Randomized study on adjuvant chemotherapy in stage I high-risk ovarian cancer with evaluation of DNA-ploidy as prognostic instrument

PURPOSE Adjuvant chemotherapy versus observation and chemotherapy at progression was evaluated in 162 patients in a prospective randomized multicenter study. We also evaluated DNA-measurements as an additional prognostic factor. PATIENTS AND METHODS Patients received adjuvant carboplatin AUC 7 every 28 days for six courses (n = 81) or no adjuvant treatment (n = 81). Eligibility included surgically staged and treated patients with FIGO stage I disease, grade 1 aneuploid or grade 2 or 3 non-clear cell carcinomas or clear cell carcinomas. Disease-free (DFS) and disease-specific (DSS) survival were end-points. RESULTS Median follow-up time was 46 months and progression was observed in 20 patients in the treatment group and 19 in the control group. Estimated five-year DFS and DSS were 70% and 86% in the treatment group and 71% and 85% in the control group. The hazard ratio was 0.98 (95% confidence interval (95% CI): 0.52-1.83) regarding DFS and 0.94 (95% CI: 0.37-2.36) regarding DSS. No significant differences in DFS or DSS could be seen when the log-rank test was stratified for prognostic variables. Therefore, data from both groups were pooled for the analysis of prognostic factors. DNA-ploidy (P = 0.003), extracapsular growth (P = 0.005), tumor rupture (P = 0.04), and WHO histologic grade (P = 0.04) were significant independent prognostic factors for DFS with P < 0.0001 for the model in the multivariate Cox analysis. FIGO substage (P = 0.01), DNA ploidy (P < 0.05), and histologic grade (P = 0.05) were prognostic for DSS with a P-value for the model < 0.0001. CONCLUSIONS Due to the small number of patients the study was inconclusive as regards the question of adjuvant chemotherapy. The survival curves were superimposable, but with wide confidence intervals. DNA-ploidy adds objective independent prognostic information regarding both DFS and DSS in early ovarian cancer.

[1]  J. Thigpen.  Chemotherapy for advanced ovarian cancer: overview of randomized trials. , 2000, Seminars in oncology.

[2]  V. Torri,et al.  The accuracy of staging: an important prognostic determinator in stage I ovarian carcinoma. A multivariate analysis. , 1998, Annals of oncology : official journal of the European Society for Medical Oncology.

[3]  E. Mooney,et al.  Surgical Pathology of the Ovaries, Second Edition , 1998 .

[4]  S. Pecorelli,et al.  Management of early ovarian cancer. , 1998, Seminars in oncology.

[5]  Fleuren,et al.  The yield of surgical staging in presumed early stage ovarian cancer: Benefits or doubts? , 1998 .

[6]  F Landoni,et al.  Analysis of failures after negative second-look in patients with advanced ovarian cancer: an Italian multicenter study. , 1998, Gynecologic oncology.

[7]  H. Fox.  Clinical value of new techniques of gynecological tumor assessment , 1997 .

[8]  M. Gore,et al.  Natural history and prognosis of untreated stage I epithelial ovarian carcinoma. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  J. Vermorken,et al.  Clinical trials in patients with epithelial ovarian cancer: past, present and future. , 1996, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[10]  L. Cobellis,et al.  Systematic pelvic and paraaortic lymphadenectomy for advanced ovarian cancer: prognostic significance of node metastases. , 1996, Gynecologic oncology.

[11]  N. Colombo,et al.  Multimodality therapy of early-stage (FIGO I-II) ovarian cancer: review of surgical management and postoperative adjuvant treatment , 1996, International Journal of Gynecologic Cancer.

[12]  V. Torri,et al.  Adjuvant treatment for early epithelial ovarian cancer: Results of two randomised clinical trials comparing cisplatin to no further treatment or chromic phosphate (32P) , 1995 .

[13]  K. Nasu,et al.  [Characterization of intraoperative rupture of epithelial ovarian cancer at early stage]. , 1995, Nihon Sanka Fujinka Gakkai zasshi.

[14]  V. Torri,et al.  Controversial issues in the management of early epithelial ovarian cancer: conservative surgery and role of adjuvant therapy. , 1994, Gynecologic oncology.

[15]  B. Goff,et al.  Prognostic importance of intraoperative rupture of malignant ovarian epithelial neoplasms , 1994, Obstetrics and gynecology.

[16]  J. Berek,et al.  Prognostic importance of intraoperative rupture of malignant ovarian epithelial neoplasms. , 1994, Obstetrics and gynecology.

[17]  H. Stettner,et al.  Lymphadenectomy in stage I ovarian cancer , 1994, American journal of obstetrics and gynecology.

[18]  J. Ferlay,et al.  Estimates of the worldwide mortality from eighteen major cancers in 1985. Implications for prevention and projections of future burden , 1993, International journal of cancer.

