- Email: [email protected]
Primary Surgery for Early and Advanced Epithelial Ovarian Cancer
Primary Surgery for Early and Advanced Epithelial Ovarian Cancer Wylam Faught, MD, FRCSC, 1 Michael Fung Kee Fung, MB, BS, FRCSC, 2 1
2
Assistant Professor, Associate Professor, Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, University of Ottawa, The Ottawa Hospital (General Campus), Ottawa, Ontario
Abstract: surgery has been and continues to be the foundation upon which ovarian cancer treatment is built. Surgery in apparent early stage disease is focused on appropriate surgical pathological staging and, in selected patients, the use of a fertility sparing procedure. Primary surgical therapy in advanced disease is most effective when maximal cytoreduction is achieved. Surgical therapy in suspected or established ovarian cancer should ideally be provided by trained personnel. Resume : Ia chirurgie continue d'etre Ia base du traitement du cancer de l'ovaire. Au stade pnkoce de Ia maladie, Ia chirurgie vise a determiner les stades pathologiques chirurgicaux appropries, et, dans certains cas, le recours a des interventions susceptibles de preserver Ia fecondite de Ia patiente. Au stade avance de Ia maladie, Ia therapie chirurgicale primaire est Ia plus efficace lorsqu'une reduction maximale de Ia tumeur est pratiquee. ldealement, le traitement chirurgical du cancer de l'ovaire, soup~onne ou etabli, devrait etre pratique par des specialistes.
J Soc
Obstet Gynaecol Can 2000;22(4):935-41
INTRODUCTION
Epithelial ovarian cancer is the most common cause of death from gynaecological malignan-
cy. In Canada, in 1999, an estimated 2,600 women will be found to have this disease and 1,500 will die. 1 Unfortunately, in part due to lack of effective screening methods, most patients present with advanced stage disease where median progression-free survival is often only 12 to 18 months. Conversely, when disease is surgically confined to the ovary, five-year survival may be as high as 80 to 90 percent. 2 Although other approaches may be important in ovarian cancer treatment, surgery has been and still is the cornerstone of effective management of this disease. Surgical treatment of early stage disease essentially involves removal of the primary tumour, accompanied by comprehensive surgical staging and selective adjuvant theraPY. Treatment of advanced stage disease includes both cytotoxic chemotherapy and surgical tumour debulking of the primary and metastatic disease. Survival in advanced disease is very dependent on the volume of residual disease remaining after the tumour debulking procedure and the tumour response to primary cytotoxic chemotherapy. 3.4 EARLY STAGE DISEASE
KeyWords Epithelial ovarian cancer, surgery, staging. Received on June 7th, 1999. Revised and accepted on August 17th, 1999.
There is a vast body of literature demonstrating the potential of ovarian cancer spread in the face of disease apparently confined to the ovary (Table 1). 5- 7 The rational interpretation of these data would support the concept and approach that comprehensive surgical staging of apparent early stage disease is vital to the appropriate management of ovarian cancer. Not only may patients who require adjuvant therapy be identified, but equally importantly, those patients with stage I low-risk disease not in need of additional therapy can be selected. 8·9 Despite these evidence-based concepts, patients with apparent early stage dis-
TABLE I EARLY OVARIAN CANCER SPREAD
No. of patients with metastasis at site/ total No. of patients with site sampled Study
Peritoneal Omentum cytology
Young et a/. 1983 6 Piver et a/. 19785 Schueler et a/. 1988 7 Total
8/31 3/45 11/76 (14.5%)
6/57 0/5 3/45 9/107 (8.4%)
Diaphragm nodes
Pelvic nodes
Para-aortic
2/58 1/31 1/45 4 (3.0%)
1/1 I
6/52 0/5 2/45 8/102 (7.8%)
