General information
Ovarian cancer is the second most common gynecologic cancer in developed countries. The average age of onset of the disease is 63 years, while the probability of a woman being infected during her lifetime is 1.3%. Exceptions are women who have the corresponding genetic predisposition.
What are the risk factors for developing ovarian cancer?
The factors that increase the risk of developing ovarian cancer include:
- Advanced age (usually women> 60 years old)
- The onset of menstruation at an early age and/ or delayed menopause
- Nulliparity and infertility
- Endometriosis
- Family history of endometrial, breast or ovarian cancer, especially if the woman has a mutation in certain genes (e.g. BRCA1, BRCA2)
- Family history of Lynch syndrome
Women who have one or more of the above risk factors will not necessarily manifest ovarian cancer in the future. However, consulting individualized doctors would be useful.
How can a woman reduce the risk of developing ovarian cancer?
Unfortunately, there is no way to provide complete protection against ovarian cancer. However, the following may reduce the risk of developing the disease:
- Use of contraceptives
- Pregnancy
- Most likely, breastfeeding
- Tubal ligation as part of contraception
- Salpingectomy
In case of hereditary predisposition, more details on ways to prevent the disease can be found here.
What are the signs of ovarian cancer?
Ovarian cancer may cause a variety of signs and symptoms, including:
- Indefinite pain or feeling of pressure in the lower abdomen
- Back pain
- Bloating
- Trouble eating or feeling full quickly
- Nausea and/ or vomiting
- Unexplained changes in body weight or extreme tiredness (fatigue)
- Changes in bowel movements (mainly, emerging constipation)
- Urinary symptoms such as urgency (always feeling like you have to go) or frequency (having to go often)
- Bleeding or unusual vaginal discharge after menopause
Unfortunately, in more than 70-80%, ovarian cancer is diagnosed when it is already at an advanced stage. The most important reason that prevents the early diagnosis of the disease is the absence of characteristic symptoms. Many of the above clinical manifestations are usually compatible with benign diseases (e.g., irritable bowel syndrome, endometriosis, etc.), so that patient does not pay due attention.
What should I do if I have the above symptoms?
Do not ignore symptoms (e.g., bloating) that insist for more than 2 weeks. Consult your doctor and discuss any changes in your body, no matter how small the chance for something serious may be. If, after a gynecological examination or an ultrasound of the genitals, your doctor finds a tumor in the ovarian area, he/ she will probably ask you to have an MRI of the lower abdomen with an intravenous contrast agent. In addition, the doctor will recommend measuring tumor markers in the blood, such as CA-125 (mainly), CEA, CA 19-9, AFP, hCG, LDH and inhibin-B. It is to be noted that not all ovarian tumors are necessarily malignant. Moreover, finding elevated tumor markers does not necessarily mean that there is cancer, as often they can be higher than normal in benign conditions, as well. However, all the information that your doctor will get from the clinical examination, the screening test and the tumor markers can determine the degree of suspicion for ovarian cancer.
What should I do if it is suspected I have ovarian cancer?
If the examinations show an increased likelihood of ovarian cancer, the next step for the patient is to visit a Gynecologic Oncologist, that is a Gynecologist with official individualization in treating gynecologic cancers. The Gynecologic Oncologist has all the necessary knowledge and technical skills to evaluate the patient, provide the appropriate surgical treatment and coordinate the rest of the treatment and the subsequent follow-up of the patient.
Surgical treatment
What screening tests are needed before surgery?
Ovarian cancer is definitively diagnosed only after surgery and histological examination of the removed tissue. Before that and if there is suspicion for ovarian cancer, the patient should undergo a CT scan of the chest, upper and lower abdomen with intravenous and oral administration of contrast agent. The available options include MRI and PET/CT. This determines the extent of the disease (e.g., metastases) and its resectability. If there is no previous examination, the doctor will suggest preoperative measurement of the tumor markers in the blood (CA-125, CEA, CA 19-9, AFR, LDH, hCG, inhibin B). Tumor markers can provide further information on the malignant nature of the pelvic tumor and its histological identification, while, in particular, they contribute to the evaluation of the response to treatment and the monitoring of the patients for any possible recurrence.
How is early stage of ovarian cancer treated surgically?
When ovarian cancer is diagnosed via screening tests in the pelvis, its surgical staging is performed. The purpose of the staging operations is to reveal microscopic metastases, which occur in almost 30% of the cases. After entering the peritoneal cavity, the staging includes:
- Collection of the free peritoneal fluid to investigate whether it contains cancer cells (cytological examination). Alternatively, this check is done in peritoneal lavage.
