Neoadjuvant chemotherapy, interval debulking surgery or primary surgery in ovarian carcinoma FIGO stage IV?

OBJECTIVES: The aim of this study was to investigate the impact of surgical approach, the extent of surgery and chemotherapy on overall survival in patients with ovarian carcinoma (OC) stage IV. METHODS: We retrospectively collected population-based data from the Norwegian Radium Hospital code registry on the diagnosis and surgery of 238 patients diagnosed with OC stage IV from 1996-2005. All patients received platinum-based chemotherapy. Surgical approach was registered as primary debulking surgery (PDS), interval debulking surgery (IDS) and delayed primary surgery (DPS). Surgery level was classified as radical surgery (RS), standard surgery (SS) or suboptimal surgery (SUBS). Univariate and multivariate analyses identified prognostic factors in PDS, IDS and DPS groups and subgroups. RESULTS: There were no differences in overall survival between the PDS, IDS and DPS groups. Surgery level was significantly associated with overall survival in the whole cohort (p<0.001), the PDS and IDS groups, but not in the DPS group. More patients with RS achieved no residual tumour (RT), but overall survival was not superior compared to no RT in the SS group. In 66 patients with no RT there were no differences in overall survival between those who underwent PDS, IDS and DPS. Chemotherapy with platinum/paclitaxel tended to improve survival. RT, World Health Organisation (WHO) performance status and histology were prognostic factors for overall survival in the whole cohort. CONCLUSION: No RT remains the objective, whether PDS, IDS or DPS is performed, and no differences in overall survival were found in the three treatment groups.

A risk model for secondary cytoreductive surgery in recurrent ovarian cancer: an evidence-based proposal for patient selection.

BACKGROUND: To develop a risk model for predicting complete secondary cytoreductive surgery (SCR) in patients with recurrent ovarian cancer. METHODS: Individual data of 1075 patients with recurrent ovarian cancer undergoing SCR from 7 worldwide centers were pooled and analyzed. The risk model was developed based on the factors impacting on SCR surgical outcome. Additional data on 117 patients who were not included in the development of the model were used for external validation and to assess the discrimination of the model. RESULTS: Of the 1075 patients, 434 (40.4%) underwent complete resection. Complete secondary cytoreduction was associated with six variables: FIGO stage (odds ratio [OR] = 1.32, 95% confidence interval [95% CI]: 0.97-1.80), residual disease after primary cytoreduction (OR = 1.69, 95% CI: 1.26-2.27), progression-free interval (OR = 2.27, 95% CI: 1.71-3.01), Eastern Cooperative Oncology Group (ECOG) performance status (OR = 2.23, 95% CI: 1.45-3.44), CA125 (OR = 1.85, 95% CI: 1.41-2.44), and ascites at recurrence (OR = 2.79, 95% CI: 1.88-4.13). These variables were entered into the risk model and assigned scores ranging from 0 to 11.9. Patients with total scores of 0-4.7 were categorized as the low-risk group, in which the proportion of complete cytoreduction was 53.4% compared with 20.1% in the high-risk group (OR = 4.55, 95% CI: 3.43-6.04). In external validation, the sensitivity and specificity was 83.3% and 57.6%, respectively. Area under the curve of the receiver-operating characteristics for predicting complete SCR was 0.68 (95% CI: 0.60-0.79). CONCLUSIONS: This model and scoring system may well predict the outcome of SCR and could potentially be useful in future clinical trials to determine which patients with recurrent ovarian cancer should have SCR as part of their management.

Prognostic significance of residual tumor in patients with epithelial ovarian carcinoma stage IV in a 20 year perspective.

