What are Ovaries?
The ovaries are paired, almond-shaped, female-reproductive glands, which sit on either side of the uterus (the hollow, pear-shaped organ that accommodates the growing fetus) and held in position by supporting ligaments.
The main functions of the ovaries include the production of the eggs for reproduction and secretion of the female sex hormones (estrogen and progesterone). The ovaries are made up of mainly 3 types of cells: epithelial cells (that cover the surface of the ovaries), germ cells (that produce the egg/ova), and stromal cells (that provide structural support to the ovary and produce female sex hormones). Each of these cells can develop into one or more types of cancer.
What are the Types of Ovarian Cancer?
Epithelial ovarian cancers
These are the most commonly encountered (about 90% of all cases) ovarian cancers. Epithelial ovarian cancers are further divided into following subtypes based on their histology (appearance under a microscope): serous, endometrioid, mucinous, and clear cell. Primary peritoneal cancers and fallopian tube cancers are very much similar to ovarian epithelial cancers and are generally managed via similar treatment approach.
Germ cell ovarian tumors
These constitute about less than 5% of all ovarian cancers. They are further classified into following subtypes based on the type of cells involved: teratomas, dysgerminomas, endodermal sinus (yolk sac) tumors, choriocarcinomas, and embryonal tumors. They generally occur as a mix of these subtypes.
Ovarian (or sex chord) stromal tumors
These constitute about less than 7% of all ovarian cancers. They are further classified into following subtypes based on the type of cells involved and type of treatment approach usually followed for such tumors: granulosa cell tumor (most common), Sertoli-Leydig cell tumor, thecoma, fibroma, and fibrosarcoma.
How is the Staging of Ovarian Cancer done?
The staging system for ovarian cancer is called as FIGO staging system. It helps in disease prognostication and choosing an appropriate treatment regimen.
Ovaries are paired globular structures located on either side of the uterus. Fallopian tubes are tubular structures that carry the ovum produced from the ovary to uterus.
This figure shows the pelvic anatomy from top. Uterus is connected to both ovaries with fallopian tubes, with urinary bladder present in front and rectum present behind. On both sides are the ureters.
FIGO Stage I
Tumor is localised to one or both the ovaries with/without capsular rupture, but no spread of tumor to adjacent structures.
Stage IA – Tumor is localised to one ovary and has not spread to ovarian surface or elsewhere, ie, capsule of ovary is intact.
Stage IB – Tumor is localised to both ovaries and has not spread to ovarian surface or elsewhere, ie, capsule of ovary is intact.
Stage IC – Tumor cells present on ovarian surface or in ascitic fluid, but no extension to adjacent organs. Capsule rupture during surgery or spontaneously may be the reason.
FIGO Stage II
Spread of the tumor to adjacent organs like fallopian tube, uterus, urinary bladder or rectum.
Stage IIA – Tumor extends locally involve fallopian tubes and/or uterus.
This figure shows spread to fallopian tube.
And here, it has spread to fallopian tube and uterus.
Stage IIB – Tumor infiltrates into urinary bladder and/or rectum.
This figure shows tumor infiltrating into urinary bladder.
And here, it infiltrates into rectum.
FIGO STAGE III
Spread of the tumor to retroperitoneal lymph nodes and/or peritoneum, capsule of liver and/or spleen.
Stage IIIA1 – Tumor limited to ovary/fallopian tube with involvement of only retroperitoneal lymph nodes
Stage IIIA2 – Tumor limited to ovary/fallopian tube with microscopic peritoneal deposits with/without involvement of retroperitoneal lymph nodes
Stage IIIB – Tumor limited to ovary/fallopian tube with macroscopic peritoneal deposits (</=2 cm) with/without involvement of retroperitoneal lymph nodes.
Stage IIIC – Tumor limited to ovary/fallopian tube with macroscopic peritoneal deposits (>2 cm) with/without involvement of retroperitoneal lymph nodes. There may be spread to capsule of liver and/or spleen, without parenchymal involvement.
FIGO STAGE IV
Stage IVA – Spread of the tumor to pleural cavity to cause pleural effusion.
Stage IVB – Spread of the tumor to parenchyma of liver and/or spleen and/or organs outside the abdomen (like lungs, bones, etc) and/or nodes other than the retroperitoneal lymph nodes.
What is the Treatment approach for Ovarian Cancer?
Treatment of ovarian cancer depends on the stage, type (epithelial tumor, germ cell tumor, sex cord stromal tumor, etc) performance status of the patient, along with other factors. But the final treatment decision is taken by the oncologist after clinical evaluation of the patient.
Depending on the resectability of the tumor and performance status of the patient, along with other factors, one of the following decisions may be taken-
If the disease appears to be upfront resectable according to the surgeon, primary cytoreductive surgery is the preferred treatment in such cases. Then, depending on the subtype, stage and grade of the tumor after surgery, chemotherapy may be added. Intraperitoneal chemotherapy is also an option for certain subsets of patients.
There are mainly 2 aims of surgery in ovarian cancer: first is to stage the disease and second is to remove maximum possible cancerous tissue (this is also called as debulking). This help in establishing accurate stage and thus selecting an appropriate adjuvant treatment for the disease.
