Quality of life and sexual function in patients with borderline tumors of the ovary. A substudy of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) study group ROBOT study.

PURPOSE: Borderline tumors of the ovary (BOT) represent an entity of ovarian neoplasms with low malignant potential and excellent prognosis. Mainstay of therapy is surgery including adequate staging and complete tumor resection, possibly inducing long-term side effects, especially in premenopausal women. The aim of this study was to evaluate quality of life (QoL) and sexual function in patients treated for BOT, also with respect to treatment modalities. METHODS: This prospective study was part of an ambidirectional multicentric cohort study in patients with BOT in Germany. Patients from seven centers completed three questionnaires after completion of therapy. QoL and sexual function data were correlated with treatment characteristics: surgical approach, lymphadenectomy, and fertility sparing surgery. RESULTS: One hundred ten patients returned the questionnaires. Median follow-up was 4.0 years. The majority lived in a relationship (n = 85, 77%, missing n = 4), and 49% (n = 54, missing n = 6) were sexually active. The main reason for sexual inactivity was "no partner" (38%). The women had a mean global health status of 69.8 (SD 22.7; min 0, max 100), with 100 implying perfect health. Mean QoL score was 73.7 (SD 23.3, range 0 to 100). Both scores showed no difference regarding fertility preserving surgery, surgical approach, and lymphadenectomy. Sexually active women had a significantly higher QoL (78.7 vs. 67.4, p = 0.0156) and global health status (75.9 vs. 60.9, p = 0.0013) than inactive patients. CONCLUSIONS: In this prospective study, patients who had been diagnosed with BOT had a very good quality of life and global health status. Sexually inactive women stated lack of a partner as the main reason and had an inferior HRQoL compared to sexually active women.

The Value of Serum CA125 in the Diagnosis of Borderline Tumors of the Ovary: A Subanalysis of the Prospective Multicenter ROBOT Study.

OBJECTIVE: The value of the serum tumor marker CA125 in borderline tumors of the ovary (BOTs) is not well defined, with unclear benefit in both diagnosis and follow-up. The aim of the present project was to identify the predictive value of CA125 for stage and relapse. METHODS: CA125 data were extracted from the ROBOT multicenter study of patients with BOT treated between 1998 and 2008 in 24 German centers. While patients' data were retrieved retrospectively from hospital records and clinical tumor registries, follow-up and independent central pathology review were performed prospectively. RESULTS: We identified 127 patients from the ROBOT database fulfilling the eligibility criterion of available CA125 at initial diagnosis. Eighty-three (65.3%) patients had increased CA125 levels (>35 U/L). Of the patients, 85.0% presented with serous and 13.4% with mucinous BOT histology, whereas 29.9% had stage I disease. Fifteen (11.8%) patients experienced a relapse. Multivariate analysis identified raised CA125, young age, and serous histology as independent predictors of peritoneal implants of any type at initial presentation. Raised CA125 at initial diagnosis was, however, not an independent predictor of future relapse. DISCUSSION: Elevated CA125 seems to be associated with the presence of peritoneal implants of any type at initial diagnosis of serous BOT, but failed to have any independent predictive value on future relapse. Prospective multicenter studies are warranted to evaluate CA125 measurements in the follow-up management of BOT.

Borderline tumors of the ovary: clinical course and prognostic factors.

BACKGROUND: The prognosis in borderline tumors of the ovary (BOT) is generally favorable. However, some patients experience recurrence, and mortalities occur. There is a need to better characterize prognostic factors to be considered for individualized treatment planning. PATIENTS AND METHODS: The data of 158 consecutive patients who underwent surgery for BOT at a tertiary referral center for gynecologic oncology between 1997 and 2008 were retrospectively analyzed. RESULTS: Most patients had early stage disease, and advanced stages FIGO II/III only occurred in 23.4%. Serous histology was most frequent (68%), followed by mucinous histology (22%). All patients received surgery as initial treatment with no adjuvant systemic therapy. 37 patients (40.7% of the patients under the age of 50) had fertility-sparing surgery (FSS). Recurrent disease occurred in 18 (11.4%) patients, and 4 (2.5%) patients died. Independent risk factors for recurrence were FIGO stages > I (hazard ratio (HR) 37.1; 95% confidence interval (CI) 4.5-155.5), tumor rupture (HR 12.4; 95% CI 1.5-61.5), incomplete staging (HR 5.9; 95% CI 1.6-21.3), and FSS in patients < 50 years (HR 8.0; 95% CI 2.0-31.6). CONCLUSION: Intraoperative tumor rupture, incomplete staging, and FSS - all influenced by the surgeon - may impose a substantial recurrence risk. Therefore, careful counseling and balancing of risk and benefit are mandatory before therapy is applied, especially if FSS is planned.

