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Endometrial carcinoma stages I and II: is surgery adequate?

Endometrial carcinoma stages I and II: is surgery adequate?

Im J Kadiarron Oncology tlml CZPergamon Press Ltd.. 1980 036&03I6/80/003&0365$02.00/0 Phys.. Vol. 6. pp. 365-366 Printed m the US A ??Current Conce...

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Im J Kadiarron Oncology tlml CZPergamon Press Ltd.. 1980


Phys.. Vol. 6. pp. 365-366 Printed m the US A

??Current Concepts in Cancer: Uterine Fundal Cancer



Corpus., Carcinoma,


MORROW, Hospital.


1240 North Mission Rd., Los Angeles, CA 90033

Surgery, Treatment.

identified the vagina and especially the vaginal apex as a major area of metastasis or recurrence. Although considerable surgical-pathologic data accumulated in the literature that the pelvic nodes were an important site of metastasis in clinically early endometrial cancer4 the information was largely ignored or discounted since it was believed that few of these women survived long. This somewhat fallacious impression was given by reports dealing with cases of advanced disease and node metastasis. Lewis, Stallworthy and Cowdell reported the first systematic surgical-pathological study of pelvic node metastasis in endometrial cancer demonstrating a significant risk for patients with deep myometrial invasion or with less than well differentiated lesions. Four of their eleven patients with positive nodes survived five years or more. This study was flawed by the failure to evaluate the status of the aortic nodes. A more recent study undertaken at Duke University, the University of Mississippi and the University of Southern California as a Gynecologic Oncology Group pilot confirmed the report of Lewis, et al, regarding pelvic node metastasis in endometrial carcinoma.’ Among 140 women with International Federation of Gynecology and Obstetrics (FIGO)’ Stage I endometrial carcinoma I6 (I 1.4%) had pelvic node metastasis. Occult aortic node metastases were detected in eight of 100 patients undergoing routine node sampling. Further analysis revealed that two-thirds of the patients with pelvic node metastasis had aortic node disease while only one patient had aortic node involvement without pelvic node metastases. The risk of nodal metastasis was clearly related to depth of myometrial penetration and histologic grade (Table I). When the cervix or isthmus was involved by tumor (8% of cases) the incidence of pelvic node metastasis was 33%. In addition to cervical extension and nodal spread 7% had adnexal metastasis and 5% had peritoneal implants and/or positive peritoneal cytology. Based on these data the behavior of endometrial carci-

Treatment of any malignant disease must be based upon its pattern of spread. To a certain degree this dictum has not been applied to endometrial carcinoma, the treatment of which evolved from reported end results focusing on one site of spread or recurrence, the vagina. Data regarding the natural history of endometrial carcinoma has accumulated from autopsy studies, clinical observation and surgical-pathologic investigations. This disease does not have a uniform behavior. Even within the same clinical or surgical stage, there are wide variations in its natural history and, therefore, prognosis. But treatment can modify its natural history. Is surgery alone adequate’? If the malignant tumor is not just apparently confined to the uterus (Stage I) but is actually limited to the primary site, cure would always result from hysterectomy. And if the disease were always lirrlited to the uterus there could be no discussion about “prognosis”. The ability of endometrial cancer to spread out:;ide the uterus, however, has been documented by every publication about this disease. Clinical studies have established that the prognosis in endometrial cancer correlates with the extent of disease outside the uterus, the virulence of the malignancy and its susceptibility to treatment. In Stages I and II. by definition, it is the clinically occult disease at the time of diagnosis which must be reckoned with in treatment planning to improve the prognosis of the group as a whole. If surgery alone is to be adequate therapy presumably it must remove the primary lesion and all extrauterine deposits. The design of an operation more extensive than a simple hysterectomy must be patterned after a very precise knowledge of the predictable sites of spread of endometrial cancer. In the past, misconceptions developed from anatomic studies of lymphatic drainage of the uterus and also from necropsies on women who died with (usually of) endometrial cancer. These studies emphasized the aortic nodes as the primary site of lymphatic drainage from the fundus, and metastases from endometrial carcinoma. Clinical experience, on the other hand, Accepted for publication


