wolfe St, Baltimore, MD 21205. 0 1990 W.B. Saunders Company. 0749-2081/90l0403-0006$05.00i0

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germ cell and stromal tumors, comprise a distinct and important group in terms of origin, incidence, and treatment. This article discusses epithelial ovarian cancer, the nonepithelial germ cell and stromal tumors, and the overall nursing management of patients with ovarian cancer. EPITHELIAL OVARIAN CANCER

Epidemiology

Epithelial ovarian cancers account for 85% to 90% of all ovarian cancers seen in the United States.Epidemiologic studies to evaluate risk factors for epithelial ovarian cancer indicate that nulliparous and low parity women have a higher incidence of ovarian cancer.4The risk of ovarian cancer correlates with the time in a woman’s life when ovulation is not suppressedby pregnancy, lactation, or oral contraceptives.5These observations support the theory that the ovarian epithelial surfacemay be sensitive to the chronic irritation of “incessant ovulation. ’ ‘6 When ovulation is suppressedby pregnancy and the use of oral contraceptives, gonadotropin levels are low. Gonadotropin levels are high during the postmenopausal years and may account for the increasedincidence of ovarian cancer in women over 45 years of age.7 Environmental factors are suspectedas risk factors since the highest incidence of ovarian cancer occurs in industrialized countries with the exception of Japan. Japaneseimmigrants to the United Stateshave an increasedrate of ovarian cancerthat approachesthe rate for white women by the second generation.* Women with higher education, which is correlated with higher income and differences in childbearing practices and dietary habits, have a higher incidence of ovarian cancer.3Y5 Studies regarding dietary fat as a risk factor in ovarian cancer report contradictory findings. The consumptionof animal fat as a risk factor has been reported by some investigators, but not by others.8,9Consumptionof cigarettes, alcohol, and/ or coffee have not been associated with an increasedrisk of ovarian cancer.8*9 The migration of industrial by-products, such as talc, from the vagina via retrograde flow through the reproductive tract to the peritoneal cavity may accountfor the exposureof the ovaries to carcino.%minars in Oncology Nursing, Vol 6, No 3 (August), 1990: pp 214-227

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CANCER

genie agents. However, investigations of talc exposure revealed no significant correlation with disease.lo Genetic and familial predisposition are factors in only a small proportion of women with ovarian cancer.6In families in which ovarian cancer is evident in two or more first-degree relatives, the first-degree relative has a threefold increase in risk. Hereditary ovarian cancer refers to a pattern of autosomaldominant segregationof ovarian cancer in which other cancers, such as breast, endometrial, and colon cancer, are associated with ovarian cancer.‘i Patients in the type A blood group also have a higher incidence of ovarian cancer.I2 Viruses have been suspectedas a factor in the development of ovarian cancer. The mumps parotitis virus causing asymptomatic mumps has been investigated as an etiologic agent. However, no evidence exists to incriminate this or any particular virus. * Despite the many factors associatedwith ovarian cancer, no etiology has been identified. This failure to determinethe causeof ovarian cancerhas frustrated efforts in primary prevention and early detection of the disease. Pathophysiology and Natural History

The epithelial cancersof the ovary are classified histologically as serous, mutinous, endometrioid, mesonephroid (clear cell), Brenner, and undifferentiated types. The histologic types of epithelial ovarian cancer have similar presentation and dissemination patterns. Histologic type alone has little prognostic significance with the exception of clear cell carcinoma, which is much more aggressive in nature.13 Ovarian cancer originates in the ovary, grows locally, and then invades the capsuleand mesovarium. After invading the capsule, cells most commonly exfoliate into the peritoneal cavity, where they are carried in the peritoneal fluid via the posterior gutters to the subdiaphragmaticsurfaces.All peritoneal surfacesare potential sitesfor tumor implants. Cells may implant on the diaphragm, liver, bowels, bladder, or omentum. Cells may also enter the pleural cavities via the diaphragm and implant on the pleural surfaces.When tumor cells obstruct lymphatic channels, malignant ascites may accumulate. Tumor cells may also invade the uterus, fallopian tubes, and other pelvic structures by di-

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rect extension or through lymphatic channels. Para-aortic lymph node involvement is common, although hematogenousspread is not. Although ovarian cancer usually remains confined to the peritoneal cavity, it may metastasizeto other organs, such as liver, lung, and pleura.194*‘3 Ovarian cancer has been described in women whose ovaries have been previously removed.‘4,15 The explanation for such an occurrence is not clear, but it has been suggestedthat the coelomic epithelium may undergo neoplastic transformation. Signs and Symptoms

Ovarian cancer is a disease with no specific early symptoms. Frequently, there will be months of delay in detecting the diseasebecausethe vague symptoms of dyspepsia, abdominal discomfort, pelvic pressure, urinary frequency, and other digestive symptoms are dismissed as insignificant and related to personal stressesor midlife changes. Attention to these abdominal complaints as possible early symptoms of ovarian cancer, especially in the nulliparous woman over 40 yearsof agewith a negative gastrointestinal (GI) workup, may facilitate earlier detection. Detection occurs primarily when the tumor is large enough to be palpable, or when ascites and abdominal distention develop. Other presenting symptomsinclude pain, dyspnea, and weight 10~s.‘~ Early Detection and Diagnosis

The pelvic examination remains an important means for detecting early ovarian cancer. A palpable ovary in a woman 3 or more years after menopauseshould suggest an ovarian neoplasm. However, only one ovarian cancer in 10,000 asymptomatic women will be detected by pelvic examination.* Currently, there is interest in evaluating pelvic ultrasound for screening in the asymptomaticwoman.” Diagnosis of early ovarian cancer with specific tumor-associatedantigens has been investigated. Antigens such as CA-125 and NB/70K have been identified. These antigens have been found to correlate with the stage and amount of residual disease. However, serum levels are often undetectable in the presenceof minimal residual disease. The antigens are useful in monitoring progression or recurrence of disease, but are not useful as a screening tool. ’ 8-20Other types of immunologic