Excision repair cross-complementation group 1 protein overexpression as a predictor of poor survival for high-grade serous ovarian adenocarcinoma.

OBJECTIVE: The excision repair cross-complementation group 1 (ERCC1) expression is a predictor of survival after surgical treatment for several malignancies. Its overexpression has been reported as a marker of platinum resistance in lung cancer. However, the relevance of ERCC1 expression in ovarian cancer (OC) is the subject of controversy, both as a predictive parameter for platinum resistance and because of its association with poor prognosis. Therefore, we performed a retrospective study investigating ERCC1 expression and its correlation with patients' survival in OC. METHODS: We analyzed the ERCC1 protein expression using four different ERCC1 antibodies (clone 8F1) with different staining protocols. Immunohistochemistry was performed on multi-tissue microarrays (77 patients with primary serous ovarian cancer treated between 1999 and 2004; median age at diagnosis 67 years; range 32 to 88 years; 90% FIGO III+IV). In all cases cytoreductive surgery was followed by platinum-based chemotherapy. RESULTS: The Kaplan-Meier analysis revealed that the survival of patients with ERCC1-negative OCs (n=45; 62%) was significantly better (median survival 50.0 months) compared with the ERCC1-positive group (n=32; 38%; 20 months; p=0.004). Furthermore, ERCC1 expression was of prognostic relevance (p=0.002) in the case of negative expression in patients with residual tumor, where a higher survival rate was observed (median survival 30 months compared to 7.8 months in the ERCC1-positive group). CONCLUSIONS: ERCC1 protein overexpression may act as a prognostic marker for poor survival of high-grade OC even in patients operated with residual disease.

Abdominal wall metastases in patients with ovarian cancer after laparoscopic surgery: incidence, risk factors, and complications.

OBJECTIVES: Laparoscopy is the standard procedure to clarify undefined ovarian masses. However, laparoscopy could induce tumor spread in ovarian cancer (OC). The aim of this study was to assess the incidence, the risk factors, and the complications of abdominal wall metastases (AWM) in patients with OC after laparoscopy. METHODS: Retrospective study of patients with primary diagnosis of OC who had laparoscopy before cytoreductive surgery and resected port sites in laparotomy between 1999 and 2008 at our institution. Patients with borderline or nonepithelial ovarian tumors were excluded. RESULTS: Of 537 patients with a first diagnosis of OC, 101 had laparoscopy before definitive operation after a median of 31 days. Histological examination at final cytoreductive surgery of the port sites was conducted in 66 patients, whereas 31 patients (47%) showed AWM. Patients experiencing AWM had higher tumor stages and peritoneal carcinomatosis. Ascites with more than 500 mL was a further independent risk factor for AWM (odds ratio: 7.2; 95% confidence interval, 1.5-35.8; P = 0.016). Abdominal wall metastasis did not impact on survival in our cohort; however, affected patients showed significant larger abdominal wall resections (mean [SD]): 41.0 (angled brace 13.1) cm versus 9.1 (angled brace 1.4) cm in comparison with patients without AWM (P = 0.013), and 2 patients developed abdominal wall recurrences. CONCLUSIONS: The incidence of AWM in patients experiencing OC was considerably high when laparoscopic surgery was conducted before cytoreductive surgery. Patients experiencing AWM seem to have more surgical burden. However, our series did not show a dramatic impact of AWM on long-term outcome. Patients with highly suspected advanced OC and ascites with more than 500 mL should be referred directly to a gynecologic oncologist who is able to balance risks of laparoscopic staging and direct cytoreductive surgery.

