2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

International Perspective on the Global
Advances in Gynecologic Oncology
Overview: The treatment of gynecologic cancer has evolved
over the years, with greater emphasis on tailored surgery and
reducing morbidity and mortality related to surgery, particularly
in the management of vulvar and cervical cancer. The
addition of concurrent chemotherapy to radiation regimens
has improved survival of patients with cervical cancer in
developed countries; however, most women with cancer in
developing countries have advanced, untreatable disease and
minimal access to anticancer therapies. In the past 15 years
there has been intense research into alternatives to cervical
GYNECOLOGIC ONCOLOGY includes a spectrum of
cancer that affects the vulva, vagina, cervix, uterus,
tubes, ovaries, peritoneum, and, in some European countries,
breast. Cancers of the lower genital tract, most of
which are etiologically associated with infection with highrisk
types of human papillomavirus (HPV), are more commonly
found in developing compared with developed
countries. The inverse is true for cancers of the upper genital
tract. Over the years, substantial advances have been made
in the management of gynecological cancers. This article
explores those advances.
Vulvar Cancer
Vulvar cancer is the fourth most common gynecologic
cancer, accounting for 4% to 5% of all malignant tumors of
the female genital tract. Age standardized incidence rates
(ASIRs) vary from 0.1 per 100,000 population (Algeria) to
1.6 to 1.7 per 100,000 population (Zimbabwe and United
Kingdom, respectively). 1 Vulvar cancer is usually diagnosed
in older women (mean age, 65 to 70 years), who often
have lichen sclerosus et atrophicus or differentiated vulvar
intraepithelial neoplasm, which is not related to HPV.
Increasingly, however, vulvar cancer is diagnosed in
younger women, which relates to persistent infection with
HPV and infection with HIV. Toki and colleagues 2 found
the mean age of patients with HPV-related vulvar cancer to
be 55 years, whereas that of patients with non–HPVassociated
vulvar cancer was 77 years. Eva and colleagues 3
found that 85.7% of 70 women who were diagnosed as
having differentiated vulvar intraepithelial neoplasm had
concurrent, previous, or subsequent vulvar squamous cell
carcinoma. However, only 25% of women with HPV-related
undifferentiated vulvar intraepithelial neoplasm and 33%
of women with lichen sclerosus et atrophicus and squamous
cell hyperplasia had a history of developing invasive vulvar
cancer.
Treatment of vulvar cancer is primarily surgical. Up to the
late 1980s the most common procedure was a radical vulvectomy
with en bloc resection of bilateral groin node lymphadenectomy—the
so-called butterfly incision pioneered by
Antoine Basset in 1912. In the 1940s, Frederick Taussig
adapted the Basset operation by performing separate groin
incisions, which resulted in improved survival rates, albeit
with very high operative morbidity and mortality rates. The
triple incision technique was introduced, and although no
randomized controlled trials have compared this technique
330
By Lynette Denny, MD, PhD
cytologic testing, particularly in low resourced regions but
also in an attempt to improve on cytologic testing in developed
countries. Surgical staging in endometrial cancer has
enabled the use of adjuvant radiation to be individualized to
the patient’s particular risk factors for recurrence. The management
of ovarian cancer, long stagnant since the introduction
of platinum and paclitaxel as chemotherapeutic agents, is
set to change with the onset of molecular and genetic profiling
and the introduction of novel therapies.
with the butterfly incision, retrospective studies found no
inferior outcomes and a low risk of bridge recurrence
(2.4%). 4,5 Compared with en bloc resection, rates of associated
morbidity, such as wound breakdown and lymph drainage
problems, were substantially lower with the triple
incision technique. 6 However, this technique still involved
removal of external genitalia.
The introduction of radical wide local incision further
reduced operative morbidity, and this approach, which often
allowed preservation of anatomy, was not shown to be
inferior in terms of oncologic safety. Current guidelines
suggest that 1 cm of disease-free tissue around the invasive
lesion represents a safe margin; however, hard data on the
value of disease-free margins are lacking, and some recent
publications suggest that margins are irrelevant if the
entire lesion is excised. 7 Radical wide local excision has
enabled a reasonably accurate definition of lateral compared
with central lesions. Central lesion refers to the ability to
remove the invasive lesion with 1 cm of disease-free tissue
without damaging or removing central structures (e.g., clitoris,
urethra, and anus). Lateral lesion allows 1 cm of
disease-free tissue without compromising central structures.
To preserve the central structures, it is possible to
perform primary chemoradiation and to only perform surgery
for residual disease. Moore et al treated 58 women with
T3 or T4 tumors not amenable to surgical resection with
radiation (1.8Gy daily � 32 fractions) plus weekly cisplatinum
(40mg/m 2 ), followed by surgical resection of residual
tumor or biopsy to confirm pathological complete response.
Forty of the 58 women completed treatment and 37/58 (64%)
women had a complete clinical response. Of these women,
34 underwent biopsy and 29 (78%) of these women had a
complete pathological response. 8 Rogers et al reported on a
retrospective study of 50 women treated with chemoradiation
for advanced vulvar cancer in Cape Town from 1982 to
2001. Only 14 (28%) of the women had a complete response,
29 (58%) had a partial response. Of the women who under-
From the Department of Obstetrics & Gynaecology, University of Cape Town/Groote
Schuur Hospital, Cape Town, South Africa.
Author’s disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Lynette Denny, MD, PhD, Department of Obstetrics &
Gynaecology, University of Cape Town/Groote Schuur Hospital, H45, Old Main Building,
Groote Schuur Hospital, Observatory 7925, Cape Town, South Africa; email: lynette.
denny@uct.ac.za.
© 2012 by American Society of Clinical Oncology.
1092-9118/10/1-10