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Stage 4 Ovarian Cancer

 

People diagnosed with stage 4 ovarian cancer have disease that has spread outside the abdomen or into the liver. Currently, the standard treatment for stage 4 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 4 ovarian cancer as many new treatments are being developed.

 

Doctors use a combined approach to treat stage 4 ovarian cancer consisting of neoadjuvant therapy followed by surgery, adjuvant therapy, and maintenance therapy.  A multidisciplinary treatment team is essential.

 

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.

 

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 4 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.

 

Maintenance Therapy: Following the primary treatment of stage 4 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.

 

Possibilities 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 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 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. HIPEC is currently being evaluated in stage IV ovarian cancer.

 

The successful treatment of ovarian cancer requires the involvement and coordination of several different treatment approaches, including surgery, systemic therapy, and, in rare cases, radiation therapy. Nearly all women with ovarian cancer will undergo surgery and systemic treatment. The role of surgery in the initial management of ovarian cancer is to obtain a biopsy specimen of the cancer to confirm the diagnosis, determine the stage of cancer and to provide local treatment of the cancer in the pelvis and abdomen.  The tissue sample is also evaluated for prognostic information and may be sent for genomic testing to determine whether any precision cancer medicines can be used.

 

Laparotomy (Initial Cytoreductive Surgery)

 

For patients diagnosed with ovarian cancer during surgery, the first phase of treatment is surgical laparotomy or exploration of the abdomen. During a laparotomy, the surgeon makes an incision down the middle of the abdomen and attempts to remove as much of the cancer within the abdomen and pelvis as possible. The goal of laparotomy is to accurately diagnose and stage the cancer and gain prognostic information that can determine the most appropriate additional therapy.

 

Typical debulking during the laparotomy includes:

 

• A total hysterectomy (removal of the uterus)

• Bilateral salpingo-oophorectomy (removal of the ovaries and fallopian tubes)

• Omentectomy (removal of a flap of fatty tissue covering the bowel in the abdomen).

• Removal of any visible cancer within the abdomen.

• If the cancer appears to be limited to the ovaries or the pelvis, the surgeon will also cut small pieces of tissue (biopsy) from the upper abdomen.

• Peritoneal washings -collection of abdominal fluid samples and removal of lymph nodes so that they can be examined under a microscope to determine whether they contain cancer.

 

These extensive and time-consuming surgeries are best performed by a gynecologic oncologist, who is a surgeon specialized in the treatment of female pelvic cancers.

 

For patients with metastatic ovarian cancer (cancer detected outside the abdomen), surgery may be beneficial for relief of symptoms and to improve duration of survival. Surgery to remove cancer in the abdomen may help relieve pain, prevent obstruction or blockage of the bowel, and improve a patient’s nutritional status.

 

The typical surgery for ovarian cancer prevents women from future childbearing because the reproductive organs (ovaries and uterus) are removed. Occasionally, ovarian cancer will occur in a younger woman who wishes to maintain fertility. If the cancer involves only one ovary and the surgery shows no cancer beyond a single ovary, a unilateral salpingo-oophorectomy (removal of one ovary and fallopian tube) can be performed. This allows the patient to bear children and still provides adequate treatment for the cancer. After childbearing is complete, the remaining ovary and the uterus are often removed in an effort to prevent a recurrence.

 

Despite surgical removal of the cancer, the majority of patients with stage II-IV ovarian cancer will experience a recurrence if no additional systemic treatment is given. This is because patients have undetectable microscopic cancer cells that have spread from the original site of cancer to distant locations in the body and were not removed by surgery. In other cases, patients have visible spread of cancer cells outside the ovary into the abdomen, pelvis, or lymph nodes that cannot be completely removed by surgery.

 

• When the cancer is removed with surgery so that no remaining cancer is larger than 1 cm (about three-quarters of an inch), the cancer is referred to as “optimally debulked” or “optimally cytoreduced.”

• When cancer larger than 1 cm remains after the surgery, the cancer is referred to as “suboptimally debulked” or “suboptimally cytoreduced.”

 

Patients with optimally cytoreduced cancer are more likely to survive longer and less likely to experience cancer recurrence following systemic therapy than patients who are suboptimally cytoreduced.

 

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. HIPEC is currently being evaluated in other stages of ovarian cancer.

 

Patients who undergo laparotomy for ovarian cancer may experience lower abdominal pain after the operation. Complications related to surgery may include bleeding, infection, a slow recovery of bowel function, temporary difficulty emptying the bladder or other less common conditions. Your surgeon should explain the risk of side effects associated with treatment.

 

Second-Look Laparotomy

 

After completion of systemic therapy, patients undergo a physical examination, a CA-125 blood test and radiologic studies to evaluate the effectiveness of treatment. When all of these tests are negative for cancer, a patient is said to be in a complete clinical remission. Many patients in complete remission still have microscopic cancer that was not detected with the available tests. Some doctors recommend an additional surgical evaluation after completion of systemic therapy in order to further evaluate the response to treatment. This operation is called a “second-look laparotomy.” A second-look laparotomy is the most accurate method of detecting persistent cancer cells when CA-125 levels are normal.

 

Second-look laparotomy will detect evidence of cancer in at least half of patients thought to be in clinical remission. Even when the second-look laparotomy does not detect any cancer cells, cancer still recurs in approximately 30-50% of patients.

 

Routine second-look laparotomy is no longer recommended as standard treatment. Many doctors recommend that it only be used as part of a clinical trial. This is because a second-look laparotomy only has value to a patient if the information gained during the laparotomy can change a patient’s outcome or subsequent treatment options. This is important for patients to understand because undergoing a second or unnecessary surgery is associated with additional risks and emotional discomfort. These risks include bowel obstruction, adhesions and pain.

 

Clinical Trials:

 

New anti-cancer therapies continue to be developed and evaluated in clinical trials. There are three phases of clinical trials before approval.  See our clinical trials section for more information.

 

Managing Liver Metastases

 

When gastric cancer spreads to the liver, it doesn’t always cause symptoms. It may be picked up by liver function tests, which are blood tests that measure certain levels of enzymes and proteins in the blood. Abnormal levels can indicate liver disease or damage.

 

If liver metastasis causes symptoms, they can include:

 

• pain or discomfort in the mid-section

• fatigue and weakness

• weight loss/poor appetite

• fever

• bloating

• swelling in the legs

• a yellow tint to the skin or the whites of the eyes

 

In addition to liver function tests, doctors use imaging tests to diagnose liver metastases. These may include MRI (magnetic resonance imaging), CT scan (computed tomography), ultrasound, and/or PET scan (positron emission tomography). Sometimes, a combined PET/CT scan is used.

 

Your doctor also may recommend getting a sample of the suspicious area(s) for examination under a microscope (biopsy). He or she may involve an interventional radiologist to obtain precise and minimally invasive imaging.

 

The most common treatments for metastatic gastric cancer in any location (bone, brain, lung, or liver) are systemic medications, which treat cancer throughout the entire body. Systemic medications include chemotherapy, targeted therapies, and clinical trials that have already been discussed.  Liver directed therapies, including surgery, may be an option.

 

Liver Directed Therapies: There are numerous liver directed therapies available for those who are faced with a Stage 4 cervical cancer diagnosis with liver metastases or gastric cancer that has spread to the liver.  These therapies are dependent on the size, number, and location of the liver tumors. These liver directed therapies may include chemoembolization, cryoablation, cyberknife, hepatic arterial infusion, liver resection, proton beam therapy, radioembolization or SIRT, radiofrequency ablation, or SBRT.  You can learn more on our treatment page under liver directed therapies.