78,216 women aged 55–74 years randomized to 6 annual rounds of screening with CA 125 and TVUS for 4 years (n = 39,105) or a group with usual care (n = 39,111).

Examined the efficacy of multimodal screening including annual CA 125 with risk of ovarian cancer algorithm (ROCA) and TVUS as a second line test versus screening with TVUS alone.

UK FOCSS 2 modified screening by employing Q4 month assessments with online system notifying physicians when additional/testing referral was required.

A total of 4,531 women were enrolled.

Patients with >10 % lifetime risk of ovarian cancer + age >35.

Sensitivity ranged from 75 to 100 % and specificity 96.1 % with PPV of 13 %.

Currently, no organization recommends screening average-risk women for ovarian cancer.

In 2012 USPSTF recommended against screening for ovarian cancer (D recommendation) given lack of reduction in ovarian cancer related mortality in completed studies.

High grade serous (75–80 %).

Endometrioid (10 %).

Clear cell (10 %).

Mucinous (3 %).

Low grade serous (<5 %).

Transitional cell/Brenner (<1 %).

High grade serous and low grade serous carcinomas are now considered different neoplasms with independent pathogenesis.

Most common type of ovarian neoplasm and rarely confined to the ovary (<10 %) at the time of diagnosis.

Can range in size from microscopic to >25 cm.

Typically cystic and multilocular.

Microscopic examination traditionally shows papillary, glandular, microcystic, and solid patterns.

Psammoma bodies may be present but traditionally to a lesser degree than with low grade serous lesions.

Marked cytologic atypia and prominent mitoses are common.

Diffusely express p53 and p16.

Can additionally express WT-1, estrogen, and Pax-8.

Uncommon and accounts for less than 5 % of ovarian cancers [10].

Commonly diagnosed in advanced stage with poor long term prognosis.

Commonly found in association with borderline component.

Microscopically characterized by destructive stromal invasion.

Lower mitotic activity and less nuclear atypia than high grade lesions.

Molecular studies show common mutations in KRAS and BRAF.

Nearly all present with early stage disease (Stage I).

Tend to be large (>20 cm) at the time of presentation/resection.

Bilateral in 5–10 % of cases (bilaterally may indicate GI metastases to ovary).

Microscopically cells resemble those of endocervix, intestine, or gastric pylorus.

Commonly express GI markers including CDX2 and CK20.

Over 75 % have a KRAS mutation.

Commonly identified at an early stage with significantly better prognosis.

Typically low grade, but chemosensitive.

Associated with endometrial cancer 15–20 % of the time.

Grossly solid and/or cystic and may arise in background of endometriosis.

Microscopically resembles low grade endometrioid adenocarcinoma of the uterus.

Typically express vimentin, ER, PR, and CA 125.

The most common somatic mutations are found in beta-catenin and PTEN (analogous to endometrial adenocarcinoma).

Bilateral in up to 15 % of cases.

Similar to endometrioid histology, clear cell commonly presents at an early stage with good prognosis.

But, if presents in advanced stage, worse prognosis and outcome compared to serous or endometrioid carcinoma (not as chemo-responsive to platinum).

Often associated with and arising from endometriosis.

Traditionally large and cystic on gross inspection.

Sheets of cells with clear cytoplasm characterize the solid pattern.

Lack expression of ER and WT-1.

Associated with mutation in ARID1A.

Can be serous or mucinous (Table 1.2).

Account for 3–5 % of ovarian cancers, with the majority (70 %) presenting as Stage I lesions (ovary confined disease).

Most common age at presentation 10–30 years.

These lesions are almost always unilateral aside from dysgerminoma, which is bilateral in up to 15 % of cases.

Amongst malignant germ cell tumors: dysgerminoma, immature teratoma, yolk sac, and mixed account for 90 % of cases.

hCG: embryonal, choriocarcinoma, mixed germ cell.

AFP: yolk-sac/endodermal sinus, embryonal, mixed germ cell.

LDH: dysgerminoma.

Struma ovarii is a “monodermal” teratoma composed almost entirely of mature thyroid tissue.

Non gestational choriocarcinoma is exceedingly rare, and has a propensity for early hematogenous spread.

In a subset of patients with advanced stage ovarian cancer, primary surgical cytoreduction is not feasible due to:

In these setting, neoadjuvant chemotherapy is commonly administered.

Additionally, given the potential morbidity associated with surgical cytoreduction, as well as the variability in achieving microscopic residual disease, an interest in the administration of neoadjuvant chemotherapy has emerged over the last decade.

To date, 2 prospective phase 3, randomized clinical trials have been performed in Europe comparing neoadjuvant chemotherapy to up-front surgery in patients with advanced stage ovarian cancer (Table 1.4) [25].

Neither trail showed primary cytoreduction to be superior to neoadjuvant chemotherapy with respect to oncologic outcome.

Vergote et al. [26]—The hazard ratio for death in the group assigned to neoadjuvant chemotherapy followed by interval debulking, as compared with the group assigned to primary debulking surgery followed by chemotherapy, was 0.98 (90 % CI, 0.84 to 1.13; P =0.01 for non inferiority), and the hazard ratio for progressive disease was 1.01 (90 % CI, 0.89–1.15).

MRC CHORUS (2013 ASCO annual meeting) randomized phase 3 trial, comparing neoadjuvant chemotherapy (NACT) to primary surgery (PS) for newly diagnosed advanced ovarian cancer (Abstract 5,500) was discussed [27].

Currently, we await the results of Japanese Clinical Oncology Group (JCOG) protocol 0602, once again evaluating the question of up-front surgery versus neoadjuvant chemotherapy.

Benefit of chemotherapy in the management of patients with early stage, high-risk disease, has been studied in three large clinical trials (Table 1.5) [28].

These patients are defined as having Stage Ia and Ib grade II–III tumors, all grades of Ic–IIa and all clear cell carcinomas.

Patients presenting with advanced stage ovarian cancer are managed with maximal surgical resection followed by adjuvant platinum and taxane based chemotherapy.

Prior to the discovery and introduction of cisplatin patients were treated with the alkylating agents melphalan, thiotepa, cyclophosphamide, or chlorambucil as single agents.

Our understanding of the therapeutic benefits of regimens containing cisplatin and paclitaxel originated following the results of Gynecologic Oncology Group (GOG) protocol 111 [33]

OV-10, a European–Canadian trial, studied 680 patients treated with cisplatin (75 mg/m²) and paclitaxel (175 mg/m² over 3 h) or cisplatin (75 mg/m²) plus cyclophosphamide (750 mg/m²) [34].

Following completion of GOG 111, the GOG opened protocol 158 [35].

The combination of carboplatin and paclitaxel was then studied with gemcitabine, topotecan or liposomal doxorubicin in sequential doublets or triplets in GOG 182/ICON5 [36].

In addition to intravenous (IV) therapy, the GOG also investigated intraperitoneal (IP) treatment options.

Following completion of 2 randomized phase III intergroup trials comparing IV to IV + IP therapy that showed positive results, the GOG opened protocol 172, which compared IV paclitaxel (135 mg/m²) over 24 h with IV cisplatin (75 mg/m²) on day 2, versus IV paclitaxel (135 mg/m²) over 24 h, followed by IP cisplatin (100 mg/m²) on day 2 and IP paclitaxel (60 mg/m²) on day 8 (Table 1.6) [25, 37–39].