216

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markers are being investigated. These include monoclonal antibodies and radiolabeled antibodies to detectmetastasis,and tumor-associatedantigens that act as targets for antibody-directed treatment. Routine diagnostic tests are not particularly useful in the evaluation of ovarian cancer, except to rule out possible sites of origin of a pelvic mass. Ultrasound and computed tomography (CT) scans are useful in detecting a pelvic mass, but cannot differentiate between a benign and a malignant process. When pelvic massesare known to exist, these tests may help determine extent of disease, but they do not replace the need for exploratory surgery for diagnosis and staging.2*21 Paracentesisto obtain fluid for cell block and cytologic smearis not done if surgery is planned. Paracentesiscould result in the puncture of a selfcontained malignant cyst and causetumor seeding along the needle tract, which would increase the stageof diseaseand decreasesurvival2 Barium enema may be performed to rule out a primary colorectal tumor with metastasesto the ovary. Proctosigmoidoscopyand a GI series may be indicated in women with intestinal tract symptoms. Chest x-ray is done to assessfor pleural effusion and parenchymal metastases.Intravenous pyelogram is helpful in identifying the relationship of the ureters to the tumor and other pelvic structures.2 Although these studies are helpful in the evaluation of a pelvic mass, they cannot provide a definitive diagnosis. Definitive diagnosis of ovarian cancer requires histologic examination of tumor tissue obtained at the time of laparotomy. Surgery Surgical

staging and cytoreductive

surgery.

Surgical staging and cytoreductive surgery provide the basis for treatment of ovarian cancer. The International Federation of Gynecology and Obstetrics (FIGO) staging system, which was revised in 1985, is the currently acceptedstaging system(Table 1). The staging laparotomy is performed to diagnose the malignancy and to accurately determine the extent of disease(Table 2). This procedure consists of a systematic exploration of all peritoneal surfaceswithin the abdominal cavity to determine volume and distribution of the ovarian tumor. This is accomplishedvia a vertical midline incision from the pubis symphysis to above the

Table 1. FIG0 Shahs Stage I IA IB IC

II IIA IIB IIC

Ill

IIIA

IIIB

IIIC

IV

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for Ovarian Cancer

Growth limited to the ovaries. Growth limited to one ovary; no ascites. No tumor on the external surface; capsule intact. Growth limited to both ovaries; no ascites. No tumor on the external surfaces; capsules intact. Tumor either stage IA or IB, but with tumor on surface of one or both ovaries, with capsule ruptured, with ascites present containing malignant cells, or with positive peritoneal washings. Growth involving one or both ovaries with pelvic extension. Extension and/or metastases to the uterus and/or tubes. Extension to other pelvic tissues. Tumor either stage IIA or IIB, but with tumor on the surface of one or both ovaries, with capsule(s) ruptured, with ascites present containing malignant cells, or with positive peritoneal washings. Tumor involving one or both ovaries with peritoneal implants outside the pelvis and/or positive retroperitoneal or inguinal nodes. Superficial liver metastasis equals stage Ill. Tumor grossly limited to the true pelvis with negative nodes, but with histologically confirmed microscopic seeding of abdominal peritoneal surfaces. Tumor of one or both ovaries with histologically confirmed implants of abdominal peritoneal surfaces, none exceeding 2 cm in diameter. Nodes are negative. Abdominal implants greater than 2 cm in diameter and/or positive retroperitoneal or inguinal nodes. Growth involving one or both ovaries with distant metastases. If pleural effusion is present, there must be positive cytology to allot a case to stage IV. Parenchymal liver metastasis equals stage IV.

umbilicus. Once the peritoneal cavity is entered, the presenceof ascites is noted and fluid is obtained for cytopathology. If no fluid is present, peritoneal washings are obtained and sent for cytopathology. All peritoneal surfacesare then carefully examined to determine presenceof disease. Attention is paid to the diaphragm, pericolic gutters, serosaof the bowels, pelvic sidewalls, culde-sac, and omentum. Multiple, selective biopsy specimensare obtained. The ovaries, if identifiable, are inspected to determine the presence of bilaterality, tumor excrescenceson the capsule, rupture, and adhesions. A total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy(BSO), omentectomy, selective pelvic and para-aortic lymph node sampling, and cytoreductive surgery is performed. The

OVARIAN

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CANCER

Table 2. Staging

Laparotomy Ovarian

Procedure Cancer

for Patients

With

Vertical midline incision from the pubis symphysis to above the umbilicus Peritoneal cytology (ascitic fluid or washings) from pelvic paracolic gutters, infradiaphragmatic area Examination and palpation of all peritoneal surfaces Omentectomy Abdominal hysterectomy and bilateral salpingooophorectomy Multiple selective biopsy specimens taken from cul-de-sac, pelvic sidewalls, paracolic gutters, and diaphragm Selective pelvic and para-aortic lymph node sampling Cytoreductive surgery Assessment for residual disease

goal of cytoreductive surgery is to remove all tumor massesgreater than 1 cm in size without undue surgical morbidity. This debulking may include extensive dissection of tumor massesand the formation of a colostomy to prevent obstruction. Occasionally, in the caseof a young woman who wishes to maintain fertility and has a stage IA, well-differentiated tumor or a tumor of low malignant potential, only the involved ovary is removed. The contralateral ovary is sampledand a complete exploration of the abdominal cavity is accomplished. Five-year survival in this selectpopulation is comparable to that of patients in whom all reproductive organs are removed.22 Second-look laparotomy. A “second-look” laparotomy, which is a second operation for exploratory purposes, is performed in patients who have had a complete clinical responseto primary therapy. A negative CT scan or ultrasound and a negative CA-125 are useful in deciding who should proceed to a second-look procedure. The purposesof this procedure are to evaluate the effectivenessof treatment, to determine diseasestatus and the need for further treatment, and to debulk any residual tumor identified. The surgical procedure is similar to the initial staging laparotomy in that it consists of peritoneal washings or sampling of peritoneal fluid, a systematicevaluation of all peritoneal surfaces,and selective, multiple biopsy procedures. The impact of secondlook laparotomy and secondary cytoreductive surgery on survival remains controversial.l3 Exploratory surgery may also be performed when complications develop. The most common complication is a bowel obstruction that may require ostomy formation or bypass surgery.23