[19]  B. Nilsson,et al.  Different types of rupture of the tumor capsule and the impact on survival in early ovarian carcinoma , 1993, International Journal of Gynecologic Cancer.

[20]  V. Abeler,et al.  Analysis of prognostic factors in stage I epithelial ovarian carcinoma: importance of degree of differentiation and deoxyribonucleic acid ploidy in predicting relapse. , 1993, American journal of obstetrics and gynecology.

[21]  J. Ferlay,et al.  Estimates of the worldwide incidence of eighteen major cancers in 1985 , 1993, International journal of cancer.

[22]  C. Wolfe,et al.  Early atnniocentesis: alphafetoprotein levels in amniotic fluid, extraembryonic coelomic fluid and maternal serum between 8 and 13 weeks , 1992, British journal of obstetrics and gynaecology.

[23]  M. E. Kirk,et al.  Surgery without adjuvant chemotherapy for early epithelial ovarian carcinoma after comprehensive surgical staging. , 1991, Gynecologic oncology.

[24]  D. Alberts,et al.  Chemotherapy in advanced ovarian cancer: an overview of randomised clinical trials. Advanced Ovarian Cancer Trialists Group. , 1991, BMJ.

[25]  Y. Collan,et al.  Tumour ploidy, morphometry, histological grading and clinical features in ovarian carcinoma: mutual relations. , 1991, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[26]  V. Abeler,et al.  Cellular DNA content as a new prognostic tool in patients with borderline tumors of the ovary. , 1990, Gynecologic oncology.

[27]  S. Ellenberg,et al.  Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials , 1990, The New England journal of medicine.

[28]  A. Stenwig,et al.  Prognostic Factors in Patients With Stage I Epithelial Ovarian Cancer , 1990, Obstetrics and gynecology.

[29]  P. Sevelda,et al.  Prognostic value of the rupture of the capsule in stage I epithelial ovarian carcinoma. , 1989, Gynecologic oncology.

[30]  H. Joensuu,et al.  Influence of Cellular DNA Content on Survival in Ovarian Carcinoma , 1989, Obstetrics and gynecology.

[31]  H. Stettner,et al.  1 The spread of ovarian cancer , 1989 .

[32]  O. Dalesio,et al.  Carboplatin in combination therapy for ovarian cancer. , 1988, Cancer treatment reviews.

[33]  D. Hedley,et al.  Prediction of long-term survival by flow cytometric analysis of cellular DNA content in patients with advanced ovarian cancer. , 1988, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  O. Kallioniemi,et al.  Prognostic significance of dna index, multiploidy, and S‐phase fraction in ovarian cancer , 1988, Cancer.

[35]  R. Young.  Initial therapy for early ovarian carcinoma , 1987, Cancer.

[36]  O. Iversen,et al.  Ploidy assessment of benign and malignant ovarian tumors by flow cytometry. A clinicopathologic study , 1987, Cancer.

[37]  Robert C. Leif,et al.  Convention on nomenclature for DNA cytometry , 1984 .

[38]  L. Melton,et al.  Prognostic significance of histologic classification and grading of epithelial malignancies of the ovary. , 1984, American journal of obstetrics and gynecology.

[39]  P. Philips,et al.  A study of 656 patients with "early" ovarian cancer. , 1984, Gynecologic oncology.

[40]  I W Taylor,et al.  Method for analysis of cellular DNA content of paraffin-embedded pathological material using flow cytometry. , 1983, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[41]  B. Gullberg,et al.  Prognostic factors in malignant epithelial ovarian tumors. , 1983, Gynecologic oncology.

[42]  J. Baak,et al.  Disagreement of histopathological diagnosis of different pathologists in ovarian tumors-with some theoretical considerations. , 1982, European journal of obstetrics, gynecology, and reproductive biology.

[43]  L. Lagasse,et al.  The role of adjuvant therapy in Stage I ovarian cancer. , 1980, American journal of obstetrics and gynecology.

[44]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[45]  I. Vergote,et al.  Randomized trial on adjuvant carboplatin versus no treatment in stage I high risk ovarian cancer by th Nordic Ovarian Cancer Study Group (NOCOVA) , 1997 .

[46]  T. Tong,et al.  Cancer statistics, 1993 , 1993, CA: a cancer journal for clinicians.

[47]  I. Taylor,et al.  Influence of cellular DNA content on survival in advanced ovarian cancer. , 1984, Cancer research.

[48]  W. Hiddemann,et al.  Convention on nomenclature for DNA cytometry. Committee on Nomenclature, Society for Analytical Cytology. , 1984, Cancer genetics and cytogenetics.

[49]  David R. Cox,et al.  Regression models and life tables (with discussion , 1972 .