GYNECOLOGIC ONCOLOGY 35, 349-35 1 (1989)

Ovarian Management at the Time of Radical Hysterectomy for Cancer of the Cervix

SHERI OWENS, M.D., WILLIAM S. ROBERTS, M.D.,’ JAMES V. FIORICA, M.D., MITCHEL S. HOFFMAN, M.D., JAMES P. LAPOLLA, M.D., AND DENIS, CAVANAGH, M.D.

Division of Gynecologic Oncology, Department of Obstetrics und Gynecology, University of South Florida College of Medicine, Tumpu, Floridu 33612

Received November 14, 1988

Ovarian management at the time of radical hysterectomy for cervical cancer was reviewed retrospectively over a 7-year period. All patients had early-stage cancer except three who had stage IIB disease. Approximately 80% of patients had squamous cancer and 20% adenocarcinoma or adenosquamous carcinoma. The mean age was 44, and 24% of patients were 35 or younger. Ninety- nine patients had their ovaries removed. None of the ovaries contained metastatic disease including 22 patients with adeno- carcinoma or adenosquamous carcinoma. Of the 17 patients with retained ovaries 14 had transposition into the paracolic gutters. Only one of the 14 patients with transposed ovaries developed symptoms of ovarian failure. No patients with retained ovaries developed metastatic disease or required reoperation secondary to new ovarian pathology. It is our opinion that normal ovaries can be preserved in young women at the time of radical hyster- ectomy for early cervical cancer regardless of histologic type. 0 1989 Academic Press, Inc.

INTRODUCTION

Cervical carcinoma occurs in a significant number of young women with many years of ovarian function re- maining. Since the mean age of menopause in the United States is 51.4 years [I], as many as 50% of patients treated with radical hysterectomy for early-stage carci- noma of the cervix will have 10 or more years of ovarian function left. In these women the benefit of continued ovarian function must be weighed against the risk of microscopic metastatic disease, the later development of ovarian malignancy, and the development of benign ovar- ian pathology requiring further surgery. The risk of mi- croscopic ovarian metastases in early-stage carcinoma of the cervix is almost negligible [2,3]. Early-stage ad-

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enocarcinoma may be an exception, but this is contro- versial [4,5].

The incidence of subsequent development of ovarian malignancy after hysterectomy has been estimated to be 0.2% [6,7]. Between 3 and 24% of patients with ovarian cancer have had a previous abdominal hysterectomy or pelvic laparotomy of some type [8-l 11. Three to four percent of these patients are under age 40 when they have these operations [8-l 11. It would seem that the development of subsequent ovarian malignancy is not a prohibitive risk in terms of ovarian preservation at the time of radical hysterectomy for carcinoma of the cervix.

The incidence of development of benign ovarian pa- thology requiring reoperation after hysterectomy is es- timated to be 2 to 4% [ 12-141. Unfortunately, the surgery may be technically difficult with accompanying morbid- ity. This is especially true in patients who have had radical hysterectomy. However, once again the risk of this complication is too low to eliminate consideration of ovarian preservation at the time of radical hyster- ectomy.

With the availability of estrogen replacement therapy the question arises as to whether the patient should face the apparently minimal risk of ovarian preservation at all. The comparability of estrogen replacement therapy to endogenous hormone production in terms of side ef- fects, delayed complications, and alleviation of post- menopausal symptoms is really not known. As a result it is impossible to determine whether the risk of ovarian preservation is more or less than that of estrogen re- placement therapy.

In this controversial setting we decided to review our experience with ovarian management at the time of rad- ical hysterectomy for cervical cancer.

349 0090-8258189 $I SO

Copyright 0 1989 by Academic Press, Inc. All rights of reproduction in any form reserved.

350 OWENS ET AL.

MATERIALS AND METHODS

The medical records of 116 patients undergoing radical abdominal hysterectomy with pelvic lymphadenectomy for invasive cervical cancer between January 1980 and August 1987 were reviewed retrospectively. The medical records of nine additional patients could not be located. The records were reviewed with emphasis on the his- tology of the ovaries, the symptoms of estrogen defi- ciency and the need for estrogen replacement in patients whose ovaries were not removed, and the need for ad- ditional surgery as a result of ovarian preservation.

