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Optimal surgical therapy in stage I and II ovarian malignancies
036(r3016/82/020247-03SO3.C0/0 Copyright 0 1982 Pergamon Press Ltd.
Inr. 1. Radiation onrology Biol. Phys.. Vol. 8. pp. 247-249 Printed in the U.S.A. All rights reserved.
0 Current Concepts in Cancer: Ovary--Management
of Stage I and II Disease
OPTIMAL SURGICAL THERAPY IN STAGE I AND II OVARIAN MALIGNANCIES M.
STEVEN PIVER,
M.D.
Deputy Chief, Department of Gynecologic Oncology, Roswell Park Memorial Institute and Clinical Professor of Gynecology, State University of New York at Buffalo, Buffalo, New York 14263 surgical staging to be certain that occult or subclinical metastases are not present. Borderline carcinomas. Borderline carcinomas of the ovary are the counterparts of invasive serous, mutinous, clear cell, and endometrioid adenocarcinomas. Borderline carcinomas, however, are characterized by proliferative activity of the glands and nuclear abnormalities of the cells, but without invasion of the stroma. Since unilateral borderline carcinomas have an approximate 100% survival rate, unilateral salpingo-oophorectomy without adjuvant therapy is optimal treatment for those patients desiring to retain future child-bearing capacities.’ Sex cord stromal tumors. Females sex cord stromal tumors consist of granulosa, granulosa-theta, and thecoma. A diagnosis of malignancy by histologic criteria of a unilateral granulosa or granulosa-theta cell tumor is most difficult. This is in part because these tumors are composed of cells with the appearance of the granulosa layer of the developing follicle and frequently lack the common characteristics of anaplasia. Therefore, it is difficult for the pathologist to actually state whether malignancy is present or not. In addition, they have a very low malignant potential as evidenced by the reported 5 year actuarial survival rates of 97% for granulosa and granulosa-theta and 100% for thecomas.’ Since only approximately 5% of these tumors are bilateral, metastasis are rare, and it is difficult to distinguish benign from malignant granulosa-theta cell tumors histologically, only conservative unilateral salpingo-oophorectomy should be carried out in children and young women. Male type sex cord stromal tumors consist of sertolileydig (arrhenoblastoma), sertoli, and hilus cell tumors. The rationale applied to the feminizing sex cord stromal tumors also applies to male type sex cord stromal tumors: they have a low rate of bilateraiity, metastases are rare, it is difficult to distinguish benign from malignant male type sex cord stromal tumors, and they have a low malignant potential. The latter is evidenced by the 5%
Optimal surgical treatment in clinical Stage IA (limited to one ovary) ovarian cancer depends on: 1) the age of the patient, 2) the histology of the ovarian tumor, 3). the incidence of bilateral ovarian involvement, and 4) necessity for and the type (radiation or chemotherapy) of adjuvant therapy. Stage IB (bilateral ovarian involvement) or Stage II ovarian malignancies (metastasis to.the uterus, fallopian tube, or pelvic structures) always require non-conservative surgery (hysterectomy and bilateral salpingo-oophorectomy) regardless of the age of the patient, the histology of the tumor, or the type of adjuvant therapy. Conservative surgery (unilateral salpingo-oophorectomy) would only be appropriate for young women with limited ovarian malignancies (IA) which have a low incidence of bilaterality and in which adjuvant therapy, if required, would not destroy reproductive capabilities. Conservative unilateral salpingo-oophorectomy (Table 1) Germ cell tumors. Endodermal sinus tumor, embryonal cell carcinoma, immature teratoma, and choriocarcinoma are germ cell tumors that occur primarily in adolescents, are frequently unilateral, and in which adjuvant chemotherapy has significantly improved survival over surgery alone.” Moreover, successful pregnancies have been reported after conservative unilateral salpingo-oophorectomy and the use of adjuvant chemotherapy in these malignancies4 Dysgerminoma, a germ cell tumor, also occurs primarily in adolescents. However, the requisite adjuvant therapy+xternal irradiation-would preclude future pregnancies in these patients. Conservative unilateral salpingo-oophorectomy for Stage IA dysgerminomas without postoperative radiation therapy is associated with a recurrence rate of approximately 25%’ Consideration for conservative unilateral salpingo-oophorectomy without adjuvant radiation therapy requires careful
Accepted for publication 7 October 198 1. 241
248
Radiation Oncology 0 Biology 0 Physics
Table 1. Unilateral salpingo-oophorectomy Stage IA: Young patients Endodermal sinus tumor Embryonal carcinoma Immature teratoma Choriocarcinoma Dysgerminoma* Granulosa Granulosa-theta Thecoma Sertoli-leydig Sertoli Hilus ceil Borderline serous, mutinous, clear cell, or endometrioid carcinoma *See text.
