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ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of ovarian cancer
Annals of Oncology 12 1205-1207,2001 © 2001 Kluwer Academic Publishers Primed in the Netherlands
Special article ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of ovarian cancer Incidence
Stage III
Diagnosis The definitive diagnosis of epithelial ovarian cancer requires a surgical specimen. Pathological diagnosis should be made according to the WHO classification. Established subtypes are: serous, mucinous, endometnoid, clear cell, Brenner, mixed, and undifferentiated carcinomas.
Staging and risk assessment • Surgical staging requires a laparotomy with a thorough examination of the abdominal cavity. If disease appears confined to the ovary, biopsy of the diaphragmatic peritoneum, paracolic gutters, pelvic peritoneum, para-aortic and pelvic nodes, infracolic omentum are required in addition to peritoneal washings. If possible, surgery should be performed by an experienced gynaecologic oncologist [///, B]. • Staging is described using the American Joint Committee on Cancer (AJCC) classification and the Federation Internationale de Gynecologie et d'Obstetrique classification (FIGO) as in table below: Stage 1 la Ib Ic
Limited to ovaries One ovary Both ovaries Ruptured capsule, surface tumour or positive washings
Stage 11 I la lib lie
Pelvic extension Uterus, tube(s) Other pelvic tissue Positive washings, ascites
Ilia IIIb IIIc
Stage IV
Distant metastases outside peritoneal cavity
Established prognostic factors besides surgical stage are: small tumour volume (prior to, and following surgery), younger age, good performance status, cell type other than mucinous or clear cell, well differentiated tumour, and absence of ascites. Low grade, absence of dense adhesions, minimal ascites, subgroups a/b versus c, and cell type other than clear cell are considered good prognostic factors for patients with stage 1 disease. Prior to surgery and/or chemotherapy, patients should have an abdomino-pelvic CT scan, chest X-ray, serum CA125, complete blood count and differential, and biochemistry for renal and hepatic function
Treatment plan • The selection of the type of surgery and postoperative therapy (chemotherapy and/or radiotherapy) depends upon the stage and other chnicopathological prognostic factors.
Early stage disease (FIGO I and II) • Surgery should involve total abdominal hysterectomy and bilateral salpingo-oophorectomy with omentectomy, with staging biopsies performed as described. In younger patients wanting to conserve fertility with localised, unilateral tumours (stage I) and favourable histology, unilateral salpingooophorectomy may not be associated with a high risk of recurrence Wedge biopsy of the contralateral ovary should be performed. Occasionally FIGO stage I tumours with dense adhesions to other pelvic structures are upstaged to FIGO II as the relapse rate appears to be equivalent • FIGO stage la/b, well differentiated, non-clear
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The crude incidence of ovarian cancer in the European Union is 17, the mortality 12 cases/100000 women/year The median age at diagnosis is 63 years. The incidence increases with age and peaks in the eighth decade. Between the age of 70-74 years the age-specific incidence is 57 cases/100000 women/year.
Abdominal extension and/or regional lymph nodes Microscopic peritoneal metastases Macroscopic peritoneal metastases < 2 c m Macroscopic peritoneal metastases > 2 cm and / or regional lymph nodes
1206
Advanced disease; FIGO stage III • Surgery should include total abdominal hysterectomy and bilateral salpingo-oophorectomy with omentectomy, with staging biopsies performed as described Maximal cytoreduction (no tumour nodules > 1 cm left in situ) should be achieved where possible [/, B]. Following surgery, chemotherapy is indicated • Chemotherapy options: 1) carboplatin plus paclitaxel every three weeks for six cycles, 2) cisplatin plus paclitaxel every three weeks for six cycles. • If initial maximal cytoreduction was not performed, interval debulking surgery (IDS) should be considered in patients responding to chemotherapy, or showing stable disease [//, B]. IDS should ideally be performed after three cycles of chemotherapy, followed by three further cycles of chemotherapy. • There is no evidence for a survival benefit for 'second-look' surgery following completion of chemotherapy in patients whose disease appears to be in complete remission. Such procedures should only be undertaken as part of a clinical trial Likewise, the value of secondary tumour reduction at the time of second-look laparotomy is not clear.