Prognostic Factors

Important prognostic factors for women with ovarian cancer are the stage of the disease, the amount of residual disease following initial debulking surgery, and the histologic grade of the tumor. Survival is associatedwith stage, and varies from 60% to 70% for stageI diseaseto less than 5% for stageIV disease(Table 3).2,4 The most important prognostic indicator in patients with advancedovarian cancer is the volume of residual tumor following primary surgery. An increased response to chemotherapy and significantly higher survival rates are noted in patients who are optimally resected.4 Histologic gradeis another factor in determining prognosis. Patients with well-differentiated (grade 1) or moderately well-differentiated (grade 2) tumors have significantly higher 5-year survival rates than those with poorly differentiated (grade 3) tumors.4,7 There is a group of ovarian tumors classified as “low malignant potential.” These tumors account for approximately 15% of all ovarian tumors, tend to occur in women less than 40 years of age, and have a favorable prognosis regardlessof the stage of disease.4 Treatment

The multimodality approach is essential for the treatmentof epithelial ovarian cancer. After initial cytoreductive surgery, treatmentis basedon stage, grade, and amount of residual disease (Table 4). StageIA or IB requires no further adjunctive therapy. StageIA and IB high-grade tumors, stageIC, and stageII tumors with minimal residual disease require treatment with single-agentchemotherapy, intraperitoneal chromic phosphate(P32), or combination chemotherapy. Stage II ovarian cancer with grossresidual diseasefollowing cytoreductive surgery is treatedwith a cisplatin-basedregimen of combination chemotherapy. Optimally resected stage III residual diseaseis also treated with cisplatin combination chemotherapy. Table 3. 5-Year Survival

stage I II III IV

Ratus for Epithelial

Ovarian

Cancer

Survival (%I 60-70 25-45 12-13 o-4

-

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ERIKSSON Table 4. Treatment

for Ovarian

Cancer

Treatment

Stage

IA or IB, grade 1

No further

IA, IB, grade 2,3

Single-agent

IC

P32 or combination

II, gross residual disease

Combination including

II, Ill G 2 cm residual disease

Combination chemotherapy including cisplatin or whole abdominal pelvic radiation

Ill > 2 cm residual disease; IV

Combination including

Refractory

Chemotherapy, immunotherapy, intraperitoneal therapy, hormonal therapy

disease

treatment chemotherapy chemotherapy

chemotherapy cisplatin

chemotherapy cisplatin

Whole abdominal and pelvic radiation therapy has been advocatedfor patients who are optimally resected.Survival rates for radiation therapy equal those for single agent chemotherapy; however, morbidity is significantly increased.’ Stage III with bulky residual diseaseand stage IV are treatedwith cisplatin-basedmultiagent chemotherapy. Hormonal manipulation is usually reserved for salvagetherapy.* Chemotherapy. Single-agent chemotherapy was considered standard treatment for epithelial ovarian cancer prior to 1976. Alkylating agents such as melphalan, cyclophosphamide, and chlorambucil were the first drugs used effectively against ovarian cancer. Overall responserates of 40% to 60% and survival rates of 21 to 35 months were reported.* Hexamethylmelamine, doxorubitin, 5-fluorouracil(5FU), and cisplatin have been found to be effective as single agents, with responseratesranging from 12% to 61%.*l In 1976, cisplatin was reported to have a responserate of 26% in pretreated patients.24Today, cisplatin is considered the single most active drug available for the treatment of ovarian cancer. Overall responserates for platinum-basedcombination therapy are as high as 90%, with complete response rates of 40% to 50%.* Since single-agent therapy has been of limited successin the treatmentof ovarian cancer, combination drug regimens have been used to treat advanced disease. Act-FuCy (dactinomycin, 5-FU, and cyclophosphamide) and Hexa-CAF (hexame-

AND WALCZAK

thylmelamine , cyclophosphamide, methotrexate, and 5-FU) were compared with melphalan, with statistically significant increased response and survival.* With the introduction of cisplatin into combination chemotherapeuticregimens, response rates improved significantly.25*26 Controversy exists over the effectiveness of other drugs in cisplatin-based combination regimens. Cyclophosphamide and cisplatin (CP), or cyclophosphamide, cisplatin with doxorubicin (CAP), are the most effective combinations presently used. The Gynecologic Oncology Group (GOG) reported similar response,disease-freeinterval, and survival rates with CP and CAP in optimally debulked, stage III patients.27 Several researchers**“’ found that CAP had a higher complete responserate (62%) than CP (39%). However, survival rates were not significantly different. Most women with ovarian cancer develop recurrence after an initial response to chemotherapy; therefore, additional therapy is given. Second-line chemotherapy, used after failure of initial chemotherapy, produces limited effects. Although many single agents and combination regimens, such as 5-FU, etoposide, high-dose cisplatin, hexamethylmelamine, cisplatin, CAP, and CHAP (cyclophosphamide, hexamethylmelamine, doxorubicin, cisplatin) have been used, the highest responserates are achieved when cisplatin is used alone or in combination with other agents. Response rates range from 22% to 72%. However, most were partial responsesof short duration (4 to 6 months).7 Carboplatin, a cisplatin analogue, is as active as cisplatin in patients with advancedepithelial ovarian cancer3’ and germ cell tumors.32 Carboplatin as well as cisplatin is associatedwith a significant dose response;that is, the responserate is proportional to the dose of drug administered. It is also the most effective agent for patients previously responsive to cisplatin, but who are unable to tolerate cisplatin due to neurotoxicity or nephrotoxicity. Carboplatin is gaining recognition as an important drug in the treatment of ovarian cancer.31,33 A new investigational drug, taxol , is a diterpene plant product and antineoplastic agent which has a mechanism of action that is unique in that it is unlike other antimicrotubule agents. Tax01 has demonstratedan overall responserate of 30% in pretreatedpatients. Further evaluation of this drug,

