Stages of Ovarian Cancer

Texas Oncology provides expert care and advanced therapies to treat and manage Stage I-V ovarian cancer, helping patients reduce recurrence risk.

Stage I Stage II Stage III Stage IV

Stage I Ovarian Cancer

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

Adjuvant systemic therapy

The delivery of 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 for patients with stage I ovarian cancer 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.

Low-risk stage I 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 ovarian 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. Because up to 40% of patients with high risk stage I ovarian cancer may experience a recurrence 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.

Before deciding to receive adjuvant chemotherapy treatment, women should ensure that they understand the answer to the following 3 questions:

What is my prognosis (risk of cancer recurrence) without adjuvant chemotherapy treatment?
How will my prognosis be improved with chemotherapy treatment?
What are the risks of chemotherapy treatment?

Stage II Ovarian Cancer

Stage II ovarian cancer is limited to the ovaries and other pelvic organs, but has not spread to the upper abdomen, lymph nodes or sites outside the abdomen. Each person with stage II ovarian cancer is unique, and the specific characteristics of your condition will determine how it is managed. The information on this Web site is intended to help educate you about treatment options and to facilitate a shared decision-making process with your treating physician.

The combination of cytoreductive surgery and chemotherapy treatment is the standard of care for treatment of stage II ovarian cancer. Individuals with stage IIA disease experience cancer recurrence rates of 30-40% and those in patients with more advanced stage IIB disease are even greater. This is because patients with stage II ovarian cancer are often left with microscopic disease following surgery and currently available chemotherapy is unable to eradicate all of the remaining cancer.^{1,2,3,4,5,6,7}

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 chemotherapy and therefore, decreases the likelihood of the cancer developing a resistance to chemotherapy. 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, all patients with stage II ovarian cancer are offered additional systemic treatment with the goal of destroying any remaining cancer not removed by surgery. Currently, this treatment is chemotherapy.

Neoadjuvant chemotherapy

Neoadjuvant chemotherapy (NACT) refers to chemotherapy that is given prior to surgery. When surgery is performed after chemotherapy treatment, it is referred to as interval cytoreduction. Neoadjuvant chemotherapy can reduce the size of the cancer, thereby allowing easier surgical removal and more effective results from the subsequent chemotherapy.

Adjuvant systemic therapy

Adjuvant chemotherapy is administered to decrease the risk of cancer recurrence following recovery from surgery because clinical trials have demonstrated that adjuvant chemotherapy improves survival compared to treatment with surgery alone. Standard systemic therapy typically consists of a platinum and taxane chemotherapy drug, however several other chemotherapy and precision cancer medicine drugs are available, and others are being developed in clinical trials.

Because many patients still experience recurrence of their cancer following standard therapy, patients should consider participation in clinical trials evaluating new treatment approaches as their initial option.

Before deciding to receive adjuvant systemic therapy treatment or to participate in a clinical trial, women should ensure they understand the answer to 3 questions:

What is my prognosis (risk of cancer recurrence) without adjuvant therapy treatment?
How will my prognosis be improved with adjuvant treatment?
What are the risks of treatment?

Upon completion of adjuvant systemic therapy doctors perform a series of tests in order to 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.

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 the PARP inhibitors or Avastin have both been demonstrated to improve outcomes in select patients with stage III or IV ovarian cancer and are being evaluated in stage II disease.^{1,2,3,4,5,6,7}

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 Genetech. (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;

Stage III Ovarian Cancer

Patients diagnosed with stage III ovarian cancer have cancer that has spread from the ovaries and pelvic organs into the upper abdomen or lymph nodes. Currently, the standard treatment for stage III ovarian cancer consists of both surgery and systemic treatment with chemotherapy. Historically, less than 40% of patients experienced long-term survival following standard treatment for stage III ovarian cancer. This was because it was difficult to completely remove the cancer with surgery and the available chemotherapy was unable to eradicate the remaining cancer.

Doctors are improving on these results by using a combined approach 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.

HIPEC: Intraperitoneal (IP) chemotherapy 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. This treatment 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. In a pivotal trial evaluating HIPEC median overall survival was 33.9 months for surgery compared to 45.7 months in the surgery-plus-HIPEC group.³

Adjuvant Therapy: All patients with stage III 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

References

1 https://www.cancer.gov/types/ovarian/patient/ovarian-epithelial-treatment-pdq

2 Wright AA, et al. J Clin Oncol 2016; 34:3460-73

3 https://www.nejm.org/doi/full/10.1056/NEJMoa1708618

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 at: 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

Stage IV Ovarian Cancer

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

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

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.

References

1 https://www.cancer.gov/types/ovarian/patient/ovarian-epithelial-treatment-pdq

2 Wright AA, et al. J Clin Oncol 2016; 34:3460-73

3 https://www.nejm.org/doi/full/10.1056/NEJMoa1708618

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