Impact of treatment guidelines and implementation of a quality assurance program on quality of care in endometrial cancer.

BACKGROUND: The treatment guidelines in the last decade have shown a trend towards increasing surgical radicality in endometrial cancer. Little information is available on the implementation of standards into clinical reality. We evaluated the adherence to standard therapy before and after introduction of an internal quality management system and determined the reasons for non-adherence. PATIENTS AND METHODS: A retrospective analysis of the inhouse tumor registry was performed. Included were all patients with Federation of Gynecology and Obstetrics (FIGO) I-III endometrial cancer and therapy at the Dr. Horst Schmidt Klinik (HSK) from 1997 to 2007. RESULTS: 206 patients with epithelial endometrial cancer in stage FIGO I-III underwent primary surgery at the HSK. 140 (68%) patients were operated as recommended by the guidelines. 20% of patients were operated less radically (17% vs. 22% before and after introduction of guidelines; p = 0.33) and 12% more radically. The latter was significantly reduced after implementation of quality management (21% vs. 7%; p = 0.004). Comorbidities and age played an important role in less-than-standard treatment. CONCLUSIONS: Adherence to guideline-based therapy for endometrial cancer can be achieved in most patients. Implementation of standards and quality assurance primarily helps to avoid surgical overtreatment but failed to reduce less-than-standard treatment radicality. The latter seemed to be more defined by patient characteristics than by institution standards.

Borderline tumours of the ovary: A cohort study of the Arbeitsgmeinschaft Gynäkologische Onkologie (AGO) Study Group.

BACKGROUND: Borderline ovarian tumours (BOTs) are recognised as a unique entity of ovarian tumours that do not exert infiltrative destructive growth or stromal invasion. Prognosis of BOT is much better compared to the more common invasive epithelial ovarian cancer. Information regarding prognostic factors is inconclusive and no prospective studies exist that evaluate therapeutic strategies. We therefore started a retrospective-prospective cohort study to better understand BOT and identify scenarios in which future studies could be developed. METHODS: Consecutive patients with BOT treated between 1998 and 2008 in 24 German centres were analysed. The retrospective part of the study retrieved patients' data from hospital records and clinical tumour registries while active follow-up and an independent central pathology review were carried out prospectively. FINDINGS: BOT was confirmed in 950 patients, two thirds had serous BOT and 30.5% mucinous BOT. Most were diagnosed in stage I (82.3%); 7.6% and 10.1% had stages II and III, respectively. Overall, 74 patients (7.8%) experienced relapse and 43 (4.5%) died within the observation period. Multivariate analysis revealed higher stage, incomplete staging, tumour residuals, and organ preservation as independent prognostic factors for disease recurrence. Neither microinvasion nor micropapillary growth pattern showed any significant impact. Of 74 relapsed patients, 30% had malignant transformation to invasive ovarian cancer with five-year progression-free survival and overall survival of 12% and 50%, respectively. INTERPRETATION: Prognosis of BOT correlates with tumour-related as well as surgery-related factors. The balance between recurrence risk and organ preservation and fertility-sparing surgery is an important issue deserving further research.

Poly(ADP-ribosyl)ation polymerases: mechanism and new target of anticancer therapy.

Poly(ADP-ribose)polymerase (PARP) is a ubiquitously present nuclear enzyme that is not only involved in many important cellular pathways but also contributes to chromosomal structure and genomic stability. The development of highly selective and potent PARP inhibitors has become of increasing clinical interest because of their promising efficacy in patients with breast or ovarian cancer. Furthermore, recent Phase I and Phase II trials have demonstrated that PARP inhibitors have low toxicity rates. In particular patients with either deficiency or dysfunction of BRCA, which is involved in DNA double strand break repair, appear to benefit from PARP inhibition. This article summarizes the present knowledge regarding the physiological function of PARP and ([poly]ADP-ribose) PAR, the functional product of PARP, the development of PARP inhibitors, the recent clinical data of PARP inhibitors in cancer treatment and the selection of patients who may benefit from PARP inhibition.