Sentinel Lymph Node Mapping in Endometrial Cancer: An Update

 Lymph node removal for staging, as part of the initial surgical management of patients with endometrial carcinoma, remains a controversial topic in gynecologic oncology. There is currently wide variability among clinical practices, with surgical approaches ranging from no nodal evaluation to comprehensive pelvic and aortic lymphadenectomy. Lymphatic mapping has emerged as an increasingly popular option over the past few years, with several attractive features in its concept, innovative surgical approach, and encouraging preliminary results. At this time, however, several different techniques have been described and used for lymphatic mapping in endometrial cancer, incorporating a variety of mapping agents and injection sites. Although recently published results are encouraging, they are limited to single-institution series or multi-institutional collaborations undertaken without the aegis of a prospective randomized controlled trial. However, the surgical staging of endometrial cancer with lymphadenectomy was historically established based not on randomized trial data but on prospective clinicopathologic studies. Another evolving field in endometrial cancer staging is the interpretation of pathologic ultrastaging of sentinel lymph nodes (SLNs), which can identify low-volume metastases for which the clinical significance and the ideal management remain uncertain. This is particularly an issue with extremely low-volume nodal metastasis and isolated tumor cells. Furthermore, it has become apparent that applying a predefined SLN algorithm can decrease false-negative rates. The Memorial Sloan Kettering Cancer Center SLN algorithm can be used as a checklist to ensure standardization of care and to reduce the chance of missing nodal disease. Prospective trials are under way at many institutions to help establish the definitive role of SLN mapping for staging of endometrial cancer. The objective of this study was to provide an update on the latest clinical data related to lymphatic mapping for the staging and management of endometrial cancer and its role in clinical practice.

Implications for Practice:

Lymphatic mapping is an increasingly popular option in the surgical treatment of endometrial cancer. The aim of using this tool is to target the lymph nodes that are the most likely to be involved with metastatic cancer cells (sentinel lymph nodes) and thereby limit the extent of surgery needed and decrease surgical complications and long-term side effects associated with extensive lymph node removal. By examining a limited number of sentinel lymph nodes, a more detailed examination of the node can be done (ultrastaging). This allows for the detection of a small number of cancer cells (low-volume metastasis) that can be missed with standard techniques.

Bisphosphonates Linked to Lower Endometrial Cancer Risk

A class of drugs that prevents bone loss may also help reduce women’s risk of developing endometrial cancer, according to a new study published online December 22 in Cancer.

Women who had a history of taking bisphosphonates were about half as likely as women who had not taken the drugs to develop endometrial cancer.

The study looked only at bisphosphonates that contain nitrogen, which have the strongest anticancer effects among the class of drugs, according to prior studies.

Sharon Hensley Alford, PhD, from the Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan, and colleagues looked at data from 29,254 women aged 60 years and older in the National Cancer Institute’s Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The survey included a questionnaire on bone health and use of medications, including bisphosphonates.

Among the women who had used bisphosphonates, the researchers saw 8.7 cases of endometrial cancer per 10,000 person-years, compared with 17.7 cases per 10,000 person-years among women who had never used the drugs (rate ratio, 0.49; 95% confidence interval, 0.30 – 0.80).

After adjusting for a variety of variables, including age, race, smoking history, hormone therapy history, and body mass index, the hazard ratio for women taking the drugs compared with those not taking them was 0.56 (95% confidence interval, 0.34 – 0.93).
Endometrial cancer is the fourth most common cancer in women and the eighth most common cause of cancer death. Nearly half of all gynecologic cancers are endometrial. Endometrial cancer is most often diagnosed in women in their 60s and 70s, when they are postmenopausal and their bone density has decreased.

Previous research showed that bisphosphonates can slow tumor growth and the spread of cancer cells in patients with certain types of cancer, but no study had specifically looked at endometrial cancer.

