Retreatment with progestin for recurrence after complete response with fertility-sparing treatment in patients with endometrial cancer

Abstract

ObjectiveTo assess the outcomes of retreatment using progestin for recurrence after a complete response with fertility-sparing treatment in patients with early endometrial cancer.MethodsWe retrospectively reviewed the data of patients with presumed stage IA, grade 1 endometrioid endometrial cancer who developed intra-uterine recurrence after a complete response with fertility-sparing treatment using progestin. Oncological and pregnancy outcomes were analyzed after repeated fertility-sparing treatment. Logistic and Cox regression analyses were performed to analyze the prognostic factors associated with a complete response with secondary fertility-sparing treatment and recurrence-free survival after secondary fertility-sparing treatment, respectively.ResultsFifty patients with a median age of 31 years (range 23–40) underwent secondary fertility-sparing treatment. With a median secondary progestin treatment duration of 9 months (range 3–55), the complete response rate was 78% (39/50) and no patients had extra-uterine spread of disease. Among the 26 (67%) patients who attempted to conceive after complete response, 10 became pregnant (3 spontaneous abortions, 7 live births). Eighteen (46.1%) patients had a second recurrence, with a median recurrence-free survival after secondary fertility-sparing treatment of 14 months (range 3–36); 15 patients received tertiary fertility-sparing treatment and nine (60%) achieved a complete response. Polycystic ovary on ultrasound (OR 5.82, 95% CI 1.1 to 30.6, p=0.037) was associated with an increased complete response rate with secondary fertility-sparing treatment. Multivariable analysis revealed that recurrence-free survival after initial hormonal treatment >6 months (HR 0.11, 95% CI 0.02 to 0.51, p=0.005) and pregnancy after secondary fertility-sparing treatment (HR 0.27, 95% CI 0.08 to 0.98; p=0.047) were significantly associated with longer recurrence-free survival after secondary fertility-sparing treatment.ConclusionsRepeated progestin treatment was associated with a 78% response rate and it was safe in patients with intra-uterine recurrent endometrial cancer. Thus, it might help preserve fertility after first and second recurrences.

Prognosis of patients with endometrial cancer or atypical endometrial hyperplasia after complete remission with fertility-sparing therapy

“…First, pregnancy itself can reduce the recurrence rate of endometrial cancer because of the high levels of progesterone during pregnancy [ 14 ]. Additionally, the endometrium is shed during delivery, which is equivalent to curettage [ 3 , 4 ]. The other hypothesis suggests that the molecular biology of the uterine endometrium that leads to endometrial cancer is similar to that of the uterine endometrium that makes implantation difficult.…”

“…Generally, patients undergo total hysterectomy if MPA therapy fails to eliminate lesions. Although the response rate to MPA is as high as 53.2–79.9% [ 1 – 3 ], 9.5–40% of patients develop recurrence after complete remission (CR), and the median time to recurrence after CR is approximately 20 months [ 3 – 10 ]. However, despite the high recurrence rate of EC and AEH, management after achieving CR, such as whether to perform total hysterectomy after the patient gives birth, the timing of hysterectomy, and the duration of estrogen-progestin (EP) therapies, is likely to depend on the physician, institution, and patient.…”

“…Progestin is often used after complete remission, and cyclic low-dose progestin therapies or progestin-containing intrauterine devices are reported to lower the recurrence rate of EC and AEH [ 11 ]. In addition, previous reports have demonstrated that re-administration of fertility-sparing progestin therapy after recurrence has a good response rate in some patients [ 2 , 3 , 12 ]. Further, in patients with early EC, the CR rate for repeated therapy tends to be equal to or better than that of the initial treatment, and the pregnancy rate associated with repeated treatment is at least equivalent to that associated with the initial treatment [ 12 ].…”