Treatment Modalities for Gynecological Cancers

Catherine Robertson

T HE American Cancer Society estimates 73,400 new cases of cancer of the female

genital tract in 1986.’ Endometrial cancers com- prise about 13% of all malignant tumors in women: uterine cervix, 6%; ovarian tumors, 6%: and other gynecologic malignancies, 2% to 3%.* This paper will discuss the major treatment modal- ities (surgery, radiation, and chemotherapy) for gynecologic malignancies involving the endome- trium, cervix, ovary/fallopian tube, vulva, and va- gina.

TREATMENT FOR CANCER OF THE CORPUS UTERI

Endometrial cancer is the most common malig- nant tumor of the female genital tract. Staging should be done jointly by the gynecologist and ra- diation oncologist. The history, physical, biman- ual pelvic and rectal examination (preferably under general anesthesia), and a fractional dilata- tion and curretage are the primary procedures for diagnosing and evaluating endometrial cancer.* The staging system most commonly used is the one proposed by the International Federation of Gynecology and Obstetrics (FIGO) (Table 1). In addition, endometrial carcinoma is classified by the degree of tumor differentiation: grade I, well- differentiated; grade II, moderately differentiated; and grade 111, poorly differentiated. The majority of patients will have stage I disease and over 90% of the tumors are adenocarcinomas.

Surges and Radiation Therapy

Surgery is the primary treatment for endome- trial cancer. The treatment for stage I adenocarci- nomas is a total abdominal hysterectomy and bilateral salpingo-oophorectomy. However, con- troversy exists regarding the role of radiation ther- apy in the treatment of endometrial cancers. The dispute centers around whether radiation should be given preoperatively or postoperatively.

Advantages of preoperative irradiation include ( 1) inoperable lesions may be converted to opera- ble ones, (2) extent of surgical resection may be decreased, (3) well-oxygenated tumor tissue is ir- radiated, and (4) the incidence of distant metasta- sis may be decreased since radiation is given prior to surgical manipulation. Advantages of postoper-

ative irradiation are (1) a higher dose may be given without the risk of surgical morbidity. (2) there is more accurate staging at the time of hur- gery, (3) healing is better in nonirradiated tissues, and (4) evaluation of surgical specimen may show that radiation therapy is not indicated.‘,’

The current preference at the University of Texas M.D. Anderson Hospital is to use preopera- tive radiation therapy followed by a total abdomi- nal hysterectomy and salpingo-oophorectomy. Pa- tients with small well-differentiated tumor> are treated with hysterectomy alone. Patients with stage IA and stage IB, grade 1 and grade 11 carci- nomas will receive one 72-hour intracavitary radi- um followed by a hysterectomy and bilateral sal- pingo-oophorectomy. The current procedure is to admit a patient on Monday and insert the radium on Tuesday, remove it on Friday, allow the patient to ambulate for two days, and then do the surgical procedure the first part of the following NJeek. Pa- tients with stage I1 disease may receive an addi- tional 4,000 rads of whole pelvis irradiation to cause tumor shrinkage and thereby provide more uniform radium insertion. Six weeks later the pa- tient will undergo a hysterectomy. Patients with stage 111 and stage IV disease are uncommon and treated with a variety of modalities, such as radia- tion, surgery, chemotherapy, or hormonal t hera- p~.~ The treatment plan is tailored to each patient based on the volume and extent of disease, age, and medical condition of the patient. Radiotherapy is often considered the primary mode of therapy in these patients since extensive tumors are techni- cally inoperable.2

Hormonal Them-p?

Response to hormonal therapy is dependent upon the grade of tumor and the presence or ab- sence of estrogen and progesterone receptors. Pro- gestins usually cause no serious side effects and

-. --___ From the Division @‘Nursing. Untcersit~ ofTuu\ MD. An-

derson Hospital and Tumor Institute at Houston.

Address reprint requests to Cafherine Robertsorz. RN, MS. CS, DiGsion of Nursing. Box 82, Universiry cf Texa.\ M.D.

Anderson Hospital. 6723 Bertner AL’<, Hou.sron. Tk’ 77030. 0 1986 by Crune & Stratton, Inc.

