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Treatment Effectiveness in Stage I and II Ovarian Cancer



Introduction

Ovarian cancer is a widespread medical issue nowadays. It refers to the buildup and growth of malignant cells in the ovaries (women’s reproductive glands that produce an egg each month in the female organism of childbearing age) arising from the epithelium and spreading to the fallopian tubes and nearby tissues. It should not be confused with benign (noncancerous) tumors that may develop in ovaries. Benign cancer differs from the malignant one in terms of its capacity to spread over the other parts of the organism through the blood or lymph nodes (Ovarian Cancer Research Fund Alliance). The disease is one of the prevalent cancers diagnosed among women all over the world. Thus, 1 out of 75 women (1.3%) are diagnosed with ovarian cancer (Vaughan, et al. 719).

Additionally, the disease remains one of the most prominent causes of cancer-related mortality among the female population in the US (Alsop et al. 2655). Consequently, 1 out of 100 women are under the threat of dying from ovarian cancer. Furthermore, the survival rate decreases with age and progression of the disease. The aim of this paper is to discuss the importance of the early diagnosis and treatment of ovarian cancer and analyze their role in the recovery of the patients. In particular, the risk factors, symptoms, treatment options, and survival of stage I and II ovarian cancer patients will be discussed. The research aims to define whether early diagnosis and treatment of stage I and II ovarian cancer can ensure complete recovery.

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Biology of the Disease

Cancer cells may start to grow in different places of the ovary. Thus, in the majority of cases, ovarian cancer starts in the epithelium, which is the thin tissue that covers the ovaries. It is typical of older women who already had menopause. Cancer may also develop in the cells that form eggs in the ovaries. This type of cancer is called germ cell carcinoma (carcinoma is a malignant epithelial tumor); it accounts for about 5% of all ovarian cancer cases and tends to affect younger women. Similarly, stromal carcinoma cases make up the other 5% of ovarian cancer cases. In such cases, cancer starts in the connective tissue cells that produce female hormones, estrogen, and progesterone. Normally, it can be diagnosed at the second stage. Small cell carcinoma of the ovary (SCCO) affects the health of young women and has a rate of 0.1% (Ovarian Cancer Risk Fund Alliance).

Risk Factors for Ovarian Cancer

Researchers have not yet identified any specific cause of ovarian cancer. However, there are some factors increase the risk of developing malignancy. Thus, the risk of developing the cancer of ovaries depends on the age of a woman, her inherited susceptibility, personal history of gynecologic cancers, etc. Norqvist defined the following risk factors associated with a high possibility of developing ovarian cancer: strong family cancer history, age over 65, high number of total lifetime ovulations, infertility (or infertility treatment), breast cancer, hormone replacement therapy (HRT), obesity or overweight, and endometriosis. The most relevant of them will be discussed further in the paper.

  • First, the major risk factor for ovarian cancer is a strong family history of gynecologic cancer. Thus, a woman whose family members suffered from either ovary or breast cancer is highly likely to have ovarian cancer in her lifetime (Buys et al. 2995). In particular, the lifetime risk of a woman with the family history equals 5%, which is more than threefold higher in comparison with the general population, where the percentage is equal to 1.4% (Ovarian Cancer Research Fund Alliance).
  • Secondly, genetic predisposition is related to a high percentage of ovarian cancer cases. Thus, BRCA1 and BRCA2 gene mutations account for about 20-25% of ovarian cancer cases (Ovarian Cancer Research Fund Alliance). The mutation of either of these genes increases the lifetime risk of the malignancy to 27-44%. In addition, the risk increases with age; thus, the age onset of ovarian cancer due to mutation of BRCA1 and BRCA2 is 45 and 60 year respectively (Jelovac and Armstrong).
  • Thirdly, ovarian cancer risk is associated with Lynch syndrome among approximately 1% of the patients. The latter is the type of colorectal cancer, which emerges in the case of mutations and modifications in the structure of DNA (Jelovac and Armstrong). Fourthly, ovarian cancer risk increases two-threefold due to personal history of endometriosis (the abnormal growth of endometrial cells outside the uterus instead of inside that is associated with pelvic pain).

