2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

women living in developing countries because of the lack of
effective screening programs. Most women with cancer in
developing countries have advanced and untreatable disease.
In addition, palliative care remains out of reach of
most women in developing countries, leaving these women
to die painful and undignified deaths. Cervical cancer is the
one cancer that illustrates the gross inequities of health care
between rich and poor countries.
Endometrial Cancer
Worldwide, endometrial cancer is the most common cancer
of the female genital tract and the seventh most common
cause of death from cancer in women in western Europe.
Yearly, approximately 7,406 cases are registered in the
United Kingdom, 88,068 in the European Union, and 40,102
in the United States. 14 The median age of cancer occurrence
is in the sixth decade, and more than 90% of cases occur in
women older than 50 years. Approximately 5% of endometrial
cancers are associated with Lynch syndrome II (hereditary
nonpolyposis colorectal carcinoma syndrome); women
with this syndrome have a 30% to 60% risk of developing
endometrial cancer.
Type 1 endometrial cancer, or endometrioid adenocarcinoma,
represents 80% of cancers, with serous carcinomas
being the prototype of type II uterine cancers. Clear cell
cancers are rare and comprise approximately 1% of endometrial
adenocarcinomas.
Since 1988, the International Federation of Gynecology
and Obstetrics (FIGO) has recommended surgical staging of
endometrial cancer, which includes systematic pelvic and
para-aortic lymphadenectomy. FIGO adopted a new staging
system in 2009 in which the old FIGO stage 1a and 1B were
amalgamated into stage 1A and the old 1C became stage 1B.
In stage II cancer, the distinction between superficial and
deep stromal invasion was merged as stage II in which
stromal invasion is documented.
The role of systematic lymphadenectomy has been the
subject of numerous studies and much controversy. The
Adjuvant External Beam Radiotherapy in the Treatment of
Endometrial Cancer (ASTEC) trial 15 randomized 1,408
women from 85 centers with histologically proven endometrial
cancer to standard surgery (704 women with hysterectomy,
bilateral salpingo-oophorectomy, peritoneal washings,
and palpation of para-aortic lymph nodes) or to standard
surgery plus lymphadenectomy (704 women). The study
found no evidence of benefit in terms of either overall or
recurrence-free survival for pelvic lymphadenectomy in
women with early endometrial cancer. This study was,
however, criticized for numerous protocol violations, and
some authors thought that it did not adequately assess the
role of effective lymphadenectomy or the role of individualized
adjuvant radiotherapy in endometrial cancer. 16
The current recommendation for new FIGO stage 1A
cancer is to perform standard surgery only, but for high-risk
cases (i.e., 50% invasion, grade 3 lesions), systemic lymphadenectomy
should be performed. The value of this approach
is that approximately 30% of women with high-risk stage I
disease will not require adjuvant whole pelvic irradiation
because their cancer is node negative. Vaginal brachytherapy
would still be indicated for women with high-risk
characteristics to reduce local recurrence. 17
The value of adjuvant radiation for women with endometrial
cancer localized to the uterus is still under scrutiny.
332
External beam whole pelvic radiation has been shown to
reduce the rate of locoregional recurrence in intermediaterisk
endometrial cancer; however, a number of trials have
failed to demonstrate that radiation improves overall or
disease-specific survival. Post-Operative Radiotherapy in
Endometrial Cancer 2 (PORTEC-2), a randomized trial
comparing vaginal brachytherapy with external beam radiation,
also did not find overall improved survival; however,
quality of life was better in women treated with vaginal
brachytherapy only. 17
Ovarian Cancer
LYNETTE DENNY
The ASIR of ovarian cancer in the European Union in
2008 14 was 13.4 per 100,000 women, with a mortality rate of
7.6 per 100,000. In the United Kingdom the ASIR was 17.5
per 100,000 women, with a mortality rate of 9.6 per 100 000.
In 2011 in the United States, there were 21,990 new cases of
ovarian cancer diagnosed and 15,640 deaths, making ovarian
cancer the second most lethal cancer among women in
the United States. 18 Approximately 80% of advanced stage
ovarian cancers have high-grade histologic features, and
these tumors can arise from the fimbrial end of the fallopian
tube, the peritoneal cavity, or the surface epithelium of the
ovary. Efforts to improve on the long-term results of primary
therapy (a combination of “maximum effort” surgery, including
hysterectomy, bilateral salpingo-oophorectomy, infracolic
omentectomy, and maximum debulking of all
macroscopic tumor to � 2 cm of residual disease, followed by
chemotherapy using a combination of carboplatin and paclitaxel)
through the addition of additional cytotoxic agents
have not been successful.
New and effective therapies for ovarian cancer have not
been reported since the introduction of platinum-based
drugs and paclitaxel. Neither these drugs nor second-line
therapies (e.g., gemcitabine) have produced substantial advances
in overall survival.
Recently, however, two phase III clinical trials of bevacizumab,
an angiogenesis inhibitor and vascular endothelial
growth factor–neutralizing monoclonal antibody, have
shown improvements in progression-free survival but not
overall survival. Tumor angiogenesis, a process in which
cancers induce the formation of new blood and lymphatic
vasculature to enable proliferation, invasion, and growth of
metastasis, appears to be essential to disease progression in
women with epithelial ovarian cancer (EOC). Several antiangiogenic
agents have been investigated in clinical trials,
most directed against vascular endothelial growth factor, a
central promoter of the initiation of angiogenesis. Two trials
(Gynecologic Oncology Group 0218 and ICON7) 19,20 were
conducted in a total of 3,401 women with newly diagnosed
cancers, and the third (OCEANS) 21 was conducted in 484
women with platinum-sensitive relapse. Although the data
from these studies are yet to mature, the results indicate a
substantial prolongation of progression-free survival when
administered with standard platinum-based combined chemotherapy
followed by continuation of bevacizumab therapy.
Several vascular endothelial growth factor receptor tyrosine
kinase inhibitors are under evaluation as either
monotherapy or combination therapy in recurrent ovarian
cancer. One of this class of drugs, cediranib has demonstrated
in a phase II trial a clinical benefit rate of 30% and
median progression-free survival rate of 5.2 months. 22