Broome Oncology

Stage I-II Ovarian Cancer

Stage I-II ovarian cancer is limited to the ovaries and has not spread to other pelvic or abdominal organs, lymph nodes or sites outside of the abdomen. Each person with ovarian cancer is unique, and the specific characteristics of your condition will determine how it is managed.

Stage I ovarian cancer is curable in the majority of patients with surgical removal of the cancer and systemic therapy. Despite surgical removal of the cancer, 5-20% of patients with stage I ovarian cancer, and 30-40% of those with stage II will experience a recurrence of their cancer. This is because some patients have microscopic cancer cells that have spread outside the ovary and therefore were not removed by surgery. Following surgery patients may benefit from additional systemic therapy to further decrease the risk of cancer recurrence.

Surgical Cytoreduction

Surgical cytoreduction (also called debulking) refers to the surgical removal of as much of the cancer as possible. Cytoreduction 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 developing a resistance. Initial cytoreductive surgery in ovarian cancer is currently considered the standard of care because clinical studies have shown that patients who have had optimal cytoreduction live longer and have a longer time to cancer recurrence than patients who have had suboptimal cytoreduction.

Following cytoreductive surgery, many patients are offered additional systemic treatment with the goal of destroying any remaining cancer not removed by surgery. Currently, systemic treatment is with chemotherapy.

Systemic Therapy

The delivery of systemic cancer treatment following local treatment with surgery is referred to as “adjuvant” therapy and may include chemotherapy, precision cancer medicines, radiation therapy and/or immunotherapy.

Adjuvant chemotherapy is administered to decrease the risk of cancer recurrence following recovery from surgery because clinical trials have demonstrated that adjuvant chemotherapy treatment improves survival compared to treatment with surgery alone. Several factors may affect an individual’s decision regarding the type of primary chemotherapy to receive. Patients at a low risk of cancer recurrence may consider less aggressive therapy or may opt not to receive any additional treatment, whereas patients at a high risk of cancer recurrence may choose more aggressive therapies or participate in clinical studies evaluating innovative treatment strategies.

Upon completion of adjuvant systemic therapy doctors perform a series of tests o determine the effectiveness of treatment. These typically include a CT or MRI of the chest/abdomen/pelvis and a CA-125. The cancer will either be undetectable (a complete response) or still present. If cancer remains additional therapy for recurrent or resistant disease will be offered.

If a complete response or remission is achieved patients should discuss the potential benefits of additional maintenance therapy with their doctor. This is a lower dose therapy designed to prolong the remission and improve the chance of cure.

Low-Risk Ovarian Cancer

Patients with stage I ovarian cancer are considered to be at low risk of cancer recurrence if the cancer appears to be of low or moderate grade (aggressiveness) under a microscope and no cancer cells were found in the abdominal fluid or on the surface of the ovary. Local treatment with surgery cures the majority of individuals with low-risk stage I ovarian cancer. For women who do receive chemotherapy, however, treatment typically consists of a combination of platinum and taxane chemotherapy regimen.

High-Risk Stage I and Stage II Cancer

Patients with stage I ovarian cancer are considered high-risk if the cancer appears high-grade under the microscope, has a “clear cell” histology or if cancer cells were found in the abdominal fluid or on the surface of the ovary. Up to 40% of patients with high risk stage I cancer may experience recurrence so chemotherapy is routinely administered.  Approximately 80% of patients with high-risk stage I ovarian cancer treated with surgery and adjuvant chemotherapy survive without evidence of cancer 5 years from surgery and chemotherapy treatment.

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. In addition to continued development of chemotherapy treatment regimens active investigation aimed at improving the treatment of early stage ovarian cancer includes the following:

Improvement of Adjuvant Chemotherapy:  Clinical trials are currently ongoing to develop and compare adjuvant chemotherapy treatment regimens in women with Stage II ovarian cancer to improve outcomes.

Development of Precision Cancer Medicines:  Research is ongoing to develop new medications that specifically target cancer cells in clinical trials.  These trials typically require a sample of the cancer or liquid biopsy to be available in order to evaluate for biomarkers. Patients should learn about options to participate in these trials prior to surgery in order to ensure that cancer tissue is obtained correctly.

PARP Inhibitors: The poly ADP-ribose polymerase (PARP) enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. A new class of precision cancer medicines that target and inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy and are called PARP inhibitors.  By blocking this 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.

PARP inhibitors have the greatest effect in women with mutations of the BRCA genes but may benefit additional patients with different genetic profiles as well.  BRCA genes are involved with repairing damaged DNA and normally work to prevent tumor development. The best way to incorporate PARP inhibitors into the overall management of ovarian cancer is being determined however they already have been shown to improve outcomes when used as maintenance therapy following completion of chemotherapy.1,2,3

Avastin® (bevacizumab: A targeted therapy that is showing promise in the treatment of ovarian cancer is Avastin®.4 Avastin slows or prevents the growth of new blood vessels by inhibiting a protein known as VEGF; this deprives the cancer of oxygen and nutrients. Avastin may also improve the delivery of chemotherapy to cancer cells by normalizing blood supply.

Among women with optimally debulked Stage III ovarian cancer, a phase III clinical trial compared treatment with intravenous (IV) chemotherapy alone to treatment with both IV and IP chemotherapy. Women who received both IV and IP chemotherapy survived more than a year longer than women who received only IV chemotherapy, but also experienced more severe side effects.5,6

Maintenance Therapy: Consolidation therapy, also called maintenance therapy, refers to extra systemic therapy that is given after completion of standard adjuvant chemotherapy.  Maintenance therapy with Taxol or the PARP inhibitor Zejula (Niraparib) have both been demonstrated to improve outcomes in select patients.1,7

Neoadjuvant Chemotherapy: Neoadjuvant chemotherapy refers to chemotherapy that is given prior to surgery. When surgery is performed after chemotherapy treatment, it is referred to as interval cytoreduction. Some doctors believe that neoadjuvant chemotherapy can reduce the size of the cancer, thereby allowing easier surgical removal and more effective results from the subsequent chemotherapy. Although ongoing work is being done to explore the neoadjuvant chemotherapy-surgery-adjuvant chemotherapy format, current results do not suggest that this format shows an advantage over the more conventional format of surgery followed by adjuvant chemotherapy. There are current clinical trials attempting to further define the answer to this question.

References


1 http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm427554.htm

2 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).

3 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 at: http://ir.tesarobio.com/releasedetail.cfm?ReleaseID=977524. Accessed July 6, 2016.

4 (2016.) FDA Approves Genetech’s Avastin® (Bevacizumab) Plus Chemotherapy for a Specific Type of Advanced Ovarian Cancer. [Press release.] Can be retrieved from https://www.gene.com/media/press-releases/14647/2016-12-06/fda-approves-genentechs-avastin-bevacizu

5 Armstrong DK, Bundy B, Lenzel L et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. New England Journal of Medicine. 2006;354:34-43.

6 ACOG Committee on Gynecologic Practice. Intraperitoneal chemotherapy for ovarian cancer. Obstetrics and Gynecology. 2008;111:249-251.

7 Markman M, Liu PY, Wilczynski S et al. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: A Southwest Oncology Group and Gynecologic Oncology Group trial. Journal of Clinical Oncology. 2003

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