According to the present epidemiologic data, cancer occurrence is also dependent on such environmental factors like smoking. Besides, there is a direct correlation between cancer and the number of lifetime ovulations. Thus, the higher the number of ovulations a woman has, the higher is the probability of developing ovarian cancer. Women aged 55-64 who were not pregnant, had early menarche (the first menstruation) and later menopause, went through hormone replacement therapy, and have a history of gynecologic inflammatory diseases such as endometriosis (increases the risk by 30%) are associated with an increased risk of the disease. On the contrary, longer time of lactation, full-term pregnancies, and use of oral contraceptives decrease the risk of ovarian malignancy (Jelovac and Armstrong).

Apart from that, there exist surgical factors that can reduce the risk of the disease. Thus, bilateral salpingo-oophorectomy (an operation of removing ovaries and fallopian tubes) substantially reduces the risk of ovarian cancer (Ovarian Cancer Research Fund Alliance). However, this procedure incurs some possible adverse effects for women; therefore, it should be considered for patients with a genetic predisposition to malignancy only. According to the American Cancer Society, the tubal ligation, which presupposes tying the fallopian tubes, reduces the risk of ovarian cancer by 33%. Analogically, the hysterectomy, known as the operation of removing the uterus, declines the chances of incidence of ovarian cancer by 67% (Ovarian Cancer Research Fund Alliance).

All in all, causative factors for ovarian cancer are not yet identified, but certain risk factors are known to increase the possibility of developing the disease. Hormonal and hereditary reproductive factors are the major issues determining a high likelihood of ovarian cancer among women.

Classification of Ovarian Cancer

The choice of treatment and patient survival is closely connected with the stage and type of the disease. Staging refers to the spread of cancer in the body, whereas ovarian cancer types are related to the structure of a cancerous cell. The Cancer Research Institute reports about more than 20.000 US women who get diagnosed with ovarian cancer. For about 15.000 of them, this cancer may appear to be lethal (Ovarian Cancer Research Fund Alliance).

High mortality results from many factors, namely problems with disease detection. Thus, only 15% of all cases of ovarian cancer are diagnosed at stage I, when cancer is confined to one or two ovaries (Ovarian Cancer Research Fund Alliance). Commonly, cancer does not display itself in any noticeable symptoms. Thus, it can be diagnosed only at the advanced stages, when the mutated cells are spreading all over the body. Not surprisingly, ovarian cancer is known as the silent killer.

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Ovarian cancer manifests itself in various symptoms and causes. Epithelial ovarian cancer (EOC) is the type of cancer where cancerous cells develop in the outer (epithelial layer of the ovaries) is the prevalent type of the disease accounting for about 90% of all cancerous malignancies (Buys et al. 2301). It usually develops among elder women (the average age of epithelial ovarian cancer is 63) and accounts for 21,880 cases annually, most of which (13,850 cases) end in mortality.

It is the second most frequent gynecologic cancer and the major cause of death among American women with gynecologic malignancies. Apart from that, it is subdivided into the serous, endometrioid, clear cell, mucinous, and undifferentiated or unclassifiable ovarian cancer. Other types of ovarian tumors are germ cell cancer (accounting for 1-2 % of all ovarian cancers) and borderline ovarian tumors (about 10% of cases). Germ cell ovarian cancer starts from the egg that makes cells of the ovary. Borderline tumors show higher recovery potential and do not require adjuvant therapy.

There is a special system of cancer staging, which has been developed by the FIGO Committee for Gynecologic Oncology in 2014. The system shows that the first stage of cancer is characterized by the confinement of the tumor to the ovaries and fallopian tubes. The second stage is capable of affecting both ovaries and pelvis (Prat). According to Jayson et al., it is possible to distinguish between three substages within the first one: substage IA, substage IB, and substage IC (1379). In substage IA, the cancer is confined to one ovary and the tissues of the fallopian tubes. In substage IB, both ovaries are affected with cancer; and in substage IC, the malignancy spreads to the outer surface of the ovaries. In stage II, cancer affects not only the ovaries and the fallopian tubes but also the bladder, colon, and the rectum.

