2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

GLOBAL ADVANCES IN GYNECOLOGIC ONCOLOGY
went post radiation surgery (7 patients), survival was significantly
better. 9
Systematic inguinofemoral lymphadenectomy comprises
resection of superficial inguinal lymph nodes and deep
femoral nodes. Although current guidelines recommend at
least 6 nodes per groin be removed, systematic lymphadenectomy
is associated with substantial morbidity, such as
leg edema, lymphocysts, wound breakdown, and erysipelas.
To avoid these complications, the use of sentinel node
dissection in vulvar cancer has been investigated. Sentinel
nodes were studied in a large, prospective, multicenter study
(Groningen International Study on Sentinel nodes in Vulvar
cancer [GROINSS-V]), which included 403 women with
unifocal vulvar cancer stage I or II, tumor size less than
4 cm, stromal invasion greater than 1 mm, and clinically
negative lymph nodes. 10 Lymphadenectomy was not performed
in women with sentinel node–negative cancer. Groin
recurrences occurred in 2.3% of patients, with a median
follow-up of 35 months. Overall disease-specific survival was
97% after 3 years, and morbidity was substantially reduced.
These results are equivalent to results of systematic inguinofemoral
lymphadenectomy from an oncologic point of
view.
Vaginal Cancer
Primary cancer of the vagina is rare and accounts for
approximately 2% of all cancers of the female genital tract.
Most women are older than 60 years, and only 10% to 15%
are younger than 50 years. The most common type of vaginal
cancer is squamous carcinoma (80% to 90%) and adenocarcinoma
(4% to 10%). Infection with HPV-16 is believed to be
an important etiologic factor. Prognosis is dependent on age,
histologic type, and tumor stage. The optimal treatment is
still controversial because of the rarity of the disease and
lack of appropriate clinical trials. Standard therapy is radiation,
either alone or concurrently with platinum-based
chemotherapy. The advantage of radiation is the preservation
of the vagina, although the vagina does not always
remain fully functional.
KEY POINTS
● The modern management of vulvar cancer is to distinguish
between central and lateral lesions and to
adapt surgery and radiation to reduce morbidity and
enhance quality of life.
● Management of cervical cancer has not changed substantially
in the past 10 to 20 years; however, approaches
to cervical cancer prevention have
undergone a re-evaluation at both the primary and
secondary prevention levels.
● The surgical staging of endometrial cancers has enabled
the use of adjuvant therapies to be tailored to
the individual patient.
● Current novel therapies undergoing trials bring hope
to the long stagnant progress in the management of
ovarian cancer.
● Quality of life in the treatment of patients with
gynecological malignant tumors should inform all
treatment decisions.
Cervical Cancer
The most noteworthy advances in cervical cancer in the
past 15 years have been the exploration of alternative
approaches to cytologic testing and colposcopy for the prevention
of cervical cancer in developing countries. In addition,
the approach to screening in developed countries has
changed from conventional cytologic testing to the introduction
of liquid-based cytologic and HPV DNA testing. In fact,
many molecular tests to increase the sensitivity and specificity
for the detection of cervical cancer precursors are
currently undergoing clinical trials.
The potential utility of HPV DNA testing was shown in a
randomized trial conducted in South Africa. 11 This trial of
more than 6,500 unscreened women, aged 35 to 65 years,
showed a substantial reduction of high-grade cervical cancer
precursors in women who screened positive with Hybrid
Capture 2 (Qiagen Inc, Gaithersburg, MD) for high-risk
types of HPV DNA and who underwent treatment with
cryotherapy, and this reduction was sustained for 36
months. After 36 months the decrease in the cumulative
detection of grade 2 or higher cervical intraepithelial neoplasia
in the HPV treatment arm compared with the
control (delayed treatment) arm was 1.5% compared with
5.6% (difference, 4.1%; p � 0.001). The difference, however,
in the visual inspection with acetic acid (VIA) treatment
group compared with the control arm was significantly less
(3.8% vs. 5.6%; difference, 1.8%; p � 0.002). In India,
Sankaranarayanan and colleagues 12 screened 131,746
healthy women who were randomly assigned to one of
four groups: screening by HPV testing, cytologic testing,
VIA, or no screening (standard of care). There was a
reduction in the numbers of advanced cancers and cancer
deaths in the HPV treatment group (hazard ratio, 0.47; 95%
CI, 0.32 to 0.69) compared with no reductions in the VIA or
the cytologic testing treatment groups. These studies and
others conducted in developed countries suggest that HPV
DNA testing has the potential to substantially reduce the
incidence of and mortality from cervical cancer. More technologically
accessible and affordable tests for HPV DNA
testing are awaited for implementation in low-resource
settings.
In developed countries, HPV DNA testing has been recommended
as a primary screen in women older than 30
years, with cytologic testing as a triage for women with
positive test results. Only women with positive results on
both tests would be referred for colposcopy and treatment. 13
Other methods of triage include p16-INK4A overexpression
and testing for HPV-E6/7 messenger RNA, which are still
under study.
The trends in terms of cervical cancer treatment include
the following: (1) fertility-sparing surgery in young women
with early-stage disease; (2) laparoscopic radical hysterectomy
and node dissection; (3) use of sentinel nodes to
prevent morbidity associated with systematic lymphadenectomy
(still under study) and; (4) use of concurrent
cisplatinum-based chemotherapy concurrently with radiation,
which has shown substantial improvement in overall
survival and disease-free survival in women with advanced
disease.
Although cervical cancer is a relatively rare disease in
developed countries with functional screening programs,
cervical cancer remains the most common cancer among
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