Two of the radical hysterectomies were associated with pregnancy and were preceded by cesarean section. The mean age of the patients at the time of surgery was 44 years, with a range of 25 to 86 years. Fifty percent of the patients were less than 41 years old and 24% were 35 years of age or less. The mean parity was 2.8, with a range of 0 to 10. Two patients had stage IA disease, one hundred eight patients had stage IB disease, two patients had stage IIA disease, three patients had stage IIB disease, and one patient had recurrent cancer after pelvic radiation therapy. Of the 116 patients, 90 (78.4%) had squamous carcinoma. Seventeen patients (15.5%) had adenocarcinoma, six patients (5.1%) had adenos- quamous carcinoma, one patient had a carcinosarcoma, one patient had an embryonal rhabdomyosarcoma, and one patient had a lymphoma.

RESULTS

Of the 116 patients, 99 had both ovaries removed at the time of radical hysterectomy. Two patients had only one ovary removed. No metastatic disease was detected in any of the removed ovarian tissue on histologic re- view. All but one of the patients with adenocarcinoma or adenosquamous carcinoma had both ovaries removed at the time of surgery. The one patient whose ovaries were preserved at the original operation had her ovaries removed at the time of exploration for pelvic exenter- ation, and histologic evaluation was negative for meta- static disease.

Of the 17 patients in whom one or both ovaries were preserved, 14 had stage IB disease and 2 of the 14 had only one ovary transposed.

Sixty-five (56%) of the patients in this series received postoperative external pelvic radiation therapy for pos- itive pelvic lymph nodes, deep cervical stromal invasion, or extensive lymphatic space involvement. Eight of the fourteen patients who had transposition of their ovaries had postoperative radiation therapy. Only one of these patients required estrogen replacement therapy for es- trogen deficiency symptoms. This patient was one of the two who had only one ovary transposed. There were no

discernible complications in the transposed ovary group and no patients developed metastatic disease in the trans- posed ovary. The median follow-up was 18 months, with a range of 6 months to 3 years. Of the three patients with retained ovaries without transpositions, two re- ceived postoperative pelvic radiation therapy. Both of these patients developed estrogen deficiency symptoms and required estrogen replacement therapy. One of these patients later had a unilateral oophorectomy in conjunc- tion with surgery for a pelvic lymphocyst. In view of multiple confounding factors and the relatively short fol- low-up of the patients, no attempt was made to analyze survival in terms of comparing patients with ovarian preservation with those who had their ovaries removed.

DISCUSSION

While cervical cancer typically strikes women in their forties and fifties, a significant number of women with invasive cancer of the cervix are under 40 and these numbers appear to be increasing. These younger women potentially have many years of ovarian function left. It would be unfortunate to prematurely castrate these women unncessarily. This may not only interfere with quality of life, but may predispose to the complications of estrogen deficiency such as osteoporosis.

While ovarian preservation has been advocated by some for several years, there has been concern among others as to the metastatic potential of cancer of the cervix to the ovaries. Recently, Mann et al. cited two case reports of microscopic metastases in two patients with stage IB adenocarcinoma of the cervix [41. How- ever, Kjorstad and Bond reported only two cases of ovarian metastases in 150 patients with adenocarcinoma of the cervix. In both patients the carcinoma had ex- tended to the uterine fundus [5]. Others have also noted a low potential for cancer of the cervix to metastasize to the ovaries [2,3]. In our study there were no ovarian metastases in any patient regardless of the histologic type of cervical cancer. It appears that although cervical can- cer has the potential to metastasize to the ovaries it does so infrequently. This makes it difficult to justify routine oophorectomy in young women undergoing radical hys- terectomy for cervical cancer.

Continued function in retained ovaries after radical hysterectomy for cervical cancer is supported by the gynecologic literature. Ellsworth et al. assessed the ovar- ian function of 20 women after radical hysterectomy for cervical cancer. They measured the levels of serum FSH, LH, and progesterone and found that 80% of the women retained ovarian function [15]. Others have also dem- onstrated continuing ovarian function after radical hys- terectomy [3,7,16]. In our series only one of the 14 pa- tients with transposed ovaries required estrogen

OVARIAN MANAGEMENT IN

replacement therapy for symptoms of estrogen defi- ciency. This patient had only one ovary transposed and also received postoperative pelvic radiation therapy. Ells- worth et al. noted a higher incidence of ovarian failure in patients in whom only one ovary was transposed [ 151.

A residual ovary syndrome has been described by Christ and Lotze [17]. Studies involving ovarian pres- ervation after radical hysterectomy have shown that reo- peration for complications associated with retained ova- ries is not excessive [3,7,15,16]. In our study only one patient subsequently underwent unilateral oophorectomy associated with reoperation for a pelvic lymphocyst.