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particularly in combination with cisplatin, is under way.34 Probably the newest and most experimental therapy for advanced ovarian cancer is that of high-dose chemotherapy with autologous bone marrow transplantation. A variety of drugs, including cyclophosphamide, melphalan, carboplatin, and etoposide, have been used in limited populations of both epithelial and germ cell cancersof the ovary. Although preliminary data is promising, further investigation is needed.35”7 Zntruperifoneaf chemotherapy. Intraperitoneal chemotherapyoffers an alternative to intravenous second-line therapy in patients who have minimal residual disease following second-look laparotomy. Intraperitoneal administration of chemotherapeutic agentsdirectly into the abdominal cavity has four advantagesover intravenous chemotherapyin this selectpopulation: (1) a higher concentrationof the drugs in the peritoneal cavity is obtained with intraperitoneal rather than systemic exposure, (2) drugs can be administered directly to the tumor sites, (3) systemic toxicity from the drug is minimized, and (4) immunoresponsein the abdominal cavity is enhanced.38,39 Administration of chemotherapeuticagentsinto the peritoneal cavity requires the useof a catheter. Semipermanentcatheters, such as the Tenckhoff dialysis catheter or a peritoneal catheter with an implanted port, are used for multiple administrations. Both types have advantagesand disadvantages. The major problem with both types of catheters is the formation of a fibrin sheath, causing obstruction of the outflow. Occasionally, the infusion of drugs may not be possible.40,41A large intercooperative group study comparing intraperitoneal versus intravenous administration of cisplatin in combination with intravenous cyclophosphamide as first-line treatment is under way for optimal stage IIl disease.42 Immunotherapy. Immunotherapeutic agents have beenusedin combination with chemotherapy to treat ovarian cancer. Increasing tumor cell kill by nonspecific cellular activation and increased recognition and response to specific tumor antigenshave beentested. Initially, it was thought that Corynebacterium parvum and bacillis CalmetteGuerin (BCG) in combination with chemotherapy would show a higher responserate than treatment with chemotherapy alone. However, additional randomized trials were not able to produce the

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results.43*44 Intraperitoneal administration of interferons and interleukin-II have also shown promise in initial studies.45*46 Radiation therapy. Radioisotopes,P32 and radioactive gold, have been widely used to treat ovarian cancer. Radioisotopes are effective in treating patients with early stage disease,with reported survival rates of 67% to 95% for stage I diseaseand 25% to 67% for stage II disease. The radioisotopes are administered into the peritoneal cavity.* Chromic phosphate is preferred becauseof its longer half-life and lack of gammairradiation. The radiation from P32 penetratesto a maximum depth of 4 to 5 mm so it is only used with microscopic disease.* Chromic phosphate is usually infused postoperatively in 500 ml normal saline into the peritoneal cavity through a catheter. The patient’s position is changedevery 10 to 15 minutes to promote adequatedistribution of the isotope. External beam radiotherapy is given to the whole abdomenand pelvis in selectedpatients with minimal residual disease.The kidney and the right lobe of the liver are shielded, usually after the maximum tolerated dose of 2,000 to 2,500 cGy and a pelvic boost of approximately 2,000 to 3,000 cGy are given. Nausea and vomiting as well as significant myelosuppression frequently interrupt and sometimes prevent completion of the full course of therapy. These effects are compounded becausemany of the patients have received previous myelosuppressivetherapy.47 Endocrine therapy. Ovarian cancer may be viewed as an endocrine-relatedtumor becausethe ovaries are a primary source of estrogen and progesteroneas well as a target organ for these and other hormones. Endocrine therapy consisting of progestins, antiestrogens,and other hormones has been tested. Progestins,such as medoxyprogesteroneacetate (MPA) and megestrol acetate,have only a 10% to 15% objective responserate, and most responses were seenin patients with serousand endometrioid tumors.6 Progestins have been tested in combination with chemotherapy, with high responserates of 76% to 85% in initial studies, but thesewere not replicated in prospective controlled randomized tSidS.7

Responserates of 14% to 18% were achieved with the combination of MPA and ethynylestradiol. An increase in responsewas reported when

ERIKSSON AND WALCZAK

220

estrogens and progestins were administered in a simultaneous and sequential fashion.48An objective responserate of 4% was seenwith tamoxifen therapy alone. However, stabilization of disease occurred in 8% to 80% of the patients. The luteinizing hormone-releasing hormone agonist, DTrp-6-LHRH (decapaptyl), has been used in the treatment of ovarian cancer; stabilization of diseaseand a decreasein tumor size was noted in 50% of cases.49It is believed that decreasinggonadotropins may minimize the steroid output of ovarian cancer. In studies with ovarian cancer, estrogen receptors are seenin 63% of patients, progesteronereceptors in 48%, and androgenreceptorsin 69% of tumors. Both estrogen and progesteronereceptors are found in 36% of ovarian cancers.The presence of estrogen and progesteronereceptors is a good predictor of response in endometrioid tumors.50 Other studies are neededto further define the correlation between hormonal receptorsand response to treatment. NONEPITHELIAL TUMORS