ease continue to have inadequate surgical therapy at the time of initial surgical intervention. McGowan et al 10 reported that only 54 percent of patients with carcinoma of the ovary underwent a proper staging procedure. Unfortunately, other reports have confirmed the often inadequate staging of apparent early ovarian cancer, a situation particularly common when the surgeon is not a gynaecological oncologist. 8•11 Table 2 outlines what the data would support as an adequate staging procedure in suspected early stage ovarian carcinoma. With the advent and development of minimal access surgical techniques, ovarian cancer may be managed initially by an endoscopic technique. Unfortunately, new and novel surgical approaches for adnexal masses and a suspicion of early ovarian cancer have not undergone the same scrutiny as either open procedures or chemotherapeutic agents. The endoscopic surgical approach to early ovarian cancer leaves unresolved questions about recurrence and survival following intra-operative tumour rupture and the inability to palpate peritoneal surfaces. The FIGO substages of stage I supported by published data imply that malignant cytological findings, tumour rupture and the presence of a tumour on the ovarian surface confer a poor prognosis. 12 •13 Other investigators have failed to demonstrate a poor prognosis for tumour rupture. 14 •15 Although there is controversy as to whether tumour rupture compromises survival, these patients are assigned to a higher stage according to FIGO staging, and many are subsequently treated with cytotoxic chemotherapy. In addition, there have been reports of trocar port-site hernias and port-site recurrences in patients undergoing laparoscopic management of ovarian cancer. 16 •17 Careful pre-operative assessment of an adnexal mass is, therefore, mandatory, particularly in the post-
I!II (9.1%)
menopausal patient. Guidelines for the laparoscopic management of adnexal masses have recently been published by The Society of Obstetricians and Gynaecologists of Canada. 18 These guidelines were based on data outlining the risk of ovarian malignancy following a thorough pre-operative and intra-operative assessment.
CONSERVATIVE (FERTILITY-PRESERVING} SURGERY Although the vast majority of epithelial ovarian cancers are in post-menopausal women, younger patients and those desirous of future childbearing may be managed in a conservative fashion. Careful pre-operative counselling and consent are required in those patients undergoing a surgical procedure for a suspicious adnexal mass. Ideally, if an apparent stage I ovarian cancer is encountered, the patient would have access to an appropriate surgical staging procedure. In consideration of the patient's desire for future fertility, the formal staging would not primarily include resection of the uterus and contralateral ovary. If the final pathology report describes an epithelial tumour with high-risk features (grade 2 or 3) or a tumour on the ovarian surface, then consideration may be given to a brief course of chemotherapy. Likewise, if metastatic disease is confirmed with the staging procedure, then chemotherapy, hysterectomy, and completion of a bilateral salpingo-oophorectomy should be considered. A patient, however, with a grade I, stage I a tumour may be managed expectandy. 8 ADVANCED STAGE DISEASE
PRIMARY CYTOREDUCTION Although there have been great efforts made towards increasing early detection and treatment of epithelial cancer of the ovary, the majority of patients are diagnosed with advanced stage disease. 