tumor related deaths of 132 women with male sex cord stromal tumors.6 Therefore, unilateral salpingo-oophorectomy in a young patient should be the surgery of choice. When germ cell tumors, borderline carcinomas and sex cord stromal tumors occur in adults, hysterectomy and bilateral salpingo-oophorectomy should be carried out. Non-conservative bilateral salpingo-oophorectomy hysterectomy (Table 2) The common epithelial ovarian tumors-serous,
plus muci-
nous, clear cell, endometrioid and undifferentiated carcinoma-occur primarily in adult women, are frequently bilateral, and require adjuvant therapy even when clinically limited to the ovary. This is evidenced by the report of Fuks’ in which 30% of the women treated by surgery (primarily bilateral salpingo-oophorectomy-hysterectomy) for Stage I ovarian cancer were dead of their malignancy in less than 5 years. Similarly, in Stage II ovarian cancer, 61% of the women treated by surgery were dead of their disease in less than 5 years. The low survival rate after such surgical therapy indicates that a significant number of patients did have unsuspected or subclinical metastasis at the initial surgery. Moreover, the incidence of bilaterality of an occult metastasis in a normal appearing ovary has varied from 12%*to as high as 43%’ Because of the low survival rates for Stage I and II ovarian cancer and the high incidence of bilaterality, optimal surgical therapy requires bilateral salpingo-oophorectomy and hysterectomy plus surgical Table 2. Bilateral salpingo-oophorectomy Stage I & II
plus hysterectomy:
Serous carcinoma Mutinous carcinoma Clear cell carcinoma Endometrioid carcinoma Undifferentiated carcinoma Germ cell tumors: Stage IB or II Sex cord stromal tumors: Adults Borderline carcinoma: Stage IB or II
February 1982, Volume 8, Number 2
staging to detect occult or subclinical metastases. The uterus should be removed in all such instances and is especially important in endometrioid ovarian carcinoma where there is a 25% incidence of concomitant endometrial adenocarcinoma. Surgical staging
In 1973 Bagley and co-authors* first reported the occurrence of unsuspected diaphragmatic metastasis in Stage I and II ovarian carcinomas. This important discovery partly explains why some 30 to 40% of the women with Stage I ovarian carcinoma treated by surgery or surgery plus radiation primarily directed to the pelvis were dead of their disease in less than 5 years. ‘Shortly after the report by Bagley et al., other investigators embarked upon a more formalized surgical staging procedure in Stage I and II ovarian malignancies. We reported a collected review of women who were believed to have limited ovarian cancer (Stage I and II) and who underwent surgical staging for subclinical or occult metastasis (Table 3).” In addition to diaphragmatic metastasis, occult or subclinical metastasis from presumed localized ovarian malignancies were present in the omentum, para-aortic lymph nodes, pelvic lymph nodes, and in cytologic preparations made from saline aspirates from the pelvis and peri-colic spaces. Specifically, 11% of the Stage I and 23% of the Stage II patients were found to have unsuspected diaphragmatic metastasis; 10% of Stage I and 10% of Stage II women had subclinical metastasis to the para-aortic lymph nodes; 8% of Stage I ovarian cancer patients had subclinical metastasis to the pelvic lymph nodes; 33% of Stage I and 13% of Stage II had positive cytologic washings; and 3% of Stage I and none of the Stage II patients had metastasis to the omentum. In a similar study by the Ovarian Cancer Study Group, (National Cancer Institute, Mayo Clinic, M.D. Anderson Hospital and Tumor Institute, and Roswell Park Memorial Institute), 50 patients with Stage I or II ovarian malignancies underwent surgical staging after referral to the above Institutions within 2 months of the initial surgery.” In all such instances the referring physician felt there was no residual malignancy. Of these 50 women, 5% were found to have diaphragmatic metastasis, 15% para-aortic lymph node metastasis, 12% pelvic lymph node metastasis, and 7% omental metastasis. Table 3. Occult or subclinical metastasis in Stage I & II ovarian carcinoma” Metastasis