Response evaluation • CA125 levels can accurately correlate with tumour response and with survival during chemotherapy [III, A]- Prior to each cycle of chemotherapy, serum CA125 should be performed. • For patients with abnormal CT scans at baseline, this should be repeated after cycle 6 Patients with normal CT scans at baseline do not need further CT scans, provided there is no clinical or biochemical indication of disease progression. An interim CTscan after three cycles of chemotherapy should be considered for a patient who is negative for serum CA125, or for whom IDS is being considered • Randomised trials have not shown a benefit for chemotherapy beyond six cycles, but did not include taxane-based regimens. Patients with a partial response after six cycles of chemotherapy but continuing evidence of response by CA125 can be considered for a further three cycles of the same chemotherapy [V, B]
Follow-up • History, physical examination including pelvic examination every three months for two years, every four months during the third year and every six months during year 4 and 5 or until progression is documented. • If no progression within two years of chemotherapy, extend the follow-up interval to three months for the third year, and to four months for the fourth year. Thereafter, patients should be seen every six months • CA125 can accurately predict tumour relapse [/, A], and should be performed at each follow-up visit. CT scans should be performed if there is clinical or CA125 evidence for progressive disease.
Note
Advanced disease; FIGO stage IV • Patients with stage IV disease obtain a survival advantage from being maximally surgically cytoreduced at initial laparotomy [///, B], although randomised trials have not addressed this question. • Young patients with good performance status, pleural effusion as only site of disease outside abdominal cavity, small volume metastases, and no major organ dysfunction should be considered for surgery • If surgery is not planned, the diagnosis should be confirmed by biopsy and chemotherapy administered Suitable chemotherapy regimens are as for FIGO Stage III disease.
Levels of Evidence [I-VJ and Grades of Recommendation [A-D] as used by the American Society of Clinical Oncology are given in square brackets Statements without grading were considered justified standard clinical practice by the expert authors and the ESMO faculty
Literature 1 Aabo K, Adams M, Adnitt P et al Chemotherapy in advanced ovarian cancer Four systematic meta-analyses of individual patient data from 37 randomized trials Advanced Ovanan Cancer Tnahsts'Group Br J Cancer 1998, 78 1479-87 2 Hoskins WJ Surgical staging and cytoreductive surgery of epithelial ovanan cancer Cancer 1993, 71 1534-40 3 Neijt JP, du Bois A, Williams C (eds). Advanced Ovanan Cancer What Do We Know and What Do We Need1? Ann Oncol 1999, 10 (Suppl 1) 1-92
Downloaded from https://academic.oup.com/annonc/article-abstract/12/9/1205/170791 by guest on 19 January 2019
cell histology, surgery alone is adequate [/, A]. FIGO stage Ia/b poorly differentiated, densely adherent, clear cell histology, FIGO stage Ic optimal surgery and staging should be performed, and adjuvant chemotherapy considered [IV, B\. • FIGO stage II: Surgery and staging should be performed to remove all or most of the tumour, followed by chemotherapy. • Chemotherapy options: carboplatin AUC 5 or 6 every three weeks for six cycles or carboplatin (or cisplatin) plus paclitaxel every three weeks for six cycles.
1207 4
Berek JS, Bertelsen K., du Bois A et al Advanced epithelial ovarian cancer 1998 consensus statements Ann Oncol 1999, 10 (Suppl 1) 87-92 5 Rustin GJ, Nelstrop AE, McClean P et al Denning response of ovarian carcinoma to initial chemotherapy according to serum CA 125 J Qin Oncol 1996, 14 1545-51
Approved by the ESMO Guidelines Task Force October 2000
Coordinating author for the ESMO Guidelines Task Force. Paul A Vasey, Beatson Oncology Centre, Glasgow, UK
Correspondence to ESMO Guidelines Task Force ESMO Head Office Via La Santa 7 CH-6962 Lugano Switzerland
Downloaded from https://academic.oup.com/annonc/article-abstract/12/9/1205/170791 by guest on 19 January 2019
Special article ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of ovarian cancer Incidence
Stage III
Diagnosis The definitive diagnosis of epithelial ovarian cancer requires a surgical specimen. Pathological diagnosis should be made according to the WHO classification. Established subtypes are: serous, mucinous, endometnoid, clear cell, Brenner, mixed, and undifferentiated carcinomas.