The study conducted by Prat shows that only a quarter of all cases of ovarian cancer are connected with the confinement to ovaries solely. In about 20% of cases, cancer bears a regional character, while about 69% of the cancer occurrences can be examined as the distant disease (Prat). Stage I is often referred to as an ‘early stage.’ Until recently, stage II was also designated as an ‘early’ ovarian cancer. However, it is currently categorized as ‘advanced’ ovarian cancer due to the high recurrence rate. It is important to mention that the second stage of ovarian cancer is the most difficult one for diagnosis as there are no clear anatomic lines between the pelvis and upper abdomen (Prat). This paper will analyze stage I and II ovarian cancer, in particular its symptoms, available treatment options, recurrence, and survival.

Symptoms of Ovarian Cancer

Ovarian cancer causes a few specific symptoms that could facilitate diagnosing a person with the disease. The onset of this type of cancer is either asymptomatic (has no symptoms), or the symptoms that arise are usually attributed to other health conditions such as premenstrual syndrome, irritable bowel syndrome, or a temporary bladder syndrome (Norqvist). Meanwhile, cancer metastasizes, spreading to other tissues and parts of the body, thus hindering treatment and reducing the possibility of survival. Due to the lack of visible symptoms, ovarian cancer is sometimes called “the cancer of the whispers.”

The first stage of this cancer does not possess and visible symptoms or noticeable characteristics. If a woman does have any symptoms, they are vague. These include pain in the lower abdomen or side and bloated, full feeling in the abdomen (Vaughan et al. 719). Progression of the disease and growth of the cancerous tumor at stage II may cause such symptoms as irregular menstruation periods or vaginal bleeding after menopause, abdominal pain (pain in the lower side of the body below the chest that contains the stomach, bowels, etc.), back pain, frequent and urgent urination, constipation, pain during sexual intercourse, a swollen abdomen, early satiety (feeling full quickly when eating), or the loss of appetite (Vaughan et al. 720).

Among other symptoms of ovarian cancer, the following ones should be mentioned:

  • pain in the pelvis (the wide curved set of bones at the bottom of the body that the legs and spine are connected to);
  • pain in the lower stomach;
  • indigestion, or dyspepsia (pain caused by difficulty in digesting food);
  • heartburn (pain that feels like something burning in the chest caused by indigestion) (Norqvist).

In addition, these symptoms may be also accompanied by nausea, weight loss, breathlessness, tiredness, and the loss of appetite.

Since the majority of symptoms are general, it is of paramount importance to undergo regular medical examinations to be able to detect ovarian cancer at its early stages. If some of the symptoms last for more than a year, there is a pressing need for consulting with the specialists to define whether they indicate the incidence of ovarian cancer. Thus, a positive symptom index (occurrence of any of the abovementioned cancer-related symptoms for more than 12 days per month in a less than a one-year period) indicates ovarian cancer in a variety of 56.7% and 79.5% of early and advanced stages of the disease respectively (Prat). Therefore, if any of these symptoms persist for a period of a few weeks or more, the woman having them should consider consulting a doctor.

Treatment of Ovarian Malignant Tumors

Treatment of ovarian cancer and its effectiveness depends on a number of factors that include the stage and type of the disease, the age of the patient, etc. Regardless of the stage, the patients undergo two standard treatment options for the disease, namely surgery, and chemotherapy. The aim of ovarian cancer treatment is to remove the largest possible area affected by cancer through surgery and kill malignant cells that may remain in the body after surgery by performing additional (adjuvant) therapy, chemotherapy in particular (Prat).

