Will shorter time interval to diagnose ovarian cancer improve early detection? A perspective from the dualistic model

Ovarian cancer is the most lethal gynaecological malignancy; over 200 000 women are diagnosed annually worldwide, and the 5-year survival rate is <50%. Early diagnosis has been proposed as the portal to reduce cancer mortality, but studies have found significant delays from onset of symptoms to diagnosis, both from first symptom to consultation and from consultation to diagnosis (Wikborn et al. Int J Gynaecol Obstet 1996;52:263–7). Consequently, educating women about specific ovarian cancer-related symptoms has been advocated to improve early diagnosis. We must examine not only whether such campaigns promote early diagnosis, but also whether they decrease disease-associated mortality. In this issue, Lim et al. report no significant correlation between time from first symptom to diagnosis and clinical stage in ovarian cancer (BJOG 2016;123:1012–1020). An Australian case–control study also found that once women have noted ovarian cancer symptoms, decreasing time from symptoms to diagnosis would not affect stage or overall survival (Nagle et al. J Clin Oncol 2011;29: 2253–8). This report by Lim et al., however, is the first to assess this by separating ovarian cancer according to the dualistic model (Shih and Kurman Am J Pathol 2004;164:1511–18). This is critical because ovarian cancer is a heterogeneous group of diseases that can be divided into type I (low-grade serous carcinoma, mucinous carcinoma, clear-cell carcinoma, endometrioid carcinoma and malignant Brenner tumour) and type II (high-grade serous carcinoma, carcinosarcoma and undifferentiated carcinoma). Their pathogeneses are distinct; type I develops stepwise, usually from borderline tumours, while type II often evolves from a precursor lesion in the fallopian tube (serous tubal intraepithelial carcinoma; STIC). This new paradigm that STIC is the precursor in many type II ovarian cancers has been supported by epidemiological, clinicpathological and molecular studies, and has substantial impact on prevention, detection and treatment of type II diseases (Kuhn et al. Curr Obstet Gynecol Rep 2012;1:1). Type II cancers are more aggressive than type I and present at later stages. It is therefore imperative that when studying ovarian cancer, we distinguish by type. Lim et al. evaluated the differences in time interval to diagnosis for women with type I and type II ovarian cancers. Type II cancers, due to rapid progression, have been thought to result in shorter time from symptom to diagnosis and thus to possibly be detectable at earlier stages, allowing effective therapeutic intervention. However, this study suggests that this may not be the case; time from symptom to diagnosis in type II cancers is almost identical to that of slow-growing type I tumours, and the majority of type II diseases are diagnosed in later stages regardless of time to diagnosis. Awareness of the symptoms of ovarian cancer is beneficial to getting women timely medical attention. However, if we wish to diagnose ovarian cancer earlier, we may consider shifting our focus to precursors, as was successful with cervical cancer. Detecting and prophylactically removing STICs via salpingectomy in women with increased risk may be seriously considered for type II ovarian cancer. Recent innovations in genomic technology using liquidbased cervical cytology specimens may be able to detect somatic mutations associated with ovarian cancer and even STIC. Positive results may prompt presymptomatic surgical intervention. The American Congress of Obstetricians and Gynecologists has proposed that preventive salpingectomy may be preferable to saplingooopherectomy, as the latter not only necessitates hormone therapy but also may increase the risk of cardiovascular disease, cognitive impairment, and osteoporosis (Committee on Gynecologic Practice Obstet Gynecol 2015;125:279–81; Shuster et al. Menopause Int 2008; 14:111–16).