2 Not uncommonly, a patient presents with ascites and a large volume of solid disease. Treatment of these patients has traditionally included surgical cytoreduction followed by cytotoxic chemotherapy. Cytoreduction (or debulking) describes a procedure in which the objective is to remove as much tumour as possible in a patient with metastatic ovarian cancer. Many investigators have supported the theoTABLE 2 STAGING LAPAROTOMY FOR EARLY OVARIAN CANCER retical benefits ofsurgical cytoreduction. Based on tumour kinetics and the mechanisms of cytotoxic • Peritoneal washings • Inspection/palpation of peritoneal surfaces chemotherapy, they can essentially be summarized • Total abdominal hysterectomy and bilateral salpingo-oophorectomy as enhanced chemosensitivity of smaller residual (unilateral salpingo-oophorectomy for fertility preservation) tumour nodules versus large bulky tumour mass• Omentectomy es. These perceived benefits are based on Gom• Peritoneal biopsies pertzian tumour growth, the log cell kill hypothesis • Pelvic/para-aortic lymphadenectomy of chemotherapy and an increased probability of JOURNAL SOGC
APRIL 2000
CONCLUSION
TABLE 3 SURVIVAL AND VOLUME OF RESIDUAL DISEASE Study
Wharton and Henson2 1 Piver et a/. 22
Omura et a/. 23
Residual Disease
Median Progression
Median
Free Survival
Survival
(months)
(months)
Optimal
28
Suboptimal
IS
::;2 em
25
~2 em
13
0
48
I em
21
tumour mutation as tumour size increases. 19·20 Numerous studies have also demonstrated the relationship between patient survival and the volume of residual disease following cytoreduction (Table 3). 21 -23 There appears to be a clear survival benefit to those patients with a lower volume of disease after surgery. The number of patients debulked to optimal disease range, in the literature, from 15 to 90 percent. Less apparent is the definition of 'optimal' residual disease, as there may only be a distinct survival advantage when the residual disease approaches microscopic. 23 Tumour biology as well as surgical cytoreduction also appear to influence patient survival. Hoskins et a/. 24 reported two groups of patients. The first group was found during initial surgery to have disease less than one em in diameter while the second group had larger volume disease but were cytoreduced to one em or less. The survival of the first group was longer, implying that, in addition to tumour debulking, tumour biology determines patient survival. Nevertheless, the recommendation of a 1994 NIH Consensus Development Conference on Ovarian Cancer was that "aggressive efforts at maximal cytoreduction are important since minimal residual tumour is associated with improved survival". 25 INTERVAL SURGERY
Based on the knowledge that patients with suboptimal residual disease after primary surgery have such a poor rate of survival, some reports have examined the effectiveness of'interval' surgical debulking, following two to four cycles of cisplatin-based chemotherapy. Van der Burg et af.2 6 reported on a trial evaluating a second or 'interval' cytoreduction in patients with suboptimally reduced ovarian cancer. Interval surgery was preceded and followed by three cycles of chemotherapy. Results of this trial, demonstrating an improved disease-free survival (18 versus 13 months), have led the Gynaecologic Oncology Group to perform a similar trial of interval debulking. 27 Although it would be premature to conclude that interval surgery is the standard of care for suboptimally debulked patients, preliminary data certainly reinforce the goal of optimal cytoreduction in the setting of bulky intraperitoneal disease.
The management of epithelial ovarian cancer, although often multifaceted in its approach, virtually always includes surgical therapy as the cornerstone of effective treatment. Surgery for apparent early stage disease ideally should involve a comprehensive staging procedure by trained personnel. Advanced stage ovarian cancer, although there is debate on the timing and number of surgical procedures, responds best when maximally cytoreduced.
REFERENCES I. 2.
3. 4. 5. 6.
7.
8.
9.
I0. II. 12. 13.
14.
15.
16.
17. 18.
