The Key to Improving Survival in Ovarian Cancer: Better Screening of Women With Vague Symptoms, Leading to Earlier Diagnosis, More Effective Surgery

Regular pelvic examinations and the use of cervical cytology have resulted increasingly in early diagnosis and high cure rates in patients with cancers of the vulva, vagina, and cervix. Comprehensive use of human papillomavirus (HPV) vaccinations for young girls could soon make these cancers exceedingly rare. Prompt evaluation of postmenopausal bleeding will lead to the early diagnosis of most cancers of the endometrium. Only cancers of the fallopian tube and ovary remain difficult to diagnose at an early stage-which means that cure rates have remained lower as well.

Over the past two decades, there has been progressive improvement in the survival rates for patients with advanced ovarian cancer. This improved survival is due to an increased awareness that aggressive surgical resection of ovarian cancer combined with multi-drug therapy using combinations of taxol and platinum drugs offers patients the best chance for prolonged survival. Survival is directly related to the size and amount of disease remaining following the initial surgical procedure. Patients with residual disease < 2 cm have better survival than patients with larger residual masses. Patients with residual disease < 1 cm have even better survival, and the best survival is seen in patients with no visible residual disease. Several studies have shown that patients managed surgically by gynecologic oncologists are more likely to have adequate surgical removal of tumor. Finally, other studies have shown that combinations of platinum drugs and taxol given by the intraperitoneal route improved survival in patients with complete or near-complete removal of the ovarian cancer.

Patients whose ovarian cancer is diagnosed early are more likely to have all of their tumor removed surgically. Because of this, gynecologic oncologists have stressed the need for physicians who care for women to be aware of the often vague symptoms of ovarian cancer and to make liberal use of transvaginal ultrasounds and available tumor markers to improve the rate of early diagnosis.

For many years, serum cancer antigen 125 (CA-125) was the only available serum marker, and unfortunately this marker was not elevated in up to 50% of stage I ovarian cancers. The review by Simmons and colleagues in this issue of ONCOLOGY describes another serum marker for ovarian cancer. This marker, human epididymis protein 4 (HE4), when combined with CA-125, may result in improved early diagnosis. HE4 appears to complement CA-125 by being more often elevated in early ovarian cancer.

Continued improvement in the survival of patients with ovarian cancer requires that physicians who care for women have a high index of suspicion, make liberal use of transvaginal ultrasound, and order tumor marker assays that may aid in early diagnosis. The review by Simmons and colleagues shows that the combination of CA-125 and HE4 will improve the chances that early ovarian cancers will be identified and that patients will be referred in a timely manner to a gynecologic oncologist for surgical evaluation and treatment. Clearly, the combination of earlier diagnosis and adequate surgical intervention will result in continued improvement in survival.

Although the combination of CA-125 and HE4 appears indicated for use in symptomatic patients or in patients with an adnexal mass, there is no evidence that it would be indicated as a screening test in asymptomatic patients. The exception to this might be patients with BRCA1 or BRCA2 mutations, in whom the use of these two markers as a screening test may make sense. A prospective trial in these patients would be warranted.