Neoadjuvant chemo often bests primary surgery for advanced ovarian CA
Last Updated: 2010-09-01 19:25:51 -0400 (Reuters Health)
By Karla Gale
NEW YORK (Reuters Health) - Debulking is the standard first-line approach to advanced ovarian cancer, but starting with chemotherapy before surgery doesn't hurt survival - and in fact has some benefits, a multinational team reports September 2nd in the New England Journal of Medicine.
Compared with primary surgery, neoadjuvant chemo causes fewer post-operative deaths, less bleeding and fewer episodes of sepsis, lead author Dr. Ignace Vergote from University Hospitals, Leuven, Belgium, told Reuters Health.
"This is an incredibly important study for the field and particularly for gynecologic oncologists who manage ovarian cancer patients," said Dr. Mark H. Einstein, Director of Clinical Research for Women's Health and Gynecologic Oncology at Albert Einstein College of Medicine (no relation) in Bronx, New York. Dr. Einstein did not participate in the research.
"The general dictum is to perform debulking primarily followed by chemotherapy," Dr. Einstein told Reuters Health in an email. "However, in medically inoperable patients, or patients who have signs of inoperable disease by exam or imaging, we often resort to neoadjuvant therapy followed by end staging. This randomized trial gives us comfort that we can safely go the route of neoadjuvant therapy with no effect on survival."
Between 1998 and 2006, Dr. Vergote and associates enrolled 670 women with biopsy-proven stage IIIC or IV invasive epithelial ovarian carcinoma, primary peritoneal carcinoma, or fallopian-tube carcinoma in a randomized trial.
Three hundred thirty-six women had primary debulking surgery followed by at least six courses of platinum-based chemotherapy; the remaining 334 had three courses of neoadjuvant platinum-based chemo followed by so-called interval debulking surgery in those with a response or stable disease, and then three more courses of chemo.
During a median follow-up of 4.7 years, the median progression-free survival on intent-to-treat analysis was 12 months in both groups. The median overall survival was 29 months in the primary-surgery group and 30 months in the neoadjuvant-chemotherapy group.
Results were similar for the per protocol analysis, which included 310 women in the primary surgery group and 322 in the neoadjuvant chemotherapy group.
In multivariate analysis, the only independent predictors of prolonged survival were the absence of residual tumor after surgery; stage IIIC disease; small tumor size before randomization; endometrioid histologic type (followed in descending order by serous, mixed, undifferentiated, mucinous, and clear-cell types), and younger age (p </= 0.005 for each).
When comparing the primary surgery and neoadjuvant chemotherapy groups, the postoperative death rates (within 28 days) were 2.5% and 0.7%, respectively, and the postoperative hemorrhage rates were 7.4% and 4.1%, respectively. Infection occurred in 8.1% and 1.7%, respectively, and venous complications in 2.6% and 0%, respectively.
Quality-of-life scores obtained at various points did not differ between groups, the report states.
Dr. Vergote told Reuters Health it's crucial to evaluate the extent of disease laparoscopically before debulking surgery.
"It's quite difficult to decide which approach to take," he said. Computed tomography is good for evaluating lymph node involvement and hepatic or extra-abdominal metastases, but "it's not so good for seeing peritoneal carcinomatosis on the peritoneum and bowel," he said.
When the patient is young, otherwise healthy, and "with not too extensive disease," primary surgery - likely to take about three to four hours - will yield results as good as with neoadjuvant chemotherapy, Dr. Vergote said.
But when the patient has multiple comorbidities and extensive disease, "with tumor all over the bowel and diaphragm and pelvis and lymph nodes," and surgery is likely to take six or seven hours - "you can avoid complications and postoperative death...by starting with neoadjuvant chemotherapy," he said.
Dr. Vergote also strongly urges referring these cases to a gynecological oncologist.
Dr. Eric Pujade-Lauraine, Head of the Medical Oncology Department at Hopital Hotel-Dieu, AP-HP in Paris, told Reuters Health by e-mail that neo-adjuvant chemotherapy allows patient renutrition when necessary, to better prepare her for a large surgery and to decrease the extent of the surgery.
"It should be stressed that these results should be applied only in patients with bulky advanced ovarian cancer," said Dr. Pujade-Lauraine, who did not work on the study.
Dr. E. L. Trimble, from the National Cancer Institute in Bethesda, Maryland, observed that the survival rates in this trial were not as good as in other recent trials."Which leads me to worry about the chemotherapy that the patients got," he told Reuters Health, "particularly whether it included taxane treatment," known to improve survival when used with platinum-based chemotherapy.
"Here in the U.S., we tend to recommend primary surgery, with neoadjuvant therapy reserved for those too sick to undergo primary surgery," he said.
Dr. Vergote and his research team conclude: "Complete resection of all macroscopic disease, whether performed as primary treatment or after neoadjuvant chemotherapy, remains the objective whenever cytoreductive surgery is performed."
SOURCE:http://link.reuters.com/buw78n
N Engl J Med 2010;363:945-953.
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