National Cancer Institute of Canada: Canadian Cancer Statistics 1999. Toronto, Canada 1999. Ozols RF, Rubin SC,Thomas G, Robboy S. Epithelial Ovarian Cancer. In: Hoskins WJ, Perez CA,Young RC (Eds). Principles and Practice of Gynecologic Oncology. 2nd ed. Philadelphia: Lippincott-Raven 1997: pp. 919-86. Griffiths CT. Surgical resection of tumor bulk in the primary treatment of ovarian carcinoma. Natl Cancer lnst Monogr 1975;42: I01-4. Redman JR, Petroni GR, Saigo PE, Geller NL, Hakes TB. Prognostic factors in advanced ovarian carcinoma. J Clin Oncol 1986;4(4):515-23. Piver MS, Barlow JJ, Lele SB. Incidence of subclinical metastasis in stage I and II ovarian carcinoma. Obstet Gynecol 1978;52( I): I00-4. Young RC, Decker DG,Wharton JT, Piver MS, SindelarWF, Edwards BK, Smith JP. Staging laparotomy in early ovarian cancer. JAMA 1983; 250(22):3072-6. Schueler JA, Trimbos JB, Hermans J, Fleuren GJ. The yield of surgical staging in presumed early stage ovarian cancer: benefits or doubts? lntJ Gynecol Cancer 1998;8:95-102. Young RC,Walton LA, Ellenberg SS, Homesley HD,Wilbanks GD, Decker DG, Miller A, Park R, Major F Jr. Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials. N Engl J Med 1990;322( IS): I021-7. Faught W. Lotocki RJ, Heywood M, Krepart GV. Early ovarian cancer: value of a negative staging laparotomy. Eur J Gynaecol Oncol 1996; XVII(3):200-3. McGowan L, Lesher LP. Norris HJ, Barnett M. Misstaging of ovarian cancer. Obstet Gynecol 1985;65(4):568-72. Munoz KA, Harlan LC,Trimble EL. Patterns of care for women with ovarian cancer in the United States. J Clin Oncol 1997; 15( II ):3408-15. Webb MJ, Decker DG, Mussey E et al. Factors influencing survival in stage I ovarian cancer. Am J Obstet Gynecol 1973; I 16:222-8. Sains de Ia Cuesta R, Goff B, Fuller A, Nikrui N, Eichborn J, Rice L. Prognostic importance of intraoperative rupture of malignant ovarian epithelial neoplasms. Obstet Gynecol 1994;84: 1-7. Dembo A, Davy M, Stenwig A, Berle E, Bush R, Kjorstad K. Prognostic factors in patients with stage I epithelial ovarian cancer. Obstet Gynecol 1990;75:263-72. Seveida P, Dittrich C, Saizer H. Prognostic value of the rupture of the capsule in stage I epithelial ovarian carcinoma. Gynecol Oncol 1989; 35:321-2. Kadar N, Reich H, Liu CY, Manko GF, Gimpelson R. lncisional hernias after major laparoscopic gynecologic procedures. Am J Obstet Gynecol 1993; 168(5): 1493-5. Kadar N. Port-site recurrences following laparoscopic operations for gynaecological malignancies. Br J Obstet Gynaecol 1997; I04: 1308-13. Guidelines for the laparoscopic management of the adnexal mass. SOGC Clinical Practice Guidelines (No. 76, September 1998). J Soc Obstet Gynaecol Can 1998;20( I0):983-9.
19. Griffiths CT. Surgery at the Time of Diagnosis in Ovarian Cancer. In: Blackledge G, Chan KK (Eds). Management of Ovarian Cancer. London: Butterworth and Col 1986:pp.60-75. 20. Goldie JH, Coldman JA. A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 1979;63: 1727-33. 21. Wharton JT, Herson J. Surgery for common epithelial tumors of the ovary. Cancer 1981 ;48:582-9. 22. Piver MS, Lele SB, Marchetti DL eta/. The impact of aggressive debulking surgery and cisplatin based chemotherapy on progression-free survival in stage Ill and IV ovarian carcinoma. J Clin Oncol 1988;6:983-9. 23. Omura GA, Bundy BN, BerekJS eta/. Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 1989;7:457-65. 24. Hoskins WJ, Bundy BN,Thigpen JT et al. The influence of cytoreductive surgery on recurrence-free interval and survival in small-volume stage Ill epithelial ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol 1992;47: 159-66. 25. National institutes of Health Consensus Development Conference Statement. Ovarian cancer: screening, treatment, and follow-up. Gynecol Oneal 1994(supp1);55:S4-14. 26. Van der Burg MEL, van Lent M, Kobierska A et al. Intervention debulking surgery (IDS) does improve survival in advanced epithelial ovarian cancer (EOC): an EORTC Gynecologic Cancer Cooperative Group (GCCG) study. Proc Am Soc Clin On col 1993; 12:258. 27. Ozols RF. Gynecologic Oncology Group trials in ovarian carcinoma. Semin Oneal 1997;24( ISuppl 2):S2-I 0-2.
