New guidelines on the diagnosis, treatment, and follow-up of endometrial cancer, the most common gynecologic cancer in developed countries, have been issued jointly by the European Society for Medical Oncology (ESMO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Gynaecological Oncology (ESGO).
The comprehensive list of recommendations has been published simaultaneously in the Annals of Oncology, the International Journal of Gynecological Cancer, and Radiotherapy and Oncology.
“I think very highly of this work,” Patricia J. Eifel, MD, professor, Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas, told Medscape Medical News.
“Endometrial cancer is fraught with challenges as a subject for investigation. These guidelines provide a good road map for a reasonable approach to managing this disease, based on current data,” Dr Eifel, who wrote an accompanying editorial, said.
Time for a Consensus
“Endometrial cancer is the most frequent gynecological malignancy in developed countries, but many controversies still exist about the optimal treatment of this disease,” lead author of the guidelines, Nicoletta Colombo, MD, from the European Institute of Oncology, University of Milan-Bicocca, Italy, told Medscape Medical News.
“ESMO felt that it was time to organize a conference on the management of endometrial cancer in order to reach a consensus among experts and produce a document which could serve as a guideline for the treatment of this malignancy,” Dr Colombo said.
“Since the treatment of endometrial cancer encompasses several strategies, such as surgery, radiotherapy, and chemotherapy, ESGO and ESTRO were also involved from the beginning of the consensus process,” she said.
Forty experts in the management of endometrial cancer convened in December 2014 to develop recommendations on prevention, screening, surgery, adjuvant treatment, and advanced and recurrent disease.
The experts reviewed all relevant scientific literature but did not undertake a systematic literature search, she noted.
Reaching a consensus was easy in a few areas, but more difficult in others, Dr Colombo said.
“For example, regarding surgery, the most controversial issues were the need for lymphadenectomy as part of the staging procedure, and also the extent of lymphadenectomy,” she said.
“The indications for adjuvant treatment and the type of adjuvant therapy were also highly debated. The most controversial areas related to the indications for brachytherapy or external-beam radiotherapy and the use of chemotherapy combined with, or instead of, radiotherapy,” Dr Colombo said.
Lack of Good Data to Guide Decision Making
In all, the consensus panel made 31 recommendations regarding adjuvant treatment. Of these, 60% were scored as only grade B or C recommendations based on level III or IV evidence.
This situation reflects the particular challenges of endometrial cancer as a subject for study, Dr Eifel said.
“Endometrial cancer is not an easy disease to study because most patients with endometrial cancer are cured with hysterectomy alone. Relatively few patients have high-risk endometrial cancer. If a trial has narrow eligibility criteria, including only patients who have high-risk disease, it is difficult to accrue enough patients to get an answer. However, if a trial has broad eligibility criteria that encompass relatively low-risk patients who have a small margin for improvement from the adjuvant treatment that you are investigating, a potentially important benefit from adjuvant treatment may be obscured,” she said.
“Also, older studies may lose relevance as diagnostic and treatment methods evolve. For these reasons, we have little high-level data to guide the use of adjuvant treatments,” Dr Eifel said.
Of the more than 100 recommendations made in the consensus document, only two were scored as grade A recommendations backed by level I evidence, she pointed out. They are the suggested use of minimally invasive surgery for low- and intermediate-risk endometrial cancer and the recommendation to withhold any adjuvant treatment from patients with very-low-risk disease.
Trust in the Guidelines
For practicing clinicians, being able to trust secondary sources is important, Dr Eifel said.
“Trying to go back to the primary references, which are so complex, is probably not the best thing to do unless you really are making a study of an aspect of endometrial cancer management. The ESMO/ESGO/ESTRO guidelines involved 40 people, all very knowledgeable in this field. Their guidelines provide clinicians with a practical guide to the application of various treatment options in the context of current evidence,” she said.
In addition to the new ESMO guidelines, two other guidelines exist: the American Society for Radiation Oncology (ASTRO) guidelines, published in 2014, and the National Comprehensive Cancer Network guidelines, which are updated annually.
The ASTRO guidelines focus on the role of adjuvant treatment, whereas the ESMO guidelines are more comprehensive, Dr Eifel said.
Ultimately, much more study is needed before clinicians can be confident that they understand how to best use adjuvant treatments in the management of endometrial cancer, she said.
In the mean time, the ESMO/ESGO/ESTRO and ASTRO guidelines “help to bring order to a complex and often confusing literature and provide an invaluable framework for clinical decision making,” Dr Eifel said.
“We hope that this consensus statement will help people make informed decisions about the treatment of patients with endometrial cancer,” Dr Colombo added.
We may also expect to see a more uniform treatment philosophy emerge.
“As a result, we may also expect to see a more uniform treatment philosophy emerge, which could help future analyses of retrospective data and an improved interpretation of outcomes. We also hope that the identification of several areas for which level I evidence does not exist will stimulate investigators to launch prospective, randomized studies to clarify these unanswered questions and facilitate international collaboration,” she said.
Dr Colombo and Dr Eifel report no relevant financial relationships.