The study’s main findings focused on the more common type 1 endometrial cancer, which is related to high estrogen levels. Researchers called for further studies with a larger sample to better assess the drug’s relationship to the more aggressive type 2 endometrial cancer, which is not hormonally related.


Do Your Genes Increase Your Risk of Getting Cancer Twice?

If you knew you had an 85 percent lifetime risk of breast cancer — a risk six and a half times higher than for most women — would you be more vigilant?

If you knew your risk of developing a second cancer was eight times higher than most people’s, would you talk to your doctor right away?

These questions are not meant to be scary. They’re the types of questions patients with genetic mutations need to ask. They can save your life.

Our most recent research shows that people with a certain genetic mutation are much more likely to develop cancer a second time. Knowing about such risks helps you, as a patient, make better decisionsabout screening and treatment.

What the study shows

“A second ‘primary’ cancer is completely different. It’s a distinct type of cancer from the first, and it can strike different parts of your body.”

Charis Eng, MD, PhD

Founding Chairwoman of the Genomic Medicine Institute

When I say “second cancer,” I do not mean a recurrence of the same type of cancer. A second “primary” cancer is completely different. It’s a distinct type of cancer from the first, and it can strike different parts of your body.

To study this risk, our research group followed 114 patients with a PTEN gene mutation for seven years. Out of those patients, 40 percent developed a second primary cancer.

The results are stunning. According to our analysis, people with this PTEN mutation are nearly eight times more likely than the general population to develop a second cancer. For women, the risk of a second primary breast cancer is nine times higher. For endometrial cancer, it’s 14 times higher.

For people with inherited cancer genetic mutations, knowing about this increased risk matters, both for treatment and monitoring.

What the results mean for patients

Once a patient knows about a PTEN mutation — or other high-risk mutations — screening and monitoring must become a lifetime habit.

For example, a high-risk woman may need to start MRI screenings and mammograms earlier than the general population. She also needs to continue them indefinitely, remaining vigilant for life.

But better screening isn’t the only important outcome. Women with an especially high risk of breast cancer — both a first and second type — should discuss prophylactic (preventive) mastectomy with a doctor. It’s a hard conversation to have, but when your risk is so high, it’s also worthwhile.

Likewise, we found that men with the PTEN mutation have a much higher risk for a second primary thyroid cancer. That has implications for surgery. Often a surgeon treating thyroid cancer will leave part of the thyroid intact. But for men with such a high risk, the surgeon may want to remove all of the thyroid. Doing so would decrease the man’s chances of developing a second cancer.

We hope other independent researchers will validate our results in their own studies. In addition, future research should explore whether other genetic mutations increase the risk for second primary cancers. This study is just a first step in understanding a little-known risk — and how patients can decrease it.

Vaginal Bleeding.


70-year-old woman was seen in this hospital because of vaginal bleeding. An endometrial-biopsy specimen showed a poorly differentiated malignant neoplasm that was suggestive of mixed müllerian tumor (carcinosarcoma). A diagnostic and therapeutic procedure was performed.

The underlying cause of abnormal vaginal bleeding is age-dependent. Ten percent of premenopausal women with abnormal bleeding have a malignant tumor. In contrast, 75% of women over 70 years of age with postmenopausal bleeding have cancer, and the risk rises with age in postmenopausal women.

Clinical Pearls

• What is the typical presentation of carcinosarcoma of the uterus?

Postmenopausal vaginal bleeding is the most common manifestation of carcinosarcoma. Patients with carcinosarcoma also frequently present with the classic triad of painful postmenopausal bleeding, an enlarged uterus, and prolapsed tumor visible at the cervical os.

• Under what circumstances is surgery not the primary treatment for uterine cancer?