While there is a risk of complications with retained ovaries, the risk is small and probably should not pre- clude preservation of normal-appearing ovaries at the time of radical hysterectomy for cervical cancer. There does not seem to be an increased risk of ovarian cancer in women with retained ovaries who have received ex- ternal pelvic radiation [ 181. Follow-up in our group of patients is too short to calculate survival rates for pa- tients with retained ovaries as compared to patients with bilateral oophorectomies. However, in the study by Webb et al. there was no difference in survival between the two groups at 5 years [18].

It would seem that young women undergoing radical hysterectomy for early cancer of the cervix, regardless of the histologic type, should be given the option of ovarian preservation. If the ovaries are preserved, they should be transposed to the paracolic gutters to avoid excessive radiation in patients who receive postoperative pelvic radiation.

REFERENCES

I. Speroff, L., Glass, R. H., and Kase, N. G. Clinical gynecologic endocrinology and infertility, Williams & Wilkins, Baltimore, 3rd ed. pp. 114-133 (1983).

2. Parente, J. T., Sillberblatt, W., and Slone. M. Infrequency of metastases to ovaries in stage I carcinoma of the cervix, Amer. J. Obstet. Gynecol. 90, 1362 (1964).

3. Webb, G. A. The role of ovarian conservation in the treatment of

4.

5.

6.

I.

8.

9.

IO.

II.

I2

I3

I4

I5

I6

17.

18.

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carcinoma of the cervix with radical surgery, Amer. J. Obstet. Gynecol. 122, 416-484 (1975). Mann, W. T., Chumas, J., Amalfitano, T., Westerman, C.. and Patsner, B. Ovarian metastases from stage I-B adenocarcinoma of the cervix, Cancer 60, 1123-l 126 (1987). Kjorstad, K. E., and Bond, B. Stage I-B adenocarcinoma of the cervix: Metastatic potential and patterns of dissemination, Amer. J. Obstet. Gynecol. 150, 297-299 (1984).

Reycraft, J. L., in discussion, Counsellor, V. S., Hunt, W., and

Haigler, F. H. Carcinoma of the ovary following hysterectomy, Amer. 1. Obstet. Gynecol. 69, 538-546 (1955). Ranney, B., and Abu-Ghazaleh, S. The future function and fortune of ovarian tissue which is retained in vivo during hysterectomy, Amer. .I. Obstet. Gynecol. 128, 626-632 (1977). Counsellor, V. S., Hunt. W., and Haigler, F. H. Carcinoma of the ovary following hysterectomy, Amer. J. Obstet. Gyneco/. 69, 538-546 (1955). Terz, J. J.. Barber, H. R. K., and Brunschwig, A. The incidence of carcinoma in the retained ovary, Amer. J. Surg. 113, 51 I-515 (1967). Gibbs, K. E. Suggested prophylaxis for ovarian cancer, Amer. J. Obstet. Gynecol. 111, 756-765 (1971). Finazzo, M. S., Hoffman, M. S., Roberts, W. S., and Cavanagh, D. M. Previous pelvic surgery in patients with ovarian cancer, South Med. J. 81, 1518-1520 (1988).

Mattingly, R. F., and Thompson, J. D. TeLinde’s operative gyne- colog.v, J. B. Lippincott, Philadelphia, 6th ed., pp. 226-227 (1985). DeNeff, J. C., and Hollenbeck, Z. J. R. The fate of ovaries pre- served at the time of hysterectomy, Amer. J. Obstet. Gynecol. 96, 1088-1098 (1967). McKenzie, L. L. On discussion of the frequency of oophorectomy at the time of hysterectomy, Amer. J. Obstet. Gynecol. 100, 724- 726 (1968). Ellsworth, L. R., Allen, H. H., and Nisker, J. A. Ovarian function after radical hysterectomy for stage I-B carcinoma of cervix. Amer. J. Obstet. Gynecol. 145, 185-188 (1983).

Hodel, K., Rich, W. M.. Austin, P., and DiSaia, P. J. The role of ovarian transposition in conservation of ovarian function in radical hysterectomy followed by pelvic radiation, Gynecol. Oncol. 13, 195-202 (1982).

Christ, J. E., and Lotze, E. C. The residual ovary syndrome. Obstet. Gynecol. 46, 551-556 (1975). Smith, P. G., and Doll, R. Late effects of X irradiation in patients treated for metropathia haemorrhagica, &it. J. Radiat. 49, 224- 232 (1976).