Neoadjuvant chemotherapy is the preferred treatment option for women with advanced ovarian and related cancers if it is unlikely that primary cytoreductive surgery (PCS) can reduce disease to less than 1 cm. It is also an alternative to surgery for women with potentially resectable disease who prefer the neoadjuvant approach, as chemotherapy is not inferior to surgery in terms of progression-free or overall survival, new guidelines indicate.
The new guidelines were issued jointly by the American Society of Clinical Oncology and the Society of Gynecologic Oncology and were published online August 8 in the Journal of Clinical Oncologyand Gynecologic Oncology.
“For a long time, physicians assumed that doing immediate surgery when a woman was diagnosed with ovarian cancer was the best possible treatment,” lead author Alexi Wright, MD, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, told Medscape Medical News.
“Yet, because ovarian cancer is a disease that tends to be diagnosed at a late stage when the disease is present in many different places, many women have undergone surgeries that had a lot of complications,” she added.
“So one of the things that was very important to us [when writing the guidelines] was to ensure that all women who are diagnosed with ovarian cancer meet with a gynecologic surgeon before embarking on any treatment at all,” Dr Wright commented.
“We also agreed that any woman who has stage IV ovarian cancer ― which is incurable ― could get either neoadjuvant chemotherapy or surgery first, because they are equivalent,” she added.
Standard treatment of stage IIIC or IV invasive epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer has traditionally been with primary cytoreductive surgery followed by chemotherapy, Dr Wright and colleagues explain.
And primary cytoreduction is still preferred over neoadjuvant chemotherapy for women in whom there is a high likelihood of achieving cytoreduction to less than 1 cm of disease (and, ideally, to no visible disease).
However, physicians may offer either neoadjuvant chemotherapy or cytroreductive surgery to women who have potentially resectable disease even if they are fit enough to undergo surgery, as studies show that the neoadjuvant approach is not inferior to surgery, either in terms of progression-free or overall survival, they write.
Neoadjuvant chemotherapy should also be the preferred option for women at high perioperative risk or for whom there is a low likelihood of achieving cytoreduction to less than 1 cm of disease (and, ideally, to no visible disease).
Similarly, neoadjuvant chemotherapy should be recommended over surgery in women for whom it is unlikely that surgery will result in cytoreduction to less than 1 cm of disease (ideally, to no visible disease), even if they are fit enough to withstand surgical resection.
As guideline authors point out, the main advantage to neoadjuvant chemotherapy is that it is associated with less perioperative and postoperative morbidity and mortality than surgery, although surgery may result in better overall survival in select patients.
“Before NACT [neoadjuvant chemotherapy] is delivered, all patients should have histologic confirmation (core biopsy preferred) of an invasive ovarian, fallopian tube, or peritoneal cancer,” Dr Wright and colleagues add.
If a biopsy cannot be performed, then oncologists should carry out a cytologic evaluation. Together with a finding of serum CA-125 to carcinoembryonic antigen ratio in excess of 25, the evaluation should confirm the primary diagnosis and exclude the presence of a nongynecologic cancer.
The preferred regimen for women undergoing neoadjuvant chemotherapy is a platinum/taxane-based combination, although an alternative, platinum-containing regimen may be considered on an individual basis.
Interval cytoreductive surgery should also be performed after four or fewer cycles of neoadjuvant chemotherapy in women who either respond to treatment or whose disease stabilizes in response to chemotherapy.
In contrast, “patients with progressive disease on NACT have a poor prognosis,” the authors observe.
For these women, options include the introduction of an alternative chemotherapy regimen, referral to an appropriate clinical trial, or initiation of end-of-life care.
Surgery for these women is not advised unless it is required for palliative needs.
“It sounds very basic, but this is one of the first guidelines to address the minimal amount of testing that women should undergo when diagnosed with ovarian cancer,” Dr Wright observed.
The primary clinical evaluation should therefore now include a CT scan of the abdomen and pelvis with oral and intravenous contrast and chest imaging, preferably with CT, to evaluate the extent of disease and the subsequent feasibility of surgical resection.
Laparoscopic evaluation or additional radiographic imaging may also be used to refine the evaluation.
Deciding whether or not a patient is eligible for either medical or surgical treatment should only be made in consultation with either a gynecologic oncologist or a medical oncologist with expertise in gynecology.
“For patients faced with a decision between PCS and NACT, it is essential that providers first explain the diagnosis, including the extent of disease identified, stage, and prognostic implications of what is known,” Dr Wright and colleagues conclude.
“Sharing data about comparative morbidity, survival, and quality-of-life outcomes in plain language can help to ensure understanding and help patients make more informed decisions,” they add.
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