0749-208118610204-n009$05.00/0

Semmars m Oncology Nursing, Vol 2, No 4 (November), 1986: pp 275-280 275

276 CATHERINE ROBERTSON

Table 1. FIG0 Staging System for Cancer of the Corpus Uteri

Stage 0

Stage I

Stage IA

Stage IB

Stage II

Stage III

Stage IV

Stage IVA

Stage IVB

Carcinoma in situ

Carcinoma confined to corpus

Cases are subgrouped with regard to histologic type

Grade 1, highly differentiated adenomatous carcinoma

Grade 2, moderately differentiated adenomatous carcinoma

Grade 3, undifferentiated carcinoma

Length of uterine cavity is 8 cm or less

Length of uterine cavity is more than 8 cm

Carcinoma involves corpus and cervix

Carcinoma has extended outside uterus but not outside true pelvis

Carcinoma has extended outside true pelvis or has involved mucosa of bladder or rectum

Spread to adjacent organs

Spread to distant organs

are generally recommended over chemotherapy for patients with recurrent disease. The use of an antiestrogen, tamoxifen, with or without proges- tins, is currently being investigated.5

Chemotherapy

Because progestins have proved beneficial and are free of adverse effects, the use of cytotoxic drugs with endometrial cancer has been limited. Doxorubicin was the first drug to be systematical- ly used in treating endometrial cancer. Drugs used in combination may be more effective and are cur- rently under investigation. One such combination includes cyclophosphamide, doxorubicin, and cis- platin. Generally, cytotoxic chemotherapy is re- served for patients who have failed hormonal ther- aw6

TREATMENT FOR CANCER OF THE CERVIX UTERI

Cancer of the uterine cervix is one of the most common malignant tumors in women after breast,

colorectal, endometrial, and ovarian cancer. The gynecologist and radiation oncologist should jointly perform the evaluation and staging of the patient with carcinoma of the cervix. The FIG0 classification system (Table 2) should be based on clinical evaluation, cytology, colposcopy, endo- cervical curretage and biopsies, and radiographic studies.

Carcinoma in Situ

Carcinoma in situ is treated by removal of the affected area. This removal can be accomplished by a variety of techniques, including cryosurgery, electrocautery, laser treatments, conization, and hysterectomy.

Conization is the conical removal of a large portion of the exocervix and endocervix. Coniza- tion is considered conservative management for women who desire to have more children.7

Hysterectomy is the treatment of choice for pa- tients who do not desire fertility. The decision to

Table 2. FIG0 Staging System for Cancer of the Cervix Uteri

Stage 0

Stage I

Stage IA

Stage IB

Stage II

Stage IIA Stage IIB

Stage Ill

Carcinoma in situ

Carcinoma confined to cervix

Microinvasive

Invasive Carcinoma involves vagina but not lower third of vagina

No obvious parametrial involvement Obvious parametrial involvement Carcinoma has extended to pelvic wall; tumor involves lower third of vagina; all cases with hydronephrosis

or nonfunctioning kidney

Stage IIIA No extension to pelvic wall

Stage IIIB Extension to pelvic wall or hydronephrosis or nonfunctioning kidney

Stage IV Carcinoma has extended beyond true pelvis or has clinically involved mucosa of bladder or rectum

Stage WA Spread to adjacent organs

Stage IVB Spread to distant organs

GYNECOLOGICAL CANCERS: TREATMENT 277

remove the ovaries will depend on the age of the patient and the status of the ovaries.

Cryosurgery, electrocautery , and laser treat- ments are also being used to treat carcinoma in situ. These techniques require special skills and close follow-up to assure that the entire lesion has been destroyed. However, cryotherapy and laser therapy are frequently used to treat cervical dys- plasias.5

Stage IA

Early carcinoma of the cervix can be treated with a hysterectomy or intracavitary radiation. However, whether to do a simple or radical hys- terectomy with pelvic lymphadenectomy is an area of controversy. When the depth of tumor invasion is 3 mm or less, a lymph node dissection or pelvic irradiation is not required since the incidence of lymph node metastasis is 1% or less.2 A Wert- heim’s radical hysterectomy with pelvic lymph- adenectomy may be required with more extensive lesions. A variety of operations may be termed radical hysterectomy or Wertheim’s hysterectomy. The extent of the dissection away from the cervix identifies the extent of radical surgery.

At the University of Texas M.D. Anderson Hospital, a classification system for radical hys- terectomies is utilized. Type I, extrafacial hyster- ectomy or modified radical hysterectomy, in- volves the complete removal of the cervix and 1 to 2 cm of vaginal cuff. Type II radical hysterectomy preserves the blood supply to the lower ureter and vagina; two thirds of the parametrium and the upper third of the vagina are removed. Type III radical hysterectomy removes the parametrium, the uterosacral ligament, and approximately half of the vagina. The incidence of bladder atony is increased because of the complete resection of the utereosacral ligaments and rectal pillars.8 Current- ly, there is a trend for the surgeon to be less radi- cal in performing these procedures. For example, 2 to 3 cm of the vagina may be removed instead of half of the vagina with the type III radical hyster- ectomy .