Nonepithelial ovarian tumors represent only 10%to 15% of all ovarian cancersand are the most common gynecologic tumors in childhood and adolescence. Staging of these tumors is accomplished in the same manner as for epithelial tumors, using the FIG0 system (Table 1). The majority of these tumors consist of germ cell tumors and stromal tumors of the ovary. Germ Cell Tumors The understanding of germ cell tumors as a group of neoplasms arising from the gonads has evolved over the last four decades. Primordial germ cells originate from cells differentiating in the caudal region of the yolk sac. They then migrate along the dorsal mesenteryof the developing embryo into the newly forming gonads and are incorporated into the sex cords, where they develop into oogonia in women.51Cells arrestedduring the processof migration may give rise to both benign and malignant tumors in midline sites such as the retroperitoneal and sacrococcygealregions. However, most germ cell tumors arise from undifferentiated germ cells within the o~ary.~~ The human fetal yolk sac synthesizes several proteins, including albumin, prealbumin, alpha-

1-antitrypsin, and transferrin. Alpha-fetoprotein (AFP) is a protein produced by the fetal liver and GI tract. It is replaced by albumin as the fetus matures.Alpha-fetoprotein and alpha-4-antitrypsin reappearas certain types of germ cell tumors grow and spread. These tumors include embryonal carcinoma and endodermal sinus tumors (yolk sac carcinoma).53 Syncytiotrophoblastic cells of the human placenta produce human chorionic gonadotropin (HCG), a polypeptide, which disappears from fetal circulation after birth; however, HCG can be identified in syncytiotrophoblastic giant cells in germ cell tumors and can be found in the circulation as the tumor grows and spreads.52,54 The dysgerminoma is a primitive malignant germ cell tumor distinct from embryonal carcinoma. It has not differentiated to form embryonic or extraembryonic structures.It is the female counterpart of testicular seminoma.Dysgerminomasoften contain elements of other malignant germ cells.54 Kurman et al54proposeda classification of germ cell tumors into germinomasand embryonal carcinomas based on their relationship with AFP and HCG (Fig 1). Embryonal carcinoma, a tumor composedof undifferentiated cells, is the progenitor of embryonic and extraembryonic tumors, and synPRIMORDIeL

GERMINOMA Seminoma or Dysgerminoma AFP (-) HCG (-)

GERM CELL

EMBRYONAL CARCINOMA Aw (+I HCG (+)

Embryonic Differentiation

Extraembryomc Differentiation

t Trophoblast f Choriocarcinoma AFP (-) HGC (+)

Yolk

Sac

Endodermal Sinus Tumor AFP (+) HGC (-)

Immature AFP (-) HCG (-) t Mature Teratoma AFP (-) HCG (-)

Fig 1. Histogenic and immunohistogenic classification of germ call tumors. AFP, alpha-fetoprotein; HCG, human chorionic gonadotropin. (Reprinted with permission.‘9

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thesizesboth AFP and HCG, while the dysgerminoma synthesizesneither in a majority of cases.54 The presentingsymptomsin descendingorder of frequency include acute and chronic abdominal pain, asymptomaticmass,abnormal vaginal bleeding, amenorrhea, and abdominal distention.55 Ovarian germ cell tumors are usually rapidly growing tumors and causea significant amount of pain. The pain can becomesevereas a result of rupture or torsion of the mass. A hemoperitoneum from rupture of the capsuleof the rapidly growing mass is a classic initial sign of dysgerminoma55(Table 5). Dysgerminoma. Dysgerminoma is the most common malignant germ cell tumor of the ovary, accounting for 3.5% of ovarian malignancies. It may occur at any age; however, the majority ap-

pear in adolescenceand early adulthood (between 10 to 30 years of age). Dysgerminoma can be associated with gonadal dysgenesis and a gonadoblastoma, and is the only germ cell tumor in which bilateral ovarian involvement may exist. Dysgerminomashave a predilection for lymphatic spread, although metastasismay also occur through extension through the capsuleand by peritoneal and vascular spread. Mediastinal and supraclavicular lymph node involvement, bone metastasis, and brain, liver, or lung involvement are late manifestations of the disease. About 25% of the patients will have metastaticdiseaseat the time of exploratory surgery.52 A young patient with stageIA diseasewho wants to preserve fertility should have a unilateral salpingo-oophorectomy combined with aggressive

Table 5. Germ Cell Tumors of the Ovafl” Type

Description

Tumor Markers

Dysgerminoma

3.5% of ovarian malignancies; highest incidence, lo-30 years of age; bilaterality can occur; spread via lymphatics, vascular channels, direct extension, and peritoneal flow; 25% metastatic at diagnosis

AFP HCG -

Endodermal sinus tumor

Second most common germ cell tumor of ovary; highest incidence in adolescents and young adults (mean age, 18 years); presenting symptom: abdominal pain in 77% of patients; characterized by rapid growth and intra-abdominal spread; survival with surgery and chemotherapy approaches 70% 4% of malignant germ cell tumors; mean age of incidence, 15 years; survival rates, 39% to 50% Two groups: gestational and nongestational; arises as a germ cell differentiating toward trophoblastic structures; usually occurs primarily in prepubescent children but also in young women; precocious puberty in prepubescent girls; adults have signs of ectopic pregnancy Tumor with immature or embryonal tissue arising from ectodermal, mesodermal, and endodermal germ layers; contains neuroepithelial elements; third most common germ cell tumor; usually occurs in the first two decades of life; usually unilateral

