Agc, ultrasound score, menopausal status, B clinical inipression score and serum CA 125 level were assesscd to scc how they could best distinguish between patients with benign ( n = 101) and malignant ( n = 42) pelvic masses. Each criteria uscd alone provided statistically significant discrimination. Thc most useful individual criteria were a serum CA 125 level of 30 U/m1 (sensitivity 81 %) , specificity 75%)) anti an ultrasound score of 2 (sensitivity 71 %. specificity 83%). Three criteria could be combined in a risk ol malignancy index (RMI) which is siniply calculated using thc product of the serum CA 125 level (Uitnl), the ultrasound scan result (expressed as a score of 0, 1 or 3) and the menopausal status (1 if premenopausal and 3 if postmenopausal). This index was statistically virtually as effective a discriminant hetween cancer and benign lesions as more formal methods. Using an KMI cut-off level of 200, the sensitivity was 85%) and thc specificity was 97%. Patients with an RMT score of grcatcr than 200 had, on average, 32 times the background risk of cancer and those with a lower value 0.15 times the background risk.The greatest opportunity to influence the naturai history ol' ovarian cancer occurs at the time of the initial laparotamy. The aims of surgical management at this time arc to determine accurately the cxtent of disease and to I-educe residual tumour volume to a minimum (Griffiths l9S7 Hackcr 1987). In spite of the knowlcdgc of thc bcncfits of accurate surgical staging and cyto-reductive surgery, many patients do not receive appropriate surgery at the time of surgical diagnosis (Young ff d. . Adequate treatment at primary laparotamy is generally considered to require persistent, time consuming and aggi-essive surgery that ia oftcn not fcasihlc during a routine operatiiig list. Ideally. patients with ovarian maligiiancy should therefore he referred

Objective To compare surgical outcomes and occult cancer rates at risk-reducing salpingo-oophorectomy in BRCA carriers and high-risk women who had not undergone genetic testing.Design Prospective cohort study.Setting Tertiary high-risk familial gynaecological cancer clinic.Population Women undergoing risk-reducing salpingooophorectomy between January 2005 and November 2009.Methods Women at high-risk of ovarian/tubal cancer were identified on the basis of the inclusion criteria for the UK Familial Ovarian Cancer Screening Study. Risk management options discussed with 1456 high-risk women included risk-reducing salpingo-oophorectomy. A strict histopathological protocol with serial slicing was used to assess tubes and ovaries.Results In total, 308 high-risk women (191 with unknown mutation status; 117 known BRCA1/BRCA2 carriers) chose risk-reducing surgery; 94.5% of procedures were performed laparoscopically. The surgical complication rate was 3.9% (95% CI 2.0-6.7). Four ovarian and ten tubal occult invasive/in situ cancers were found. The overall occult invasive cancer rate was 5.1% (95% CI 1.9-10.83) in BRCA1/BRCA2 carriers and 1.05% (95% CI 0.13-3.73) in untested women. When tubal in situ cancers were included, the overall rate was 4.55% (95% CI 2.5-7.5). Two untested women with tubal carcinoma in situ were subsequently found to be BRCA carriers. The median ages of BRCA carriers (58 years; IQR 13.4 years) and untested women (49.5 years; IQR 20.6 years) with occult invasive/in situ cancer were not significantly different (P = 0.454).Conclusions Both high-risk women of unknown mutation status and BRCA carriers have a significant (although higher in the latter group) rate of occult invasive/in situ tubal/ovarian cancer, with a similar age distribution at detection. The data has important implications for counselling high-risk women on the likelihood of occult malignancy and perioperative complications at riskreducing salpingo-oophorectomy. Women with occult disease should be offered genetic testing.

