Individuals diagnosed with stage IV ovarian cancer have disease that has spread outside the abdomen or into the liver. Currently, the standard treatment for stage IV ovarian cancer consists of both surgery and systemic treatment. Optimal cytoreductive surgery and platinum-based chemotherapy prolong the time to cancer recurrence and improve overall survival. Poly ADP-ribose polymerase (PARP) inhibitors, Avastin, and other newer precision cancer medicines are further improving upon the outcomes achieved with platinum-based chemotherapy. All patient should discuss the role of clinical trials in the management of stage IV ovarian cancer as many new treatments are being developed.
Doctors use a combined approach to treat stage IV ovarian cancer consisting of neoadjuvant therapy followed by surgery, adjuvant therapy, and maintenance therapy.
Neoadjuvant Therapy refers to systemic chemotherapy that is given prior to surgery. Neoadjuvant therapy consisting of 3 cycles of chemotherapy prior to surgical cytoreduction reduces the side effects of surgery and leads to more optimal cancer debulking.2
Cytoreductive Surgery: also called debulking occurs following neoadjuvant therapy and the surgeon attempt to remove as much of the ovarian cancer as possible. Cytoreductive surgery is beneficial because it reduces the number of cancer cells that ultimately need to be destroyed by systemic therapy and therefore, decreases the likelihood of the cancer becoming resistant.
Adjuvant Therapy: All patients with stage IV ovarian cancer are offered additional systemic chemotherapy treatment after surgery to eradicated remaining undetectable cancer that have spread outside the ovary and were not removed by surgery. Adjuvant chemotherapy is administered to decrease the risk of cancer recurrence following recovery from surgery because treatment with combination chemotherapy prolongs the duration of survival and prevents more recurrences of cancer compared to treatment with alone.1
Maintenance Therapy: Following the primary treatment of stage IV ovarian cancer with surgery and neoadjuvant and/or adjuvant chemotherapy additional treatment with “maintenance therapy” may also be recommended. Maintenance therapy is also systemic therapy administered with the goal to “maintain” a remission or prevent or delay the cancer’s return if the cancer is in remission after initial treatment. Some doctors believe the term "continuous therapy" is more appropriate since the cancer is essentially being treated on an ongoing basis. Maintenance therapy using Avastin and PARP inhibitor medications for 2 years has been shown to significantly decrease the risk of ovarian cancer recurrence in women who are in partial or complete remission after platinum-based chemotherapy.
PARP Inhibitors: The poly ADP-ribose polymerase (PARP) enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. PARP inhibitors are a new class of precision cancer medicines that contribute to cancer cell death and increased sensitivity to chemotherapy. By blocking the PARP enzyme, DNA inside the cancerous cells is less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth. Although all women appear to benefit from PARP treatment, individuals who test positive for BRCA and HRD appear to derive the greatest benefit.4,5,6
Strategies to Improve Treatment
The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies and patients should discuss trial participation with their treating physician.
Development of Precision Cancer Medicines: & Immunotherapy: Research is ongoing to develop new medications that specifically target cancer cells. Genomic biomarker testing is performed on the cancer in order to determine whether cancer causing genetic mutations are present that can be targeted with specific precision cancer medicines or immunotherapy drugs. Patients should learn about options to participate in these trials prior to surgery in order to ensure that cancer tissue is obtained correctly.
HIPEC: Hyperthermic (or Heated) Intraperitoneal Chemotherapy is a surgical procedure where surgeons pump a powerful dose of heated chemotherapy inside a patient’s abdomen. HIPEC Intraperitoneal (IP) delivers chemotherapy directly into the abdominal cavity, where there is the greatest number of cancer cells. The chemotherapy is administered through a large catheter that is placed into the abdomen during the surgery to remove the cancer. The 108-degree chemotherapy bath circulates throughout the peritoneal cavity, delivering highly concentrated doses of hot chemotherapy. After about 90 minutes of the infusion, the chemo is washed out and incisions are closed.
HIPEC appears to be most effective if surgery or other therapy has already reduced the size of any remaining cancer deposits to less than 1 cm, or about half an inch (this is sometimes referred to as “optimally debulked”). Among patients with stage III epithelial ovarian cancer, the addition of HIPEC to interval cytoreductive surgery delays cancer recurrence and prolongs overall survival compared to treatment with surgery alone.3 HIPEC is currently being evaluated in stage IV ovarian cancer.
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2 Wright AA, et al. J Clin Oncol 2016; 34:3460-73
4 Shapira-Frommer R, Oza AM, Domchek SM, et al. A phase II open-label, multicenter study of single-agent rucaparib in the treatment of patients with relapsed ovarian cancer and a deleterious BRCA mutation. Journal of Clinical Oncology. 33, 2015 (supplement; abstract 5513).
5 Tesaro Inc., press release. Tesaro’s niraparib significantly improved progression-free survival for patients with ovarian cancer in both cohorts of the phase 3 NOVA trial. Available: http://ir.tesarobio.com/releasedetail.cfm?ReleaseID=977524. Accessed July 6, 2016.
6 Moore KA, et al. N Engl J Med 2018; 379:2495-2505