Usually Usually

Embryonal carcinoma Chorocarcinoma

Teratoma, immature

AFP + HCG + HCG +

HCG AFP-

HCG AFP +

Treatment Unilateral salpingo-oophorectomy if fertility desired in stage IA; TAH and BSO if tumor > 10 cm, tumor adherent to other organs, ascites present, or evidence of metastasis If patient is pregnant, maintain pregnancy if encapsulated; TAH and BSO if tumor not encapsulated or if tumor > 10 cm Adjuvant chemotherapy: VAC, VBP, BEP Radiation to whole abdomen and pelvis is an option unless fertility is desired Surgical debulking followed by combination chemotherapy: VAC, MAC, and BEP being tested; radiation not useful

Unilaterial salpingo-oophorectomy with combination chemotherapy: VAC and BEP; not radiosensitive Surgical removal followed by combination chemotherapy MAC

Unilateral salpingo-oophorectomy; adjuvant combination chemotherapy if tumor is grade 2 or 3, ascites present, tumor ruptures, disease persistent, or recurrent; VAC, MAC, and PVB; radiation is of little value

Abbreviations: HCG, human chorionic gonadotropin; AFP, alpha-fetoprotein; VAC, vincristine, dadnomycin, mide; VBP, vinblastine, cisplatin, and bleomycin; BEP, bleomycin, etoposide, and cisplatin; MAC, methotrexate, cyclophosphamide; t, positive serum tumor markers; -, negative serum tumor markers.

and cyclophosphadactinomycin, and

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staging. A TAH and BSO are performed when tumor is greaterthan 10 cm in diameteror attached to other organs, ascitesis present, or there is evidence of metastasis.A pregnancy is left uninterrupted if an encapsulatedtumor can be removed intact. If not, TAH and BSO are recommended.52 Dysgerminomas are highly radiosensitive and whole abdominal and pelvic radiation have been used. However, conservative treatment with preservation of fertility is a major considerationfor the majority of patients who are young. Surgery alone for stageI diseaseand combination chemotherapy for higher stage diseasehave also produced good results. Regimensused in the treatmentof dysgerminoma consist of vincristine, dactinomycin, and cyclophosphamide (VAC); vinblastine, bleomytin, and cisplatin (VBP); and bleomycin, etoposide, and cisplatin (BEP).3,52*56”58 Dysgerminomasmay occur in combination with gonadoblastoma,a tumor that always occurs with dysgenic gonads. Treatment in this situation requires bilateral oophorectomy becauseof the frequency of bilateral tumors and absenceof normal ovarian function. The uterus is left intact for possible future in vitro fertilization. Genotype and karyotype studies of patients are recommended, especially in patients with developmental abnormalities or a history of virilization.3 Endodermal sinus tumor. Endodermal sinus tumor (EST) is the secondmost common form of malignant germ cell tumor of the ovary. It is characterized by rapid growth and extensive intraabdominal spread. The presenting symptom is abdominal pain in approximately 77% of patients.52 Patients are usually seenwithin 2 weeks of developing symptoms. Endodermal sinus tumor is seen primarily in girls and young women with a median age of 18 years.52Human chorionic gonadotropin is usually negative. Since the AFP is frequently elevated, it servesas a good tumor marker. The FIG0 staging systemis not an accuratepredictor of response to treatment or survival. The GOG has categorizedEST into two categories:all gross tumor resected and unresectablediseaseor incompletely resecteddisease.As expected, those with all tumor resected have a more favorable prognosis.52 Treatment consistsof cytoreductive surgery followed by multiple-agent chemotherapy. Until recently, the majority of patients with EST died within 2 years of diagnosis. In 1975, Smith and

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AN0

WALCZAK

Rutledge59reported VAC chemotherapy as effective treatment for advanced EST. Creasman and Soper@found comparable results using the combination of methotrexate, dactinomycin, and cyclophosphamide(MAC). The BEP regimen is currently being tested in EST. Survival with surgery and chemotherapy approaches70%.52 Radiotherapy has not been found to be effective with this diseasedespite some initial responses.55 Embryonal carcinoma. Embryonal carcinoma accounts for only 4% of the malignant ovarian germ cell tumors. It is one of the most malignant cancersof the ovary. Initial presentation is by abdominal or pelvic mass. A large percentageof patients also have signs and symptoms of hormonal stimulation, including precocious pseudopuberty, amenorrhea, irregular uterine bleeding, or hirsutism. The mean age of occurrence is 15 years.55 Embryonal carcinoma arisesfrom primordial germ cells that have begun to differentiate, but have not differentiated into embryonic or extraembryonic tissue. The tumors contain AFP, HCG, and syncytiotrophoblast-like cells. Alpha-fetoprotein and HCG are useful markers to monitor this disease. Survival is reported as 50% for stage I tumors, with a 39% actuarial survival rate for all stages.61 Treatment consists of unilateral salpingooophorectomy and combination chemotherapy. The VAC regimen is active in treating embryonal carcinoma, but not as active as VBP in advanced cases.The BEP regimen is currently being evaluated. Radiation therapy is not an effective treatment modality for this disease.52 Choriocarcinoma. Choriocarcinoma of the ovary is divided into two groups: gestational choriocarcinoma, which is discussedelsewherein this issue, and nongestational choriocarcinoma. Nongestational choriocarcinoma of the ovary arisesas a germ cell differentiating toward trophoblastic structures and secretesHCG. In the majority of tumors, choriocarcinomais mixed with other neoplastic germ cell elements. Choriocarcinoma arises primarily in prepubescent children and young adults. Sexual precocious puberty with growth of pubic and axillary hair, breast development, and uterine bleeding is especially noticeable in prepubescentchildren. Adult women have signs of ectopic pregnancy. Serum and urinary HCG levels are useful diagnostic tests. Unlike gestational choriocarcinoma, nongestational choriocarcinoma is not as sensitive to che-