- Removal of the appendage (fallopian tube and ovary) containing the tumor, making every effort not to rupture its capsule. The resected material is sent for rapid biopsy, during which the Pathologist will respond in a short time if it is cancer. In case of undeniable malignancy, the surgery continues based on the following:
- Removal of the uterus along with the cervix (total hysterectomy) and heterolateral part (fallopian tube and ovary).
- Systematic removal of the pelvic (common, internal, external iliac and thyroid lymph nodes) and paraaortic lymph nodes (up to the level of the renal vessels).
- Omentectomy, at least supracolic.
- Careful examination of peritoneal areas for any metastatic foci of the disease. In case nodules or adhesions are found that could represent metastases, it is necessary to remove them. Otherwise, random biopsies are obtained from the pelvis, the paracolic gutters and the peritoneal surface of diaphragm.
- Appendectomy on mucinous carcinomas of the ovary. In these tumors, pelvic and paraaortic lymph node removal is not required.
It is noted that the operations mentioned above are performed in the vast majority of patients with early-stage epithelial ovarian cancer. If a patient wants to maintain her reproductive potential and meets the corresponding, strict conditions, or in certain NON-epithelial ovarian cancers (e.g., granulocytic tumors), the surgical plan is formed accordingly.
What determines the success of advanced stage ovarian cancer surgeries?
When ovarian cancer is at an advanced stage, more extensive surgery (primary cytoreduction) is required. Its success is determined by the size of the residual tumor, i.e., the maximum diameter of the foci remaining in the abdomen after the operation. Traditionally, a surgical treatment is considered optimal when this diameter does not exceed 1cm. Nevertheless, numerous studies have repeatedly shown that the best oncological results are ensured when primary cytoreduction leads to complete -macroscopic- resection of the metastatic foci. In some cases, the extent of the disease or the general condition of the patient (e.g., advanced age, serious health problems in other organs, poor nutrition) does not allow the above goals to be achieved without a high risk of complications. Chemotherapy (neoadjuvant chemotherapy) is then preferred to shrink the disease, followed by surgery (intermediate cytoreduction) at a second stage. These decisions (primary cytoreduction or neoadjuvant chemotherapy) should be performed by doctors highly qualified in treating gynecological malignancies as they significantly affect the patient’s subsequent course.
How does the Gynecologic Oncologist assess the resectability of the disease and therefore the possibility of successful primary cytoreduction?
The initial assessment of the extent of the disease and the possibility of surgically removing metastatic foci is done by imaging methods (CT and/or MRI). If the disease is considered inoperable from the outset, confirmation of the diagnosis in order to administer the suitable chemotherapy is done by puncture of the abdomen and collection of free fluid (ascites), if any, for cytological examination or, even better, by taking a biopsy. This can be realized in the context of diagnostic laparoscopy or by an Interventional Radiologist under the guidance of a CT scanner.
Other times, the resection of the disease is not clear by the screening tests. Then, the Gynecologic Oncologist will recommend diagnostic laparoscopy to assess the size and exact localization of metastatic foci under direct vision. If the disease is considered inoperable, the doctor will receive biopsies for histological identification and refer the patient for neoadjuvant chemotherapy. It is noted that the small incisions used for laparoscopy allow the patient to recover very quickly and start chemotherapy in a timely manner. If the disease is considered operable, the Gynecologic Oncologist will proceed to primary cytoreduction at the same time or after a few days.
What may primary cytoreduction include for the successful treatment of advanced stage ovarian cancer?
For the successful primary cytoreduction, it is necessary to perform a middle vertical incision that usually extends from the sternum to the lower part of the pelvis. Surgical time includes the suction of the ascites that may coexists and the removal of the uterus, the fallopian tubes and ovaries, and the omental cake. Individual procedures that may be considered necessary to resect all metastatic foci are the resection of parts of the large and/or small intestine, appendectomy, removal of the peritoneum, even from diaphragm, and splenectomy. More rarely, peripheral pancreatectomy, partial gastrectomy, resection of parts of the liver, cholecystectomy and partial removal of the bladder or re-implantation of the ureter may be required. All swollen or suspected metastatic lymph nodes should be removed. On the other hand, recent data have shown that systematic pelvic and paraaortic lymphadenectomy in patients with advanced stage ovarian cancer and, screeningly or intraoperatively, normal lymph nodes are not an option. When the above procedures are performed by Gynecologic Oncologists with corresponding qualifications, the literature has shown that the oncological results are better. Depending on the specific needs of each patient, a successful surgical treatment of the disease may also require collaboration with groups of doctors of other surgical specialties.
