Routine Surgical Staging in Grade 1 Endometrial Cancer Appears Beneficial

Abstract & Commentary

By Robert L. Coleman, MD, Associate Professor, University of Texas; M.D. Anderson Cancer Center, Houston TX. Dr. Coleman is on the speaker’s bureau for GlaxoSmithKline, Bristol Myers-Squibb, and Ortho Biotech.

Synopsis: Surgical staging in patients presenting with grade 1 endometrial cancer significantly impacted postoperative treatment decisions in 29% of patients. Omitting lymphadenectomy in patients presenting with grade 1 endometrial cancer may lead to inappropriate postoperative management.

Source: Ben-Shachar I, et al. Surgical staging for patients presenting with grade 1 endometrial carcinoma. Obstet Gynecol. 2005;105:487-493.

Endometrial cancer is the most common gynecologic malignancy and is usually characterized by limited disease at presentation. Among the number of known prognostic factors, grade of disease is one frequently used to triage patients for formal surgical staging. Ben-Shachar and colleagues address the clinico-pathological features and treatment recommendations of well-differentiated (grade 1) endometrial cancer in a retrospective review of surgically staged patients. Over a 6.5-year period, 181 patients were identified with pre-operative grade 1 endometrial cancer. Whether defined by endometrial biopsy or dilation and curettage, all patients underwent formal surgical staging including pelvic and para-aortic lymphatic dissection, cytology and for intraoperatively identified high-risk histology, intraperitoneal biopsies or debulking. Final histology of grade 1 was seen in 81% of patients with no difference identified between the preoperative sampling techniques. Two patients with grade 1 preoperative sampling were found intraoperatively to have sarcoma.

In all, half of the patients were found with non-invasive disease. The remainder had myometrial invasion (33%), cervical extension (7%), adnexal metastases or positive cytology (4%), nodal spread (4%), or intra-abdominal spread (3%). Based on commonly used criteria for surgical staging (grade 1-2 with depth of invasion > 50%, grade 3, cervical extension, high-risk histology), 26% of these grade 1 lesions would have warranted complete staging. Importantly, more than half of these of patients (n = 30/54) with high-risk uterine features required no further therapy based on their surgical findings. Overall, 29% of grade I patients (12% treated and 17% untreated) were benefited by information gained by formal surgical staging. Ben-Shachar et al conclude that even this apparent “low-risk” group of patients requires formal surgical evaluation for treatment precision.

Commentary

Following a series of prospective clinico-pathological observational studies, FIGO, in 1988, changed the staging schema of uterine cancer from one derived from preoperative clinical findings to one based on surgical evaluation of the uterine and extra-uterine sites as well as grade. Appropriate assignment of stage now requires resection of the uterus, evaluation of peritoneal cytology, retroperitoneal node evaluation and peritoneal inspection. The immediate implication from this new classification algorithm was that specialized and directed surgical biopsy is needed to provide information that more accurately describes the distribution of disease. While the principal goal of staging is to facilitate communication among physicians and patients regarding a designated disease status, the allocation of a particular stage is often used for treatment triage and in many cases, has prognostic implications. A check on surgical staging in a 1996 report revealed that less than a third of newly diagnosed endometrial patients were undergoing staging procedures.1 While likely increased today, there is still a prevailing bias that the earliest lesions (grade 1) don’t carry enough risk to warrant routine formal surgical staging. This is the principal focus of the current paper by Ben-Shachar et al.

Precision of treatment in this disease implies that those who need adjuvant treatment get it and those who don’t, don’t get it. For instance, 20 patients with grade I tumors were found with nodal or intraperitoneal metastases, including 4 in whom no other clues to its presence (depth of invasion or higher grade tumor) were apparent. In addition, 30 patients with high-risk uterine features but without metastases were not treated after surgical staging. This mirrors the results of a survey of gynecologic oncologists who would recommend adjuvant therapy based on whether surgical staging data were available. In nearly every category of grade and depth of invasion, a significant “overuse” of adjuvant therapy would be recommended in the absence of surgical staging data.2 Further, some investigators have advocated complete lymphadenectomy as a therapeutic maneuver in patients with uterine cancer.3 However, study limitations such as patient selection bias have made this a controversial topic. Fortunately, the merits of this procedure are being evaluated in a prospective randomized trial (MRC-ASTEC trial).4

The case for routine surgical staging in medically fit patients is usually counterbalanced by concerns of morbidity and simple availability. Although, experience from prospective randomized trials and retrospective series suggests the morbidity is low, there is little solution for those patients treated in areas where gynecologic oncology expertise is unavailable. Knowledge of staging procedures by the gynecologist can aid other surgeons if called upon to provide the needed samplings. In this regard, an important distinction should be made for high-risk histology (eg, papillary serous), where intraperitoneal spread rates, even among apparent stage I patients, occurs sufficiently high enough to warrant intraperitoneal staging similar to ovarian cancer.5

There’s little controversy that patients with grade 1 lesions are most likely to have the most favorable uterine findings. However, utilizing that rule of thumb to plan surgical management overlooks more than a quarter of patients who would benefit from formal evaluation. Whether that is accomplished by patient referral or co-management with gynecologic oncology is immaterial as long as the appropriate data are retrieved.6

References

1. Partridge EE, et al. The National Cancer Data Base report on endometrial cancer. J Surg Oncol. 1996;61:111-123.

2. Naumann RW, et al. The use of adjuvant radiation therapy by members of the Society of Gynecologic Oncologists. Gynecol Oncol. 1999;75:4-9.

3. Seago DP, et al. Potential benefit of lymphadenectomy for the treatment of node-negative locally advanced uterine cancers. Gynecol Oncol. 2001;83:282-285.

4. Creutzberg CL, et al. Outcome of high-risk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the Postoperative Radiation Therapy in Endometrial Carcinoma Trial. J Clin Oncol. 2004;22:1234-1241.

5. Slomovitz BM, et al. Uterine papillary serous carcinoma (UPSC): a single institution review of 129 cases. Gynecol Oncol. 2003;91:463-469.

6. Pearl ML, et al. Outcomes of endometrial cancer patients undergoing surgery with gynecologic oncology involvement. Obstet Gynecol. 2002;100:724-729.