223

motherapy. Treatments have included MAC and other combination chemotherapeuticregimens.52 Terutoma. There are two types of teratoma, the immature teratomaand the mature teratoma. A tumor with immature or embryonal tissue arising from the ectodermal, mesodermal, and endodermal germ layers is defined as an immature teratoma. The immature teratoma accounts for less than 1% of ovarian teratomas.It usually occurs in the first two decadesof life. An immature teratoma contains immature neuroepithelial elements by definition. The metastatic potential is generally correlated with the grade of the primary tumor.62 In general, the grade of metastasis reflects the gradeof the primary lesion and is the bestpredictor of survival. Presenting signs and symptoms include pelvic masswith or without pain, abnormalbleeding, and capsulerupture. Signs of abnormal hormonal stimulation are not observed. Immature teratoma is usually unilateral. Treatment consistsof unilateral salpingo-oophorectomy.Combinationchemotherapy is addedfor patientswith grades2 and 3 tumors and for all patients with malignant ascites,ruptured tumors, and persistentor recurrentdisease.The VAC and MAC treatment regimens have proven to be effective for ovarian teratomas.55’63 However, postoperative chemotherapyhas not improved survival for patients with grade 1 lesions. Radiotherapy is of little value in treating immature teratomas.52 Mature cystic teratoma, also called a dermoid cyst, accounts for more than 95% of all ovarian teratomas. Mature cystic teratomas are the most common ovarian tumors in the 20- to 30-year-old age group. They account for 22% to 40% of ovarian tumors in pregnancy.52The majority of these benign cystic tumors contain mature tissue from the three germ layers. The most frequently observedelementsare from the ectodermallayer and may include hair, skin, sweat glands, bone cartilage, and teeth. When only tissue from the ectodermal layer is found, the tumor is considered a true dermoid cyst. Often, the multicystic lesions contain a mixture of mature tissue. The tumor is usually slow growing. Presenting symptoms are related to its size, compression of surrounding structures, torsion, or a chemical peritonitis secondary to intraabdominal rupture. Torsion is the most frequently observedcomplication. Treatment consists of removal of the lesion.55,52,60 Mixed germ cell tumors. Malignant mixed

germ cell tumors contain at least two malignant germ cell elements.Dysgerminomais the most frequently occurring element, followed by endoderma1sinus tumor, immature teratoma, choriocarcinoma, and embryonal carcinoma.64 Prognosis is determined by the size and composition of tumor: prognosis is poor when the tumor is more than 10 cm and when more than one third of the tumor contains endodermal sinus tumor, choriocarcinoma, or grade 3 immature teratoma elements. Surgery alone or followed by radiotherapy has beenfound to be ineffective.55Chemotherapywith the VAC and MAC regimens has been used, but the BEP and VBP regimens are being evaluated in the treatmentof malignant mixed germ cell tumors of the o~ary.~* Strom& Tumors Malignant sex cord stromal tumors account for approximately 1% to 3% of all ovarian tumors.52 They include collagen-producing stromal cells, granulosacells, theta cells, sertoli cells, and Leydig cells. Most of these tumors are hormonally active and capable of producing estrogens, androgens, progestins, and certain corticosteroids (Table 6). Granulosa cell tumors occur primarily in postmenopausal women. Only 5% occur before puberty. The most common presenting symptom is a palpable abdominal or pelvic mass. Abdominal distention, pain, vague GI complaints, and acute abdominal pain secondaryto hemoperitoneum are other presenting symptoms.65Approximately 70% of women experienceabnormal uterine bleeding as a result of hormonal stimulation. Granulosa cell tumors are usually unilateral. They are generally considered low-grade malignancies, with survival rates of 75% to 90% reported for all stages.55 Treatment consists of unilateral salpingo-oophorectomy in women wishing to retain fertility, or TAH and BSO for perimenopausaland postmenopausal patients.52 Androblastoma and arrhenoblastoma are used synonymously with Sertoli-Leydig cell tumors; the cells resemble testis cells and may cause virilization. These tumors account for less than 0.5% of all ovarian neoplasms. Most Sertoli-Leydig tumors occur in women between 20 to 40 years of age. The majority of Sertoli-Leydig tumors are hormonally active (88%) and cause progressive masculinization.6G68 Sertoli-Leydig cell tumors tend

224

ERIKSSON

Table 6. Stromal TVP~

Granulosa tumors

cell

Sertoli-Leydig cell tumors

Tumors

AND WALCZAK

of the Ova#‘*aMd)-”

Description

Signs/Symptoms

Treatment

1% to 3% of all ovarian tumors; highest incidence in postmenopausal women; 5% occur before puberty; lowgrade malignancies; 75% to 90% survival

Palpable abdominal or pelvic mass; abdominal distension, GI complaints; acute abdominal pain due to hemoperitoneum; abnormal uterine bleeding due to hormonal stimulation in 70% of patients Palpable abdominal or pelvic mass; masculinization

Unilateral salpingooophorectomy; TAH and SSO for perimenopausal and postmenopausal patients

Androblastoma or arrhenoblastoma; cells resemble testes; ~0.5% of all ovarian tumors; most occur at 20 to 40 years of age; hormonally active, causing progressive masculinization; remain confined to pelvis; 70% to 90% survival

to remain confined to the pelvis and have a 5-year survival rate of 70% to 90%. Treatmentconsistsof unilateral salpingo-oophorectomyin young women desirous of childbearing.52Y66*67 NURSING MANAGEMENT OF OVARIAN CANCER PATIENTS

