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

Abstract

Abstract. Tropé C, Kaern J, Hogberg T, Abeler V, Hagen B, Kristensen G, Onsrud M, Pettersen E, Rosenberg P, Sandvei R, Sundfor K, Vergote I. 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. 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 5 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% 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. Conclusion. 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.

Prognostic factors for high‐risk early‐stage epithelial ovarian cancer

“…These findings have also been confirmed by other, smaller studies. 11,14,16,30,[36][37][38][39][40][41][42][43][44] In this current analysis, malignant cytology was an independent prognostic factor for increased risk of recurrence and poorer survival. Early studies have demonstrated that patients with positive washing have a poorer prognosis.…”

“…13,16,[29][30][31][32][33] Patients in this current study with stage I cancers have a 5-year disease-specific survival of 84% compared with 76% in those with stage II disease. An analysis on the subgroups of stage I cancers found that those with stage IA or IB disease have a survival of 85.9%.…”

“…[2][3][4][5][6][7] The clinical and pathologic prognostic factors that have been previously described for patients with early-stage epithelial ovarian cancers include: age, stage, tumor rupture, cell type, tumor grade, large volume ascites, and dense adhesions. [8][9][10][11][12][13][14][15][16] The limitations of many of these prior studies include the small sample size, inadequacy of surgical staging, inclusion of borderline tumors, stage III cancers with minimal residual disease, lack of central pathology review, and variation in adjuvant therapies.…”

Heterogeneity of tumor chemosensitivity in ovarian epithelial cancer revealed using the adenosine triphosphate-tumor chemosensitivity assay

“…These patients demonstrate good survival rates with surgical treatment alone, whereas adjuvant chemotherapy is recommended for all other patients. Several studies have identified age, capsular rupture, histological subtype, stage, grade and positive cytology results as prognostic factors for recurrence and survival in early-stage ovarian cancers (26)(27)(28)(29)(30), and other studies have reported improved survival for adjuvant treatment in early-stage patients with high-risk factors (31). Swart et al (32) analyzed long-term follow-up data of patients with early-stage ovarian cancer and reported a significant benefit of adjuvant chemotherapy.…”

The treatment and outcomes of early-stage epithelial ovarian cancer: have we made any progress?

“…Prior reports have shown that age, stage, cell type, tumour grade, large volume ascites, and dense adhesions are important clinical and pathological prognostic factors (Dembo et al, 1990;Sevelda et al, 1990;Young et al, 1990;Finn et al, 1992;Bertelsen et al, 1993;Vergote et al, 1993;Sjovall et al, 1994;Ahmed et al, 1996;Holschneider and Berek, 2000;Trope et al, 2000). Recently, Chan et al (2008) reported on patients with high-risk early-stage patients defined as stage I, grade 3; stage IC; stage II; or clear cell epithelial ovarian cancer after adjuvant therapy from two Gynecologic Oncology Group studies.…”