Surgery (Debulking)

At the beginning of treatment, a series of procedures and tests are performed to analyze and define the stage and the grade of the disease. The major procedure is the initial surgery called surgical cytoreduction or debulking. It refers to surgical removal of as much of cancer tumor as possible. It is considered the standard of care for ovarian cancer. In the course of the operation, the surgeon makes an incision on the side of the abdomen and takes the damaged tissues out of the body. The removal of the tissues depends on the complexity of the case and stage of the disease. In the most serious cases, the ovaries, fallopian tubes, uterus, omentum, and lymph nodes can be removed (Ovarian Cancer Research Fund Alliance). In addition, the doctor may take fluid from the abdomen to perform further analysis and define whether and how far the disease metastasized. Precise histologic diagnosis is essential for the prognosis of the stage of the disease and the needed treatment.

Apart from that, surgical treatment depends on the patient’s age and general health. The removal of both ovaries results in early menopause, thus infertility among younger women. If a young woman without children gets diagnosed with ovarian cancer, the operation will still remove only one fallopian tube and one ovary in order not to harm her fertility in the future (Ovarian Cancer Research Fund Alliance). On the contrary, elder patients may need to undergo chemotherapy prior to operation (neoadjuvant therapy) in order to shrink the tumor to the minimal size possible, thus facilitating its removal during the initial surgery.

In such a way, a large portion of cancer is removed from the body during debulking, which reduces the number of cancerous cells to be destroyed by chemotherapy. In addition, it decreases the likelihood of disease recurrence and resistance to chemotherapy. However, the data from two parallel European clinical trials on stage I and II ovarian cancer patients showed that only 0.64% of women recover completely after surgery and do not need adjuvant therapy (Prat). This proportion is true in regard to the individuals diagnosed with stage IA or IB and Brenner tumors (Kim 1). In general, stage IA and IB patients have 91-94% of 5-year survival rate, which means that the disease does not return within five years or more after surgery. However, from the stage IC disease, the patients need to receive a course of chemotherapy.

In the majority of cases, surgery cannot remove all cancerous tissues since a small number of cancerous cells that are spread within the body cannot be detected by any of the available tests. These cells that spread in the body through blood or lymph nodes are referred to as micrometastases (Valastyan and Weinberg 276). They are responsible for the recurrence of the condition after the initial surgery. Thus, stage IIA and stage IIB patients experience a 30-40% and 60-80% recurrence rate respectively (Valastyan and Werinberg 277). As a result, the following procedure in the treatment of ovarian cancer includes the course of chemotherapy aimed at cleaning the body from the damaged tissues.

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Chemotherapy

Chemotherapy (also referred to as cytotoxic medication) is a course of additional procedures in the treatment of ovarian cancer. The main aim of chemotherapy is to kill all cancerous cells that might remain in the body after the initial surgery. The cytotoxic drugs destruct the structure of the malignant cells, thus preventing them from dividing and growing (Norqvist). It may be performed either after surgery (in case the patient is young and the stage of the cancer is early, namely stage IC and stage II) or both before and after surgery (in case of treatment of older patients with stage III or IV cancer and patients with additional negative health conditions) (Prat).

During chemotherapy, the medicine is administered directly into the peritoneal area through a surgically implanted port and catheter (IP therapy) or into the veins through a catheter (intravenous, or IV therapy). According to Jelovac and Armstrong, IV therapy has greatly contributed to patients’ survival. The National Cancer Institute recommends combining both types of chemotherapy to ensure better treatment of cancer (National Cancer Institute). Chemotherapy usually involves 3-6 courses of treatment (Aslop et al.). As a rule, the combination of platinum-based (carboplatin) and taxane-based (paclitaxel) treatment is used during chemotherapy (Buys et al.).

Chemotherapy is highly effective in the early stages of ovarian cancer. Thus, three to six cycles of chemotherapy reduce the risk of disease recurrence by 24% within five years after its treatment (Prat). The chemotherapy is associated with a complete response (no visible evidence of disease on imaging scans and normal blood tests) in 80% of patients (Prat). Moreover, the olaparib maintenance monotherapy proves to be an effective intervention after the main course of chemotherapy, which provides the product recovery and rehabilitation for the patients with ovarian cancer (Ledermann et al.).