Staging and risk assessment • Surgical staging requires a laparotomy with a thorough examination of the abdominal cavity. If disease appears confined to the ovary, biopsy of the diaphragmatic peritoneum, paracolic gutters, pelvic peritoneum, para-aortic and pelvic nodes, infracolic omentum are required in addition to peritoneal washings. If possible, surgery should be performed by an experienced gynaecologic oncologist [///, B]. • Staging is described using the American Joint Committee on Cancer (AJCC) classification and the Federation Internationale de Gynecologie et d'Obstetrique classification (FIGO) as in table below: Stage 1 la Ib Ic
Limited to ovaries One ovary Both ovaries Ruptured capsule, surface tumour or positive washings
Stage 11 I la lib lie
Pelvic extension Uterus, tube(s) Other pelvic tissue Positive washings, ascites
Ilia IIIb IIIc
Stage IV
Distant metastases outside peritoneal cavity
Established prognostic factors besides surgical stage are: small tumour volume (prior to, and following surgery), younger age, good performance status, cell type other than mucinous or clear cell, well differentiated tumour, and absence of ascites. Low grade, absence of dense adhesions, minimal ascites, subgroups a/b versus c, and cell type other than clear cell are considered good prognostic factors for patients with stage 1 disease. Prior to surgery and/or chemotherapy, patients should have an abdomino-pelvic CT scan, chest X-ray, serum CA125, complete blood count and differential, and biochemistry for renal and hepatic function
Treatment plan • The selection of the type of surgery and postoperative therapy (chemotherapy and/or radiotherapy) depends upon the stage and other chnicopathological prognostic factors.
Early stage disease (FIGO I and II) • Surgery should involve total abdominal hysterectomy and bilateral salpingo-oophorectomy with omentectomy, with staging biopsies performed as described. In younger patients wanting to conserve fertility with localised, unilateral tumours (stage I) and favourable histology, unilateral salpingooophorectomy may not be associated with a high risk of recurrence Wedge biopsy of the contralateral ovary should be performed. Occasionally FIGO stage I tumours with dense adhesions to other pelvic structures are upstaged to FIGO II as the relapse rate appears to be equivalent • FIGO stage la/b, well differentiated, non-clear
Downloaded from https://academic.oup.com/annonc/article-abstract/12/9/1205/170791 by guest on 19 January 2019
The crude incidence of ovarian cancer in the European Union is 17, the mortality 12 cases/100000 women/year The median age at diagnosis is 63 years. The incidence increases with age and peaks in the eighth decade. Between the age of 70-74 years the age-specific incidence is 57 cases/100000 women/year.
Abdominal extension and/or regional lymph nodes Microscopic peritoneal metastases Macroscopic peritoneal metastases < 2 c m Macroscopic peritoneal metastases > 2 cm and / or regional lymph nodes
1206
Advanced disease; FIGO stage III • Surgery should include total abdominal hysterectomy and bilateral salpingo-oophorectomy with omentectomy, with staging biopsies performed as described Maximal cytoreduction (no tumour nodules > 1 cm left in situ) should be achieved where possible [/, B]. Following surgery, chemotherapy is indicated • Chemotherapy options: 1) carboplatin plus paclitaxel every three weeks for six cycles, 2) cisplatin plus paclitaxel every three weeks for six cycles. • If initial maximal cytoreduction was not performed, interval debulking surgery (IDS) should be considered in patients responding to chemotherapy, or showing stable disease [//, B]. IDS should ideally be performed after three cycles of chemotherapy, followed by three further cycles of chemotherapy. • There is no evidence for a survival benefit for 'second-look' surgery following completion of chemotherapy in patients whose disease appears to be in complete remission. Such procedures should only be undertaken as part of a clinical trial Likewise, the value of secondary tumour reduction at the time of second-look laparotomy is not clear.