Stage IB and 1IA

A type III radical hysterectomy and pelvic lymphadenectomy or radiation therapy are equally effective in treating stage IB and stage IIA carci- noma of the cervix. The radical hysterectomy has been preferred by some physicians because it pre-

serves ovarian function.4 On the other hand, radia- tion therapy avoids major surgery and possible postoperative complications such as hemorrhage and bowel obstruction.2 The choice of treatment depends upon the gynecologist and radiation ther- apist, the size of the lesion, status of lymph nodes, age and medical condition of the patient, and the patient’s preference.

Stages IIB, 111, and IVA

Patients with stages IIB, III, and IVA cervical cancer are treated with irradiation alone. External irradiation and intracavitary radium therapy are used in various combinations. Patients with stage IVA disease can be treated with either irradiation or pelvic exenteration. The treatment plan is tai- lored to each patient based on the extent of dis- ease.

Chemotherapy

The management of recurrent cervical cancer has not significantly improved despite the progress of modern chemotherapy. Many of these women have received prior pelvic irradiation, and this may be one factor contributing to a low respon- siveness. Previous radiation may result in de- creased tumor vascularity, leading to decreased drug absorption in the tumor. The amount of drug that can be given will be compromised by the in- creased myelosuppression associated with prior ra- diation.9 Another factor is that approximately 95% of cervical cancers are squamous cell, and squa- mous cell cancers are less responsive to most chemotherapeutic agents. Furthermore. many drugs are nephrotoxic or have limited usefulness because of the ureteral obstruction associated with advanced cervical cancers.lO However. single agents (eg. cisplatin) as well as combinations of drugs have been used with some success. Intra-ar- terial infusions of chemotherapeutic agents have had limited success. No evidence exists that cervi- cal cancers are sensitive to hormonal manipula- tion.”

Recurrent Disease

Once treatment by radiation therapy has failed, further radiation is rarely useful. Selected patients may be candidates for pelvic exenteration. How- ever, exenteration should only be used in the pa- tient whose tumor is resectable. Chemotherapy is not successful with recurrent disease.

27% CATHERINE ROBERTSON

TREATMENT FOR CANCER OF THE OVARY AND FALLOPIAN TUBE

Ovarian cancer is the fifth most frequent cause of cancer death in women and is the leading cause of gynecologic cancer death in the United States. i* Treatment of ovarian cancer involves surgery plus either chemotherapy or radiation therapy. The ini- tial surgery for ovarian cancer determines the stage of the disease and future therapy. Staging is based on the FIG0 nomenclature (Table 3).

with a residual tumor less than 2 cm in diameter have a better prognosis than those with residual disease greater than 2 cm. I3

Chemotherapy

Primary cancer of the fallopian tube is the least frequent of all gynecologic tumors, comprising between 0.5% and 1.1% of all gynecologic malig- nancies.* The staging system for fallopian tube cancer has been modified from the ovarian cancer staging system (Table 4). Often treatment of fallo- pian tube cancer is similar to treatment of ovarian cancer and will be included here with the discus- sion of ovarian cancer management.

Surgery

Approximately two thirds of the women with ovarian cancer have stage III, and IV disease that is not surgically curable. i4 Thus, following tumor- reductive surgery, patients with epithelial ovarian tumors usually receive chemotherapy. Chemother- apy treatment of ovarian cancer has evolved from single agent therapy to the use of aggressive com- bination chemotherapy regimens. The overall re- sponse rate to combination chemotherapy is be- tween 60% and 90% with a complete response rate of 40% to 60%. l4 A drug combination that is commonly used is cisplatin, cyclophosphamide, and doxorubicin. Patients usually receive about six to twelve courses of this drug regimen. The clinical value of intraperitoneal chemotherapy re- mains under investigation.

A patient suspected of having ovarian or fallo- pian tube cancer should be operated on as soon as the diagnostic workup is complete. Ovarian cancer commonly spreads by peritoneal seeding and im- plantation. Common sites of metastasis are the peritoneum, omentum, and bowel surfaces, al- though spread to other pelvic organs does occur.