Objective To evaluate factors affecting uptake of risk-reducing salpingo-oophorectomy (RRSO) over time in women at high-risk of familial ovarian cancer.Design Prospective observational cohort.Setting Tertiary high-risk familial gynaecological cancer clinic. Methods Risk management options discussed included RRSO and ovarian surveillance. Outcome data were analysed from a bespoke database. The competing risk method was used to model the cumulative incidence function (CIF) of RRSO over time, and the sub-hazard ratio (SHR) was used to assess the strength of the association of variables of interest with RRSO. Gray's test was used to evaluate the difference in CIF between two groups and multivariable competing risk regression analysis was used to model the cumulative probabilities of covariates on the CIF.Results Of 1133 eligible women, 265 (21.4%) opted for RRSO and 868 (69.9%) chose screening. Women undergoing RRSO were older (49 years, interquartile range 12.2 years) than those preferring screening (43.4 years, interquartile range 11.9 years) (P < 0.0005). The CIF for RRSO at 5 years was 0.55 (95% CI 0.45-0.64) for BRCA1/2 carriers and 0.22 (95% CI 0.19-0.26) for women of unknown mutation status (P < 0.0001); 0.42 (95% CI 0.36-0.47) for postmenopausal women (P < 0.0001); 0.29 (95% CI 0.25-0.33) for parity ‡1 (P = 0.009) and 0.47 (95% CI 0.39-0.55) for a personal history of breast cancer (P < 0.0001). Variables of significance from the regression analysis were: a BRCA1/2 mutation (SHR 2.31, 95% CI 1.7-3.14), postmenopausal status (SHR 2.16, 95% CI 1.62-2.87)) and a personal history of breast cancer (SHR 1.5, 95% CI 1.09-2.06).Conclusions Decision-making is a complex process and women opt for surgery many years after initial risk assessment. BRCA carriers, postmenopausal women and women who had breast cancer are significantly more likely to opt for preventative surgery.

As the overall prognosis for patients with ovarian cancer is poor, the management of this condition should be restricted to expert multi-disciplinary teams in gynaecological oncology. Apparent early stage ovarian cancer requires accurate and complete staging so that potential sites for metastases are not missed. Omitting adequate staging may have significant consequences including a negative impact on survival rates in young patients. The challenge with advanced ovarian cancer is to obtain a detailed appreciation of the extent of disease. This information allows treatment with primary chemotherapy if the cancer is considered to be inoperable and/or the general condition of the patient renders her unfit for appropriate surgery. Available data would suggest that a 5-year survival rate of 50% is only possible for those patients who have had complete cytoreduction of all tumour. Therefore, the best surgical option for patients with advanced ovarian cancer is a complete primary surgical procedure that achieves complete clearance of the abdominal cavity rather than optimal surgery that leaves tumour nodules up to 1 cm in diameter in situ in the patient.

Background. Previous studies have established that soluble interleukin‐2 receptor alpha (sIL‐2Rα) levels are elevated in ascites and sera from individuals with advanced ovarian cancer (International Federation of Gynecology and Obstetrics [FIGO] Stage III/IV). This study was undertaken to evaluate sIL‐2Rα levels in individuals with benign ovarian neoplasms and early stage ovarian cancer (FIGO Stage I/II). Comparison with CA 125 levels was performed to assess screening potential. Methods. Sera from 92 healthy individuals, 61 with benign adnexal masses, 12 patients with FIGO Stage I/II ovarian cancers, and 27 patients with FIGO Stage III/IV ovarian cancers were assayed for sIL‐2Rα by enzymelinked immunosorbent assay and CA 125 by radioimmunoassay. Results. The mean serum sIL‐2Rα levels for benign pelvic masses, and Stage I/II and Stage III/IV epithelial ovarian cancer were 1507±82, 1631±274, and 2596±384 U/ml, respectively. The difference between mean serum sIL‐2Rα levels in individuals with benign adnexal masses and Stage III/IV epithelial ovarian cancer was statistically significant (P < 0.05). In addition, of the four individuals with FIGO Stage I/II ovarian cancer who had CA125 levels below 35 U/ml, the accepted upper limit of normal, three patients had elevated serum sIL‐2Rα levels. Eleven of 12 patients (92%) with potentially curable Stage I/II disease had elevated serum levels of either sIL‐2Rα or CA125 and 8 of 12 (67%) had elevations of both sIL‐2Rα and CA125. Sensitivity and specificity of a combination of CA 125 and soluble IL‐2R alpha were 88.5% and 27.1%, respectively. Conclusion. Soluble interleukin‐2 receptor alpha levels do not appear to differentiate between benign adnexal lesions and early malignancy; however, measurement of sIL‐2Rα levels in combination with CA125 warrants further evaluation to determine if together they will identify individuals with Stages I and II ovarian cancer. Cancer 1995;76:1615–20.