Stage I %
Stage II %
Diaphragm Omentum Para-aortic nodes Pelvic nodes Malignant cytologic washings
11 3 10 8 33
23 0 10 13
249
Surgical therapy in ovarian malignancies 0 M. S. PIVER
Table 4. Ovarian cancer study group:‘*restaging laparotomy in Stage I & II ovarian carcinoma Metastasis Diaphragm Omentum Para-aortic lymph nodes Pelvic lymph nodes Total unsuspected metastases
% 5 7 15 12 24
Twenty-four percent of these patients thought to be free of disease at initial surgery were found to have residual disease at restaging laparotomy. (Table 4) Therefore, on discovery of a clinical Stage I or II ovarian carcinoma through a previously made subumbilical incision, the incision should be extended above the umbilicus to enable one to inspect the diaphragm and remove the omentum from the transverse colon. Biopsy of any raised lesion on the diaphragm can easily be done
with laparoscopic biopsy forceps and is associated with minimal or no morbidity. Routine biopsy of a normal appearing diaphragm is not advocated. Pelvic and pericolic washings for cytologic evaluation for malignant cells are obtained by instilling 100-200 cc of saline into the pelvis and a similar amount into the right and left peri-colic spaces respectively and aspirating the fluid for cytologic evaluation. Most women with ovarian cancer still are primarily operated upon by gynecologists not trained in para-aortic and pelvic lymph node sampling. Ideally, however, women with clinical Stage I or II ovarian cancer should have biopsy of any palpable paraaortic or pelvic lymph node. Such careful surgical staging will define those patients who are apt to truely have Stage I or II ovarian cancer, improve and refine adjuvant therapy for Stage I and II ovarian carcinoma, and allow for adjuvant therapy for patients found to have Stage III ovarian cancer discovered at the time of surgical staging for presumed localized ovarian cancer.
REFERENCES 1. Asadourian, L.A., Taylor, H.B.: Dysgerminoma: An analysis of 105 cases. Obstet. Gynecol. 33: 370-379, 1969. 2. Bagley, C.M., Jr., Young, R.C., Schein, P.S., Chabner, B.A., DeVita, V.T.: Ovarian carcinoma metastatic to the diaphragm-Frequently undiagnosed at laparotomy. A preliminary report. Am. J. Obstet. Gynecol. 116: 397, 1973. 3. Buka, N.J., MacFarlane, K.T.: Malignant tumors of the ovary. Am. J. Obstet. Gynecol. 90: 383-387, 1964. 4. Forney, J.P.: Pregnancy following removal and chemotherapy of ovarian endodermal sinus tumor. Obstet. Gynecol. 52: 36&362,1978. 5. Fuks, Z.: The role of radiation therapy and the management of ovarian carcinoma. Isr. J. Med. Sci. 13: 815-827, 1977. 6. Ireland, B.K., Woodruff, J.D.: Masculinizing ovarian tumors. Obstet. Gynec. Surv. 31: 83-111, 1976. I. Julian, C.G., Woodruff, J.D.: The biologic behavior of low
grade papillary serous carcinoma Gynecol. 40: 860-867, 1972.
of the ovary.
Obstet.
8. Munnell, E.W.: The changing prognosis and treatment in cancer of the ovary: A report of 235 patients with primary ovarian carcinoma 1952-1961. Am. J. Obstet. Gynecol. loo: 790-805,1968. 9. Norris, H.J., Taylor, H.B.: Prognosis of granulosa-theta tumors of the ovary. Cancer 21: 255-263, 1968. lo. Piver, M.S., Barlow, J.J., Lele, S.B.: Incidence of subclinical metastasis in Stage I and II ovarian carcinoma. Obstet. Gynecol. 52: 100-104, 1978. 11. Piver, M.S., Lurain, J.: Childhood ovarian cancers: New advances and treatment, N.Y. J. Med. 79: 1196-l 199, 1979. 12. Young, R.C., Warton, J.T., Decker, D.G., Piver, MS., Edwards, B., McQuire, W.F.: Staging Laparotomy in early ovarian cancer. ASCO 20: 399, 1979.