24 October 1979. This study was supported by NIH Grant No. CA20501-02. 365




0 Biology ?? Physics

Table 1. Relationship of pelvic node metastasis to myometrial penetration and histologic grade Histologic

grade Total

Depth of invasion z l/3 5 l/3 Total

1 No. l/60 l/5 2/65

2 (%)






(1.6) 4/42 (20.0) 2/8 (3.0) 6/50

(9) (25) (12)

4/14 4/11 8/25

(28) 9/116 (7.8) (36) 7/24 (29.0) (32) 16/140(11.4)

Modified from Creasman



et al. 1976.’

noma Stage 1 and II can be summarized as follows. The cancer grows locally, invades the myometrium and advances toward the cervix. It embolizes to the pelvic and aortic nodes as well as to the para-cervical and vaginal lymphatics. The cuff recurrence, is a result of transecting lymphatics already containing tumor rather than drop metastasis at surgery.’ This phenomenon is well known in breast cancer and melanoma. Adnexal spread also occurs via lymphatics; the risk increases with tumor dedifferentiation. A little appreciated site of early “spread” is the peritoneal cavity; this was found in 5% of patients in the Gynecologic Oncology Group study based on cytologic examination. Tumor cells reach this area via the tubal lumen or from direct contamination after near full thickness penetration of the myometrium. The therapeutic implications of these data are compelling. It is obvious that, for many patients with endometrial cancer, non-radical surgery is sufficient for cure,

e.g., grade 1, negative cytology, negative cervix, and superficial or no muscle invasion. It is also apparent that surgery of any dimension cannot encompass the disease in a patient with positive aortic nodes or positive peritoneal cytology. For the remaining patients, some consider-

March 1980, Volume 6. Number 3

ation must be given to the risk: benefit ratio of extended therapy by any modality. When should the parametria. pelvic nodes and aortic nodes be treated? It is not feasible to routinely sample or remove these nodes in order to document the presence of metastasis since many of these women are elderly, especially those who are most likely to have poorly differentiated cancers. The decision to extend treatment must be based on an arbitrary judgment of the risk of extended treatment relative to the probability of metastasis. We now have good information regarding the risk of spread of the various histologic grades and degrees of myometrial invasion. When the risk of pelvic node metastasis exceeds some minimum, e.g., 5%, then treatment should be extended to the parametria and pelvic nodes. This can be accomplished by a radical hysterectomy and pelvic lymphadenectomy, an operation which has been used sporadically in Stage II endometrial cancer. It is not applicable in many cases, however, because of the commonly associated medical problems such as obesity, heart disease and diabetes. Radiation therapy has been used successfully for years to extend the treatment field of endometrial cancer to the regional lymphatics. Systemic therapy, either hormonal or cytotoxic, will undoubtedly prove to be necessary for those patient with disease outside the pelvis. In conclusion, in the average middle-upper class population among which endometrial cancer is so common, surgery alone is adequate therapy for approximately 40-50% of the patients, i.e., those with grade 1 lesions with no or early myometrial invasion. Adjunctive therapy is warranted for the other 50-60% based on our knowledge of the probability that microscopic regional metastases are present. Few patients who need extended treatment will be medically or physically suited to radical surgery.

REFERENCES Creasman, W.T., Boronow, R.C., Morrow, C.P., DiSaia, P.J., Blessing, J.: Adenocarcinoma of the endometrium: Its metastatic lymph node potential. Gynecol. Oncol. 4: 239243, 1976. International Federation of Gynecologists and Obstetricians (FIGO): Classification and staging of malignant tumors in the female pelvis. Acta Obstet. Gynecol. Stand. 50: l-12,1971. Lewis, B.V., Stallworthy, J.A., Cowdell, R.: Adenocarci-

noma of the body of the uterus. J. Obstet. Gynecol. Br. Commonw. 77: 343-348, 1970. D.E.: Current 4. Morrow, C.P., DiSaia, P.J., Townsend, management of endometrial carcinoma. Obstet. Gynecol. 42: 399-406,1973. 5. Morrow, C.P., DiSaia, P.J., Townsend, D.E.: The role of postoperative irradiation in the management of stage I adenocarcinoma of the endometrium. Am. J. Roentgenol. 127: 325-329,1976.