Second-Look Surgery

To assess the extent of disease, the surgeon vi- sually and by palpation explores the abdomen and pelvis. Cytology and biopsy specimens are also used to determine the stage of disease.

A total abdominal hysterectomy and bilateral salpingo-oophorectomy with tumor debulking is generally the treatment of choice. The smaller the volume of tumor remaining, the better the re- sponse to adjuvant therapy. Generally, patients

Second-look surgery is a technique used to de- termine the response of disease to chemotherapy and whether therapy should be continued. If there is no evidence of disease either macroscopically or microscopically, the chemotherapy is stopped and the patient is monitored for recurrent disease. If the tumor volume has decreased, chemotherapy with the same agents may be continued. If there is evidence of progressive disease, the chemothera- peutic agents will be changed.15

Radiation Therapy

External radiation therapy is effective as an ad- juvant therapy following a tumor debulking proce-

Table 3. FIG0 Staging System for Cancer of the Ovary

Stage I

Stage IA

Stage IB

Stage IC

Stage II Stage IIA

Stage IIB

Stage IIC Stage III

Growth limited to ovaries

Growth limited to one ovary; no ascites*

Growth limited to both ovaries; no ascites

Tumor either stage IA or IB, but with ascites present or 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, including peritoneum and uterus

Tumor either stage IIA or 118, but with ascites present or positive peritoneal washings Growth involving one or both ovaries with intraperitoneal metastases outside the pelvis, positive

retroperitoneal nodes, or both; tumor limited to true pelvis with extension to small bowel or omentum

Stage IV Distant metastases

l Ascites is peritoneal effusion that, in the opinion of the gynecologist, is pathological, or exceeds normal amounts, or both.

GYNECOLOGICAL CANCERS: TREATMENT 279

Table 4. Staging System for Cancer of the Fallopian Tube

Stage 0

Stage I

Stage II

Stage III

Stage IV

Carcinoma in situ

Tumor extending into submucosa or

muscu\aris, but not penetrating to

serosal surface of fallopian tube

Tumor extending to serosa of fallopian tube

Direct extension of tumor to ovary or

endometrium

Extension of tumor beyond reproductive

organs

Data from Beecham J et al.5

dure that leaves residual tumor nodules no larger than I .5 to 2.0 cm. Shielding of kidneys and liver is indicated to preserve organ function. The dose of radiation varies from institution to institution but is usually 2,000 to 3,000 rads to the abdomen and 4,500 to 5,000 rads to the pelvis over 6 to 8 weeks. l1 Potential complications associated with radiation therapy include radiation enteritis, mye- losuppression, and nausea.

TREATMENT FOR CANCER OF THE VULVA

Malignant carcinoma of the vulva comprises ap- proximately 37~ to 4% of all female genital malig- nancies.’ The FIG0 nomenclature for staging is similar to that for other gynecologic sites (Table 5). Surgery is the primary treatment for cancer of the vulva, and the extent of the procedure depends on the disease stage. The majority of vulvar cancers are squamous.

Stuge 0

Recent studies suggest that the risk of progres- sion of carcinoma in situ to invasive disease is low. Hence, treatment for carcinoma in situ may be individualized with an attempt to preserve vul- var anatomy. Usually, a local excision or partial

Table 5. FIG0 Staging System for Cancer of the Vulva

Stage 0

Stage I

Stage II

Stage Ill

Stage IV

Carcinoma in situ

Tumor confined to vulva; 2 cm or less in

largest diameter

Tumor confined to vulva; greater than 2

cm in diameter Tumor of any size with adjacent spread to

urethra, vagina, perineum, or anus;

palpable movable nodes in either or both

groins: or both

Tumor of any size infiltrating bladder or rectal mucosa; or fixed to bone, or other

distant metastases; or both

vulvectomy, excising the upper 3 to 5 mm of tis- sue is necessary. Topical 5-fluorouracil cream for a two- to three-month period or laser surgery have also been used.

Stage I

The standard treatment for stage I cancer of the vulva is radical vulvectomy with dissection of the groin nodes. However, treatment is being evaluat- ed in an attempt to minimize the extent of radical surgery. Rutledge l6 described the concept of su- perficial invasive vulvar lesions. These lesions are 2 cm or less in diameter, with stromal invasion of 5 mm. In 1974, Wharton et alI7 reported that le- sions of this type may be treated with vulvectomy without lymph node dissection. Many institutions are using less radical procedures such as wide local excisions to treat stage I vulvar lesions. However, the definition of microinvasive or su- perficial invasive carcinoma of the vulva remains controversial, and treatment varies from institution to institution.