Response evaluation • CA125 levels can accurately correlate with tumour response and with survival during chemotherapy [III, A]- Prior to each cycle of chemotherapy, serum CA125 should be performed. • For patients with abnormal CT scans at baseline, this should be repeated after cycle 6 Patients with normal CT scans at baseline do not need further CT scans, provided there is no clinical or biochemical indication of disease progression. An interim CTscan after three cycles of chemotherapy should be considered for a patient who is negative for serum CA125, or for whom IDS is being considered • Randomised trials have not shown a benefit for chemotherapy beyond six cycles, but did not include taxane-based regimens. Patients with a partial response after six cycles of chemotherapy but continuing evidence of response by CA125 can be considered for a further three cycles of the same chemotherapy [V, B]
Follow-up • History, physical examination including pelvic examination every three months for two years, every four months during the third year and every six months during year 4 and 5 or until progression is documented. • If no progression within two years of chemotherapy, extend the follow-up interval to three months for the third year, and to four months for the fourth year. Thereafter, patients should be seen every six months • CA125 can accurately predict tumour relapse [/, A], and should be performed at each follow-up visit. CT scans should be performed if there is clinical or CA125 evidence for progressive disease.
Note
Advanced disease; FIGO stage IV • Patients with stage IV disease obtain a survival advantage from being maximally surgically cytoreduced at initial laparotomy [///, B], although randomised trials have not addressed this question. • Young patients with good performance status, pleural effusion as only site of disease outside abdominal cavity, small volume metastases, and no major organ dysfunction should be considered for surgery • If surgery is not planned, the diagnosis should be confirmed by biopsy and chemotherapy administered Suitable chemotherapy regimens are as for FIGO Stage III disease.
Levels of Evidence [I-VJ and Grades of Recommendation [A-D] as used by the American Society of Clinical Oncology are given in square brackets Statements without grading were considered justified standard clinical practice by the expert authors and the ESMO faculty
Literature 1 Aabo K, Adams M, Adnitt P et al Chemotherapy in advanced ovarian cancer Four systematic meta-analyses of individual patient data from 37 randomized trials Advanced Ovanan Cancer Tnahsts'Group Br J Cancer 1998, 78 1479-87 2 Hoskins WJ Surgical staging and cytoreductive surgery of epithelial ovanan cancer Cancer 1993, 71 1534-40 3 Neijt JP, du Bois A, Williams C (eds). Advanced Ovanan Cancer What Do We Know and What Do We Need1? Ann Oncol 1999, 10 (Suppl 1) 1-92
Downloaded from https://academic.oup.com/annonc/article-abstract/12/9/1205/170791 by guest on 19 January 2019
cell histology, surgery alone is adequate [/, A]. FIGO stage Ia/b poorly differentiated, densely adherent, clear cell histology, FIGO stage Ic optimal surgery and staging should be performed, and adjuvant chemotherapy considered [IV, B\. • FIGO stage II: Surgery and staging should be performed to remove all or most of the tumour, followed by chemotherapy. • Chemotherapy options: carboplatin AUC 5 or 6 every three weeks for six cycles or carboplatin (or cisplatin) plus paclitaxel every three weeks for six cycles.
1207 4
Berek JS, Bertelsen K., du Bois A et al Advanced epithelial ovarian cancer 1998 consensus statements Ann Oncol 1999, 10 (Suppl 1) 87-92 5 Rustin GJ, Nelstrop AE, McClean P et al Denning response of ovarian carcinoma to initial chemotherapy according to serum CA 125 J Qin Oncol 1996, 14 1545-51
Approved by the ESMO Guidelines Task Force October 2000
Coordinating author for the ESMO Guidelines Task Force. Paul A Vasey, Beatson Oncology Centre, Glasgow, UK
Correspondence to ESMO Guidelines Task Force ESMO Head Office Via La Santa 7 CH-6962 Lugano Switzerland
Downloaded from https://academic.oup.com/annonc/article-abstract/12/9/1205/170791 by guest on 19 January 2019