Inr. 1. Radiation onrology Biol. Phys.. Vol. 8. pp. 247-249 Printed in the U.S.A. All rights reserved.
0 Current Concepts in Cancer: Ovary--Management
of Stage I and II Disease
OPTIMAL SURGICAL THERAPY IN STAGE I AND II OVARIAN MALIGNANCIES M.
STEVEN PIVER,
M.D.
Deputy Chief, Department of Gynecologic Oncology, Roswell Park Memorial Institute and Clinical Professor of Gynecology, State University of New York at Buffalo, Buffalo, New York 14263 surgical staging to be certain that occult or subclinical metastases are not present. Borderline carcinomas. Borderline carcinomas of the ovary are the counterparts of invasive serous, mutinous, clear cell, and endometrioid adenocarcinomas. Borderline carcinomas, however, are characterized by proliferative activity of the glands and nuclear abnormalities of the cells, but without invasion of the stroma. Since unilateral borderline carcinomas have an approximate 100% survival rate, unilateral salpingo-oophorectomy without adjuvant therapy is optimal treatment for those patients desiring to retain future child-bearing capacities.’ Sex cord stromal tumors. Females sex cord stromal tumors consist of granulosa, granulosa-theta, and thecoma. A diagnosis of malignancy by histologic criteria of a unilateral granulosa or granulosa-theta cell tumor is most difficult. This is in part because these tumors are composed of cells with the appearance of the granulosa layer of the developing follicle and frequently lack the common characteristics of anaplasia. Therefore, it is difficult for the pathologist to actually state whether malignancy is present or not. In addition, they have a very low malignant potential as evidenced by the reported 5 year actuarial survival rates of 97% for granulosa and granulosa-theta and 100% for thecomas.’ Since only approximately 5% of these tumors are bilateral, metastasis are rare, and it is difficult to distinguish benign from malignant granulosa-theta cell tumors histologically, only conservative unilateral salpingo-oophorectomy should be carried out in children and young women. Male type sex cord stromal tumors consist of sertolileydig (arrhenoblastoma), sertoli, and hilus cell tumors. The rationale applied to the feminizing sex cord stromal tumors also applies to male type sex cord stromal tumors: they have a low rate of bilateraiity, metastases are rare, it is difficult to distinguish benign from malignant male type sex cord stromal tumors, and they have a low malignant potential. The latter is evidenced by the 5%
Optimal surgical treatment in clinical Stage IA (limited to one ovary) ovarian cancer depends on: 1) the age of the patient, 2) the histology of the ovarian tumor, 3). the incidence of bilateral ovarian involvement, and 4) necessity for and the type (radiation or chemotherapy) of adjuvant therapy. Stage IB (bilateral ovarian involvement) or Stage II ovarian malignancies (metastasis to.the uterus, fallopian tube, or pelvic structures) always require non-conservative surgery (hysterectomy and bilateral salpingo-oophorectomy) regardless of the age of the patient, the histology of the tumor, or the type of adjuvant therapy. Conservative surgery (unilateral salpingo-oophorectomy) would only be appropriate for young women with limited ovarian malignancies (IA) which have a low incidence of bilaterality and in which adjuvant therapy, if required, would not destroy reproductive capabilities. Conservative unilateral salpingo-oophorectomy (Table 1) Germ cell tumors. Endodermal sinus tumor, embryonal cell carcinoma, immature teratoma, and choriocarcinoma are germ cell tumors that occur primarily in adolescents, are frequently unilateral, and in which adjuvant chemotherapy has significantly improved survival over surgery alone.” Moreover, successful pregnancies have been reported after conservative unilateral salpingo-oophorectomy and the use of adjuvant chemotherapy in these malignancies4 Dysgerminoma, a germ cell tumor, also occurs primarily in adolescents. However, the requisite adjuvant therapy+xternal irradiation-would preclude future pregnancies in these patients. Conservative unilateral salpingo-oophorectomy for Stage IA dysgerminomas without postoperative radiation therapy is associated with a recurrence rate of approximately 25%’ Consideration for conservative unilateral salpingo-oophorectomy without adjuvant radiation therapy requires careful
Accepted for publication 7 October 198 1. 241
248
Radiation Oncology 0 Biology 0 Physics
Table 1. Unilateral salpingo-oophorectomy Stage IA: Young patients Endodermal sinus tumor Embryonal carcinoma Immature teratoma Choriocarcinoma Dysgerminoma* Granulosa Granulosa-theta Thecoma Sertoli-leydig Sertoli Hilus ceil Borderline serous, mutinous, clear cell, or endometrioid carcinoma *See text.
