Gynecologic Malignancies in Older Women

The aging population poses newchallenges to all fields of medicine and to gynecologic oncology in particular. In gynecologic oncology, issuesthat are germane to general medicine, cancer chemotherapy, radical surgery, androutine gynecology are all encountered on a regular basis. In clinical practice,the "very old" are often thought to tolerate standard treatmentspoorly. While comorbid conditions may be more prevalent, management decisionsshould be based on an assessment of individual function and not solely onnumerical age. In the article by Mirhashemi and colleagues, this theme isconveyed throughout, as they describe the current management of gynecologicmalignancies in older women.

Screening forCervical Cancer

The authors begin with an accurate summary of the agingpopulation in the United States and other developed countries, and they discussthe screening mechanisms currently available for the early detection ofgynecologic malignancies. They appropriately emphasize the fact that cervicalcancer is not only a disease of young, sexually active women and that continuedroutine screening of older patients is warranted. In these patients, cervicalscreening is actually more difficult due to decreased levels of circulatingestrogens, which may lead to vaginal atrophy and cervical stenosis.

Testing for the human papillomavirus (HPV) is becoming widelyavailable and may identify early lesions at increased risk for progression tosevere dysplasia. However, the usefulness of HPV screening for early detectionof invasive carcinoma has yet to be demonstrated. To date, there are no data tosuggest that HPV testing will either decrease the incidence of invasive cervicalcarcinoma or alter the natural course of dysplasia. Results from large-scalestudies currently in progress may elucidate the properrole of HPV testing. The elderly may benefit from HPV testing in the presence ofmild dysplasia. The triage of the abnormal Papanicolaou (Pap) smear may beimproved, and the number of required invasive procedures may be minimized.

Screening for OtherGynecologic Malignancies

In sharp contrast to cervical cancer, there are few practicalscreening tests for ovarian or endometrial cancers. Although measurement ofCA-125 levels by transvaginal sonography is often undertaken, there are noclinical trials to show that this is an efficacious method for detecting early-stage ovarian cancer. Ovarian cancerscreening should be limited to clinical trials from which pooled data will leadto meaningful analyses and abnormal results can be appropriately interpreted.There is also no recommended or efficacious screening test for endometrialcancer, even for patients receiving tamoxifen (Nolvadex) therapy. Given the lackof such a test, any postmenopausal bleeding should be thoroughly evaluated withan adequate office biopsy or diagnostic hysteroscopy.

One area that requires further discussion involves the changesin mental status that occur in the elderly. Among patients over 70 years of age,10% have clinically identifiable memory loss. Dementia isan independent risk factor for poor surgical outcome in hip fracture patientsand may also contribute to poor outcomes in cancer surgery.[1]A mental status evaluation shouldbe part of the routine assessmentof older patients with a gynecologic malignancy.

Management of Cervical and Advanced Ovarian Cancer

The authors correctly state that advances in anesthesia andpostoperative care now make it possible to safely perform radical surgery in theelderly. The standard management of advanced ovarian cancer is described;however, neoadjuvant chemotherapy administered prior to debulking surgery forselect patients is not discussed.

Trials are currently in progress to study the use of neoadjuvantchemotherapy in advanced ovarian cancer, and those with multiple comorbidconditions may achieve significant benefit. Additionally, consolidation withintraperitoneal therapy has been associated with long-term survival when givento patients with no clinical evidence of disease after primary treatment. Trialsare also in progress to better define the role of intraperitoneal therapy in themanagement of ovarian cancer.

New data suggest that whole pelvic irradiation given as adjuvanttherapy for endometrial cancer can be avoided in patients with stage I tumorswho have undergone complete negative lymphadenectomy.[2] This can diminish therisk of bowel and bladder complications and should be a consideration in olderpatients.

Cervical cancer has been treated effectively with surgery orradiation therapy for many decades, as mentioned in the article. Recent reportsnow suggest that a combined approach with chemotherapy and radiation therapy forstage IB2 and greater lesions will result in improved outcomes.[3] This shouldbe a primary consideration in the treatment of old and young patients alike.

Elderly Patients in Clinical Trials

As in all fields of oncology, treatment regimens for gynecologicmalignancies should stem from the results of randomized clinical trials.Unfortunately, the elderly are underrepresented in these studies, as has beenrecently described.[4] Almost one-half of ovarian cancer patients are 65 yearsof age or older, yet only 30% of patients in ovarian cancer clinical trials arein this age group (P < .001). Overall, 63% of cancer patients are age 65 orolder, yet they comprise only 25% of participants in cancer-treatment trials.

The ability of older patients to tolerate experimental therapiesis more likely to be related to underlying medical conditions than toage-related physiologic changes. No age limitation exists for entry intoNational Cancer Institute-sponsored clinical trials, and the participation ofolder patients should be encouraged, unless medically contraindicated. Advancedage is an independent prognostic factor for endometrial and ovarian cancer, butalso a surrogate for advanced stage at diagnosis and high-risk histologicsubtype.[5-7] Because age is both a poor prognostic factor and associated withunfavorable tumors, older patients should be treated aggressively.

Conclusions

This review by Mirhashemi et al calls attention to the oftenoverlooked issue of gynecologic malignancies in the elderly. The authors providea brief but complete overview of the changing demographics in the United Statesand how these trends will affect medical care in the coming decades. They haveattempted to summarize a large body of literature in just a few pages.

It is important to emphasize that the treatment of older womenwith gynecologic malignancies should follow community standards and should onlybe modified as necessary for comorbid illnesses, not because of the numericalage of the patient. We applaud the authors’ efforts in drawing attention tothe important issues surrounding the treatment of gynecologic malignancies inthe elderly.

References:

1. Holmes J, House A: Psychiatric illness predicts poor outcomeafter surgery for hip fracture: A prospective cohort study. Psychol Med30:921-929, 2000.

2. Anderson JM, Stea B, Hallum AV, et al: High-dose ratepostoperative vaginal cuff irradiation alone for stage IB and IC endometrialcancer. Int J Radiat Oncol Biol Phys 46:417-425, 2000.

3. National Cancer Institute: Concurrent chemoradiation forcervical cancer. Clinical Announcement, February 1999.

4. Hutchins LF, Unger JM, Crowley JJ, et al: Underrepresentationof patients 65 years of age or older in cancer-treatment trials. N Engl J Med341:2061-2067, 1999.

5. Cirisano FD, Robboy SJ, Dodge RK, et al: The outcome of stageI-II clinically and surgically staged papillary serous and clear cellendometrial cancers when compared with endometrioid carcinoma. Gynecol Oncol77:55-65, 2000.

6. Behbakht K, Yordan EL, Casey C, et al: Prognostic indicatorsof survival in advanced endometrial cancer. Gynecol Oncol 55:363-367, 1994.

7. Markman M, Lewis JL, Saigo P, et al: Impact of age onsurvival of patients with ovarian cancer. Gynecol Oncol 49:236-239, 1993.