Carlo Ronsini, MD Department of Woman, Child, and General and Specialized Surgery Obstetrics and Gynecology Unit, University of Campania Italy

For patients with early-stage endometrial cancer (EC), standard treatment has been hysterectomy with bilateral salpingo-oophorectomy with lymphadenectomy, note the authors of a study published in Frontiers in Oncology. However, for women who wish to retain their fertility, fertility-sparing treatment (FST) is a welcome option for particular cases.

Carlo Ronsini, MD, and colleagues conducted a systematic review and meta-analysis that examined conservative management for patients with stage 1a, grade 2 (G2) EC. They selected five studies based on patients of reproductive age seeking pregnancy with a histological diagnosis of EC stage 1a G2 and at least one evaluated oncologic outcome. Search terms were “G2 or stage 1a” AND “oncologic outcomes” AND “endometrial cancer” AND “fertility sparing.”

Rigorous Criteria for Patients With EC Seeking Fertility-Sparing Treatment

The criteria for patients seeking FST are strict, according to the study team, and include:

  • Women younger than 40 planning to conceive shortly after remission
  • Grade 1 EC histology
  • Stage of disease verified by an MRI
  • Tumor diameter of less than 2.0 cm
  • FIGO stage 1a with neither adnexal nor myometrial involvement
  • Negative lymphovascular space invasion (LVSI)

“This kind of patient shows excellent 5-year progression-free survival rates—95%—if the tumor is grade 1 with overall survival rate of 90%,” the study authors wrote. Treating patients with G2 is much more controversial, however, with many experts suggesting thrombospondin, they added. Therefore, they sought to “evaluate the oncologic outcomes of patients affected by 1a G2 EC who have been administered FST.”

Patients (N=103) included in the study were treated with a combination of medroxyprogesterone acetate (MPA), levonorgestrel intrauterine device (LNG-IUD) plus megestrol acetate (MA), gonadotrophin-releasing hormone (GnRH) plus MPA/MA, dilation and curettage, or hysteroscopic resectoscope.

After second-round therapy prolongation up to 12 months, the study team observed 70% to 85% complete response. However, they acknowledged that rigorous measures must be considered temporary to allow for pregnancy and to subsequently conduct counseling prior to approving surgery. Therefore, “it would be appropriate to plan specific counseling for patients undergoing this experimental approach for fertility preservation, although the ideal FST of EC is not yet defined,” they wrote.

Fertility-Sparing Management Not Considered Gold Standard for EC

Although fertility-sparing management can be recommended for patients with early-stage G1 EC wishing to preserve reproductive function, it is not considered the standard for young women with EC, according to Dr. Ronsini and colleagues. “It seems clear that greater standardization in the selection of patients is necessary, and a risk classification even within a pattern of patients—with 1a G2 EC—is already considered at extreme limits of acceptability in FST,” they wrote.

Physicians should assess patients’ inherent risk and in those at higher risk, pay particular attention to the context of the proposed clinical pathway, the study authors noted. They added that there is a need to create clinical trials that minimize the bias related to tumor features and not to the proposed FST. Although results are encouraging, the study authors noted that future research should be conducted using larger patient samples.