tumor related deaths of 132 women with male sex cord stromal tumors.6 Therefore, unilateral salpingo-oophorectomy in a young patient should be the surgery of choice. When germ cell tumors, borderline carcinomas and sex cord stromal tumors occur in adults, hysterectomy and bilateral salpingo-oophorectomy should be carried out. Non-conservative bilateral salpingo-oophorectomy hysterectomy (Table 2) The common epithelial ovarian tumors-serous,
plus muci-
nous, clear cell, endometrioid and undifferentiated carcinoma-occur primarily in adult women, are frequently bilateral, and require adjuvant therapy even when clinically limited to the ovary. This is evidenced by the report of Fuks’ in which 30% of the women treated by surgery (primarily bilateral salpingo-oophorectomy-hysterectomy) for Stage I ovarian cancer were dead of their malignancy in less than 5 years. Similarly, in Stage II ovarian cancer, 61% of the women treated by surgery were dead of their disease in less than 5 years. The low survival rate after such surgical therapy indicates that a significant number of patients did have unsuspected or subclinical metastasis at the initial surgery. Moreover, the incidence of bilaterality of an occult metastasis in a normal appearing ovary has varied from 12%*to as high as 43%’ Because of the low survival rates for Stage I and II ovarian cancer and the high incidence of bilaterality, optimal surgical therapy requires bilateral salpingo-oophorectomy and hysterectomy plus surgical Table 2. Bilateral salpingo-oophorectomy Stage I & II
plus hysterectomy:
Serous carcinoma Mutinous carcinoma Clear cell carcinoma Endometrioid carcinoma Undifferentiated carcinoma Germ cell tumors: Stage IB or II Sex cord stromal tumors: Adults Borderline carcinoma: Stage IB or II
February 1982, Volume 8, Number 2
staging to detect occult or subclinical metastases. The uterus should be removed in all such instances and is especially important in endometrioid ovarian carcinoma where there is a 25% incidence of concomitant endometrial adenocarcinoma. Surgical staging
In 1973 Bagley and co-authors* first reported the occurrence of unsuspected diaphragmatic metastasis in Stage I and II ovarian carcinomas. This important discovery partly explains why some 30 to 40% of the women with Stage I ovarian carcinoma treated by surgery or surgery plus radiation primarily directed to the pelvis were dead of their disease in less than 5 years. ‘Shortly after the report by Bagley et al., other investigators embarked upon a more formalized surgical staging procedure in Stage I and II ovarian malignancies. We reported a collected review of women who were believed to have limited ovarian cancer (Stage I and II) and who underwent surgical staging for subclinical or occult metastasis (Table 3).” In addition to diaphragmatic metastasis, occult or subclinical metastasis from presumed localized ovarian malignancies were present in the omentum, para-aortic lymph nodes, pelvic lymph nodes, and in cytologic preparations made from saline aspirates from the pelvis and peri-colic spaces. Specifically, 11% of the Stage I and 23% of the Stage II patients were found to have unsuspected diaphragmatic metastasis; 10% of Stage I and 10% of Stage II women had subclinical metastasis to the para-aortic lymph nodes; 8% of Stage I ovarian cancer patients had subclinical metastasis to the pelvic lymph nodes; 33% of Stage I and 13% of Stage II had positive cytologic washings; and 3% of Stage I and none of the Stage II patients had metastasis to the omentum. In a similar study by the Ovarian Cancer Study Group, (National Cancer Institute, Mayo Clinic, M.D. Anderson Hospital and Tumor Institute, and Roswell Park Memorial Institute), 50 patients with Stage I or II ovarian malignancies underwent surgical staging after referral to the above Institutions within 2 months of the initial surgery.” In all such instances the referring physician felt there was no residual malignancy. Of these 50 women, 5% were found to have diaphragmatic metastasis, 15% para-aortic lymph node metastasis, 12% pelvic lymph node metastasis, and 7% omental metastasis. Table 3. Occult or subclinical metastasis in Stage I & II ovarian carcinoma” Metastasis