Nonetheless, in some cases, the patients may be resistant to platinum-based treatment, which proves the most effective type of chemotherapy. As a result, platinum-resistant patients have progression or relapse of the disease within half a year after the course of chemotherapy (Prat). These patients show the highest mortality level among ovarian cancer patients since there is no effective treatment for such patients currently. Therefore, the only available option for them is to enroll in clinical trials.

Furthermore, this type of treatment causes such side effects as nausea, vomiting, diarrhea, loss of appetite, hair loss, mouth sores, anemia, and infections due to the reduced levels of white blood cells (leucopenia).

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Effectiveness of Stage I and II Ovarian Cancer Treatment

In general, treatment outcomes (both survival and recurrence of the disease) depend on a number of factors. Thus, treatment outcome mostly depends on the cancer stage when a patient started to be treated. The more cancer has spread, the less promising its treatment is. On the contrary, if the patient is at stage IA or IB of the disease and the surgeon removes the whole tumor during the initial surgery, the patient has an almost 95% chance of complete recovery. With each subsequent cancer stage, the survival chances reduce inversely to the disease 5-year recurrence rate. Thus, approximately 90% of women with stage I and 40% of those with stage II ovarian cancer show 5-year survival after treatment (Cancer Research UK). For all the types of ovarian cancer taken together, about 3 out of 4 women with ovarian cancer live for at least one year after the diagnosis (Ovarian Cancer Research Fund Alliance).

In addition, general health and fitness may also affect survival. Thus, patients with a better performance status (assessment of how well and physically healthy a woman is) are likely to have better treatment outcomes. Similarly, young age positively affects women’s survival after surgery (and adjuvant chemotherapy).

Low survival probability at stage II and increased risk of lifetime mortality due to recurrent ovarian cancer suggest that the currently available treatment cannot ensure a complete recovery. The basic reasons behind low patient survival rate at the first two stages of the condition are as follows:

  1. First, although there is a defined standard of treatment, less than 40% of patients achieve the required help (according to Bristow et al.).
  2. Second, there are only two options for the treatment of first and second stages of ovarian cancer due to the blurred character of their symptoms and the impossibility to set the direct anatomic boundaries between different parts of the body (Prat).
  3. Third, the late-age onset (55-64 years) suggests a limited possibility of the organism to fight against malignancy and an increased likelihood of nonadherence to treatment.
  4. Fourth, the inability to locate and target all cancer cells in stage II ovarian cancer results in an 80% recurrence rate after the first treatment and a more than 50% mortality rate within five years afterward.
  5. Fifth, since stage I and II of the disease account for only about 30-32% of all cancer cases, the survival rate for these stages do not have a high impact on the general cancer survival rate. The majority of individuals are diagnosed at advanced stages, which result in high recurrence, short remission intervals, resistance to chemotherapy, and, thus, high mortality (Jayson et al.).

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Conclusion

Ovarian cancer is one of the most significant causes of cancer-related deaths among the female population of the US. It also remains one of the leading causes of death in gynecology. It affects the ovaries and the fallopian tubes in the early stages (stage IA- IC) of the disease and may spread to other organs and tissues of the body in advanced stages (stage II-IV). Two treatment options, particularly surgery and chemotherapy, are available for ovarian cancer patients at present. At the first stage, the ovarian cancer treatment proves to be the most effective (with about 95% patient survival rate at the onset of the disease). However, treatment outcomes are less promising at stage II disease. Hence, the research paper hypothesis about complete recovery after-treatment of the early stages of the disease was refuted.

The underlying reasons for high mortality and poor survival include both late diagnosis and lack of effective therapy. Moreover, stage II ovarian cancer patients may be resistant to chemotherapy, thus increasing the risk of disease recurrence and cancer-related mortality. Therefore, further research is needed so as to facilitate early diagnosis of the malignancy, and new treatment options should be developed to significantly improve the survival of ovarian cancer patients.

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