Jun 14, 2013
By Will Boggs, MD
NEW YORK (Reuters Health) Jun 14 – Hormone therapy may suffice for women with stage IA endometrial cancer of all grades, if they want to try to become pregnant, a new study from Korea suggests.
“The widely accepted indication for fertility-sparing progestin therapy for young women with endometrial cancer was FIGO stage IA, grade 1, without myometrial invasion,” Dr. Joo-Hyun Nam from University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea, told Reuters Health by email.
In this new study, however, progestin therapy was safe even in patients with FIGO stage IA, grade 2-3, without myometrial invasion and in patients with FIGO stage IA, Grade 1, with superficial myometrial invasion, Dr. Nam and colleagues reported in Obstetrics & Gynecology.
But for women with stage IA, grade 2-3 differentiation with superficial myometrial invasion, the recurrence rate was high (71.4%) and the durable complete response rate was low (25%). “Therefore progestin treatment in these patients cannot be routinely recommended,” the authors write.
“However,” they noted, “none of the patients had progression of disease during progestin treatment or follow-up after achieving a complete response. All recurrent disease was confined to the uterus and no one died of the disease.
Out of 22 women who tried to conceive after achieving a complete response, nine eventually gave birth to 10 healthy infants, according to the article.
“Therefore,” the researchers say, “progestin treatment in these patients may be administered on an individual basis after careful discussion with patients about the benefits and risks of this treatment.”
The retrospective study included 23 women with endometroid adenocarcinoma with stage IA, grade 1 differentiation with superficial myometrial invasion and 25 women with stage IA, grade 2-3 differentiation, with (n=8) or without (n=17) superficial myometrial invasion.
Thirty-seven patients (77.1%) had a complete response, one (2.1%) had a partial response, and 10 (20.8%) had stable disease, as reported June 5 online in Obstetrics & Gynecology.
Patients who did not achieve a complete response underwent definitive surgical treatment after six to 20 months of progestin treatment (median, nine months).
Complete response rates were similar for women with grade 1 (73.9%), grade 2-3 without superficial myometrial invasion (76.5%), and grade 2-3 with superficial myometrial invasion (87.5%).
Sixteen of 37 women who achieved complete responses had recurrent disease after seven to 69 months (median, 20 months). Three underwent definitive surgical treatment, and 13 were retreated with progestin. Nine of these 13 had another complete response, two were still receiving progestin at the time of the report, and two underwent definitive surgical treatment after not responding to progestin.
At the time of the report, all 48 women were alive without evidence of disease except the two patients who were still receiving progestin retreatment.
The five-year recurrence-free survival rate was 52%, and the median recurrence-free survival time was 69 months for the 37 women who achieved complete response. Recurrence rates, five-year recurrence-free survival rates, and median times to recurrence did not differ significantly in the three groups of women.
Twenty-two women tried to conceive after achieving a complete response. Twelve women (55%) achieved 14 pregnancies, including one twin pregnancy. These resulted in eight full-term deliveries, one preterm delivery, one ectopic pregnancy, and four spontaneous abortions.
“The routine use of this treatment in these patients cannot be justified because of the high recurrence rate,” the researchers caution. “Therefore, this treatment should be applied on an individual basis, and caution is required in patients with stage IA, grade 2-3 differentiation with superficial myometrial invasion.”
“In our previous study (http://bit.ly/150N8Jl), patients who did not respond to progestin therapy for nine months have never showed complete response after then,” Dr. Nam said. “Therefore, I would like to recommend trying progestin therapy for nine months until achieving complete response. If complete response is not achieved after nine months of treatment, it would be better to perform definitive surgery.”
“The total duration of progestin therapy did not influence the outcomes,” Dr. Nam said. “Therefore, it would be better to stop the treatment immediately after achieving complete response. If the patients want to get pregnant at this time, it would be better to try it immediately.”
“However,” Dr. Nam said, “if the patients want to postpone to get pregnant, I would like to recommend taking cyclic low dose progestin, oral pill, or levonorgestrel-releasing intrauterine device until pregnancy trial as a maintenance therapy. In our previous study, the pregnancy itself and the use of maintenance therapy until pregnancy trial significantly reduced recurrence of endometrial cancer.”
Dr. Nam added, “According to several recent articles including ours, obesity is a significant risk factor for treatment failure and recurrence after complete remission. Therefore, I would like to recommend reducing body weight during and after progestin therapy. All gynecologists should discuss this with their patients and give a prescription or instruction for weight reduction.”
Dr. Shannon N. Westin from the M. D. Anderson Cancer Center in Houston, Texas, told Reuters Health, “This manuscript provides valuable data to support conservative therapies in the appropriately chosen patient with high grade noninvasive endometrial cancer.”
“In general,” Dr. Westin said, “most responses are seen within three to six months, thus, changing treatment at that point is reasonable.”
How long to continue treatment after achieving a complete response is less clear. “No one really knows the answer to this,” Dr. Westin said. “In general, we will treat for at least a year and then discontinue if the patient would like to pursue fertility. “In those patients without contraindication, therapy can continue indefinitely.”
“Unfortunately,” Dr. Westin added, “recurrence after this treatment is still high (23-47%). There is a great need to develop markers to identify patients that have a risk of resistance or recurrence.”
Obstet Gynecol 2013;122:7-14.