Visit the
endometriosis
Z
NE
on the Internet at:
http:/ /www.endozone.org
• What's new! • Editorial Board bibliography • On-line • Endometriosis in the news • Case history • Hot topic • Education • Links Encouraging world-wide debate on the current issues in endometriosis
en
I
SIS
Panel of experts from Belgium, UK, and USA
ZENECA The Endometriosis Zone IS supported by an unconditional grant from Zeneca Pharmaceuticals
2
Assistant Professor, Associate Professor, Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, University of Ottawa, The Ottawa Hospital (General Campus), Ottawa, Ontario
Abstract: surgery has been and continues to be the foundation upon which ovarian cancer treatment is built. Surgery in apparent early stage disease is focused on appropriate surgical pathological staging and, in selected patients, the use of a fertility sparing procedure. Primary surgical therapy in advanced disease is most effective when maximal cytoreduction is achieved. Surgical therapy in suspected or established ovarian cancer should ideally be provided by trained personnel. Resume : Ia chirurgie continue d'etre Ia base du traitement du cancer de l'ovaire. Au stade pnkoce de Ia maladie, Ia chirurgie vise a determiner les stades pathologiques chirurgicaux appropries, et, dans certains cas, le recours a des interventions susceptibles de preserver Ia fecondite de Ia patiente. Au stade avance de Ia maladie, Ia therapie chirurgicale primaire est Ia plus efficace lorsqu'une reduction maximale de Ia tumeur est pratiquee. ldealement, le traitement chirurgical du cancer de l'ovaire, soup~onne ou etabli, devrait etre pratique par des specialistes.
J Soc
Obstet Gynaecol Can 2000;22(4):935-41
INTRODUCTION
Epithelial ovarian cancer is the most common cause of death from gynaecological malignan-
cy. In Canada, in 1999, an estimated 2,600 women will be found to have this disease and 1,500 will die. 1 Unfortunately, in part due to lack of effective screening methods, most patients present with advanced stage disease where median progression-free survival is often only 12 to 18 months. Conversely, when disease is surgically confined to the ovary, five-year survival may be as high as 80 to 90 percent. 2 Although other approaches may be important in ovarian cancer treatment, surgery has been and still is the cornerstone of effective management of this disease. Surgical treatment of early stage disease essentially involves removal of the primary tumour, accompanied by comprehensive surgical staging and selective adjuvant theraPY. Treatment of advanced stage disease includes both cytotoxic chemotherapy and surgical tumour debulking of the primary and metastatic disease. Survival in advanced disease is very dependent on the volume of residual disease remaining after the tumour debulking procedure and the tumour response to primary cytotoxic chemotherapy. 3.4 EARLY STAGE DISEASE
KeyWords Epithelial ovarian cancer, surgery, staging. Received on June 7th, 1999. Revised and accepted on August 17th, 1999.
There is a vast body of literature demonstrating the potential of ovarian cancer spread in the face of disease apparently confined to the ovary (Table 1). 5- 7 The rational interpretation of these data would support the concept and approach that comprehensive surgical staging of apparent early stage disease is vital to the appropriate management of ovarian cancer. Not only may patients who require adjuvant therapy be identified, but equally importantly, those patients with stage I low-risk disease not in need of additional therapy can be selected. 8·9 Despite these evidence-based concepts, patients with apparent early stage dis-
TABLE I EARLY OVARIAN CANCER SPREAD
No. of patients with metastasis at site/ total No. of patients with site sampled Study
Peritoneal Omentum cytology
Young et a/. 1983 6 Piver et a/. 19785 Schueler et a/. 1988 7 Total
8/31 3/45 11/76 (14.5%)
6/57 0/5 3/45 9/107 (8.4%)
Diaphragm nodes
Pelvic nodes
Para-aortic
2/58 1/31 1/45 4 (3.0%)
1/1 I
6/52 0/5 2/45 8/102 (7.8%)
