Uterine cancer: signs symptoms stage and diagnosis & treatment of uterine cancer.

UTERINE CANCER
■ EPIDEMIOLOGY

Several different tumor types arise in uterine corpus. Most tumors arise
in the glandular lining and are endometrial adenocarcinomas.

Benign
(leiomyomas) and malignant tumors (leiomyosarcomas) can also arise
in the uterine smooth muscle and have very different clinical features.
The endometrioid histologic subtype of endometrial cancer is the
most common gynecologic malignancy in the United States.

In 2017,
over 60,000 new corpus cancers of uterus are projected for American
women, but the surgical cure rate is high, and about 10,920 deaths
from uterine cancers are predicted.

Development of these tumors is
a multistep process with estrogen playing an important early role in
driving endometrial gland proliferation. Relative overexposure to
this class of hormones is the principal risk factor for the subsequent
development of endometrioid tumors. In contrast, progestins drive
glandular maturation and are protective.

Genetics Women with a germ-line mutation in one of the
series of DNA mismatch repair genes associated with the Lynch
syndrome, also known as hereditary nonpolyposis colon cancer
(HNPCC) syndrome, are at increased risk for endometrioid endome-
trial carcinoma. These individuals have germ-line mutations in MSH2,
MLH1, and in rare cases PMS1 and PMS2.

Individuals who carry these
mutations typically have a family history of cancer and are at markedly
increased risk for colon cancer and modestly increased risk for ovarian
cancer and a variety of other tumors. Middle-aged women with
HNPCC carry a 4% annual risk of endometrial cancer and a relative
overall risk of approximately 200-fold as compared to age-matched
women without HNPCC.

In sporadic cancers, secondary events such
as mutation of the PI3K gene or the loss of the PTEN tumor suppressor
gene likely serve as secondary “hits” in the carcinogenesis of estrogenic
excess. The molecular events that underlie less common endometrial
cancers such as clear cell and papillary serous tumors of the uterine
corpus are less well understood.
PATHOLOGY
Approximately 75–80% of endometrial cancers are adenocarcinomas
and have been characterized as type 1 (estrogen-linked) endometrial
cancers and type 2 cancers that have less clear associations with
estrogens (clear cell cancers, serous cancers, and mucinous cancers).
Endometrial serous cancers show TP53 functional loss and behave
clinically like ovarian cancers.

Serous endometrial cancers are marked
by a much higher risk of distant recurrence and a lower risk for locore-
gional spread. Prognosis depends on stage, histologic grade, and depth
of myometrial invasion.
CLINICAL PRESENTATION
The majority of women with tumors of the uterine corpus present
with postmenopausal vaginal bleeding due to shedding of the malig-
nant endometrial lining. Premenopausal women often will present
with atypical bleeding between typical menstrual cycles.

These signs
typically bring a woman to the attention of a health care professional,
and the majority of women present with early-stage disease in which
the tumor is confined to the uterine corpus and the consequent high
cure rate.

Diagnosis is typically established by endometrial biopsy.
Epithelial tumors may spread to pelvic or para-aortic lymph nodes.
Serous tumors tend to have patterns of spread much more reminiscent
of ovarian cancer, and patients may present with omental/peritoneal
disease and sometimes ascites. Some women with endometrial cancer
have a history of endometriosis.

TREATMENT
Uterine Cancer
Most women with endometrial cancer have disease that is localized
to the uterus (75% are stage I, Table 85-1), and definitive treatment
typically involves a hysterectomy with removal of the ovaries and
fallopian tubes. The resection of lymph nodes does not improve
outcome, but sentinel node resection does provide staging and
prognostic information.

Node involvement defines stage IIIC dis-
ease. Tumor grade and depth of invasion are the two key prognostic
variables in early-stage tumors, and women with low-grade and/
or minimally invasive tumors (<50% myometrial penetration) are
typically observed after definitive surgical therapy.

Patients with
high-grade tumors or tumors that are deeply invasive (stage IB) are
at higher risk for pelvic recurrence or recurrence at the vaginal cuff,
which is typically prevented by intravaginal brachytherapy.
Women with regional metastases or metastatic disease (3% of
patients) with low-grade tumors can be treated with progesterone or
tamoxifen. Poorly differentiated tumors lack hormone receptors and
are typically resistant to hormonal manipulation.

The role of adju-
vant chemotherapy in stage I–II disease is currently under investiga-
tion but is usually employed for advanced stage (III–IV) cancer and
most tumors with serous histology. Carboplatin and paclitaxel com-
binations are the current standard of care.

Chemotherapy for met-
astatic disease is delivered with palliative intent. Potentially active
drugs include bevacizumab, mTOR inhibitors (e.g., temsirolimus).
Patients with advanced cancer and known mismatch repair deficits
may respond particularly well to immunotherapy with antagonists
of the PD1/PDL1 axis.


Chemotherapy of leiomyosarcomas of the uterus with docetaxel/
gemcitabine, ifosfamide/doxorubicin, and trabectedin can have
substantial benefit. Carcinosarcomas of the uterus contain both
mesenchymal and epithelial components but will often respond to
paclitaxel and platinum complex therapy.

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