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Fig. 1: “Low-grade” pathway: frequent BRAF/KRAS mutations (61-68 %), low cellular proliferation, gradual increase in chromosomal instability, 5-year survival ≈ 55 %; “High-grade” pathway: frequent TP53 mutations (70 %), high cellular proliferation, high c

Fig. 1: “Low-grade” pathway: frequent BRAF/KRAS mutations (61-68 %), low cellular proliferation, gradual increase in chromosomal instability, 5-year survival ≈ 55 %; “High-grade” pathway: frequent TP53 mutations (70 %), high cellular proliferation, high chromosomal instability, frequent HLA-G expression, five-year survival ≈ 30 %.

APST: Atypical proliferative serous tumours, SBT = S-BOT = Serous borderline ovarian tumours, MPSC: Micropapillary serous carcinoma. From Shih and Kurman, 2004 with permission

Innere Medizin 18. April 2009

Diagnosis and treatment of borderline ovarian neoplasms

“The state of the art”

The 5-year survival for women with stage-I borderline tumours (BOT) is favourable, about 95-97 %, but the 10-year survival is only between 70 and 95 %, caused by late recurrence. The 5-year survival for stage II-III patients is 65-87 % (Table 1). Standard primary surgery includes bilateral SOEB, omentectomy, peritoneal washing and multiple biopsies. Second cytoreductive surgery is recommended for patients with recurrent disease. Adjuvant postoperative therapy is not indicated in stage-I diploid tumors. Occasional responses to chemotherapy have been reported in advanced BOTs but no study has shown improved survival.

Histologic subtypes and prognostic factors

Recently a new theory has been developed describing a subset of S-ovarian cyst adenomas that evolve through S-BOT to low grade carcinoma (Fig. 1). A more correct staging procedure, classification of true serous implants and agreement on the contribution to stage of the presence of gelatinous ascites in mucinous tumours may in the future change the distribution of stage and survival data by stage for women with BOT (Table 2). Independent prognostic factors in patients with epithelial ovarian BOT without residual tumour after primary surgery are DNA-ploidy, international FIGO-stage, histologic type and patient age. Studies on other molecular markers have not yet uncovered a reliable prediction of biologic behaviour, however, there is hope that future studies of genetics and molecular biology of these tumours will lead to useful laboratory tests. Future questions to be addressed in this lecture include the following:

  • Have patients with borderline tumours in general been over-treated and how should these patients be treated?
  • How to define the high risk patients?
  • In which group of patients is fertility-sparing surgery advisable? and
  • Do patients with borderline tumours benefit from adjuvant treatment?
Tab. 1: Multivariate survival analysis of patients with borderline tumours diagnosed between 1970 and 1993, with a 5-year follow-up: Relative risk of dying according to age, stage, period of diagnosis and histology1
  RR2 (95% ci)2 N
Age (years)      
0-44 1.00 Referent 803
45-64 4.70 (2.46-8.99) 843
65-74 11.09 (5.84-21.05) 430
75-89 34.16 (18.23-64.02) 245
Localized 1.00 Referent 2,165
Regional spread 2.52 (0.80-7.96) 21
Distant metastases 1.78 (1.08-2.94) 112
Unknown 1.14 (0.36-3.57) 23
1970-1973 1.00 Referent 331
1974-1978 1.52 (0.95-2.42) 459
1979-1983 1.42 (0.88-2.29) 372
1984-1988 1.07 (0.66-1.72) 495
1989-1993 1.24 (0.75-2.05) 664
Serous 1.00 Referent 994
Mucinous 0.72 (0.54-0.95) 1,202
Other 1.30 (0.79-2.12) 125
1RR = Relative Risk; CI = Confidence Interval 2Adjusted for all other variables in the table
Tab. 2: The Norwegian Radium Hospital – Primary Treatment Guidelines in BOT  
A. Childwish B. No childwish    
1. All stages 1. All stages    
a) Fertility sparing surgery + comprehensive staging without lymph node removal if not enlarged * 2. Radical surgery + comprehensive staging without lymph nodes removal if not enlarged *    
Pathologic centreal review
I. Invasive implants II. Invasive implants    
a) Yes b) No a) Yes b) No
1. Observe 1. Observe 1. Observe, or 1. Observe
2. Consider adjuvant EOC chemotherapy if macroscopically rest tumor 2. DNA-ploidy (prognostic factor) 2. Consider adjuvant EOC chemotherapy 2. Chemotherapy if macroscopically rest tumor
3. If aneuploid consider adjuvant EOC chemotherapy 3. If reproduction failure consider definitive radical surgical treatment with HRT 3. Chemotherapy if macroscopically rest tumor 3. HRT in premenopausal women
4. Consider radical surgery after family is completed, treatment with HRT   4. HRT in premenopausal women  
* Enlarged palpable nodes are removed
The Author
Claes Tropé, Prof, MD, PhD, Head of R&D
Department of Gynaecological Oncology
Division of Obstetrics and Gynaecology
Oslo University Hospital / The Norwegian Radium Hospital
Ullernchausséen 70
0310 Oslo
Fax: ++47/2293 4199

Claes Tropé, Department of Gynaecological Oncology, Division of Obstetrics and Gynaecology, The Norwegian Radium Hospital, Oslo, Norway, Wiener Medizinische Wochenschrift Skriptum 5/2009

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