Lymph nodes and vessels of the pelvis
Women with certain early-stage gynecologic cancers often have surgery to remove not only the uterus but lymph nodes in the pelvis so they can be examined for cancer cells that may have spread, or metastasized, from the primary tumor.
This practice, called pelvic lymphadenectomy, may reduce the threat of cancer recurrence and can help with prognosis and treatment planning. However, removal of multiple nodes often causes lymphedema, a potentially lifelong condition characterized by swelling and skin changes — in this case in the legs — as well as risk of damage to blood vessels and nerves. In most early-stage patients, no cancer cells are detected in the nodes, so the extensive surgery often offers no benefit while possibly causing lasting discomfort.
Now Memorial Sloan Kettering surgeons, led by gynecologic oncologist Nadeem R. Abu-Rustum, have pioneered a way to potentially eliminate the need for pelvic lymphadenectomy in most patients with early-stage gynecologic malignancies, such as cervical and endometrial cancer. The approach, which employs a technique called sentinel lymph node mapping (SLNM), could greatly improve patients’ quality of life without placing them at risk.
“Women with early-stage forms of cervical and endometrial cancer are cured more than 90 percent of the time, and many of them are still young — in their 30s or 40s,” Dr. Abu-Rustum says. “Sparing them unnecessary node removal and the side effects they might endure for decades would be a huge benefit.”
Tracking Cancer’s Spread
Memorial Sloan Kettering gynecologic surgeons, led by Nadeem Abu-Rustum, developed a simple technique to identify and remove the most important lymph nodes during surgery for early-stage endometrial or cervical cancers.
SLNM has been well established in the treatment of breast cancer and melanoma since the 1990s, but it is relatively new in gynecologic cancer. It involves the injection, in several locations near the tumor, of a special radioactive substance or a blue dye, or a combination of the two. Lymph fluid carries the injected substance to the sentinel nodes, the first lymph nodes to which cancer cells are likely to spread.
During the operation to remove the tumor, the sentinel nodes are identified, either visually (in the case of blue dye) or by handheld Geiger counter (if a radioactive substance is used). These nodes are removed and examined for cancer cells by a pathologist. If they are free of cancer, usually no additional lymph nodes need be taken out. If any of the nodes do contain cancer cells, the surgeon may remove more nodes for further examination and the patient may need to receive chemotherapy or radiation.
In 2003, Dr. Abu-Rustum and Memorial Sloan Kettering colleagues began investigating whether SLNM would be effective in the treatment of gynecologic cancers. Because the technique was unproven, they simply added SLNM to their standard surgical approach to see how well it tracked metastasis. Over the years, they also refined the procedure to make it simpler to perform and less burdensome for patients.
In 2006, for example, Dr. Abu-Rustum’s group demonstrated that SLNM can be performed with blue dye alone. The blue dye is injected while the patient is under anesthesia for the surgery, eliminating the need for a separate procedure that would require a nuclear medicine physician to inject a radioactive substance. The Memorial Sloan Kettering surgeons also established that injections in the cervix are effective for both cervical and endometrial cancer and showed that increased precision could reduce the number of injections from four to two.
Removing the Nodes That Matter
Dr. Abu-Rustum and colleagues have now generated a great deal of evidence to validate the use of SLNM for cervical and endometrial cancer and reported their success in a series of publications in the journal Gynecologic Oncology. One key to SLNM’s effectiveness is that removal of fewer nodes means they can be subjected to more-exhaustive examination by pathologists — a sensitive technique called ultrastaging.
“This is a much more precise, fine-tuned approach because we’re removing only the nodes that are truly important,” Dr. Abu-Rustum says. “It provides pathologists with a better specimen, and they actually find more cancer cells. This enables clinicians to be more accurate in the way they stage and define the disease. For patients, a less extensive operation decreases time spent in surgery and speeds recovery.”
In order to gain wide acceptance at all institutions, SLNM must be implemented in a way that minimizes undetected metastasis. To that end, Dr. Abu-Rustum’s group recently developed an algorithm — a specific set of steps to follow — for SLNM use with stage I cervical or endometrial cancer. An essential part of the algorithm calls for the removal of additional lymph nodes when SLNM provides inconclusive or ambiguous results.
To evaluate the algorithm’s potential, the group applied it retrospectively to gynecologic cancer patients at Memorial Sloan Kettering who had undergone surgery with simultaneous SLNM. In 2011, the team reported in Gynecologic Oncology that the algorithm had a metastasis detection rate of more than 95 percent in a study of 122 cervical cancer patients. A larger study, reported in the March 2012 issue of the journal, showed a detection rate of 98 percent in 498 endometrial cancer patients.
Although the effectiveness of SLNM will vary from surgeon to surgeon, Dr. Abu-Rustum says it is reasonable to expect a detection rate of 85 to 95 percent for endometrial cancer and more than 95 percent for cervical cancer. Memorial Sloan Kettering now incorporates SLNM into about 250 endometrial cancer and 50 cervical cancer surgical procedures per year.
Ultimately, Dr. Abu-Rustum estimates SLNM should make it possible to avoid complete pelvic lymphadenectomy in 75 percent of patients with stage I cervical and endometrial cancers while reliably detecting metastasis. He also is confident the algorithm could be broadly adopted at other institutions, where SLNM use is still rare.
“Memorial Sloan Kettering Cancer Center is leading the way with this effort, but I think it will start to be used more widely,” he says. “It took years for SLNM to become accepted as standard of care in breast cancer and melanoma, and I expect the same to happen with gynecologic surgery. The bottom line is that this is a much more accurate approach that dramatically improves patients’ quality of life.”