In only a few circumstances is surgery not the primary treatment for uterine cancer — when there is a desire to preserve fertility, high operative risk, and unresectable disease. The goals of surgical treatment are excision of all disease with at least a 1-cm margin and staging of the tumor. The initial spread is to regional lymph nodes; therefore, standard treatment is a radical total abdominal hysterectomy and bilateral salpingo-oophorectomy with lymphadenectomy. Endometrial cancers have several potential patterns of spread: direct invasion and expansion of the primary tumor, lymphatic invasion, hematogenous spread, and intraperitoneal dissemination. Because metastasis is common, preoperative combination positron-emission tomography and computed tomography (PET-CT) and a meticulous exploratory laparotomy are standard practice.

Morning Report Questions

Q: What features affect the overall prognosis of patients with carcinosarcoma?

A: Diagnostic features of malignant mixed mullerian tumor (carcinosarcoma) include the finding of a biphasic malignant tumor that is composed of high-grade carcinoma (most commonly endometrioid or serous) and sarcoma and is typically homologous (arising from mesenchymal tissue normally found in the uterus), although in up to 50% of cases, the tumor has a heterologous component (most commonly rhabdomyosarcoma or chondrosarcoma). There is no transition between the two components. Tumor stage is the most important prognostic factor in these tumors, although histologic features also affect outcome. The finding of serous or clear-cell carcinoma is associated with a more aggressive course. Sarcomatous components adversely affect the overall prognosis of patients with stage I tumors (5-year survival is 30% among patients with heterologous elements as compared with 80% among patients with homologous elements); myometrial and lymphovascular invasion are also associated with a poor prognosis.

Q: What are the treatment options for carcinosarcoma?

A: Carcinosarcoma is thought to require multiple methods of treatment. Radiation therapy has been shown to reduce the rates of local recurrence in the pelvis but does not increase the survival benefit among patients with carcinosarcoma. Adjuvant chemotherapy has not been shown to have an effect on recurrence rates or progression-free or overall survival among patients with carcinosarcoma. Hormonal therapy is of no use, since estrogen and progesterone receptors do not control tumor growth, even though they are typically present in patients with carcinosarcoma.


Sorce: NEJM

Genomic Studies Allow Better Classification of Leukemias, Endometrial Tumors.

Two studies, one of leukemia and the other of endometrial tumors, show the usefulness of genomics studies in finding unsuspected classifications, possibly useful for treating these cancers.

One study, published in the New England Journal of Medicine, examined 200 cases of acute myeloid leukemia. Genomic studies allowed the researchers to discern nine distinct categories, revealing “many potentially important biologic relationships.” For instance, certain mutations were associated with distinct patterns of RNA activity. The authors point out that the significance of such findings “is not yet clear.”

Another study, in Nature, of some 375 endometrial cancers found four distinct classes of the disease, as opposed to the two commonly used to stage treatment. In Journal Watch Oncology and Hematology, Virginia Kaklamani observes that breast cancer was the first to use molecular subtypes to guide treatment. The Nature study, she writes, is “a huge step toward applying this technique in other malignancies.”


Extended Duration of Tamoxifen Therapy Enhances Breast Cancer Survival .

Ten years of adjuvant tamoxifen therapy in women with estrogen receptor–positive breast cancer is associated with lower rates of recurrence and breast cancer mortality than 5 years of treatment, according to a Lancet article.

Researchers followed outcomes in some 6800 women with receptor-positive disease who’d completed 5 years of tamoxifen therapy, half of whom were allocated to 5 additional years of treatment.

Recurrences and breast cancer mortality were both significantly lower among those on continued therapy, with reductions being even more pronounced after 9 years. During years 5–14, mortality was 12.2% for those allocated to continue treatment versus 15.0% for controls (absolute mortality reduction, 2.8%). The incidence of pulmonary embolism (but not of death from it) was higher in the continued-treatment group, and the risk of endometrial cancer was also higher with longer treatment, including an absolute increase in mortality risk of 0.2%.

A commentator writes that confirmation of these results by meta-analysis with other tamoxifen trials “should herald a change of practice.”

Source: Lancet