Stage I %
Stage II %
Diaphragm Omentum Para-aortic nodes Pelvic nodes Malignant cytologic washings
11 3 10 8 33
23 0 10 13
249
Surgical therapy in ovarian malignancies 0 M. S. PIVER
Table 4. Ovarian cancer study group:‘*restaging laparotomy in Stage I & II ovarian carcinoma Metastasis Diaphragm Omentum Para-aortic lymph nodes Pelvic lymph nodes Total unsuspected metastases
% 5 7 15 12 24
Twenty-four percent of these patients thought to be free of disease at initial surgery were found to have residual disease at restaging laparotomy. (Table 4) Therefore, on discovery of a clinical Stage I or II ovarian carcinoma through a previously made subumbilical incision, the incision should be extended above the umbilicus to enable one to inspect the diaphragm and remove the omentum from the transverse colon. Biopsy of any raised lesion on the diaphragm can easily be done
with laparoscopic biopsy forceps and is associated with minimal or no morbidity. Routine biopsy of a normal appearing diaphragm is not advocated. Pelvic and pericolic washings for cytologic evaluation for malignant cells are obtained by instilling 100-200 cc of saline into the pelvis and a similar amount into the right and left peri-colic spaces respectively and aspirating the fluid for cytologic evaluation. Most women with ovarian cancer still are primarily operated upon by gynecologists not trained in para-aortic and pelvic lymph node sampling. Ideally, however, women with clinical Stage I or II ovarian cancer should have biopsy of any palpable paraaortic or pelvic lymph node. Such careful surgical staging will define those patients who are apt to truely have Stage I or II ovarian cancer, improve and refine adjuvant therapy for Stage I and II ovarian carcinoma, and allow for adjuvant therapy for patients found to have Stage III ovarian cancer discovered at the time of surgical staging for presumed localized ovarian cancer.
REFERENCES 1. Asadourian, L.A., Taylor, H.B.: Dysgerminoma: An analysis of 105 cases. Obstet. Gynecol. 33: 370-379, 1969. 2. Bagley, C.M., Jr., Young, R.C., Schein, P.S., Chabner, B.A., DeVita, V.T.: Ovarian carcinoma metastatic to the diaphragm-Frequently undiagnosed at laparotomy. A preliminary report. Am. J. Obstet. Gynecol. 116: 397, 1973. 3. Buka, N.J., MacFarlane, K.T.: Malignant tumors of the ovary. Am. J. Obstet. Gynecol. 90: 383-387, 1964. 4. Forney, J.P.: Pregnancy following removal and chemotherapy of ovarian endodermal sinus tumor. Obstet. Gynecol. 52: 36&362,1978. 5. Fuks, Z.: The role of radiation therapy and the management of ovarian carcinoma. Isr. J. Med. Sci. 13: 815-827, 1977. 6. Ireland, B.K., Woodruff, J.D.: Masculinizing ovarian tumors. Obstet. Gynec. Surv. 31: 83-111, 1976. I. Julian, C.G., Woodruff, J.D.: The biologic behavior of low
grade papillary serous carcinoma Gynecol. 40: 860-867, 1972.
of the ovary.
Obstet.
8. Munnell, E.W.: The changing prognosis and treatment in cancer of the ovary: A report of 235 patients with primary ovarian carcinoma 1952-1961. Am. J. Obstet. Gynecol. loo: 790-805,1968. 9. Norris, H.J., Taylor, H.B.: Prognosis of granulosa-theta tumors of the ovary. Cancer 21: 255-263, 1968. lo. Piver, M.S., Barlow, J.J., Lele, S.B.: Incidence of subclinical metastasis in Stage I and II ovarian carcinoma. Obstet. Gynecol. 52: 100-104, 1978. 11. Piver, M.S., Lurain, J.: Childhood ovarian cancers: New advances and treatment, N.Y. J. Med. 79: 1196-l 199, 1979. 12. Young, R.C., Warton, J.T., Decker, D.G., Piver, MS., Edwards, B., McQuire, W.F.: Staging Laparotomy in early ovarian cancer. ASCO 20: 399, 1979.