For most patients, surgery for ovarian cancer involves removal of the uterus (hysterectomy), along with both ovaries and fallopian tubes (salpingo-oophorectomy or BSO). Depending upon the extent of disease, omentum (the fatty tissue layer covering abdominal organs) may also be removed (omentectomy) along with the affected lymph nodes and/or other structures with high suspicion of involvement by the disease. Any fluid present in the pelvis or abdominal cavity along with peritoneal washings are also collected for analysis. Blind biopsies may also be taken from certain places in case no gross disease is visible in abdomen.
Fertility Preservation Surgery
For a young patient with disease limited to one ovary/fallopian tube and who wish to retain fertility, fertility preservation surgery (involving removal of the affected ovary/fallopian tube and retention of the uterus and other ovary/fallopian tube [unilateral salpingo-oophorectomy, USO]) is generally employed.
In some cases, upfront surgery may not be possible, and chemotherapy is the preferred treatment option in such cases. And if the disease becomes resectable after some cycles of chemotherapy, interval debulking surgery may be done.
What is the Stagewise treatment for epithelial ovarian cancer?
Primary Cytoreductive Surgery is treatment of choice in most cases. Following which, addition of chemotherapy may be considered depending on grade, stage (IA, IB or IC), and other factors.
In stage 2 also, Primary Cytoreductive Surgery followed by chemotherapy is the preferred treatment in most cases.
Decision to do surgery before chemotherapy (Primary Cytoreductive Surgery) or after chemotherapy (Interval Debulking Surgery) is taken by the oncologist after assessing the tumor extent and performance status of patient, along with other factors.
Chemotherapy with/without targeted therapy is considered the first line treatment in most cases. Surgery may be considered depending on response. Other palliative treatment may be required in some cases for relief of symptoms.
What Targeted Therapies are approved for the treatment of ovarian cancer?
Various targeted agents have been approved for the treatment of advanced-stage ovarian cancer. Following are the targeted drugs approved for the treatment of ovarian cancer:
It is an angiogenesis inhibitor that inhibits vascular endothelial growth factor (VEGF)-receptor (VEGFR), a factor that promotes angiogenesis (formation of new blood vessels). Bevacizumab is reported to be more efficacious when combined with chemotherapy for both shrinking the existing tumors and preventing recurrence of already treated ovarian cancers.
Side effects of bevacizumab include high blood pressure, fatigue, bruising or bleeding, mouth sores, loss of appetite, and diarrhea. Other rare but possibly serious side effects include severe bleeding, blood clots, gastrointestinal perforations, and slow wound healing.
A multifunctional tyrosine kinase inhibitor that inhibits many factors responsible for growth and proliferation of ovarian cancer cells including VEGFR, platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), and c-kit. It also inhibits other factors like colony stimulating factor 1, lymphocyte-specific tyrosine kinase, and interleukin (IL)-2-inducible T-cell kinase.
It is a Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor. PARPs are enzymes that are normally involved in the repair of damaged DNA by homologous recombination inside the cells. Inhibition of PARP leads to an accumulation of single-strand DNA breaks, which causes cells to die if not corrected. Such defects can be repaired by BRCA proteins via homologous recombination, a highly efficient process. However, the cells with a mutation of defective BRCA genes cannot repair such defects and die. Thus, tumors with BRCA1/2 mutation (about 10% to 20% of all cases), are particularly sensitive to PARP inhibition.
Single-agent olaparib is generally recommended for the treatment of patients with advanced, BRCA mutation positive, recurrent ovarian cancer (both platinum sensitive or resistant) who have received >/=3 lines of chemotherapy.
It can also be used as maintenance therapy for BRCA positive patients after first line platinum based therapy, and irrespective of BRCA after platinum based therapy in a platinum sensitive relapse.
Rucaparib and Niraparib are other PARP inhibitors that may be used in ovarian cancer. PARP Inhibitors may be associated with side effects like nausea, vomiting, fatigue, anemia, loss of appetite, diarrhea, taste changes, and pain in stomach, muscle, and joints.
Is Immunotherapy an option for Ovarian Cancer Treatment?
Pembrolizumab, an immune check-point inhibitor, is approved immunotherapeutic agent for the treatment of ovarian cancer . It has been approved for the treatment of advanced stage ovarian cancer as the second-line or subsequent line therapy for the treatment of unresectable/metastatic, Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) ovarian cancer that has progressed on prior treatment and for which no satisfactory alternative treatment option is available.
MSI-H ovarian cancers are observed in approximately 2% of all the cases, which indicate the limited application of immunotherapy in the treatment of ovarian cancer.
What Hormonal Drugs are used in Ovarian Cancer?
Hormonal cancer therapy includes treatment with drugs that modulate the activity of certain hormones that promote the growth of cancer cells. Hormonal drugs commonly used for ovarian cancer treatment include tamoxifen, aromatase inhibitors (anastrozole and letrozole), leuprolide acetate, or megestrol acetate among others.
Best Ovarian Cancer Specialist in Delhi
Dr Sunny Garg is a renowned Medical Oncologist in New Delhi with an experience of more than 6 years of treating ovarian cancer patients. He has practiced in leading cancer hospitals in Delhi, and currently practicing at Manipal Hospital, Dwarka.
He has a vast experience of treating ovarian cancer patients in all stages of disease. He is well versed with Immunotherapy, Targeted Therapy and Chemotherapy for Ovarian Cancer treatment and also general supportive care for patients. He works in close collaboration with surgical oncologists, oncopathologists, nuclear medicine, and genetic counselors for comprehensive cancer care for the patients.
Call +91 9686813020 for appointment.