OBJECTIVE: We aimed to evaluate prognostic factors impacting on overall survival during a 20 year period with substantial changes in surgical approach and chemotherapy management of patients with epithelial ovarian carcinoma stage IV. DESIGN: A retrospective population-based study. SETTING: The Norwegian Radium Hospital during 1985-2005. POPULATION: Three hundred and ninety-four patients with epithelial ovarian carcinoma stage IV treated at the Norwegian Radium Hospital. METHODS: The cohort was divided into two groups (1985-1995 and 1996-2005), and clinical and pathological characteristics were compared. Univariate and multivariate analyses were performed to identify prognostic factors during 1985-1995, 1996-2005 and 1985-2005. MAIN OUTCOME MEASURES: Prognostic factors and overall survival in the three periods. RESULTS: Median overall survival improved from 1985-1995 to 1996-2005 (from 1.3 to 2.1 years). More patients had macroscopic radical surgery (28 vs. 11%), received neoadjuvant chemotherapy and were treated with platinum-taxane combination therapy from 1996-2005 compared to 1985-1995. Patients with primary surgery had improved median overall survival from 1996-2005 compared to 1985-1995. In multivariate analyses, surgical approach was not a prognostic factor for overall survival, but chemotherapy was during 1985-2005. Postoperative residual tumor was a prognostic factor for overall survival in all periods. CONCLUSIONS: Macroscopic radical surgery is a strong prognostic factor for overall survival and is achievable in a subset of patients with epithelial ovarian carcinoma stage IV. Improved selection criteria for what treatment algorithm to choose for patients with epithelial ovarian carcinoma stage IV are warranted.

A controlled study of sexual activity and functioning in epithelial ovarian cancer survivors. A therapeutic approach.

OBJECTIVES: To explore sexual activity and functioning in epithelial ovarian cancer survivors (EOCSs) compared to age-adjusted controls from the general population (NORM) with focus on findings that should be given therapeutic considerations. METHODS: A cross-sectional study of 189/287 (66%) EOCSs treated at The Norwegian Radiumhospital 1979-2003 using a mailed questionnaire including demographic and somatic issues, and schedules concerning sexuality, fatigue, mental distress and quality of life. Blood tests for sex hormone determination were taken at their GPs. RESULTS: Among EOCSs 47% (95% CI 40-54%) were sexually active compared to 53% (95% CI 48-58%) in NORM. The sexually active EOCSs reported lower levels sexual pleasure (p<0.001) and higher levels of sexual discomfort than NORM (p<0.001). In sexually active EOCSs an association between higher level of sexual discomfort and both lower serum levels of estradiol (p=0.02) and higher levels of SHBG (p=0.04) was observed. Sexually active EOCSs were significantly more often in a paired relation and showed lower levels of fatigue and better quality of life compared to inactive EOCSs. Lack of interest (36%) and physical problems (23%) were significantly more common in sexually inactive EOCSs compared to NORM. In multivariable analyses of sexually active EOCSs premenopausal oophorectomy, having had chemotherapy, age at survey, mental health and body image were significantly associated with sexual functioning. CONCLUSIONS: Our findings on sexual inactivity and poorer sexual functioning among EOCSs point to issues in need of consideration. We present therapeutic strategies for evaluation and treatment for sexual problems in EOCSs.

Gene expressions and copy numbers associated with metastatic phenotypes of uterine cervical cancer.

BACKGROUND: A better understanding of the development of metastatic disease and the identification of molecular markers for cancer spread would be useful for the design of improved treatment strategies. This study was conducted to identify gene expressions associated with metastatic phenotypes of locally advanced cervical carcinomas and investigate whether gains or losses of these genes could play a role in regulation of the transcripts. Gene expressions and copy number changes were determined in primary tumors from 29 patients with and 19 without diagnosed lymph node metastases by use of cDNA and genomic microarray techniques, respectively. RESULTS: Thirty-one genes that differed in expression between the node positive and negative tumors were identified. Expressions of eight of these genes (MRPL11, CKS2, PDK2, MRPS23, MSN, TBX3, KLF3, LSM3) correlated with progression free survival in univariate analysis and were therefore more strongly associated with metastatic phenotypes than the others. Immunohistochemistry data of CKS2 and MSN showed similar relationships to survival. The prognostic genes clustered into two groups, suggesting two major metastatic phenotypes. One group was associated with rapid proliferation, oxidative phosphorylation, invasiveness, and tumor size (MRPS23, MRPL11, CKS2, LSM3, TBX3, MSN) and another with hypoxia tolerance, anaerobic metabolism, and high lactate content (PDK2, KLF3). Multivariate analysis identified tumor volume and PDK2 expression as independent prognostic variables. Gene copy number changes of the differentially expressed genes were not frequent, but correlated with the expression level for seven genes, including MRPS23, MSN, and LSM3. CONCLUSION: Gene expressions associated with known metastatic phenotypes of cervical cancers were identified. Our findings may indicate molecular mechanisms underlying development of these phenotypes and be useful as markers of cancer spread. Gains or losses of the genes may be involved in development of the metastatic phenotypes in some cases, but other mechanisms for transcriptional regulation are probably important in the majority of tumors.