Gynecologic Cancers

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As outlined in the excellent, comprehensive review by Drs. Liu and Matulonis, ovarian cancer is the most lethal gynecologic malignancy in the United States, with approximately 16,000 deaths and 22,000 new cases yearly.[1] The vast majority of patients present with intra-abdominal spread of disease at the time of diagnosis, resulting in low overall cure rates. As outlined, patients are primarily managed with primary surgical resection and subsequent platinum-based chemotherapy.

Epithelial ovarian cancer is the leading cause of death from gynecologic malignancy in the United States, with approximately 15,000 deaths per year. Platinum/taxane doublets have long been considered the standard treatment regimen for advanced-stage disease; however, recent studies have sought to improve on the outcome from this therapy. Intraperitoneal (IP) chemotherapy has been shown to yield superior progression-free survival (PFS) and overall survival (OS); however, logistical problems and toxicities have limited more widespread adoption. Recent studies have also suggested that a “dose-dense” schedule of paclitaxel in combination with carboplatin may result in improved outcomes, and the impact of biological therapies in the first-line setting is under active investigation. In the setting of recurrent disease, preliminary results suggest that novel doublet regimens such as carboplatin and pegylated liposomal doxorubicin may have similar activity to standard platinum/taxane doublets while carrying a reduced risk of allergic reactions. Additionally, targeted therapy remains an active area of investigation, with evidence of activity from agents such as PARP inhibitors, anti-angiogenics, and PI3 kinase inhibitors. Here, we review recent advances in our understanding of ovarian cancer and its treatment in both the newly diagnosed and recurrent settings.

Postmenopausal women at average risk of ovarian cancer may benefit from ROCA (Risk of Ovarian Cancer Algorithm), a new ovarian cancer screening strategy that combines information about trends in CA-125 blood test results and age, followed by transvaginal ultrasound (TVU) as needed and referral to a gynecologic oncologist. Results of a prospective multicenter trial of ROCA were reported at the 44th annual meeting of ASCO (abstract 5003). Results of ROCA testing were used to categorize women as low risk (requiring a repeat CA-125 test in 1 year); intermediate risk (repeat CA-125 test in 3 months); or high risk (TVU and referral to a gynecologic oncologist, who decides, based on clinical findings and the TVU result, whether the patient needs to undergo surgery).

Cervarix has won FDA approval for the prevention of cervical pre-cancers and cervical cancer associated with HPV-16 and HPV-18 for use in girls and young women (ages 10-25), according to GlaxoSmithKline.

The US Food and Drug Administration (FDA) has approved GlaxoSmithKline’s human papillomavirus bivalent (types 16 and 18) vaccine, recombinant (Cervarix) for the prevention of cervical precancers and cervical cancer associated with oncogenic human papillomavirus (HPV) types 16 and 18 for use in girls and young women (aged 10–25).

The Society of Gynecologic Oncologists (SGO) has published the first in a series of four papers on a variety of cervical cancer issues and topics that were the focus of its Forum “The Future Strategies for Cervical Cancer Prevention: What Do We Need to Do Now to Prepare,” held last September in Chicago.

The final analysis of the largest efficacy trial of a cervical cancer vaccine was published July 25, 2009, in The Lancet. The study, involving 18,644 women, confirmed GlaxoSmithKline’s Cervarix is highly effective at protecting against the two most common cervical cancer–causing human papillomavirus (HPV) types, 16 and 18. The study also showed that the vaccine provides cross-protection against HPV types 31, 33, and 45, the three most common cancer-causing virus types beyond 16 and 18.

Endometrial cancer is the most common gynecologic malignancy, with an estimated 40,100 cases and 7,470 deaths in 2008. This malignancy represents 6% of all cancers, and 3% of cancer deaths in women. Endometrial cancer is more prevalent in older women, with an incidence of 1 in 142 for women 40 to 59 years old, increasing to 1 in 81 women over 70 years old.[1] Median age at diagnosis is 62.[2] The mortality of endometrial cancer has decreased from 4.18 to 4.12 per 100,000 from 1991 to 2004.

Results from an 8-year trial involving more than 130,000 women published in The New England Journal of Medicine (360:1385-1394, 2009) demonstrate that in low-resource settings, a single round of human papillomavirus (HPV) testing significantly reduces the numbers of advanced cervical cancers and deaths, compared with Pap testing or visual inspection with acetic acid (VIA). This was the first randomized controlled trial to measure incidence of cervical cancer and associated rates of death as the primary outcomes, using different tools for screening.

Diffusion-weighted MRI added to standard T2-weighted scans can help spot cervical cancer in its early stages. A preliminary study from the Institute of Cancer Research in London determined that DWI can spot tumors missed by T2 imaging and bolster management options for women who wish to preserve reproductive organs.