EXPERT INSIGHT

Advances in the management of ovarian cancer: The ticking time bomb

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Dr. William Foo

Specialist in Clinical Oncology

Ovarian cancer remains the most deadly gynecologic malignancy, and its incidence has been steadily increasing over the past few decades.1 In Hong Kong, ovarian cancer is the 7th leading cause of female cancer deaths. The crude death rate was 5.5 per 100,000 female population.2 In 2017, a total of 218 women died from this cancer, accounting for 3.7% of all cancer deaths in females. In a recent interview, Dr. William Foo, Specialist in Clinical Oncology, shared his insights on the management of ovarian cancer in Hong Kong.

Introduction to ovarian cancer

Ovarian cancer is not a single disease entity, it comprises of various histologic subtypes based on differing cells of origin instead. The most common histologic types of epithelial ovarian cancers are high-grade serous carcinoma (HGSC; 70% to 80%), endometrioid carcinoma (10%), clear cell carcinomas (10%), mucinous carcinoma (3%), low-grade serous carcinoma (LGSC; <5%). The clinical behavior and molecular characteristics of these epithelial ovarian tumors are distinct from each other, highlighting the importance of a tailored treatment approach for the respective tumor subtypes.

The past few decades have witnessed various developments in the treatment of ovarian cancer, particularly the surgical and chemotherapeutic strategies.3 The prognosis for women with ovarian cancer has improved in the past several decades. This is especially true in advanced-stage diseases, particularly HGSOC. However, population-level survival in advanced-stage OCCC and MOC have not improved, exhibiting disproportionally poor survival in these diseases compared to advanced-stage HGSOC.3 Centralization of patient care and national/international collaborative work are considered as the keys to improving the outcome for rare epithelial ovarian cancer.3

The burden and the associated factors

Ovarian cancer is the most lethal gynecological cancer. Globally 230,000 women are diagnosed, with 150,000 deaths recorded annually. With a global relative survival rate of 30-40% following a 5-year post-diagnosis, ovarian cancer remains the 7th most commonly diagnosed cancer among women in the world.4 In Hong Kong, ovarian cancer ranks 6th among women cancers and 7th in lethality. One of the main factors contributing to the high mortality-to-incidence rate is the advanced stage of the disease at the time of diagnosis. Late-stage disease presentation has a 5-year relative survival rate of 29%, in contrast to 92% for early-stage disease. About 75% of patients are diagnosed at an advanced stage because of the asymptomatic nature of ovarian cancer.4 Genomic predisposition to ovarian cancer is now well recognized in up to 15% of affected women. Most are breast cancer susceptibility genes, BRCA1 and BRCA2, which have been identified in 65%–75% of hereditary ovarian cancer. Furthermore, Lynch syndrome, an autosomal dominant hereditary cancer family syndrome, accounts for 10%–15% of hereditary ovarian cancer and is typically associated with endometrioid or clear-cell tumors.4 Although exact causative factors have yet to be determined, various factors associated with ovarian cancer include the number of lifetime ovulations (absence of pregnancy, early age of menarche and late age at menopause), family history of ovarian cancer, smoking, benign gynecological conditions (including endometriosis, polycystic ovary syndrome and pelvic inflammatory disease), and potentially the use of talcum powder, need to be sorted out.5

Staging is a compulsory part in diagnosis. It is often surgical. Optimal debulking is a must in treatment.

Ovarian cancer symptoms are not specific and include abdominal bloating, early satiety, nausea, abdominal distension, change in bowel function, urinary symptoms, back pain, fatigue, and loss of weight, which typically occur at longer durations. Initial investigations include the measurement of cancer antigen 125 (CA125) concentrations and pelvic ultrasound.6 Additional characterization of ovarian cancer includes further imaging of the chest and abdomen and pelvis with CTs.

The International Federation of Gynecology and Obstetrics (FIGO) classifications for staging ovarian cancer (Figure 1) enable the development of the staging procedure, subsequently establishing the surgical stage.7,8 Furthermore, the pathological diagnosis of tumor tissue is essential due to the various histological subtypes of ovarian cancer requiring different treatment approaches. There are several histological variations with distinct precursor lesions, tissues of origin, molecular biology, clinical presentation, chemosensitivity, and patient outcome.

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Primary debulking surgery (PDS) followed by chemotherapy is the standard of care for advanced ovarian cancer.8 No residual tumor (R0) after PDS is the most important prognostic factor for survival.9 The fundamental guidelines associated with managing patients with FIGO stage IIIC and IV disease are presented in Figure 2.10 The algorithm and guideline based on the EORTC 55971 randomized trial included patients with stage IIIC disease and small metastases (<5cm). Compared to patients with stage IV disease, the incidence of overall survival with PDS was significantly higher, but the survival with neoadjuvant chemotherapy (NACT) was lower. However, when the tumor has extended beyond stages where successful resection by PDS is uncertain, neoadjuvant chemotherapy can be an alternative.

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The standard of chemotherapy is based on carboplatin and paclitaxel, with variations in dose and frequency, for six cycles. As a minority of patients present early, randomized clinical trials on the early-stage disease have been challenging to execute due to inadequate sampling.12 There are not a lot of variations of the chemotherapy regimen based on the subtypes. Intraperitoneal chemotherapy is not widely practiced and is not suitable for residual disease >1cm. The utilization of biologics such as antiangiogenic agents and PARP inhibitors may improve progression-free survival but the effect on overall survival remains to be defined.

Nonetheless, a follow-up assessment can potentially identify early disease recurrence. Despite a lack of guidelines regarding the nature and frequency of the follow-up assessments, regular physical examination is recommended generally. The earliest indication of the recurrent disease might be CA125 in patients where this has been a marker of disease. As neither radiological nor clinical evidence of the disease is available, the definition of recurrence is associated with the rise of more than twice the upper limit of normal CA125 (ULN is 35U/mL). No survival benefit has yet been observed with early treatment of relapse based on increased CA125 alone. However, relapsed/refractory disease is common with advanced-stage ovarian cancer. Knowledge in the molecular alterations, using biologics and immune checkpoint agents may cast hope on improving the outcome of relapsed disease.

Message to the physicians

In Hong Kong, the management of ovarian cancer is a multidisciplinary approach with both clinical oncologists and gynecological oncologists. However, since the diagnosis of patients occurs at later stages, public awareness regarding the knowledge of the disease is essential. It is important to educate women to seek medical help if they observe symptoms such as abdominal distension, bloating, nausea, and altered bowel movements, etc.

Conclusion

Efforts towards better understanding and characterizing different types of ovarian cancer have been leveraged into new therapies, transitioning to a standard of care. Building a strong multidisciplinary team in clinical practice is key to improve the precision medicine which will enhance patient care. The values of ovarian cancer treatment are evident for clinical benefit, toxicity, and improvements in patient symptoms or quality of life. Most importantly, enhancing awareness promotes the early identification of the disease.

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