Nursing managementof the woman with ovarian cancer is multifaceted and focuseson supportive and rehabilitative efforts to promote optimal quality of life. The care required is dependenton the treatment and stage of disease.At time of diagnosis and staging laparotomy, the woman is faced with a life-threatening disease and potentially extensive cytoreductive surgery. Aggressive preoperative teaching and postoperative care include monitoring and promoting respiratory function; assisting in early, progressive ambulation; monitoring intake and output, electrolytes, vital signs, and GI and renal function; and providing the patient and her family with ongoing emotional support. The nurse can facilitate verbalization of fears and concerns, clarify misconceptions, and initiate planning for adjuvant therapy and the patient’s return home. Since most women with epithelial ovarian cancerare diagnosedwith stagesIII and IV disease,combination chemotherapywill be given and is often initiated during the postoperativeperiod. Often with all types of ovarian cancer, the woman and her family will not only have to adjust to the diagnosis and surgery, but also to the chemotherapy regimen and its side effects, such as nausea, vomiting, diarrhea, bone marrow depres-

Unilateral salpingooophorectomy

sion, alopecia, neurotoxicity, liver and kidney damage,regular blood counts, and treatmentsevery 3 to 4 weeks. Becauseovarian cancer can occur at any age, issuesof fertility, sexuality, femininity, and roles and relationships within the family must be assessedand the need for additional support and referrals determined. Referrals may range from the informal opportunity to talk with other cancer patients to referrals to support groups and counselors. The major goals of these interventions would be to facilitate coping with the diseaseand treatmentand to enable the woman and her family to optimize and maintain positive aspectsof life. Maintaining adequatenutrition is a major challenge in the care of the woman with ovarian cancer. Extensive abdominal surgery with prolonged postoperative bowel dysfunction and combination chemotherapy with the associatednausea, vomiting, and anorexia may necessitateenteral and parenteral supplements as well as extensive dietary counseling. If the tumor progressesor resistanceto treatment develops, maintenance of adequate nutrition becomes more difficult. The disease may cause repeatedincidents of bowel obstruction, carcinomatosis ileus, anorexia, cachexia, and ascites. Although patients may be maintained indefinitely on parenteralsupplements,the potential benefits of such therapy are questionable in the face of tumor progression.Nursing efforts must focus on providing physical and emotional comfort. Helping patients and their families to understandthe goals of nutritional intervention is important since the inability to eat is often a tremendoussource of frus-

OVARIAN CANCER

225 Table 7. Nursing Care of the Patient With Malignant As&es

Symptomfrreatment

Assessment

Abdominal

distension

Respiratory

compromise

Gastrointestinal

distress

Intervention

Bulging abdomen and flanks; everted umbilicus; shiny skin Dyspnea; shortness of breath; tachypnea; use of accessory muscles Anorexia, nausea, vomiting; dyspepsia; cachexia; bowel movements

Fluid and electrolyte imbalance

Signs and symptoms of dehydration; lymphedema of lower extremities; signs of hypokalemia, hyponatremia, hypomagnesia

Paracentesis

Puncture site for signs of infection, pain, leakage of ascites, skin breakdown; reaccumulation of ascites

Peritoneovenous

shunting

Daily abdominal girths, weights; palpate for fluid wave; percuss for sounds of shifting dullness Elevate head of bed; provide rest periods; restrict activities as tolerated; oxygen as needed; analgesia as ordered Antiemetics, antacids, laxatives as ordered; small, frequent feedings, bland diet; food supplements; diversional therapy; daily weights, caloric counts Monitor serum protein, albumin, electrolytes; albumin, electrolytes, fluid replacements as ordered; daily weights, abdominal girth; monitor input and output, vital signs; highprotein diet; minimize sodium and fluid intake; diuretics as ordered; compression stockings, boots; assist patient in maintaining mobility Teach patient and family about procedure and expected results; maintain asepsis; monitor drainage of fluid; alter patient’s position as necessary to promote fluid drainage; monitor fluid and electrolytes Teaching patient and family about surgical procedure, operating room routine, methods of maintaining patency of shunt; provide shunt care; monitor fluid, electrolytes, and coagulation profile. -

Pain; infection; bleeding; skin integrity at operative site; DIC, tumor embolus

tration. Encouraging small, frequent meals or focusing on comfort measuresother than eating may help relieve the tension that patients and families often feel. Managementof ascitesfrom ovarian cancervaries from symptom relief and treatmentof the cancer to symptomatic relief by drainage of ascites and maintaining systemicfluid and electrolyte balance. As the ascites increases, severe respiratory and gastrointestinal compromisedevelop. Associated lymphatic obstruction may causeprogressive debilitating lymphedema. Nursing care focuseson comfort measuresand symptom control for a patient in great distress (Table 7). Often critical organs such as the kidney or liver are not involved with tumor to permit a timely death. Instead, ovarian cancer progressively causeslymphatic obstruction with resultant lymphedema, anasarca,massive ascites, and pleural effusion while the woman remains mentally alert2 Nurses can provide psychological and physical comfort by assisting the patient to remain active

and independentas long as possible and by making necessaryreferrals for home and hospice care. SUMMARY

Prevention, early detection, morbidity, and survival issues continue to challenge health professionals involved in the care of women with ovarian cancer. While advancesin diagnosis, staging, and treatment have been made, survival rates remain grim. Continuing researchin the areas of screening, diagnosis, and treatment is the key to improved survival. The hope of new drug therapy, such as cisplatin-taxol regimens, intraperitoneal therapy, immunotherapy, and bone marrow transplantation, needs further investigation to become reality. As new and potentially more toxic regimensare developed, the nursemust be knowledgeable about the therapies and adverse effects, and maintain a high level of clinical expertise in order to teach the patient, reinforce information, clarify misconceptions, and provide the patient with supportive physical and emotional care.

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