**6. Symptom-based screening**

Symptoms of ovarian cancer occur insidiously, with many patients presenting with non-gynaecological symptoms such as indigestion, abdominal bloating and early satiety, leading to a cascade of trial therapies and investigations until a diagnosis is reached. Hence, there may be a time lapse from initial presentation to actual diagnosis of ovarian cancer. The National Institute for Health and Care Excellence (NICE) in the UK advises primary care physicians to conduct preliminary testing if a woman reports persistent or frequent symptoms of abdominal distension, early satiety and/or appetite loss, pelvic/abdominal pain or increased urinary urgency and/or frequency [35]. This has been followed-up by a nationwide campaign, encouraging patients to present if any of the aforementioned symptoms occur.

**7.1. The University of Kentucky Ovarian Cancer Screening (UKOCS) trial**

had not participated in screening [42].

the same protocol (p < 0.001) [43].

the control group (63% vs. 38%) [44].

**Randomised Controlled Trial**

This trial was set up in 1987 to assess the efficacy of annual transvaginal ultrasonography (TVS) to detect ovarian cancer in asymptomatic women. All asymptomatic women: (1) 50 years or older and (2) 25 years or older with a family history of ovarian cancer in a first- or seconddegree relative were eligible to participate in the trial. The control group for this study consisted of those women diagnosed with epithelial ovarian cancer entered in the University of Kentucky Tumor registry or statewide Kentucky Cancer registry between 1995 and 2001, who

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A total of 37,293 women were screened over a period of 24 years between 1987 and 2011 with TVS. Women with an abnormal ultrasound at screening underwent repeat ultrasound in 4–6 weeks. If this scan was also abnormal, then further characterisation of the ovarian mass was performed with tumour indexing, colour Doppler and serum CA125 levels. Women underwent surgery if the second screen was also abnormal. However, if this screen was normal, then the scan was repeated in 6 months. As a result of screening, 47 invasive epithelial ovarian cancers and 15 epithelial ovarian tumours of low malignant potential were detected. An improved survival rate was noted in the screened group when compared to controls. The 5-year survival rate for all women with invasive epithelial ovarian cancer detected by screening as well as interval cancers was 74.8 ± 6.6% compared with 53.7 ± 2.3% for unscreened women with ovarian cancer from the same institution who had undergone treatment using

**7.2. The Shizuoka Cohort Study of Ovarian Cancer Screening (SCSOCS) trial**

**7.3. The Prostate Lung Colorectal and Ovarian (PLCO) Cancer Screening** 

A total of 82,487 asymptomatic postmenopausal women were enrolled into this study between 1985 and 1999 across 212 hospitals in Shizouka, Japan. They were randomised into an intervention group (n = 41,688) or a control group (n = 40,799) and were followed up for a mean period of 9.2 years. The women in the intervention group were screened with a pelvic ultrasound scan (USS) and a serum CA 125 test. If the USS was normal and if the CA125 was <35 U/ml, then they returned to yearly follow-up. If the scan suggested malignant disease and/or if the CA 125 was elevated, then the women were referred for surgery. However, if the scan was abnormal but suggestive of benign disease, it was repeated every 3–6 months. Also, if the CA125 was above a certain threshold with a normal scan, the women had a repeat scan in 6 months. There was no statistical difference between the number of ovarian cancers detected in the screening arm when compared to the control arm (27 vs. 32). However, there were a higher proportion of stage 1 ovarian cancers in the screened group when compared to

A total of 78,216 postmenopausal women aged 55–74 years were enrolled into this trial across 10 centres in the US. They were randomised to either annual screening (n = 39,105) or usual medical care (n = 39,111). Main outcome measure was mortality from ovarian/tubal/primary

In an effort to trigger early detection in patients presenting non-specifically, Goff et al. developed a symptom index (SI) [36]. The presence of any one of six symptoms was considered a positive result, including bloating, increased abdominal size, pelvic or abdominal pain, difficulty eating and/or early satiety. In the detection of ovarian cancer, the specificity of the SI was higher in women over 50 (90%) when compared to women under 50 (86.7%) years of age [37]. The SI also had a better sensitivity for advanced stage disease (79.5%) when compared to early stage disease (56.7%). Similar data was noted in a further study, when considering the SI as an isolated screening tool [38]. Acceptability of symptombased screening was assessed in a subsequent prospective study. Encouragingly, of the 1261 women involved, symptom-based screening yielded a mean acceptability score of 4.8/5 and 4.7/5 for TVS and CA125 utilisation, respectively [36]. A multivariate approach involving SI, CA125 and HE4 biomarkers has also been studied for suitability [38]. Use of all three variates combined yielded an overall sensitivity of 83.8% and specificity of 98.5%. The authors concluded that these combined tests could be beneficial as first-line screening tool to aid selection for second-line imaging.

Despite these results, the question still remains as to whether detection using a symptombased approach increases survival rates. Overall, there has been conflicting data regarding the correlation between symptom onset, referral and diagnostic delays, stage at presentation and overall survival rates in ovarian cancer patients. Several studies have demonstrated no such association [39]. Moreover, a recent Australian study discovered no correlation between time of symptom onset and FIGO stage III and IV disease, and concluded that longer time to diagnosis does not affect survival in women, even with advanced stage ovarian cancer [40]. A large qualitative study noted no difference between duration of symptom onset or time to diagnosis amongst patients with early to more advanced disease. Interestingly, women with advanced disease were more likely to report disregarding their symptoms [41]. Overall, current evidence suggests that the most successful direction of symptom-based detection of ovarian cancer is with a multivariate approach, but further research is required to ascertain its applicability.