Stnge II and 111

The radical vulvectomy, which consists of en bloc removal of the entire vulva from the perineal body to the upper margins of the mons pubis and a bilateral inguinal lymphadenectomy, are the stan- dard surgical treatments for invasive carcinoma of the vulva. In addition, a vaginal resection may be required, and if there is urethral involvement, the distal third of the urethra may need to be excised. The urethral meatus is usually left intact.h

Stage IV

Tumors that involve the bladder or rectal muco- sa are treated with a radical vulvectomy and pelvic exenteration. However. patients with metastasis or unresectable disease are treated palliatively for symptomatic control.

Radiation Therapy

Radiation therapy has played a minor role in the treatment of vulvar carcinomas because the cure rates from surgery alone are high and there have been problems with vulvar skin tolerance to radia- tion. However, with present methods of radiation therapy producing minimal adverse effects, radia- tion may offer an acceptable alternative to sur- gery. It may also have a palliative role in ad- vanced disease.

280 CATHERINE ROBERTSON

Chemotherapy Table 6. FIG0 Staging System for Cancer of the Vagina

Results from chemotherapy other than topical 5-fluorouracil have been disappointing, with no treatment regimens yielding a good response rate.

TREATMENT FOR CANCER OF THE VAGINA

Stage 0

Stage I

Stage IA

Stage I6

Stage IC

Carcinoma in situ

Limited to vaginal wall

Less than 2 cm in diameter

Greater than 2 cm in diameter

Involves entire vaginal wall in longitudinal

axis Cancer of the vagina is a rare disease, compris-

ing less than 2% of all gynecologic malignancies.* Approximately 90% of vaginal cancers are squa- mous cell carcinomas and 5% are clear cell adeno- carcinomas. The clinical diagnosis of carcinoma of the vagina is best made by careful speculum examination and palpation of the vagina. Cytology is helpful in detecting squamous cell carcinoma but not with clear cell adenocarcinoma.2 The stag- ing is done jointly by the gynecologist and radia- tion oncologist with multiple biopsies of the va- gina. Table 6 outlines the FIG0 staging system.

Stage II

Stage Ill

Stage IV

Involves paravaginal tissue

Extends to and fixed to pelvic wall

Extends beyond true pelvis or involves

mucosa or bladder or rectum

Stage IVA

Stage IVB

Spread to adjacent organs

Spread to distant organs

Radiation therapy is the preferred treatment for most carcinomas of the vagina. Early lesions can be effectively treated with intravaginal and inter- stitial therapy. With more advanced lesions, whole pelvis irradiation is added.5 Although a sur- gical approach is advocated by some authors, operations should be discouraged because of the

excellent tumor control with adequate radiation therapy.* The exception is stage I clear cell carci- noma of the vagina, which may be treated with either surgery or radiation therapy. Surgery in- volves a total vaginectomy or partial vaginectomy with split-thickness skin graft for vaginal recon- struction and preservation of ovarian and sexual function. Recurrence can effectively be treated with surgery including wide local excision, partial or total vaginectomy, or pelvic exenteration.* Sys- temic chemotherapy is not effective in the treat- ment of vaginal carcinoma.

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3. Barber H: Manual of Gynecologic Oncology. Philadel- phia, Lippincott , 1980

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1 I. Griffiths M, Murray K, Russo P: Oncology Nursing: Pathophysiology, Assessment, and Intervention. New York, MacMillan, 1984

12. Young R, Knapp R, Fuks Z, et al: Cancer of the ovary, in DeVita VT, Hellman S. Rosenberg SA (eds): Cancer: Princi- ples and Practice of Oncology (ed 2). Philadelphia, Lippincott, 1985, pp 1083-l 109

13. Robertson C, Moreland B: Overview of ovarian cancer. Dimens Oncol Nurs l:ll-13, 1985

14. 0~01s RF, Young RC: Chemotherapy of ovarian cancer. Semin Oncol 11:251-263, 1984

15. Barber H: Ovarian cancer: Diagnosis and surgical man- agement, in Forastiere A (ed): Gynecologic Cancer. New York, Churchill Livingstone, 1984, pp 119- 138

16. Rutledge FN: Prognostic factors in epidermoid cancer of the vulva. Obstet Gynecol 37:892-901, 1971

17. Wharton JT, Gallagher S. Rutledge FN: Microinvasive cancer of the vulva. Am J Obstet Gynecol 118:159-162, 1974