ease continue to have inadequate surgical therapy at the time of initial surgical intervention. McGowan et al 10 reported that only 54 percent of patients with carcinoma of the ovary underwent a proper staging procedure. Unfortunately, other reports have confirmed the often inadequate staging of apparent early ovarian cancer, a situation particularly common when the surgeon is not a gynaecological oncologist. 8•11 Table 2 outlines what the data would support as an adequate staging procedure in suspected early stage ovarian carcinoma. With the advent and development of minimal access surgical techniques, ovarian cancer may be managed initially by an endoscopic technique. Unfortunately, new and novel surgical approaches for adnexal masses and a suspicion of early ovarian cancer have not undergone the same scrutiny as either open procedures or chemotherapeutic agents. The endoscopic surgical approach to early ovarian cancer leaves unresolved questions about recurrence and survival following intra-operative tumour rupture and the inability to palpate peritoneal surfaces. The FIGO substages of stage I supported by published data imply that malignant cytological findings, tumour rupture and the presence of a tumour on the ovarian surface confer a poor prognosis. 12 •13 Other investigators have failed to demonstrate a poor prognosis for tumour rupture. 14 •15 Although there is controversy as to whether tumour rupture compromises survival, these patients are assigned to a higher stage according to FIGO staging, and many are subsequently treated with cytotoxic chemotherapy. In addition, there have been reports of trocar port-site hernias and port-site recurrences in patients undergoing laparoscopic management of ovarian cancer. 16 •17 Careful pre-operative assessment of an adnexal mass is, therefore, mandatory, particularly in the post-
I!II (9.1%)
menopausal patient. Guidelines for the laparoscopic management of adnexal masses have recently been published by The Society of Obstetricians and Gynaecologists of Canada. 18 These guidelines were based on data outlining the risk of ovarian malignancy following a thorough pre-operative and intra-operative assessment.
CONSERVATIVE (FERTILITY-PRESERVING} SURGERY Although the vast majority of epithelial ovarian cancers are in post-menopausal women, younger patients and those desirous of future childbearing may be managed in a conservative fashion. Careful pre-operative counselling and consent are required in those patients undergoing a surgical procedure for a suspicious adnexal mass. Ideally, if an apparent stage I ovarian cancer is encountered, the patient would have access to an appropriate surgical staging procedure. In consideration of the patient's desire for future fertility, the formal staging would not primarily include resection of the uterus and contralateral ovary. If the final pathology report describes an epithelial tumour with high-risk features (grade 2 or 3) or a tumour on the ovarian surface, then consideration may be given to a brief course of chemotherapy. Likewise, if metastatic disease is confirmed with the staging procedure, then chemotherapy, hysterectomy, and completion of a bilateral salpingo-oophorectomy should be considered. A patient, however, with a grade I, stage I a tumour may be managed expectandy. 8 ADVANCED STAGE DISEASE
PRIMARY CYTOREDUCTION Although there have been great efforts made towards increasing early detection and treatment of epithelial cancer of the ovary, the majority of patients are diagnosed with advanced stage disease. 2 Not uncommonly, a patient presents with ascites and a large volume of solid disease. Treatment of these patients has traditionally included surgical cytoreduction followed by cytotoxic chemotherapy. Cytoreduction (or debulking) describes a procedure in which the objective is to remove as much tumour as possible in a patient with metastatic ovarian cancer. Many investigators have supported the theoTABLE 2 STAGING LAPAROTOMY FOR EARLY OVARIAN CANCER retical benefits ofsurgical cytoreduction. Based on tumour kinetics and the mechanisms of cytotoxic • Peritoneal washings • Inspection/palpation of peritoneal surfaces chemotherapy, they can essentially be summarized • Total abdominal hysterectomy and bilateral salpingo-oophorectomy as enhanced chemosensitivity of smaller residual (unilateral salpingo-oophorectomy for fertility preservation) tumour nodules versus large bulky tumour mass• Omentectomy es. These perceived benefits are based on Gom• Peritoneal biopsies pertzian tumour growth, the log cell kill hypothesis • Pelvic/para-aortic lymphadenectomy of chemotherapy and an increased probability of JOURNAL SOGC