What does intermediate cytoreduction involve?
Intermediate cytoreduction should be performed after 3-4 cycles of neoadjuvant chemotherapy. In individual cases, more cycles may be required before surgery. On the other hand, if the disease progresses during chemotherapy, then it is practically considered inoperable. The main pillars of intermediate cytoreductive surgery are the removal of the uterus, along with the surrounding structures (fallopian tubes and ovaries) and the omentum. All peritoneal tissues should be carefully examined and any lesions or adhesions that raise the suspicion of metastasis should be removed. Excision of enlarged or suspected lymph nodes is necessary. It is noted that, in many cases, the administration of neoadjuvant chemotherapy does not entail a complete response of the disease. Therefore, intermediate cytoreduction may also include some of the resections of the gastrointestinal system, the peritoneum and/or the upper abdomen that were described for primary cytoreductive surgery. Hence, their performance by qualified doctors, as mentioned above, is imperative.
Adjuvant therapy
When is chemotherapy in ovarian cancer patients needed after surgery?
Chemotherapy after surgical treatment of ovarian cancer aims to reduce the likelihood of recurrence of the disease. Indications of its administration are determined by the stage of the disease, the histological type, and the degree of differentiation (grade) of the tumor. In general, with the exception of the well-differentiated IA and IB stage ovarian cancer, other cases usually require chemotherapy. This refers also to all patients with clear cell histological type, due to its aggressive biology.
The final histological examination of the tumor showed that I eventually suffer from fallopian tube cancer or primary peritoneal carcinoma. Is there any change in my treatment?
High-grade serous carcinoma of the ovaries, the fallopian tubes and the peritoneum is practically the same disease. The causes, symptoms, principles of surgical treatment and subsequent chemotherapy are the same.
What types of chemotherapy are used in ovarian cancer?
Ovarian cancer requiring chemotherapy is treated with a combination of platinum (carboplatin mainly and cisplatin) and taxane (paclitaxel mainly and doxecatel). These medicines are administered intravenously every 1 (dose dense) or 3 weeks until completion of usually 6 cycles of chemotherapy. In the latter case, the Pathologist Oncologist may recommend concomitant administration of bevacizumab, which continues for about 1 year after completion of the classical chemotherapy.
What are the most common side effects of chemotherapy in ovarian cancer?
The side effects of chemotherapy are related to the medicines used and the intervals of their administration. The most common include hair loss, nausea and vomiting, a drop in the number of blood cells and the feeling of tingle in the hands and feet. Bevacizumab is sometimes associated with increased blood pressure, headaches, and delay in wound healing. More rarely, it can cause perforation of the intestine, especially if the patient has a history of inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease) or the ovarian cancer had spread there.
What additional options do patients with a BRCA1 and BRCA2 gene mutation have after completing the chemotherapy?
In women with a mutation in BRCA1 and BRCA2 genes who responded to initial chemotherapy, maintenance therapy with Olaparib (PARP inhibitor) is associated with significantly better oncological results. The possibility of their administration to other women is subject of intensive research.
What does patient follow-up involve after the completion of treatment?
The patient follow-up after treatment is based on:
- Periodic clinical examination, including gynecological examination,
- Measurement of the tumor markers in the blood (mainly CA-125)
- Screening checks. The available options include CT or MRI and PET/CT, so decisions are made based on the doctor’s judgement, changes in tumor markers and possible symptoms of the patient.
What treatment options are available in case of recurrence of ovarian cancer?
The main factor that influences therapeutic decisions in case of relapse is the amount of time elapsed since the completion of the initial treatment. If ovarian cancer relapses soon (<6 months), the disease is considered platinum resistant, and the patient’s prognosis is burdened. If the interval is longer, the resumption of platinum-based chemotherapy is the dominant option. The addition of Bevacizumab, if not given in the initial treatment, is possible. Alternatively, PARP inhibitors (e.g., olaparib, niraparib, rucaparib) may be also administered for maintenance therapy. Depending on the time of recurrence of ovarian cancer, the location of metastases and the general condition of the patient, their surgical removal followed by chemotherapy may help to improve its prognosis.