APRIL 2000
CONCLUSION
TABLE 3 SURVIVAL AND VOLUME OF RESIDUAL DISEASE Study
Wharton and Henson2 1 Piver et a/. 22
Omura et a/. 23
Residual Disease
Median Progression
Median
Free Survival
Survival
(months)
(months)
Optimal
28
Suboptimal
IS
::;2 em
25
~2 em
13
0
48
I em
21
tumour mutation as tumour size increases. 19·20 Numerous studies have also demonstrated the relationship between patient survival and the volume of residual disease following cytoreduction (Table 3). 21 -23 There appears to be a clear survival benefit to those patients with a lower volume of disease after surgery. The number of patients debulked to optimal disease range, in the literature, from 15 to 90 percent. Less apparent is the definition of 'optimal' residual disease, as there may only be a distinct survival advantage when the residual disease approaches microscopic. 23 Tumour biology as well as surgical cytoreduction also appear to influence patient survival. Hoskins et a/. 24 reported two groups of patients. The first group was found during initial surgery to have disease less than one em in diameter while the second group had larger volume disease but were cytoreduced to one em or less. The survival of the first group was longer, implying that, in addition to tumour debulking, tumour biology determines patient survival. Nevertheless, the recommendation of a 1994 NIH Consensus Development Conference on Ovarian Cancer was that "aggressive efforts at maximal cytoreduction are important since minimal residual tumour is associated with improved survival". 25 INTERVAL SURGERY
Based on the knowledge that patients with suboptimal residual disease after primary surgery have such a poor rate of survival, some reports have examined the effectiveness of'interval' surgical debulking, following two to four cycles of cisplatin-based chemotherapy. Van der Burg et af.2 6 reported on a trial evaluating a second or 'interval' cytoreduction in patients with suboptimally reduced ovarian cancer. Interval surgery was preceded and followed by three cycles of chemotherapy. Results of this trial, demonstrating an improved disease-free survival (18 versus 13 months), have led the Gynaecologic Oncology Group to perform a similar trial of interval debulking. 27 Although it would be premature to conclude that interval surgery is the standard of care for suboptimally debulked patients, preliminary data certainly reinforce the goal of optimal cytoreduction in the setting of bulky intraperitoneal disease.
The management of epithelial ovarian cancer, although often multifaceted in its approach, virtually always includes surgical therapy as the cornerstone of effective treatment. Surgery for apparent early stage disease ideally should involve a comprehensive staging procedure by trained personnel. Advanced stage ovarian cancer, although there is debate on the timing and number of surgical procedures, responds best when maximally cytoreduced.
REFERENCES I. 2.
3. 4. 5. 6.
7.
8.
9.
I0. II. 12. 13.
14.
15.
16.
17. 18.
National Cancer Institute of Canada: Canadian Cancer Statistics 1999. Toronto, Canada 1999. Ozols RF, Rubin SC,Thomas G, Robboy S. Epithelial Ovarian Cancer. In: Hoskins WJ, Perez CA,Young RC (Eds). Principles and Practice of Gynecologic Oncology. 2nd ed. Philadelphia: Lippincott-Raven 1997: pp. 919-86. Griffiths CT. Surgical resection of tumor bulk in the primary treatment of ovarian carcinoma. Natl Cancer lnst Monogr 1975;42: I01-4. Redman JR, Petroni GR, Saigo PE, Geller NL, Hakes TB. Prognostic factors in advanced ovarian carcinoma. J Clin Oncol 1986;4(4):515-23. Piver MS, Barlow JJ, Lele SB. Incidence of subclinical metastasis in stage I and II ovarian carcinoma. Obstet Gynecol 1978;52( I): I00-4. Young RC, Decker DG,Wharton JT, Piver MS, SindelarWF, Edwards BK, Smith JP. Staging laparotomy in early ovarian cancer. JAMA 1983; 250(22):3072-6. Schueler JA, Trimbos JB, Hermans J, Fleuren GJ. The yield of surgical staging in presumed early stage ovarian cancer: benefits or doubts? lntJ Gynecol Cancer 1998;8:95-102. Young RC,Walton LA, Ellenberg SS, Homesley HD,Wilbanks GD, Decker DG, Miller A, Park R, Major F Jr. Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials. N Engl J Med 1990;322( IS): I021-7. Faught W. Lotocki RJ, Heywood M, Krepart GV. Early ovarian cancer: value of a negative staging laparotomy. Eur J Gynaecol Oncol 1996; XVII(3):200-3. McGowan L, Lesher LP. Norris HJ, Barnett M. Misstaging of ovarian cancer. Obstet Gynecol 1985;65(4):568-72. Munoz KA, Harlan LC,Trimble EL. Patterns of care for women with ovarian cancer in the United States. J Clin Oncol 1997; 15( II ):3408-15. Webb MJ, Decker DG, Mussey E et al. Factors influencing survival in stage I ovarian cancer. Am J Obstet Gynecol 1973; I 16:222-8. Sains de Ia Cuesta R, Goff B, Fuller A, Nikrui N, Eichborn J, Rice L. Prognostic importance of intraoperative rupture of malignant ovarian epithelial neoplasms. Obstet Gynecol 1994;84: 1-7. Dembo A, Davy M, Stenwig A, Berle E, Bush R, Kjorstad K. Prognostic factors in patients with stage I epithelial ovarian cancer. Obstet Gynecol 1990;75:263-72. Seveida P, Dittrich C, Saizer H. Prognostic value of the rupture of the capsule in stage I epithelial ovarian carcinoma. Gynecol Oncol 1989; 35:321-2. Kadar N, Reich H, Liu CY, Manko GF, Gimpelson R. lncisional hernias after major laparoscopic gynecologic procedures. Am J Obstet Gynecol 1993; 168(5): 1493-5. Kadar N. Port-site recurrences following laparoscopic operations for gynaecological malignancies. Br J Obstet Gynaecol 1997; I04: 1308-13. Guidelines for the laparoscopic management of the adnexal mass. SOGC Clinical Practice Guidelines (No. 76, September 1998). J Soc Obstet Gynaecol Can 1998;20( I0):983-9.
19. Griffiths CT. Surgery at the Time of Diagnosis in Ovarian Cancer. In: Blackledge G, Chan KK (Eds). Management of Ovarian Cancer. London: Butterworth and Col 1986:pp.60-75. 20. Goldie JH, Coldman JA. A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 1979;63: 1727-33. 21. Wharton JT, Herson J. Surgery for common epithelial tumors of the ovary. Cancer 1981 ;48:582-9. 22. Piver MS, Lele SB, Marchetti DL eta/. The impact of aggressive debulking surgery and cisplatin based chemotherapy on progression-free survival in stage Ill and IV ovarian carcinoma. J Clin Oncol 1988;6:983-9. 23. Omura GA, Bundy BN, BerekJS eta/. Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 1989;7:457-65. 24. Hoskins WJ, Bundy BN,Thigpen JT et al. The influence of cytoreductive surgery on recurrence-free interval and survival in small-volume stage Ill epithelial ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol 1992;47: 159-66. 25. National institutes of Health Consensus Development Conference Statement. Ovarian cancer: screening, treatment, and follow-up. Gynecol Oneal 1994(supp1);55:S4-14. 26. Van der Burg MEL, van Lent M, Kobierska A et al. Intervention debulking surgery (IDS) does improve survival in advanced epithelial ovarian cancer (EOC): an EORTC Gynecologic Cancer Cooperative Group (GCCG) study. Proc Am Soc Clin On col 1993; 12:258. 27. Ozols RF. Gynecologic Oncology Group trials in ovarian carcinoma. Semin Oneal 1997;24( ISuppl 2):S2-I 0-2.
Visit the
endometriosis
Z
NE
on the Internet at:
http:/ /www.endozone.org
• What's new! • Editorial Board bibliography • On-line • Endometriosis in the news • Case history • Hot topic • Education • Links Encouraging world-wide debate on the current issues in endometriosis
en
I
SIS
Panel of experts from Belgium, UK, and USA
ZENECA The Endometriosis Zone IS supported by an unconditional grant from Zeneca Pharmaceuticals